VOLUME 38 NUMBER 01

JANUARY 2020

Connected Strategies Are A Tale Of Two Pipelines AstraZeneca’s Fredrickson Vital For Medtechs In 2020 On Its Cancer Ambitions PAGE LEFT BLANK INTENTIONALLY invivo.pharmaintelligence.informa.com STRATEGIC INSIGHTS FOR LIFE SCIENCES DECISION-MAKERS CONTENTS ❚

January 2020

8 COVER ❚ In 2020 ESG Is Not A Tick-Box Exercise But An Opportunity William Looney

The idea that public corporations have obligations that extend beyond the fiduciary responsibility to shareholders will be the dominant measure of responsible business behavior in the coming decade. Uncertainty about the extent of these commitments – commonly referenced as the environmental, social and governance (ESG) agenda – has produced equally variable responses from companies in the health care business.

14 20 24 A Tale Of Two Pipelines Bayer US Pharmaceuticals’ Connected Strategies Are Vital DENNIS CHANG, KEITH FLAHERTY AND Sebastian Guth: Designs On For Medtechs In The Consumer- UCIANE SCARLETT A New Decaden Led 2020s Immuno-oncology has produced some WILLIAM LOONEY ASHLEY YEO exciting successes, but the field has Bayer’s ambitious campaign to Discussions on the shape of health care become intensely crowded. Enormous reposition itself as a global leader in two have moved from “reimagining” to the resources are being poured into complementary fields – health and next stage: building and executing on the duplicative work and shaky hypotheses— nutrition – will face its toughest test in vision. That is the thrust of EY’s NextWave overshadowing other pursuits in cancer the US, with its highly litigious approach Report: New Horizons 2019. Additionally, research while producing limited results. to product liability and a tendency to for medtechs seeking business continu- It is time to re-evaluate how the sector target pharmaceuticals as the source of um, “duality” is now a preoccupying should be pursuing innovation in cancer the health system’s affordability and thought. and how it can be smarter in its use of access problems. resources—financial investment, talent, bandwidth, patients and data. 30 AstraZeneca's Fredrickson On Its 28 Cancer Ambitions Roche/Genentech Partnering ALEX SHIMMINGS Team: One Face For The World Just over a year ago AstraZeneca at last To See returned to growth and set about a reorganization that placed oncology at the LUCIE ELLIS heart of its plans for continued success. In Thomas Zioncheck, global head of Vivo talked to the executive vice-president neuroscience, ophthalmology and rare of its Oncology Business Unit David diseases, Roche Pharma Partnering, talks SEBASTIAN GUTH Fredrickson about how the company to In Vivo about Roche and Genentech’s hopes to become a major cancer player. united partnering group, 2019 successes, and highlights ahead for the big phar- ma’s neuroscience pipeline.

©2016 Informa Business Information, Inc., an Informa company January 2020 | In Vivo | 1 ❚ CONTENTS

January 2020

DEPARTMENTS ❚ From The Editor AROUND THE INDUSTRY In this first issue of a brand-new decade, In Vivo 4 Executive Briefing: C-Suite And has filled its pages with a variety of content, Investors Discuss A New Decade from C-suite interviews to productivity over- WILLIAM MASTERS views and strategy analyses. 6 When Will POC Really Be On At the close of 2019, we published the annual The Cusp Of Major Uptake? Outlook issue which comprises 10 chapters of ASHLEY YEO original content, including the most recent Scrip 100 and Medtech 100 company perfor- 34 ON THE MOVE mance rankings. All of this content can be Recent executive appointments found in one place on our website: invivo.phar- in the life sciences industry LUCIE ELLIS maintelligence.informa.com/outlook. REGINA PALESKI Meanwhile, looking ahead into the new year, we have published a selection of thought leadership articles online that analyze the year ahead, predict- 38 DEAL-MAKING ing key trends and discussing hot topics like gene therapy M&A targets and Deals Shaping The Medical Industry, the advancement of digital tools. December 2019 THE STRATEGIC TRANSACTIONS TEAM The start of 2020 also marks a few changes at In Vivo Headquarters. William Looney has retired from In Vivo, however he will still be involved with the publication as a new member of our Editorial Advisory Board. The advisory board itself is undergoing some changes – look out for exciting announce- EXCLUSIVE ONLINE CONTENT ments about this in our February issue.

invivo.pharmaintelligence.informa.com Succeeding William as In Vivo’s executive editor for biopharma is Ben Comer, who joined the team on January 6, 2020. Prior to joining us, Ben was a senior ❚ AstraZeneca Veteran Returns To manager in PwC’s Health Research Institute. Previously, he was a journalist Biotech With Fresh Goals For A with Pharmaceutical Executive; Medical Marketing & Media, PRWeek and Di- New Decade rect Marketing News; and Ad-Fax Media. LUCIE ELLIS Finally, January see us launch the annual Deals Of The Year contest. Voting is open in the three categories for 2019: Top M&A, Top Alliance and Top Fi- ❚ Gene Therapy Companies Among nancing. The winners will be announced in February. Don’t miss your Top M&A Targets In 2020 chance to vote, go to our homepage for full details of the nominees. ANDREW MCCONAGHIE

❚ What Does 2020 Hold For Biopharma? In Vivo: Always Online First Don’t have an online user account? JOSEPH HAAS AND Quickly and easily create one Relevant and exclusive online-only ELEANOR MALONE by clicking on the “Create your content at your fingertips 24/7. account” link at the top of the page. Full access to our 36-year archive. ❚ The Role Of AI In Signal Detection Contact: MIRANDA GREENHALGH Access your subscription by visiting: [email protected] invivo.pharmaintelligence.informa. or call: (888) 670-8900 or +1 (908) ❚ What The New Decade Could Bring com and log in. 748-1221 for additional information. For Alzheimer’s Treatment ANDREA PFEIFER All stock images in this publication courtesy of /invivo @invivo /invivo www.shutterstock.com unless otherwise stated.

2 | In Vivo | January 2020 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com invivo.pharmaintelligence.informa.com CONTENTS ❚

❚ Up-Front SNAPSHOTS FROM JANUARY’S CONTENT

Every partnership is unique, “a rulebook approach is not useful now that the overall climate for drug development is so fast- Given the widely held view paced and competitive” that medicines, devices PAGE 20 and diagnostics are public – Sebastian Guth goods, pharma and medtech companies face a high credibility bar on environmental, social and governance activities. A tremendous amount of It is no longer standard capital and human resources practice to assign the ESG has been consumed by portfolio to the corporate policy team. PAGE 8 immuno-oncology, and there

are signs that exuberance for immunotherapy has become The future of health lies “ I want to let partners with technology. Within unsustainable. PAGE 14 2010 2011 2012 2013 2014 2015 know that we’re very the health care industries, 120% open to partnering new investors have been among 100% technologies, across the first to act on this 80% neurodegeneration, realization, funding health 60% tech, practice management 40% neuroinflammation and

20% neuromuscular diseases” and home health care ever

0% PAGE 28 more concertedly over the

Amount of royalties/milestones not disclosed  – Thomas Zioncheck past decade. PAGE 24

Note: Bubble size represents vale of upfront payment

©2016 Informa Business Information, Inc., an Informa company January 2020 | In Vivo | 3 ❚ Around The Industry

Executive Briefing: C-Suite And Investors Discuss A New Decade

From the US election to being over-focused on oncology, from the promise of artificial revenue stream. intelligence to private funding in Europe – there were a range of issues and opportuni- “All over the world, especially in the ties discussed at In Vivo’s inaugural executive briefing. emerging markets, they are all running out of money. Health care budgets are Having a commercially relevant drug completely challenged – they haven’t got means having a product that is “afford- any money at all. So even if you go into  able and accessible,” said Roel Bulthuis, ❚ PANEL SESSION: specialty pharmaceuticals, if you go into managing director of INKEF Capital. “As BIOPHARMA STATE OF rare diseases, they cost anywhere up to investors, and as an industry, we need PLAY IN 2020 AND BEYOND $2m dollars per patient. Authorities in to take an active role in defining what Brazil, India, South Korea or South Africa affordable means. If we don’t think right cannot afford these things. So, we have now about how we’re going to position CHAIR: to rethink this.” drugs in a commercially relevant setting – Mike Ward, Head of Content Bulthuis defended the idea of having meaning affordable – we’re going to lose at EBD Group different portfolios for different markets, that discretion at some point,” he said. arguing that it is the same for any in- The specter looming over the com- PANELISTS: dustry: “If I were developing software I ment, and the industry itself, is the Roel Bulthuis, MD, would start with where the market was.” current hostile political discourse sur- INKEF Capital Bulthuis made the case that developing rounding drug pricing. When asked by products for the US and Europe was a chair of the panel, Mike Ward, what was Charlotte Casebourne, different thesis than for Africa. He noted keeping the industry up at night in 2020, CEO of Theolytics & that the industry was already increasing four out of six panelists emphasized the board member at BIA investment outside of traditional mar- political climate – including the US elec- kets, moving into East and Southeast tion, Brexit, and the US-China trade war. Tobias Kloepper, CEO, Asia. While agreeing that access and The US still represents around 60% Aigenpulse affordability should rightly be champi- of industry revenues today, noted Zulf oned, Bulthuis argued that to justify an Zulf Masters, CEO, Masters, CEO of Masters Specialty Phar- investment “you have to start with where Masters Specialty Pharma maceuticals. This is still a central focus the markets are.” of the US election. Steven Powell, CEO, CHINA IS THE WATCHWORD Charlotte Casebourne, CEO and co- eTheRNA founder of Theolytics, gave insight into Steven Powell, CEO of eTheRNA, also how the start-up company is thinking Naveed Siddiqi, Partner, discussed the increasing interest by the about accessibility at an early stage. She Novo Ventures pharmaceutical industry in Asia, and said companies need to ask questions particularly China – not just for funding “at the discovery phase to ensure that but for strategic purposes as well. “You accessibility is possible.” Casebourne can see on the news that some of the big highlighted manufacturing as an aspect This issue of accessibility is not simply pharmaceutical companies are turning of the development chain that needs a question of pricing in the US (and to a their attention to the East rather than just more consideration earlier in develop- lesser extent in Europe) but also one of purely focusing on the West. I think that ment, in the preclinical or Phase I stages. geography. Early on in the discussion is going to – one way or another – lead Naveed Siddiqi, partner at Novo Masters commented: “We’re still putting to a significant amount of activity going Ventures, added: “That’s good to hear. all our eggs in one basket. Once upon a forward, from both big companies and We hear a lot of interesting science but time I think 60% of revenues came from small companies.” that question [accessibility] is not always the US, that figure did go down a little 10- Powell highlighted that it had not thought about. Oftentimes we find the 15 years ago to about 45%. I think we’re been easy, having himself spent a lot of answers a bit lacking there.” back to 60% now – the US being the main 2019 in China, to figure out how to get

4 | In Vivo | January 2020 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com invivo.pharmaintelligence.informa.com AROUND THE INDUSTRY ❚

things done. Interestingly, he also noted is now in a strong position when it comes that the US-China trade conflict could to earlier-stage financing. be beneficial in Europe. Still, Europe is “something of an unknown quantity” to DIGITAL DIALOG IN 2020S a lot of Chinese companies and investors, The panel also debated the rise of digital and there was significant nervousness technologies and AI. Tobias Kloepper, about stepping into Europe, despite the co-founder and CEO of Aigenpulse, neatly potential, Powell said. captured the hype around AI early on: “The Powell also noted there was a greater easiest thing is to add [the phrase] AI to emphasis on manufacturing in China everything you do – you get attention when compared with Europe, from both that way, but very few are actually doing Chinese venture capital and large phar- anything novel.” maceutical companies. One area where On a more serious note, Kloepper China falls short – at least in the eyes of spoke of the potential of AI in a range of western observers – is the way R&D and areas, including discovery, diagnostics intellectual property are assessed. and clinical trials. AI is infinitely better Despite these difficulties, Powell “Some of the big positioned to process large amounts of made it clear that there was great op- data, such as pathology images, than portunity in China and a strong appetite pharmaceutical humans are. for investment in, and partnerships companies are turning When it comes to tech companies with, Chinese firms. The market is large in biopharma, Kloepper said it could and structured differently, but it is by their attention to the be difficult to position yourself. Many no means inaccessible. Ward made the companies are mid-sized and are faced prediction that the coming decade will East rather than purely with investors who want to put them in a see at least one major pharmaceutical box – either as a technology or a product company announcing China as its largest focusing on the West. development company. single market for drug sales. The CEO also pointed to an issue I think that is going to around education and life sciences START-UP STRATEGY investors, stating that many did not Casebourne, representing the innovative – one way or another – understand AI. “They ask what new start-up sector, stated that Theolytics is lead to a significant algorithms you have, but that's missing open to R&D collaborations or partner- the point that the digital transforma- ships that will support them to validate amount of activity going tion journey going on in the industry is and develop what they believe is a cat- actually enabling the effective and wide- egory changing platform. forward, from both big spread use of data. We have had to put Achieving this is crucial to success in lots of energy into educating investors.” a highly competitive field; indeed oncol- companies and small Kloepper did praise the progress that ogy receives the lion’s share of global had been made in the last 4-5 years, with R&D spend. Casebourne emphasized that companies.” larger players starting to understand despite this saturated market, there was the value of information technology. significant interest in category changing He said Aigenpulse was having better modalities. Theolytics hopes to close its Steven Powell, discussions with big pharma and more Series A funding round early this year. engaged conversations. Ward pointed to Europe’s relatively CEO of eTheRNA Moving into 2020 and the next pharma poor performance for funding biotechs, cycle, the panelists were optimistic. True, which has been stagnant for some time. the increased scrutiny around drug pric- In particular he noted very little growth ing will inevitably impact the industry. in venture capital financing in Europe, But so long as companies respond to as well as later-stage funding – when concerns proactively, this threat can companies file for their initial public of- be mitigated. Industry will then be able ferings (IPOs). There is simply no viable to fully focus its attention on meeting European challenger to NASDAQ in the the great expectations of patients and US, which has prompted an increasing shallow compared with the US, in terms stakeholders for the next generation of number of European firms – such as Gen- of early funding the continent has made medicine. mab or BioNTech – to list there, despite significant progress. During the discus- IV124404 their European roots. sion Siddiqi emphasized that industry While Europe’s capital market remains should not be too harsh on Europe, which WILLIAM MASTERS

©2017 Informa Business Information, Inc., an Informa company January 2020 | In Vivo | 5 ❚ AROUND THE INDUSTRY

When Will POC Really Be On The Cusp Of Major Uptake?

Point-of-care/near-patient testing has been “two years away from a major break- become extinct. The question is precisely through” for at least two decades, but fast access to data via automation and IT means how important will it be in the future? that progress might be made at last. How the tests are paid for remains an issue. The For some diseases, decisions need to be future of POC was the theme of an investor discussion at the first DxPx conference, quick – speed is one of the parameters of held during the Medica 2019 event in Germany. POC. And here, the valid questions are: how long should physicians wait, and “We’ve heard for many years that that how long are patients willing to wait for POC is just around the corner from being certain information? a major driver in health care decisions,” The consensus was that there will said Chris Myatt, CEO of MBio Diagnostics “What works is always be conditions where a central Inc.. Myatt was addressing the inaugural lab is needed, but that its prominence DxPx diagnostics/investor partnering a five- to seven- or will diminish. event in Düsseldorf, Germany. Progress on POC adoption has been slower than eight-minute test DIGITAL DEXTERITY many had predicted, but matters are that can be Manfred Augstein, of velixX, pointed about to improve. out that digitally assisted fast access “I perceive a large uptake in POC over initiated during to information was vital. But it must be the next decade, driven by access to in- remembered that the information is be- formation,” said Myatt, whose company the consultation; ing generated via technical solutions. sells the rapid, on-the-spot portable “We’ve talked for 30 years about the need LightDeck platform, which is claimed to that is the for POC, but so far we’ve only seen small deliver lab-quality results in minutes. changes. Today, it can be accelerated, but Mobile phones have changed completely sweet spot.” only because of IT, automation and fast the time it takes to get an answer to a access to data,” he said. The technology question, and that access, plus the desire – Lars Ullerich is available, but “there is still no push from to make decisions faster, will, in the long the market to really pay for this; that has run, drive consumer demand pull. MD of GNA Biosolutions been the problem for many years.” On the Speed, cost and ease of use are the access side, testing for 10-15 parameters necessary parameters for POC – without in 30 minutes was doable, he said. these POC would never fulfill its promise, Michael Sidler, of RedAlpine Venture, Lars Ullerich, managing director of GNA Fellow panelist Daniel Parera, of TVM was of the same mind. For the past 20 Biosolutions, told DxPx delegates. Most Capital International, predicted that years, POC had been “two years away” technologies have not been able to do this POC would be redefined. Now, there is – and it still had not really arrived, he at the POC level yet. Molecular diagnostics, the ability to access information “where said. Nor will it ever replace the central the gold standard for infectious disease a person is, and right now.” Previously lab. Rather it will supplement it. “The testing, has not been fully able to deliver that was where the provider could deliver paradigm of change is that personal com- these three factors at the POC. But the the care. There has also been a redefini- puting devices, such as smart watches, sense is that it is now getting there. tion of diagnostics, away from hardware are supplementing central lab diagnoses Achieving the triple challenge in the and analytes toward a perhaps a more with multi-modal information.” POC setting has been hard, and yet the nebulous concept: of how information is One example is US company Mind- market and clinical need are there. It was processed. In any case, there is now “a Strong, whose technology can detect obvious that faster decisions would lead different dynamic now around how POC mental disorders through behavioral to better clinical outcomes, but it had diagnostics will be used,” he said. changes using a smart phone. The pat- not yet been fulfilled, said Ullerich. In Does the rising utility of POC mean the ented and FDA-approved phenotyping addition, the regulatory side has been future of the central lab is threatened? software collects data from the smart- lagging; it may even be the case that the That was an opening question from DxPx phone to provide measures of cognition regulatory landscape will not catch up panel moderator John Riddle, a manag- and emotion. with the needs of POC. “We may see POC ing director and executive committee Myatt sees the beginnings of real consumer and self- and homecare testing member at Brown Gibbons Lang’s health change in the payment structures. In actually overtaking clinical POC testing,” care and life sciences group. Responding, the US, patient self-directed testing paid Ullerich added. Ullerich was clear that the lab would not out-of-pocket is showing growth rates.

6 | In Vivo | January 2020 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com invivo.pharmaintelligence.informa.com AROUND THE INDUSTRY ❚

For example, Everlywell, a US health and price, but established routines going back fact that there has not yet been broader wellness company, is providing at-home over decades,” said Sidler. uptake is because it needs to be driven by lab testing kits promising digital results Investors in diagnostics were attracted direct need and pain point. Diabetes is a within days; and the US CVS pharmacy both by “faster is better” and by solutions very high pain point. “When we have that chain has upgraded its Minute Clinics to that meant processes did not have to be pain point, we get it. But that is not a driver be able to bill the patient for the test and changed, said the panelists. Stressing for broader POC solutions,” said Sidler. the drug all in the same visit. Bringing health rather than disease will secure He said: “Put yourself into the shoes it all together in this fashion makes the much better acceptance, as will tests that of the consumer,” and went on to de- test a small piece of the overall picture. are linked to therapeutic consequences. scribe how the only rapid test used at “The number one promise of POC is “As investors, we’re always trying to home was the pregnancy test. This, he speed. But what does that mean – five be ahead of the curve. Predictive ana- said, was a need, but it was also a test to 10 minutes, or 30 minutes? There are lytics and personalized diagnostics are that potentially produced a positive no strict parameters. And when hospitals the buzzwords, and ‘predictive’ is the result. Many other tests will produce po- buy the tests, are they really bedside? Ul- paradigm shift,” said Sidler, pointing out tentially negative results. “In our culture, lerich said it was a question of how close that in predictive diagnostics, the care is does the consumer want to find out such do we get to the patient? Some tests predicated on the individual’s baseline, things at home?” he asked. might not even fall under the definition of not on population health averages. HIV testing is a case in point. Home POC, as they might not hit the window of In certain diseases, continuous in- HIV tests have been introduced to phar- the interaction time between doctor and formation and predictive tools, e.g., in macies in the US, but it will be interesting patient and clinical workflows. diabetes, can be used, meaning predictive to see if they will be adopted by consum- Thirty minutes might be too long. The analytics start to become “doable,” Sidler ers. Although the user will be unskilled, likes of Walgreens (the second-largest US added. Some companies are reportedly will more people want to know what their pharmacy store chain, behind CVS) and predicting blood sugar level changes in status is, albeit with lower accuracy? even primary care GPs have only 15 min- a patient for immediate one to two hours Similarly, individuals can now order utes to deal with a patient. “What works ahead. This might be soon applied to STD tests and have them sent to their is a five- to seven- or eight-minute test other diseases as well. “We can start col- homes. Even though most tests done at that can be initiated during the consulta- lecting information with the help of AI and home will need to be sent back to the lab, tion with results coming back before the deep learning, and draw parallels which it would be a potential advantage to the physician needs to see the next person. can be very meaningful.” user to already know the result at home. That is the sweet spot,” said Ullerich. But “predictive” is not entirely new. If there is personal value in the process, Perera pointed to Kaiser Permanente, more people will likely choose that option. FITTING INTO THE LEGACY both a provider and a payer, that 10 years “We are talking about people getting more HEALTH CARE SYSTEM ago already claimed to have a very good clear with their own picture and wanting to Another vital consideration is how a POC predictive overview of a patient’s care – keep their health,” said Augstein. product fits into the routine of the physi- because it had the right information on a But the market pull is just not there cian and the hospital system. Entrenched patient. It claimed to predict the likelihood yet. Myatt concurred: “I agree that we’re processes are a prime reason why it is hard that the patient would walk out the door looking on a 20-30 year time frame, be- to get closer to the bedside. Clinicians are two days after an ER admission. cause of the cultural change needed, not working in systems that have been in place because of the technology.” for decades. “If you try to change the pro- POC AND PAIN POINTS IV124417 cess, they will just stick with what they’ve POC is currently driven by single areas, ASHLEY YEO been doing; it’s not the technology or the like cardiac testing and diabetes, etc. The

LET’S GET SOCIAL

@INVIVOnow

©2017 Informa Business Information, Inc., an Informa company January 2020 | In Vivo | 7 ❚ GROWTH OPPORTUNITIES Title

Executive Summary Shutterstock: Copyright Info Copyright Shutterstock:

BY AUTHOR

Fact 1

Fact 2

Fact 3 DESIGN: Gayle Rembold Furbert Rembold Gayle DESIGN:

Is ESG yet another external risk factor that Or is it a new opportunity to earn To address these questions, In Vivo recently must be handled deftly to avoid a loss of the goodwill that strengthens ties to sat down with Marshall Gordon, senior investor and consumer confidence – and customers, raises operational efficiency health analyst at New York’s ClearBridge a potential big hit to the bottom line? and attracts talent? Investments, whose involvement in impact investing extends back three decades, and today evaluates more than $115bn in assets for ESG risks and opportunities.

8 | In Vivo | January 2020 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com GROWTH OPPORTUNITIES ❚

ESG In 2020: Not A Tick-Box Exercise But A Strategic Opportunity

The idea that public corporations have obligations that extend beyond the fiduciary responsibility to shareholders will be the dominant measure of responsible business behavior in the coming decade. Uncertainty about the extent of these commitments – commonly referenced as the environmental, social and governance (ESG) agenda – has produced equally variable responses from companies in the health care business. BY WILLIAM LOONEY

stimates of the size of glob- In Vivo: ESG is not a new function in We don’t follow the usual path of relying al investment assets vary the stock trading business but its pro- on a separate unit to address the entire considerably, from the file has certainly grown in the last few range of ESG issues. In our view, every $31tn figure compiled by years. What brought you to this field industry sector is different in terms of the leading ESG advocacy and why is ClearBridge committed to what ESG means – oil companies don’t group, the Global Sustain- ESG as a key element of its investment face the same set of issues as health care able Investment Alliance, to $3tn, by the management for clients? businesses. So, we put the responsibility Ebankers at JP Morgan. There is consensus Marshall Gordon, ClearBridge for handling the ESG brief in the hands of that, whatever the number is, it is going Investments: I have a background in the sector analyst, who has the relevant up. The demographics are good – millen- investment banking, which led to my expertise to define the ESG issues that nial investors are major backers of ESG, exposure to health care – many deals count in the specific business area and to as are sovereign investment funds, public were on the table which required me know with whom to engage in determin- employee pensions and family offices to learn the industry. Subsequently, I ing how ESG will shape investment deci- backed by private equity. moved into equity research which called sions. In other investment organizations, Numerous initiatives are underway to for greater facility with data, as well as you will find that ESG sits apart from the establish better metrics to assess ESG op- an understanding of key macroeconomic real sources of sector expertise, making portunities and monitor the performance and social drivers. It also demands a high ESG more of an extracurricular policy of these assets. Nasdaq’s May 2019 ESG level of intellectual honesty to make good topic than a function that is integrated DESIGN: Gayle Rembold Furbert Rembold Gayle DESIGN: Reporting Guide 2.0: A Support Resource investment decisions, which I liked and to the business. In fact, it is still a com- For Companies is but one example. is clearly part of the ClearBridge culture. mon approach to ESG on Wall Street to Given the widely held view that medi- I also appreciated the integrative ap- allocate ESG evaluation to an external cines, devices and diagnostics are public proach to equity investment research third party who provides advice and sup- goods, funded in part by public money, at ClearBridge. Unlike most other Wall port as needed. Now that ESG has come pharma and medtech face a high cred- Street firms, ClearBridge puts the senior into its own as a determinative factor in ibility bar on ESG. It is no longer standard sector analyst – like me, for health care – investment, many investment companies practice to assign the ESG portfolio to the in the lead when evaluating ESG impacts are scrambling to make up for lost time. corporate policy team – direct access to for that sector. Every fundamental analyst In addition, the ClearBridge ESG top management is the new normal. at ClearBridge is an ESG specialist as well. platform is an expression of the overall

©2018 Informa Business Information, Inc., an Informa company January 2020 | In Vivo | 9 ❚ GROWTH OPPORTUNITIES

philosophy we take to investing. As ac- There are very few publicly traded tive managers, we choose not to own companies that are certified as a B- everything; our portfolios are generally corporation. However, this is starting to quite concentrated, often with only 50 change, as a few (small) public compa- or 60 stocks, which we hold for the long nies we review as investment candidates term – seven years, on average.This facili- are starting to explore the feasibility to tates access to management, with whom get certified in the 36 US states that now we can engage directly on business and grant eligibility for this status. ESG issues. And we don’t carry sticks. We don’t FUTURE STATES make demands. Our approach is progres- Within the space of five or six years, sive in that our goal is to make our compa- more than half the US workforce will nies aware of what we think on ESG and to be composed of individuals age 35 or share best practices we see elsewhere in younger. Surveys show that millenni- their lines of business. It’s never a “check als are the demographic group most the box” exercise. We don’t ask a drug eager to invest using ESG criteria. maker to do the same thing as a man- Family offices representing the great- aged care company or a manufacturer of est reserves of wealth are also trend- medical devices. The ideal outcome is after ing this way. How is this coming wave speaking with us, management comes to around socially responsible investing a decision on its own – it’s the soft light going to affect big companies – and of self-realization rather than the glare of particularly big pharma? being under the spotlight. We see companies Millennials tend to get the idea of ESG. The future is top of mind to them; many Can you highlight the major forces that look at ESG as have direct experience with parents who shaping the investor landscape in lost their savings during the financial health care today, and how these com- their guidepost for crisis, and they are approaching finance pare to the situation from decades ago? itself with caution. The conversations Perhaps the most significant change best practices ... young people have with their families, has been the recognition that outside schools and employers translate into a investors have a right and obligation to there are also the growing investor interest in incorporat- set the standards of governance for a ing a responsible investment dimension corporation. This includes input on such laggards that still into their finances – and the investment issues as the structure of boards of direc- industry is working toward providing it. tors, or on workforce conditions like di- don’t see ESG as a The generational demographic stok- versity, inclusion and anti-discrimination ing interest in responsible investing rules. Specifically, to health care and bio- priority or are not coincides with an equally important shift pharma, access to affordable medicines is in how institutional investors apply the now an inescapable top-of-mind issue for sure how to move fiduciary principle – the duty to always the entire C-suite, from patient assistance act in a manner that maximizes the fi- and specialty hub services programs to from PR rhetoric to nancial return for the client – which is drug benefit design and re-insurance now inclusive of a broader interpretation geared to provide cover for high-priced a full business to include consideration of social and drugs. Engagement with health care and environmental issues. The premise is pharma companies on market access commitment. that failure to consider issues like patient policies is becoming more structured and access to medicines, the environment or transparent, with the dialogue increas- workforce diversity and inclusion could ingly taking place in the public arena. Marshall Gordon result in losses for investors in the long term. The European Union, too, has been What about the possibility of incorpo- very assertive in promoting the idea that ration in the US as a B class – benefit generating wealth requires attention to – corporation, which allows boards to the underlying social consensus that pursue social and community priori- legitimizes high returns, and the US will ties like the environment in addition not be far behind. to the fiduciary obligation to share- I believe the interest in ESG represents holders? Is this adding momentum to an opportunity for big pharma. Ten years the ESG movement? ago, when I visited a big pharma or bio-

10 | In Vivo | January 2020 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com invivo.pharmaintelligence.informa.com GROWTH OPPORTUNITIES ❚

tech HQ, ESG rarely, if ever, came up. We see companies that look at ESG as picture for them. It’s a very proactive ap- Today, it is definitely on the list of key top- their guidepost for best practices and are proach that some larger companies have ics to discuss. It’s not a “check the box” always seeking that positive equilibrium taken years to figure out. exchange; we expect to be scrutinized between quality and costs and efficiency Elsewhere in health care, CVS/Care- and to justify our views with hard data. and outcome. There are also the laggards mark is a company that has adapted This comes as no surprise to me. Health that still don’t see ESG as a priority or are an ESG agenda as its market reach has care and pharmaceuticals are sectors not sure how to move from public relations expanded. The company has evolved that are well-suited to bridge the space rhetoric to a full business commitment. from an over-the-counter drug retailer between the fiduciary principle and Some are reactive and heavily dependent and pharmacy chain to a pharmacy those wider macro trends that impact on watching what their competitors might benefits manager (PBM) and, with the global economic and social well-being. do first. We also distinguish between recent addition of Aetna, to a health Health services and pharmaceutical and start-up biotechs at the pre-revenue stage, plan insurer. The company is positioning medical devices are widely seen as public those who have one or two drugs across itself as a health and wellness provider goods, where the challenge is to provide a the finish line, the more mature biotechs whose extensive retail presence gives it socially responsible product in a market with larger product portfolios and finally access to a huge population of patients, milieu. What better way is there to have the big pharma giants. which CVS can now serve in a variety of a positive social impact than discovering Every company will face different different ways. The decision to stop sell- and bringing to patients innovative prod- sets of opportunities and challenges as ing cigarettes was a major ESG response ucts that treat and cure disease? they move through these stages of the to this dramatic repositioning of the Accelerating innovation for an unmet growth cycle. However, I would say bio- business, one where management felt it need is the core mission of any success- tech companies often relate to the ESG was worth it to take a hit on revenue to ful company and biopharma has, in agenda because of the simplicity of their be consistent to its mission as a health most cases, been doing that for years. If message – they exist to help patients in care company. And now, with Aetna and drug companies do their jobs right, their a disease area for which there are few, if a PBM, the goal is to take this mission products are going to improve human any, treatments. They also don’t have the to the next step, with additional on-site health. The culture they work in doesn’t legacy traditions that keep bigger, older clinical interventions designed to achieve pose the ethical dilemmas that confront organizations from moving quickly to better health outcomes at a lower cost. some other sectors: when fossil fuel address governance issues. CVS is an example of how companies are companies do well, they help destroy the One trend we have noted is what hap- taking the ESG theme and running with planet. Instead, the challenge in health pens to a small biotech when the founder, it – to communicate and build the brand care is to do more to reduce the cost and who is usually an entrepreneurial scien- around a much broader set of metrics logistical burdens on patients to get the tist or physician, hands over the reins centered on reputation. treatments this industry has invented, to a commercial manager. Although it where nothing existed before. is often a marker of success – finally, SOCIAL IS PHARMA’S there is a product to sell – the transition SOFT UNDERBELLY How is ClearBridge handling the grow- can result in stumbles on the culture ClearBridge’s latest impact report in- ing prominence of ESG investing? and governance front if it’s not handled cludes a chart that shows the E, S and ClearBridge has invested heavily in a astutely. Suddenly, all that wonderful G weighting by sector. The biopharma firm-wide ESG integration approach. Our science must yield to the demands of sector’s biggest allocation within ESG investing criteria now covers 95% of shareholders to make real money. “ESG” is Social – 65%. Can you clarify the $145bn in the various assets held by An example where we see it being what this means? ClearBridge. Fundamentally, this means done well is Agios Pharmaceuticals, a What we mean is that society expects that an ESG analysis has been conducted Cambridge-based start-up that attracted the health sector overall to do one thing on each stock, generating an internal our interest early on; ClearBridge has a well: improve the state of human health. risk/reward and ESG rating, as well as a 2% stake. Under Agios founder and CEO That entails a set of obligations for plan to engage with the company on an David Schenkein, a physician-scientist, biopharma, which is to promote better ongoing basis. The aim is to get this num- the company has made that difficult access and affordability for medicines ber to 100% of our asset base before long. transition to a two-marketed product and vaccines. Some quarters of society company. Last year, Schenkein recruited believe that drug donations and co-pay TO EACH THEIR OWN Jacqualyn Fouse, an ex-Celgene com- assistance programs are not enough. Do you see much difference among mercial lead, to succeed him as CEO and Pricing of medicines is the fundamental biopharma companies in how they take the organization to the next level. issue, not just for established medicines approach the ESG platform? To help scale up, Fouse and her team are but for those new cures coming from gene There are substantial differences, driven consulting widely on what ESG means for and cell therapy. How is your company by factors that range from maturity and Agios’ future – and how to communicate going to make these products affordable size to the characteristics of a company’s that perspective to the investor commu- so society avoids the situation where only culture, which is often set by the CEO. nity. Good governance is a big part of the the rich will benefit? The social exposure

©2018 Informa Business Information, Inc., an Informa company January 2020 | In Vivo | 11 ❚ GROWTH OPPORTUNITIES

is so high because right now many drug giant Government Pension Investment Generally, within the ESG community companies do not answer this question Fund (GPIF) – the largest in the world – in itself, the major emphasis has been on well to public stakeholders. Another recent years decided to adopt ESG as its interacting with the large-cap companies related question is being transparent preferred moniker. In Europe the term “so- in health care. ClearBridge is going to about the value each new therapy brings cially responsible investing” (SRI) is cited give more thought to how ESG can relate and how a pricing and access strategy more frequently in place of ESG. “Impact effectively at the level of the small- and will capture and deliver that value to the investing” is another shorthand attempt to mid-cap players. I believe understanding patients who need it. place the ESG concept in a larger context. the trends here and working to position Finally, there is the most inclusive – and companies appropriately is equally, if not What is the ClearBridge message to confusing – word of all: sustainability. more, important for them as it is for big biopharma companies and investors Despite the diversity of terms, I believe pharma. This is particularly true for the on the Access to Medicines Index, an we in the investment community are much transitioning biotechs, with real products annual ranking of the 20 largest bio- closer on what we are pursuing. Business and the accompanying responsibility pharma companies produced by the has a responsibility to contribute to the for pricing, ensuring access and selling non-profit Access to Medicines Foun- communities of which they are a constitu- medicines. Helping them make their ini- dation, based in Amsterdam, with the ent part. It is good for business to do so. tial ESG steps is where I expect to spend aim of making medicines more afford- Return on investment can be validated more of my time going forward. able in countries of the developing in many ways in addition to financial We have to keep on message about ESG world. How important is the index to numbers alone – and, our own investment as a long-term, evolutionary process, as you in evaluating ESG performance? experience has shown that good corporate opposed to the current climate, where We’ve been actively working with the behavior/sustainable practices can be ad- investment decisions are pitched toward Access to Medicines Index for several ditive to long-term returns. a very short-term time horizon. While the years.We discuss the ranking with com- It’s important that we avoid taking statistics indicate US stock managers pany management.We see this as one a perspective that is too homogenous. have an average holding period of just 1.7 piece of making sure patients globally Financial metrics aren’t as relevant given years, at ClearBridge we hold stocks an have access to medicines. But it’s not that performance on social, environment average of more than seven years. That the whole picture.The initiative focuses or governance grounds will necessarily long time horizon reflects our strategy on developing countries, which is impor- vary depending on what business sector on ESG. tant, but wealthier developed countries, you choose to evaluate. In biopharma, The message we take to the C-suite including the US, are just as critical to progress in meeting a real medical need on ESG is don’t think of it as buying consider. There are still huge access is a key measure of ESG performance, and into a series of extreme actions – that issues to address, especially in the US that depends on such factors as product executing an ESG program is going to be health care system, where patients bear innovation, distribution and logistics costly, require lots of expensive outside a significant portion of the cost. to secure access, and the price of that consultants and run counter to ingrained innovation. Such aims and criteria are company culture that will take years to It seems a prerequisite for this move- impossible to harmonize across the entire transform. None of this is true. Our own ment is a clear definition of what ESG is industry. If you do that, you risk losing the efforts to advance ESG go back 30 years. – and what it stands for. Has the global individual judgment necessary to evaluate Change doesn’t happen overnight. A investor community formed a consen- what really goes on at the ground level. successful start involves putting some sus so that when this term comes up It’s also true that ESG will only succeed focus on the three buckets (E, S and G) everyone agrees what it means? as an institutional measure of perfor- and thinking more about how the com- There is some ambiguity about ESG and mance if it is used and ratified by the mar- pany’s internal processes and culture the many equivalent terms that surround kets. Government regulation is not the relate to the environmental, social and it. We were among a group of global asset only way to secure its acceptance. ESG is governance factors investors are going managers who issued a report in 2002 a form of inclusive analysis that should to be asking about – and you can be sure with the United Nations Environment rise organically due to market demand. about that. Program Finance Initiative (UNEP FI) that And that demand will only come from Looking ahead, every company has led to adoption of the term “ESG.” It was evidence that what we are doing makes to be ready to function in a world where a summary of the focus we put on Social, sense, from an investment standpoint as technology, demographics and the eco- Environmental and Corporate Governance well as the value to society. nomics of responsible growth and invest- in making the case that ESG factors can ment are converging. It is impossible now and should be incorporated into institu- LOOKING FORWARD to separate society from the investment tional investment. Our CEO favored the What are your priorities in advancing community, or vice versa. term “ESG” that was more straightforward the ClearBridge ESG agenda in the IV124408

(than socially responsible investing). Our next year – the first of a new decade Comments: position was corroborated when Japan’s of change in health care? Email the editor: [email protected]

12 | In Vivo | January 2020 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com invivo.pharmaintelligence.informa.com GROWTH OPPORTUNITIES ❚

Are you looking to reach and do business with senior decision makers in pharma and medtech?

We off er a range of marketing opportunities whether you are looking to:

• Raise brand awareness • Produce content marketing/thought leadership content • Generate leads • Engage directly with potential clients as well as cementing existing relationships

To fi nd out how our team can help visit: https://pharmaintelligence.informa.com/ marketing-services

©2018 Informa Business Information, Inc., an Informa company January 2020 | In Vivo | 13

JN2181 Marketing Services Advert US Letter.indd 1 2019/06/04 17:35 ❚ MARKET INTELLIGENCE A Tale Of Two Pipelines

Immuno-oncology has produced some exciting successes, but the field has become intensely crowded. Enormous resources are being poured into duplicative work and shaky hypotheses – overshadowing other pursuits in cancer research while producing limited results. It is time to re-evaluate how the sector should be pursuing innovation in cancer and how it can be smarter in its use of resources – financial investment, talent, bandwidth, patients and data.

BY DENNIS CHANG, KEITH FLAHERTY, n oncology clinical development, every year brings new breakthroughs: drugs AND UCIANE SCARLETT that can put previously intractable cancers into remission, or double the dura- tion of remission, or even cure cancers that were previously incurable. Rethinking translational models: At the forefront of the excitement is immuno-oncology (IO), the harnessing shifting towards greater use of patient- of the body’s immune system to fight cancer—and potentially eradicate it. The derived explants, organoids and Isuccesses of immunotherapy are breathtaking. Analysis of SEER data shows that a xenografts in humanized mice, as well decade ago, metastatic melanoma used to have a dismal median survival of only 7 as leveraging tumor atlas datasets. months. Now, immune checkpoint blockade (ICB) with regimens such as anti-PD1 nivolumab (Opdivo) combined with anti-CTLA4 ipilimumab (Yervoy) – or “nivo + Rethinking data ownership: leveraging ipi” – enables most patients to survive five years or more, as shown in the CheckMate the power of the patient to drive 067 study. Similarly, relapsed/refractory acute lymphoblastic leukemia (r/r ALL) in data sharing and building platforms for companies to collaborate on key children used to have a five-year disease-free survival of only 10-20%. However, when challenges in a pre-competitive setting. extrapolating from available clinical studies, CD19-targeted chimeric antigen receptor T (CAR-T) cell therapy tisagenlecleucel (Kymriah) may cure as many as 40% of these Rethinking the clinical paradigm: patients. The first child treated with Kymriah in 2012, Emily Whitehead, remains alive raising the bar and focusing on cancer and cancer free today. clearance rather than merely delaying These successes have fueled an explosion of IO investment and R&D activity. The progression in both clinical trials and first dramatic efficacy signals of ICB and CAR-T were reported in 2010 and 2011, respec- clinical practice. tively. An analysis, conducted by Uciane Scarlett, of the number of licensing deals and acquisitions for IO assets and companies over the approximately five years since the landmark publication of ipilimumab data in mid-2010 (see Exhibit 1) showed that every metric soared over this time period: the number of deals, the average size of IO deals and the average proportion of deals paid up-front. The IO pipeline has grown even more extraordinarily. The Cancer Research Institute has shown that from 2017 to 2018, the IO pipeline has grown across all dimensions: clinical assets, preclinical assets, targets and clinical trial sponsors (see Exhibit 2). Since 2014, there have been approximately 60 US FDA approvals for immunotherapies, including multiple indi-

14 | In Vivo | January 2020 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com invivo.pharmaintelligence.informa.com MARKET INTELLIGENCE ❚

Exhibit 1 cations for anti-PD-1 agents nivolumab An Explosion In IO Deals (Opdivo), pembrolizumab (Keytruda) and cemiplimab (Libtayo); anti-PD-L1 agents 2010 2011 2012 2013 2014 2015 atezolizumab (Tecentriq), durvalumab 120% (Imfinzi) and avelumab (Bavencio); and CAR-T cell therapies tisagenlecleucel and 100% axicabtagene ciloleucel (Yescarta). However, a tremendous amount of 80% capital and human resources has been consumed with IO, and there are signs 60% that exuberance for immunotherapy has become unsustainable. The most 40% glaring is the proliferation of copycat approaches: a lot of resources are going 20% towards replication of previous efforts. As CRI reported in September 2018, the number of CD19-targeted CAR-T cell 0% therapies in the global pipeline was 106, and the number of anti-PD1/PD-L1 assets Amount of royalties/milestones not disclosed  was 167. “Me-too” drugs are not new to Note: Bubble size represents vale of upfront payment the pharma industry, but the imitative extremes in IO have never been seen NOTE: All licensing, research, collaboration and acquisition transactions with publicly dis- before. The corresponding inefficiency closed financial terms for IO assets and companies from 2010 through June 30, 2015. Data were of resource use poses potential harm to compiled from news media sources. Bubble size represents the total deal amount ($) and may patients and to non-IO programs in the include upfront payment, shares, milestones/royalties and payments for research. Approxima- near term, as well as the potential lack of tions were made in some instances where only partial information was available. incentivization for trial participation and SOURCE: Uciane K. Scarlett, PhD investment in the long term. As Rick Pazdur, director of the FDA’s Oncology Center of Excellence (OCE) Exhibit 2 cautioned at the 2019 American Asso- Growth Of The IO Pipeline ciation for Cancer Research conference, “Patients – whether they be worldwide patients or the US patients – are not a   company’s resource, they’re a global resource… And when we have a sub- optimal way of developing drugs with Total # IO assets   + % a lot of duplication, that can result into [sic] a lack of confidence in the system of clinical trials, for example, or a lot of Clinical-stage IO assets  + %   unnecessary duplication and expense.” Moreover, the clinical trial failures and disappointments continue to accumu- Preclinical IO assets   +%  late. The first immunotherapy doublet combination to be approved, nivo + ipi in 2015, remains the only immunotherapy doublet combination to be approved (by IO molecular targets  +%  the FDA). Failed regimens include combi- nations of anti-PD-1 or PD-L1 agents with IDO1 inhibitor epacadostat, BTK inhibitor IO clinical trial  + %  sponsor organizations ibrutinib, vaccines, multiple T-cell co- stimulatory agonists and many other IO mechanisms. There have been a handful NOTE: Cancer Research Institute (CRI) analysis of the global IO preclinical and clinical pipeline of successes combining anti-PD-(L)1 shows substantial increases in assets, targets and trial sponsors in a single year. agents with cytotoxic chemotherapy (e.g., in lung, head and neck, and triple-neg- SOURCE: Tang 2018 Nat Rev Drug Discov 17:783 ative breast cancers) and with tyrosine

©2018 Informa Business Information, Inc., an Informa company January 2020 | In Vivo | 15 ❚ MARKET INTELLIGENCE

kinase inhibitors (TKIs) (e.g., in renal boom in IO. Typically, drug discovery These were three areas raised by a and endometrial cancers), and there are starts with biological concepts; then panel of oncology innovators – clinical re- other promising IO + targeted combina- tools and models are developed that are searchers, biopharma executives, venture tions in the pipeline. Still, the failures of relevant for testing those concepts; then capitalists and others – who gathered on IO far exceed the successes. Even for the those insights are translated into thera- May 8, 2019 at a summit called Emerging FDA approvals of IO treatments, the vast peutic advances. For targeted therapies Frontiers in Oncology (Cambridge, MA), majority involve incremental clinical effi- (as for the cytotoxic chemotherapies that an event to raise funds for cancer research cacy – the transformative efficacy seen in preceded them), the concepts and thus at the Fred Hutchinson Cancer Research melanoma is limited to only a few other, the tools and models are focused on the Center. Each recommendation has the rare tumor types. tumor cells. Over time, those tools and potential to transform the development of Meanwhile, the field continues to models have become better and more so- new and better cancer therapies. produce important advances in non-IO phisticated and even more importantly, we targeted therapies. For example, a Uni- have learned vast amounts from decades Rethinking Translational Models versity of Colorado study showed that of clinical findings. For IO, the concept is An MIT analysis found that only 3.4% non-small cell lung cancer (NSCLC) pa- radically different: engaging and modulat- of cancer drugs that enter Phase I are tients harboring ALK fusions now have a ing immune cells rather than the tumor eventually approved and marketed, and median overall survival exceeding seven cells directly. The tools and models are far yet virtually all these agents are sup- years, thanks to the availability of mul- less developed, hindering progress, and ported by preclinical data. Thus, current tiple potent ALK inhibitors. Inhibitors of while the clinical data are accumulating preclinical models have a >96% rate of NTRK fusion proteins like larotrectinib rapidly, it will take time to process, draw “false positives” and are a critical weak (Vitrakvi) produce objective responses connections and gain insights. link in oncology research and develop- in more than 80% of patients harboring Considering the challenges of taking IO ment. Biopharma’s tremendous failure NTRK fusions, regardless of the tumor to the next level, the clear inefficiencies rate creates huge costs to the system site or histology. Multiple combinations of current IO efforts, and the promise in the form of failed clinical trials and of targeted agents can produce around of alternative approaches, it is worth capital/human investments that could 100% response rates in chronic lympho- re-evaluating how the sector should be have gone elsewhere. cytic leukemia (CLL). PARP inhibitors pursuing innovation in cancer. There IO is no exception. Indeed, as noted like olaparib (Lynparza) can dramatically are lessons and insights that have been above, it is even more challenging to improve progression-free survival in pa- gained from past successes and failures. develop preclinical models for IO, which tients with BRCA mutations across mul- From an analysis of these events, three involves activation of immune cells to tiple cancer types, including pancreatic key themes have emerged that highlight fight cancer, than for treatments that adenocarcinoma (in the POLO study) and how industry can be smarter in resource target tumor cells directly. Cell lines in prostate cancer (in the PROfound study). allocation and its approaches to oncology culture and in mouse xenografts are not And these are just a few examples. innovation (see Exhibit 3): highly predictive in any case but do have The success of targeted therapies re- 1. Rethinking translational models some relevance for studying targets or flects the fact that the field has been work- 2. Rethinking data ownership pathways that are tumor cell intrinsic. ing assiduously on developing targeted 3. Rethinking the clinical development These models are, however, inadequate therapies for far longer than the recent and treatment paradigm for IO. Conventional xenografts involve

Exhibit 3 Three Proposals For Smarter Oncology Innovation

Lead Preclinical Discovery Phase I Phase II Phase III Post-Marketing Optimization Development

Rethinking Rethinking Rethinking translational models data ownership the clinical paradigm

SOURCE: Emerging Frontiers In Oncology Summit, May 8, 2019

16 | In Vivo | January 2020 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com invivo.pharmaintelligence.informa.com MARKET INTELLIGENCE ❚

immunodeficient mice, because a mouse men’s impact. After a few days in culture, (Also see “Coordinated Open Data Will with a competent immune system will the explant no longer resembles the in Drive Next-Level Health Research” - In Vivo, recognize human-derived cancer cells vivo TME. Thus, rather than measuring 1 Oct, 2019.) Two proposals may open the as foreign and eliminate them too eas- immune-mediated killing of the cancer data floodgates: ily. However, immunodeficient mice are cells, surrogate markers of efficacy are obviously not viable models for immuno- required, and must be validated. • Leveraging the power of the patient: therapy. Syngeneic mouse models, where Although the exuberance in IO and the mouse cancer cell lines are implanted • Patient-derived organoids: Organoids rapid proliferation of the pipeline is asso- into immunocompetent mice, seem rea- are 3-D multicellular cultures; in cancer ciated with certain risks and challenges, sonable in principle, but have proven to research, most organoids consist purely of it also presents potential opportunities. be poorly predictive of clinical responses. cancer cells on a 3-D scaffold. However, it One key dynamic is the shift in power Furthermore, a very narrow repertoire of may also be possible to assemble artificial to the patient. The demand for clinical these models (e.g., CT26 and MC38), have tumors that consist of multiple cell types: trial patients and tissue specimens has been used as the basis for nominating not just tumor cells, but also various im- never been higher, giving patients an many novel immune agents for develop- mune cells and stroma cells. Although opportunity to drive a change in the re- ment in combination with PD-1/PD-L1 more artificial than tissue explants or search system. Errik Anderson, CEO and antibodies. The repeated failure of those humanized mice, organoids have the po- founder, Alloy Therapeutics, proposed combinations indicate that we need to tential for greater multiplicity/throughput. a policy that links patient consent for look elsewhere. research participation to a requirement Many experts consider certain newer • Tumor atlas approaches may involve for public access to clinical data. This models – focusing on patient-derived tis- systematic assessment of in vivo TME is an appropriate demand given the sue – as promising approaches for better profiles and mapping them to clinical risk and burden that patients take on evaluating preclinical immunotherapies: responses. Many initiatives have already by participating in clinical trials; they conducted molecular profiling studies should expect that maximal scientific • Patient-derived xenografts in human- of thousands of cancer samples, but advancement should be gained from their ized mice: Multiple groups now have the focus to date has been largely on sacrifice. If this becomes a standard box methodologies for producing mice with the genomes and transcriptomes of the to be checked for every clinical trial, then a humanized immune system produced cancer cells. Expanded, systematic study a wealth of clinical data would become from human-derived stem cells. Patient- of the immune contexture in the TME is more widely available to guide the sec- derived cancer cells (if at least partially needed. Artificial intelligence platforms tor’s collective efforts. HLA-matched) can be implanted and may be used to analyze the datasets and then studied in the context of function- fuel IO hypothesis generation. Unlike the • Building platforms for pre-competitive ing human immune cells. Further refine- platform categories above, this is not an collaboration: The unprecedented de- ments may include less cumbersome/ option for preclinical drug screening, mand on human and capital resources more efficient stem cell engraftment and but a means to produce better biological also means that the incentive for research extending the humanization, which may insights to inform preclinical research. collaboration has also never been higher. be achieved through gene editing and One of the lessons of past failures is that microbiome replacement. These are enabling technologies that identifying the best combination regi- may greatly elevate the success rate mens and patient selection approaches • Patient-derived tissue explants: An and ROI for oncology drug development is exceptionally difficult. Greater data alternative approach to using patient- broadly. We must continue to develop sharing in the pre-competitive setting derived tumor samples in mice is to test and enhance these and other preclinical would serve to advance the science and them in culture. Tissue explant cultures models. make all research efforts more efficient include both tumor cells and non-tumor and productive. Platforms for pre- cells (including immune cells) and pre- Rethinking Data Ownership competitive collaboration include tumor serve structural features of the tumor Many leaders and advocates have called atlas initiatives for pooling biomarker microenvironment (TME). Some systems on biopharma companies to more rap- data, harmonization of biomarker test- (e.g., from Mitra Biotech) also include idly and consistently make clinical trial ing methodologies, and collaborative peripheral blood from the same patient data available, even when the results are combination trials. in the culture. Dividing the tumor sample negative. Greater data transparency would into multiple culture dishes allows for help to reduce replication and increase the Rethinking The Clinical Paradigm parallel testing of numerous drug regi- impact of research efforts. For example, In the traditional paradigm of treating mens on a single patient tissue sample. there is often a reluctance to publish failed metastatic cancer, the focus has been on However, given the differences in growth studies, but such studies provide very use- delaying disease progression. Patients kinetics of tumor cells versus stroma and ful data and new learnings. Open-source, receive a line of therapy, and any tumor immune cells, explants can only provide public data resources are already starting response or shrinkage (sometimes even very short-term evaluations of a drug regi- to emerge, but more can certainly be done. stable disease) is considered of clinical

©2018 Informa Business Information, Inc., an Informa company January 2020 | In Vivo | 17 ❚ MARKET INTELLIGENCE

benefit. If the tumor grows or spreads, single agents redoing prior trials, there is that progression triggers a new line of a proliferation of innovative mechanisms therapy. However, this algorithm is the and combination/sequencing approaches. legacy of the era of cytotoxic chemo- therapy, when curing metastatic cancer • The relatively higher success rates of IO was generally viewed as impossible. The tremendous clinical trials enable a more cost-efficient The paradigm in much of hemato- R&D model and may potentially lower logic oncology has already evolved, as infusion of capital the cost for novel drugs, enabling better improved combination regimens with or patient access to the more effective com- without stem cell transplantation may investment and talent bination approaches that will emerge. produce multi-year remissions or cures in many cases. The goalpost has begun to into the field, and the • Every drug developer – and eventually shift away from mere response to eradi- every oncologist – strives for long-term cating all detectable traces of disease. enthusiastic survival for every patient, not merely Accordingly, the molecularly defined delaying tumor growth by a few months. minimal residual disease (MRD) endpoint engagement of is increasingly used to evaluate efficacy. None of this will occur overnight, and It is overdue for this concept to be industry, health care the challenges are steep, but this is an ex- applied to solid tumors as well, for 3 citing time to be in the oncology field. The reasons. First, given the unprecedented providers and sector’s successes with immune check- proliferation of pipeline programs, we point blockade and CAR-T cell therapy need to prioritize the very best regimens patients, all present mean it is no longer unrealistic to antici- for resource and time investment; we pate “cures.” Breakthroughs in drugging need to set the bar higher. Second, the us with an traditionally “undruggable” targets are emergence of potentially curative immu- emerging. New targeted therapies aimed notherapy and next-generation targeted opportunity to at tumor cell-intrinsic vulnerabilities that therapies provide proof of principle that might also potentiate immunotherapy reaching a higher bar is possible. Third, conquer cancer if we are beginning to arise. The tremendous the biology suggests that treating prior to infusion of capital investment and tal- disease progression may produce greater deploy those ent into the field, and the enthusiastic efficacy; a cancer that has evolved to a engagement of industry, health care point where it is actively progressing de- resources well. providers and patients, all present us spite ongoing treatment tends to be more with an opportunity to conquer cancer if aggressive and challenging to treat than we deploy those resources well. one that is still partially under control. Moreover, we have at least a partial This has critical implications for how map of how to pursue cancer innova- we conduct clinical research and clinical tion in a smarter, more effective way practice: – by leveraging better, patient-derived translational models; driving clinical • Should clinicians redefine the trigger data sharing and collaboration; and re- for the next line of therapy (non-CR rather defining clinical success. Through these than progression)? efforts, the biopharma industry can do far, far better than it has ever done. • Should clinical trial investigators What Is Next For IO? IV124406 increase the use of different endpoints Robust implementation of the changes (CR or even MRD-negative rates, rather listed above would reshape the oncol- Dennis Chang, PhD, (dchang@clarion- than ORR)? ogy R&D sector. The future vision is one healthcare.com) is a principal at Clarion, in which: A Life Sciences Consultancy located in • Should drug developers make more use Boston, MA. Keith T. Flaherty, MD, (kfla- of neoadjuvant/presurgical studies to gain • Thanks to better preclinical models, [email protected]) is the director direct pathologic evidence of efficacy? the free flow of data, and widespread of clinical research at Massachusetts inter-company collaborations, science General Hospital and a professor of medi- This new paradigm would redefine and medicine rise to meet the new clini- cine at Harvard Medical School. Uciane K. what the industry views as the unmet cal bar. Scarlett, PhD, (uscarlett@oxfordsciences. need and opportunity for new drug com) was an associate at Atlas Venture development and could drive bolder • The IO pipeline is more sophisticated and is currently a principal at Oxford Sci- approaches and greater clinical impact. and diverse. Instead of 100+ anti-PD-(L)1 ences Innovation.

18 | In Vivo | January 2020 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com invivo.pharmaintelligence.informa.com MARKET INTELLIGENCE ❚

Intelligence with a Global Perspective The Premier Resource in the Life Sciences Industry.

» Biomedtracker » Medtech Insight » Datamonitor Healthcare » Pink Sheet » In Vivo » Pharmaprojects » Generics Bulletin » Scrip » HBW Insight » Sitetrove » Meddevicetracker » Trialtrove » Medtrack

To fi nd out more, visit: www.pharmaintelligence.informa.com

©2018 Informa Business Information, Inc., an Informa company January 2020 | In Vivo | 19

JN2181 Pharma Advert HBW US Letter.indd 1 2019/06/05 13:44 ❚ C-SUITE SPEAKS Designs On A New Decade: Bayer US Pharmaceuticals’ Sebastian Guth

Bayer’s ambitious campaign to reposition itself as a global leader in two complementary fields – health and nutrition – will face its toughest test in the US, with its highly litigious approach to product liability and a tendency to target pharmaceuticals as the source of the health system’s affordability and access problems.

SEBASTIAN GUTH

BY WILLIAM LOONEY eading the charge with a simple mantra “we do science well” is Bayer Pharmaceuticals’ president for the Americas, Sebastian Guth, a 45-year-old Bayer appointed Sebastian Guth management PhD who took the position just a year ago after serving as the president of pharmaceuticals, Americas pharma unit’s global head of marketing. In the following conversation with Region, comprising the USA, Canada, In Vivo, Guth outlines his plans to execute two big product launches and Central and Latin America, in December multiple deals and new investments – all buttressed by a culture reset designed to open 2018. He succeeded Carsten Brunn L the organization to a new world of digital technology opportunities. in the role, who left the company to become CEO of Selecta Biosciences. The US remains ground zero for the company in its bid to become a competitive leader in the crowded cancer space. Vitrakvi, a collaboration product with biotech start-up Loxo Oncology, is positioned for possible use against the NTRK-fusion mutation on Guth started his career in the pharmaceutical industry with Schering more than two dozen different tumor sites. AG, where he held senior roles in Asia Bayer AG’s biggest – and perhaps riskiest – bet is its determination to do what it and the Middle East. Bayer acquired takes to win in the crowded, high-cost field of cardiovascular drug development, where Schering in 2006. it is winding up a 13,000-patient clinical program on new treatments to address CVD complications associated with diabetes and chronic kidney disease. In the US, these In his new role, Guth is focused on co-morbidities are a key driver of mounting hospitalization and readmission costs, for accelerating growth by building Bayer’s which patients have few options. US pharmaceutical business to a greater scale. The firm’s oncology franchise is In Vivo: Its’s been a little more than a year since you assumed the position as critical to achieving this objective. president of Bayer Pharmaceuticals for the Americas region – the US, Canada and Latin America. What have you accomplished so far in putting your imprint on the business? Sebastian Guth: My major focus has been on the US, globally Bayer’s most im- portant single market. I took the time to consult widely – listening and learning.

20 | In Vivo | January 2020 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com invivo.pharmaintelligence.informa.com C-SUITE SPEAKS ❚

I spent the bulk of my time out in the field with my new col- the choices she has made on contraception and why education leagues meeting with physicians, patients, representatives of about those choices is critical to female empowerment. other institutions in the health sector, and our legislators in Washington. These wide-ranging discussions helped to narrow It is also true that several big pharma companies have my priorities to three: abandoned cardiovascular therapy, seeing it as a crowded chronic disease segment prone to genericization, com- • accelerating our growth momentum, building on the sig- pounded by the high cost of large population-based clinical nificant product launches Bayer has executed over the past trials. What is the rationale for Bayer’s commitment here? 12 months, including Vitrakvi (larotrectinib), a novel drug for As an industry, along with society in general, we have devel- a wide range of cancers with specific genetic features, and oped a blasé attitude toward cardiovascular disease (CVD). It Nubeqa (darolutamide), for non-metastatic, castration-resistant belies the fact that the burden of cardiovascular disease is quite prostate cancer; high and is destined to grow even more prominent as the US population ages. Specifically, we have our eye on sub-types of • expanding our pipeline portfolio, evidenced by the decision to CVD like cardio-renal dysfunction, where many patients have acquire the remaining stake in BlueRock Therapeutics, which is limited effective treatments. Yet the statistics show that more doing important work in engineered cell therapy for neurologic, than 40% of all patients with type 2 diabetes will also develop cardiovascular and immunologic applications; and chronic kidney disease, leading ultimately to heart failure and other cardiovascular illnesses. The US spends $115bn annually • strengthening Bayer’s workplace culture to expand and di- managing chronic kidney disease, so finding new treatments versify our talent base and promote productive relationships could have a major impact on costly hospitalizations and other across the organization. acute care services. Bayer is spending heavily on two clini- cal trials, FIGARO-DKD and FIDELIO-DKD, to investigate new During the transition, I benefited from my role as a member options for diabetic and kidney patients with complications of Bayer’s global Pharmaceutical Executive Committee. It is attributable to CVD. standard practice that the lead of the largest single market in the company has a seat on this committee. I find it invaluable as You spent six years as Bayer Pharmaceutical’s chief market- an opportunity to keep the rest of the global management team ing officer, based in Berlin. Given that introducing a new up to speed on the complexities of operating as an established medicine to the market is an increasingly fraught exercise local player in the US. for big pharma, what makes for a successful launch? There are three principal ingredients. The first is the quality During your on-boarding exercise, were there areas that you of the science behind the product. The science must stand on felt required a reset or change in direction? its own. It’s a necessity to significantly impact either the length I did not see the need for any radical transformation of the or quality of life in the target population – and preferably both. US business. Our focus remains one of becoming a competitive Second, you must have an impeccable access proposition, in leader in oncology, a strategy we are implementing worldwide. which those measurable attributes of the product are secured In the US, I think we are at a critical juncture in achieving this at an appropriate cost to individual patients and society too. goal, with two product launches in the past year and several Third, and very important, is an ongoing commitment to life other promising oncologic drugs in late-stage development. cycle management of the asset, particularly in investigating the We are also strongly committed to expand Bayer’s presence utility of additional indications beyond the original approved in the cardiovascular/cardiology segment, beyond our current, label. Another element is the added value that comes from the relatively narrow profile in pulmonary arterial hypertension. partnerships Bayer has secured with other big pharma and We are hopeful about a prospective US launch of finerenone, biotech players. Some of our most successful franchises were now in the largest global Phase III clinical program for patients introduced with partners like Johnson & Johnson and Regen- living with chronic kidney disease who have type 2 diabetes, a eron, where we had a common interest in investing in some of major area of unmet medical need. Like oncology, we see cardio the biggest new ideas in science. We have added to our store of and its many co-morbidities as a world-class business for us, human capital through the listening and learning we’ve done on a par with Bayer’s established therapeutic franchises like in our day-to-day interactions with these other companies, who women’s health. often bring a fresh perspective to what we do. For us, it’s a core reason that these partnerships have been so successful. The women’s health segment poses substantial safety/effi- cacy and reputational challenges, particularly in the fertility What are the elements of a good partnership for Bayer? and hormone space. Is Bayer still rigorously committed to Every tie-up comes about for reasons that are unique; a rule- this market as a revenue driver? book approach is not useful now that the overall climate for Women’s health is not an adjacency for us; it remains one of drug development is so fast-paced and competitive. Bayer will Bayer’s key global growth businesses and a source of opportuni- collaborate with small companies as well as our peers. Loxo ties going forward. We launched a US advocacy campaign this Oncology, a six-year-old biotech, is a good example. Vitrakvi, year called #WhyIUD with the US actor and singer Lucy Hale on our first tumor agnostic precision cancer drug, is the result of

©2018 Informa Business Information, Inc., an Informa company January 2020 | In Vivo | 21 ❚ C-SUITE SPEAKS

that collaboration. And it is telling that we opted to collaborate rather than take the acquisition route. But experience told us that a well-structured collaboration deal brings flexibility and a big dose of creativity that can be shared by both parties, with additional value to patients and society. We’ve certainly had that with Loxo. The example shows that insisting on full 100% control through an M&A is not the only way to achieve our strategic and revenue growth objectives.

How dedicated is Bayer to creating links with academia? Bayer has made a substantial bet on partnerships with aca- demic institutions, especially here in the US. We have an active incubator lab at the University of California San Francisco campus at Mission Bay, with 11 start-up companies on site. We have a similar incubator unit in Cambridge, MA, where we operate a research partnership with the Broad Institute and its sponsors, including Harvard and MIT as well five teaching hospitals. In addition, investment at our Berkeley, CA, opera- tions and manufacturing facility has been bolstered with a new $150m stake in cell culture technology platforms. Bayer’s new global head of business development and licensing, Marianne De Backer, will also be based in the Bay Area, giving the state We strongly support industry- of California a pole position as the company adds more heft to its innovation ecosystem. wide efforts to advance the I’ve been asking your recent predecessors the same question – is Bayer Pharmaceuticals, a formidable global player itself, policy debate to build support ready to crack the top 10 of biopharma companies active in the US market? Is there a plan to move beyond status as for innovation in a market that marketer of the oldest existing drug therapy – aspirin – and become a leading source of innovation for US patients? in many ways determines the Within my geographic remit, Bayer ranks as one of the top global future for our business. foreign-based drug producers in Latin America, while in the US Bayer has never cracked the top 10, in terms of sales. The considerable investment we are taking to upgrade our franchise in CVD indicates our desire to scale US operations significantly above where they are today. We would not be doing this if our commitment was weak or tentative. Being aggressive about this doesn’t mean we are going to end up in the top five US produc- ers overnight. Inventing and making drugs requires being in it for the long game. Nevertheless, I have no doubt that Bayer’s future. I am excited about the opportunities our combination of presence in the US will continue to grow. The innovations we businesses gives us to be creative in solving some big, impactful are introducing are distinctive because they will help resolve problems. Do I see any distractions? No – we share with our seed some of the biggest challenges facing the US health care system, and crops business a desire to innovate even if doing so poses with its desperate need for lower costs, more productivity and a risk of failure. The commitment to “do science well” unites increased access for patients, especially for those with the big- us. Bayer Pharmaceuticals’ LEAPS program, where we invest in gest health needs. breakthrough technologies with an intent to eventually cure rather than just treat, exemplifies this approach: we’ve signed five deals Bayer’s size and global reach are compounded by its stake and made five investments in the last 12 months alone. That’s not in other fields outside prescription pharmaceuticals. Does evidence of a company that is drifting without a compass. the company’s significant position in seeds, crop science and agricultural chemicals require you to work harder to What do you think about Bayer’s reputation in the US? gain the attention of senior management in ensuring the I know what I want that reputation to be. First, to be regarded long lead times necessary for drug innovation can proceed for the quality of our science. And second, for being very trans- without distractions? parent about our desire to apply that science to impact society, Our lines of business are complementary, focused on two broad in a positive way. The third is to be viewed as a company with areas – health and nutrition – that are critical to the world’s its eye on the future.

22 | In Vivo | January 2020 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com invivo.pharmaintelligence.informa.com C-SUITE SPEAKS ❚

Is influencing the US policy environment a reputational researchers are looking at more than 24 different tumor sites priority for Bayer? where we’ve uncovered NTRK-fusion mutation as a key driver We strongly support industry-wide efforts to advance the of disease. I am excited because of my genuine belief that the policy debate to build support for innovation in a market that tumor-agnostic approach will help people like my father, now in many ways determines the global future for our business. The and in the future. innovations we create have a significant impact on society, so I think we have a duty to get out and help shape the debate. I have You’ve cited Bayer’s commitment to making big bets in accepted a position on the board of the Biotechnology Innova- science, where the risks are high and the payoff, assuming tion Organization (BIO) for precisely this purpose – it’s a role I success, is long-term. How does that strategy look to you take seriously. One concern I have is this debate must extend right now? beyond our industry to include the rest of the health care sector. This is the bookend to the pipeline – our LEAPS by Bayer Simply put, health care costs are much more than the cost of a initiative where we are investing in start-up companies that drug, which accounts for a little more than 10% on the dollar. promise solutions to some of the most vexing challenges in However, there is one area where we have a vulnerability medicine. The focus is on cell and gene therapies designed to – it’s the challenge of patient co-pays and co-insurance con- deliver cures rather than incremental gains in treatment. With tributions that increasingly are forcing patients to abandon health care investment firms, such as Versant Ventures, we have filling their prescriptions or to under-medicate during the founded and financed three new biopharma companies: Case- course of treatment. The issue is too complex for us to solve bia Therapeutics, which is applying CRISPR/Cas technology to it ourselves, so I think we have to work harder to address this seek cures for severe genetic disorders; BlueRock Therapeutics, with stakeholders across the industry. using stem cells to achieve cures for CNS and cardiovascular genetic dispositions; and most recently Century Therapeutics, Can you indicate what you see as the most exciting products a start-up developing allogeneic or off-the-shelf immune cell in the current Bayer pipeline? therapies for cancer. Our pipeline is very deep, with about 50 compounds in vari- In August, we agreed to take full ownership of BlueRock to ous stages of development. As a prelude, the August launch of help advance its development program on cell-based drugs to Nubeqa for prostate cancer has been well-received in the clinical alleviate functional decline from Parkinson’s disease. In July, community. We also feel confident about prospects for finere- Bayer and Versant announced plans to join with Fujifilm Cel- none, which if approved will offer new hope for patients with lular Dynamics Inc. in a $250m stake in Century Therapeutics, a chronic kidney disease (CKD). CKD is a looming public health Philadelphia-based start-up specializing in creating allogeneic, threat and a key area of unmet medical need, as evidenced by off-the-shelf pluripotent stem cell lines against a range of incur- the Executive Order on “Advancing American Kidney Health” able cancers, including hematologic and solid tumors. Century signed by President Donald Trump on 10 July 2019. Assuming is an excellent complement to the work that BlueRock is doing finerenone is approved, we intend to focus on the community of with cell therapy, aiming to cure disorders in the CVD and CNS patients with type 2 diabetes and CKD. It’s a sizeable and diverse space. Each of these investments puts Bayer in the front line group, as an estimated 40% of all type 2 diabetics end up with toward an eventual cure for these high-profile and challenging some form of CKD. And the cost of treating this co-morbidity is diseases. Century also gives us a presence in Philadelphia’s staggering, accounting for a large segment of hospital readmis- ecosystem of basic research – companies like Spark Therapeutics sions – itself a metric of pervasive system-wide inefficiencies. Inc. also got their start in “Cellicon Valley.” In addition, I take great pride in Bayer’s oncology pipeline. I have already mentioned Vitrakvi, one of the first in a wave of Summing up, how do you intend to measure yourself and precision treatments that will change the way cancer is treated, the performance of Bayer US as we move into the first years bringing fresh hope to millions of patients with few options un- of a new decade? der the current drug armamentarium. I have a personal interest First up is accelerating growth by building Bayer’s US phar- in advancing this transition. Two years ago, my father died after maceutical business to a greater scale. Our oncology franchise battling lung cancer, where, until the very end, he was treated is critical to achieving this objective along with the expansion the traditional way, focusing entirely on isolating the tumor at of the cardiovascular segment into new areas of unmet medical its site of origin. High-throughput, next-generation sequencing need. We also intend to preserve our world-leading presence in of his cancer etiology was introduced when it was too late to women’s health care and in radiology as well as pursuing some redirect his treatment to the underlying drivers of metastasis. great niche franchise opportunities in hemophilia and multiple My father’s death convinced me it was time to change the way sclerosis. Second is expanding our pipeline through external we look at cancer and treat it. Our launch of Vitrakvi in November collaborations with innovative centers of excellence – especially 2018 gives Bayer a strong position in precision oncology, as it in academia and small biotech. As Bayer’s top pharmaceutical was the second FDA-approved drug (and the first in Europe with business representative in the US, I intend to keep reaching a tumor-agnostic label) to target the NTRK-fusion mutation that out to all the great science happening throughout the country, causes cancer cells to proliferate, using a common biomarker to promoting Bayer’s reputation as a partner of choice. identify different tumor types rather than just the tumor where IV124378 the cancer originated. Building on this initial breakthrough, our

©2018 Informa Business Information, Inc., an Informa company January 2020 | In Vivo | 23 ❚ MEDTECH GROWTH STRATEGIES Connected Strategies Are Vital For Medtechs In The Consumer-Led 2020s

Discussions on the shape of health care have moved from “reimagining” to the next stage: building and executing on the vision. That is the thrust of EY’s NextWave Report: New Horizons 2019. Additionally, for medtechs seeking business continuum, “duality” is now a preoccupying thought.

BY ASHLEY YEO he future of health lies with technology. Within the health care industries, investors have been among the first to act on this realization, funding health Health systems and organizations intent tech, practice management and home health care ever more concertedly on meeting the challenge of making over the past decade. In 2014, private equity deals in health care accounted themselves future-ready will do so only for 8% of overall investment volumes; in 2018, that had grown to 12%. So by embracing digital transformation and says EY in its most recent EY NextWave Report: New Horizons 2019. optimizing performance through agile T This series of EY reports tracks past changes and maps the future of health care, and business transformation. gives views on how and how fast health care delivery is changing. It also illustrates how stakeholders must adapt – including those who are leading the changes. The lat- Open IT infrastructures are needed for est report underscores the slow pace of uptake of digital technologies in health care, the connected health ecosystems of the future as we continue to move towards and presents the widely-held general view that health care is less innovative than a “participatory health world” in which other economic sectors. a permissions-based, frictionless flow But it also identifies the growing attraction of health care for investors, pointing of health data and information is a vital out that one in seven private equity firms made health investments in 2018, chiefly in ingredient. regulatory compliance and clinical efficiency. The theme of PE is covered is one of the report’s four sections (or “articles”). It will be the focus of a separate In Vivo article. For medtech companies, long-term values will be derived not necessarily from Connections Make The Health Care World Go Round owning data, but from new relationships Noteworthy is that the “connections” theme dominates EY’s report in its other three and having access to data pools that allow sections devoted to: consumer and physician expectations of a digitally enabled, con- algorithms and insights to be created. But nected health ecosystem; the path from fee-for-service to a future centered on value; and while they map the future, they must also the transition to a consumer-centric, participatory, outcomes-based and cost-efficient service ongoing stakeholder demands in health and well-being sector. Clinical care – while always remaining front and center what EY calls a duality approach. – is becoming a smaller contributor in an individual’s health, viewed holistically, the

24 | In Vivo | January 2020 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com invivo.pharmaintelligence.informa.com MEDTECH GROWTH STRATEGIES ❚

EY authors observe. formal technology scouting department, The technologies that underpin a including functions from corporate ❚ DIGITAL CHALLENGE connected, wellness-oriented, anytime- development and R&D groups that are IN FOCUS anywhere health ecosystem are already solely externally focused. Historically, available, says Jim Welch, EY global these companies drove their innovation EY’s recently issued New Horizons medtech leader. Innovation is arriving from internal resources and strengths. 2019 edition, part of its NextWave fast, but for medtechs intent on serving Now, they are additionally doing this in Health report series, addresses the evolving medtech market, which conjunction with providers, with whom what will be needed for the industry was valued at around $400bn globally their relationships are now extending, to to transition from reimagining the in 2018, there is an additional challenge. center on which technologies to evaluate. health care delivery ecosystem of Funding has continued to come into The need for such unique partnerships the future to making it a reality. the medtech space, via PE, venture is clear, but they are now revolving more capital and M&A and commercial deals, and more around data science. Compa- It draws conclusions and insights Welch told In Vivo. “But one of the chal- nies are thus engaging in technology out- from a survey of over 9,000 sub- lenges from an innovation standpoint reach in a more organized fashion, and jects, including 650 physicians, is that there is a duality concept going will task individuals solely with a brief from four countries. One clear on, which, for the industry, means that of scouting for AI and data-driven tech- finding was that, the core business medtech also has a responsibility to ser- nologies, which may even be a challenge of “health care” is expected to be vice and innovate around the products to their expertise and understanding. based in digitally enabled models of that are already in the market,” he said. “Given the pervasiveness of technology, care, including virtual delivery and Companies will often have huge there’s a lot to look at, but how compa- interactive person-centered tools. volumes of devices on the market that nies filter that in a logical way remains a they need to continue iterating on, to challenge,” said Welch The digital challenge is the theme of have smaller footprints, better batteries, one of four “articles” in the report, smarter features, and different levels Duality which also delve into value, private of sensors, etc. But alongside, they are Companies’ behaviors are increas- equity, and the future shape of aware of the need for disruptive thera- ingly driven by the issue of the duality of health care. pies, new treatments and technologies, growth – the need to invest and bring in including robotics. Historically, device technologies while keeping established innovation has required significant business ticking over in the near term. amounts of capital and resource, but now “A balance is required, and it has been a health care providers to suggest how their the sector has entered the era of data- challenge,” said Welch. technology could be part of a medical driven connected devices, where those Welch went further: “Fundamentally, technology offering,” Welch said. resources are just as likely to be data if you boil it down to a simple concept, There is an embedded fear of the power scientists as engineers. “It’s an expand- the need is for duality. How do we, as of the tech firms, both from a capital and ing innovation landscape, and requires partners in the ecosystem today, re- a knowledge-of-the-consumer stand- a change in skills for a patient base that main viable tomorrow, as the industry point. Medtech companies are however is not fixed.” continues to disrupt itself both from a starting to embrace and accept that, and But it still requires decisions on capital technology and commercial standpoint? work together with tech companies in allocation and R&D investment, and on That’s the world our clients are living in this era where the consumer has grow- likely returns to shareholders and navi- today,” he said. ing power. gating the channels of reimbursement. Save for a few extremely innovative Job roles in traditional medtech and And this comes at a time when companies health care systems in smaller countries care delivery are now prone to change. are not making the same margins as they that are making big strides perhaps from Excluding implantables, the people who previously secured in the overall ecosys- a low base, the same challenges, more or use medtech, and the place where it is tem. They are also alert to the risk of be- less, are being faced globally. controlled from a medtech standpoint ing disrupted by a tech company coming Health systems are dealing with non- are changing: the deliverer is increas- into the market that looks at the environ- traditional medtech companies arriving ingly the caregiver rather than the clini- ment in a completely different way. in the medtech space, including technol- cian. Care is being delivered outside the ogies such as FDA-approved algorithms traditional care setting. “Medtech is now Where To Invest? and AI that are considered to be medical more user friendly to a wider population, Having taken these dynamics into con- technology, although historically they and that’s where tech companies from sideration, Welch said a lot of choices were nothing to do with device-based design and innovation standpoints have were emerging around the areas to invest engineering. real strengths.” in the new AI and data-driven medtech “We’re also starting to see their ability The devices themselves are becoming ecosystem. to leverage consumer and other applica- part of an “ecosystem of sensors,” creat- The larger medtechs usually have a tions of consumer tech and connect with ing data that are used to drive clinical

©2018 Informa Business Information, Inc., an Informa company January 2020 | In Vivo | 25 ❚ MEDTECH GROWTH STRATEGIES

decisions and outcomes. Profoundly dif- ferent ways of approaching the delivery of health and care are underway, and physicians, more so than consumers, are anticipating the arrival of these new and non-traditional players into the health industry, says EY’s NextWave Report. New care models are already in play, for example, the Mercy Virtual Care Center and Intermountain Health’s Connect Care Pro.

Funding Of The “New” Industries A lot of funding is going into diagnostics at present, thanks to the ongoing debate around personalized medicines. In fact, digital health, genomics and early diag- nosis – which are also the three “new” industries that the UK, for instance, is striving to create under its Life Sciences Industrial Strategy – are attracting a lot of investment globally in early-stage venture rounds. This is in some ways a validation of the next wave of devices – the transformative technologies – that need investment to bring them to market. up, slowly but surely. “It will certainly be The fact that company valuations in part of the landscape and of how com- medtech have remained very high has panies need to look at reimbursement served to restrict the number of acquisi- for the foreseeable future,” said Welch. tion targets of market-ready companies We’ve got to a place In the VBHC arena, companies’ views and products. Valuations will continue of their role are changing. For them, it to rise, barring any unforeseen macro- where we know how was initially a question of “How does economic adjustment of the type last my technology/product change in a seen some 10 years ago. But this, in turn, value-based fits well value-based model?” Now that the fun- provides an even greater incentive for damental VBHC arrangement tends to investors to look elsewhere. and where it makes include multiple devices and interven- And similarly, deal-making will con- tions, and activity around the patient, tinue, with the larger organizations see- sense it is a question of: “How does my device ing value in divesting some parts of their fit into an overall outcome as part of a portfolio. There is still scope for a lot of holistic answer?” tuck-ins. Welch added: “We think the It is more straightforward in some environment will continue to be positive areas than in others. For instance, in from a deal-making perspective the next orthopedics, how a device fits into the few years.” overall puzzle is fairly clear. In the acute scenario, however, it is not so obvious, US Leads The Way In Welch said. But that should not detract Value-Based Adoption from the overall significance of value- In all this, for companies addressing the based approaches. Big strides in under- global market, succeeding in the US with standing have been made. “We’ve got to its big market and high spending on health a place where we know how value-based care is a vital step. Complex and difficult Recent information points to some fits well and where it makes sense,” said to operate in it may be, but “getting things 35% of the US health care spend coming Welch. But patience is still needed, he right in the US is incredibly important through newer payment models – the out- added, as hospitals and payers must from a commercial viability standpoint,” comes and value-based models. Adapting figure out where they fit into the overall said Welch. The US is still the dominant to these new payment models will be scheme of things while the likes of Abbott market in global medtech terms, and VC important for medtech companies in the Laboratories, Johnson & Johnson and flows come mostly from the US. future. The value-based model is scaling Medtronic will pull the industry along.

26 | In Vivo | January 2020 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com invivo.pharmaintelligence.informa.com MEDTECH GROWTH STRATEGIES ❚

Maturity Of The Mission-Based ease (COPD), chronic pain, post-surgical patients’ understanding of health and Medtech Company support and caring for the elderly; medical information is vital to enable Disruption to markets and business plan- them to make informed decisions. ning is not what companies in a mature • robots are used for prescription dis- And supporting activities that matter industry serving an often fragmented pensing, sanitation and disinfection, and to physicians, as well as patients, will market want. But for Welch, with the transporting equipment and supplies, as improve value, being in mind given the experience of a several industry cycles well as in certain surgical procedures and essential, unique drive of staff who opt behind him, including time at Abbott medical education; for a career as a caregiver. Diagnostics, this is the nature of running global businesses. “We might need to re- • practice variations and waste are elimi- Making The Transformed Health act, and pivot, but the industry continues nated; and asset performance, supply Care Vision A Reality to be really healthy and growing, and that chain and inventory management are If a consumer-centric, participatory, allows it to absorb the changes.” automated; and outcomes-based and cost-efficient health Medtechs, he said, had a focus on mis- care system is the goal, two persistent sion. “That’s why we’re here as an indus- • blockchain technologies will be used to anachronisms need to be addressed: 1) try, and why the industry keeps moving guarantee the safety and integrity of bio- much care that does not need to take forward,” he said. “We’re hyper-focused medical and pharmaceutical products. place in a high-tech facility continues to on consumer- and patient-outcomes; as occur in that very setting, adding layers long as we stay that way, we will make Value of cost and presenting hurdles for other our way through, one way or another,” he Developed markets will adopt more patient care; and 2) investment in tools added, referring to the challenges ahead, sophisticated outcomes-based models, for diagnosis and treatment far outweighs as described in EY’s NextWave Report: but this will take time, says the EY report, spending on prevention. New Horizons 2019. given the entrenched culture of fee-for- A third problem is that the basis for service and supply-push traditions in connected health ecosystems – open Digital Health Systems health care. IT infrastructures that connect all Future health care systems will be smart, Valued-based models that are worthy stakeholders and supports the easy, with a basic remit of delivering opera- of attention are being pursued, for ex- permission-based flow of information – tional efficiency and clinical excellence ample, in: is missing. in a patient-centric model. It will be a 5G Connected health ecosystems are an based-system focused on providing value. • Sweden, using evidence-based treat- essential precursor to delivering better The EY report defines value as: “providing ment guidelines, disease registries and lifelong health, says the EY report. But better care for patients and better health outcome-dependent reimbursement for they require data sets of sufficient size, for populations at a lower cost in a manner specialized care; quality and data variety to deliver ac- that prevents provider burnout.” curate or optimal results. Algorithms (analytics, machine learn- • Canada, employing a decentralized For health companies, the value will ing and other AI technologies) and ro- system where the provinces are design- not be in owning data but in the algo- botic process automation (RPA) will be ing payment systems to move away from rithms and the insights they generate able to make waves of user-generated and fee-for-service; that shape health outcomes in ways that clinical data manageable and targeted. matter to consumers, payers and other Changes in culture will be called for: • Japan, which has published a forward- health stakeholders, says the EY report. health organizations will need to become looking vision of health care policies The report details a four-step process more agile and look to build, buy or part- through to 2035, focusing on value-based that moves from “system imagining” to ner for solutions that bring their organi- improvements; and “reality” that includes: setting a trans- zations up to speed; and remote moni- formation agenda that optimizes the toring and AI technologies – to become • the US, where provider-payer partner- business of today while innovating and central health care provision concepts ships are resulting in payment models growing the business of tomorrow; us- within the next 10 years – will need to be and incentives that reward high-quality ing legacy system optimization, while factored in to enable the management of outcomes and achieve savings. transitioning to open architecture and chronic and complex diseases by remote blockchain-enabled solutions; building teams to care for people at home. EY’s report also proposes that a intelligent automation, including integrat- It will be a world where: patient-centric definition of VBHC is de- ing robotics with multiple components vised to prevent any temptation to focus from different emerging technologies; • virtual consultations will be selectively narrowly on cost reduction. Indeed, the and instilling a risk-optimization mind- used in areas where they have been shown patient perspective should be uppermost set – extending to cybersecurity solutions to have been as effective as in-person in mind. As illnesses often go beyond for medical devices and wearables – and consultations in such diverse areas as dia- physical well-being and involve emo- embedding “trust” into services. betes, chronic obstructive pulmonary dis- tional and psychological factors, aiding IV124423

©2018 Informa Business Information, Inc., an Informa company January 2020 | In Vivo | 27 ❚ PARTNERING STRATEGY Roche/Genentech Partnering Team: One Face For The World To See

Thomas Zioncheck, global head of neuroscience, ophthalmology and rare diseases, Roche Pharma Partnering, talks to In Vivo about Roche and Genentech’s united partnering group, 2019 successes, and highlights ahead for the big pharma’s neuroscience pipeline.

BY LUCIE ELLIS

oche has been praised for its messaging,” he said on the sidelines of seek product candidates in MS. Ocrevus handling of the acquisition of the 2019 BIO-Europe partnering event in saw “a very successful launch and it’s hav- biotech company Genentech Hamburg, Germany. ing a huge impact for patients,” Zioncheck Inc., which it has managed Zioncheck, who has been a part of noted. “But patients are still progressing to keep at an arm’s length Genentech for more than 30 years, said with disease, so our scientists are very andR in which it has continued to foster a the streamlined partnering group was interested in thinking about new ways to biotech spirit. Over a decade ago, in 2009, able to stand apart from its peers because complement that therapy.” Roche purchased full ownership of Genen- of Roche’s diagnostic and pharma busi- In July 2019, Roche announced a col- tech for $46.8bn, however it had owned a nesses. “We’re looking for highly innova- laboration with Convelo Therapeutics majority stake in the company since 1990. tive science. It typically has a biomarker Inc. for the discovery and development At the time of the acquisition, Viren or personalized health care component of novel remyelinating medicines for Mehta, managing member of consulting to it. Roche is differentiated in the fact patients with neurological disorders such firm Mehta Partners, told the New York that it has both the diagnostic business as MS. Convelo received an undisclosed Times that the transaction would be and a pharmaceutical business, and we upfront payment and will have research easy. “These two companies have grown think that is a unique way to leverage support from Genentech. Under terms of up closer than any two independent and maximize the probability of technical the deal, Genentech will retain an option companies could be expected to be,” he success. This offering is great for patients to acquire the company. Approved thera- said. Ten years on, the two firms are still too, as we have more of an offering to peutics in MS are focused on preventing recognized separately despite being one help patients with early diagnosis and additional myelin damage by modulat- company and Genentech continues to treatment options.” ing the immune system, but there are hold on to its innovative culture. Mehta What is on the Roche/Genentech tick no approved therapies that tackle the told In Vivo that the evolution of Roche list when it comes to potential licensing unmet clinical need to promote myelin and Genentech’s partnership to merger deals, though? Zioncheck said the group regeneration. strategy remains “a keystone template for was open to all therapeutic modalities and Zioncheck said Convelo was “an im- the biopharma M&A landscape” today. would not limit itself to humanized mono- mediate scientific and cultural fit” for More recently, Roche and Genentech clonal antibodies or small molecules. Roche. Convelo was working in an area have merged their BD organizations to “We’re very open to antisense and gene of high interest to Roche and it had only create one partnering group, which is therapies, and are even considering cell- a few assets. Zioncheck said “a typical able to source and act on deals globally. based therapies. What we pride ourselves approach might have been just to acquire The rationale behind this move was to on is following the science and being the company outright.” But this was not provide “a cleaner and more straightfor- willing to take risks if the data support it.” the approach the partnering team took ward face to the external world,” Thomas for the deal.“We talked to the scientific Zioncheck, global head of neuroscience, 2019 Deals Of Note founders and thought deeply about what ophthalmology and rare diseases, Roche However, Zioncheck’s team has a particu- expertise we had internally; we realized Pharma Partnering, told In Vivo. “It is lar interest in partnering opportunities in there would likely be more synergy and a lot easier for potential partners to be the areas of neurodegeneration, neuroin- a higher probability of technical success able to approach us with one partnering flammation, neuromuscular diseases and if we could work together to bring both group. They can see the great science that ophthalmology. of our experts to collaboration that was is going on, either in the research and Despite Roche having recently launched mutually incentivized. The Convelo team early development group in Basel, or in Ocrevus, the only drug approved for re- were very open to this notion of us work- South San Francisco at Genentech. Now lapse remitting and primary progressive ing together on milestones before doing we have a lot more consistent and clear multiple sclerosis (MS), it continues to any outright acquisition. That is just one

28 | In Vivo | January 2020 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com invivo.pharmaintelligence.informa.com PARTNERING STRATEGY ❚

example of a recent creative deal struc- as we’re negotiating it, they stick with the ture that came about just through listen- deal after it is kicked off.” The alliance ing to one another and working together.” manager is a single point of contact for Also in July 2019, Roche announced the partner and the internal staff, who is deals with Sosei Group and Skyhawk there “to make sure all questions are an- Therapeutics. In a collaboration worth swered, and we can get going right away.” up to $1bn, Genentech and Japan-based Sosei Group will discover and develop Neuroscience Focus Remains novel medicines that modulate G protein- Zioncheck said Roche had one of the coupled receptor (GPCR) targets. Sosei “deepest and broadest” late-stage neu- received $26m upfront, but it is eligible roscience pipelines in the industry, but for future milestones amounting to $1bn. many of these assets came to the com- Meanwhile, the third deal from last pany through collaboration. “Granted, summer will focus on Skyhawk’s SkyS- many of those programs came in very TAR technology platform to discover and early on, into Roche or Genentech, and a develop innovative small-molecule treat- lot of effort from our own scientific teams ments directed to certain oncology and has gone into these programs – but there neurological disease targets. The finan- was a partnering component too.” cial terms of the deal were undisclosed Zioncheck highlighted Roche’s sa- but the agreement gives Genentech an tralizumab as a stand-out asset in its exclusive worldwide license to develop neuroinflammation portfolio. The drug and commercialize potential therapeutics is being developed for the rare disease directed to multiple targets. Genentech “... I want to let neuromyelitis optica (also known as will be responsible for clinical develop- Devic’s syndrome), a neuro inflamma- ment and commercialization. Zioncheck partners know that tory condition affecting the optic nerve. said the SkySTAR platform represented “Here we have a Phase III program for a novel approach for “what have histori- we’re very open to which we’ve demonstrated great data cally been undruggable targets.” and are looking for approval this year.” partnering new The company has filed a BLA in the US, The Four-Step Approach where the orphan drug has breakthrough Zioncheck said Roche and Genentech technologies, across therapy status. The product has also been used a “simple four-step process” for filed with regulators in Japan and Europe. partnering and deal-making. neurodegeneration, A decision from the US FDA is expected “The first step is really about making between April and May 2020. sure we have a clear understanding of our neuroinflammation “I am excited about the impact we’re own internal interests and priorities,” he making in neuroscience and ophthalmol- said. This is a focus on what the in-house and neuromuscular ogy, we have a very rich and robust late- R&D team thinks are the key targets, stage pipeline. But I want to let partners pathways and disease areas. diseases.” know that we’re very open to partnering “Next, we’re out at partnering confer- new technologies, across neurodegenera- ences like BIO-Europe, we’re at scientific tion, neuroinflammation and neuromus- conferences, and we are reading the scien- Thomas Zioncheck cular diseases,” Zioncheck said. tific literature looking for new opportuni- Roche’s neuroscience pipeline is ties.” When the group sees something of spread across: Alzheimer’s disease, interest, “we’re quick to actually bring our amyotrophic lateral sclerosis, autism experts to the table – whether it be scien- spectrum disorder, Duchenne muscular tists, clinical development specialists or dystrophy, Huntington’s disease, Parkin- commercial people. We want our people son’s disease, psychiatric disorders and engaging with prospective partners, mak- spinal muscular atrophy. ing sure that we’re clear on goal, and also Roche and Genentech’s joint partner- evaluating and making sure there’s a good ing group is active globally with offices in cultural fit for the collaboration.” Shanghai, Tokyo, San Francisco, Boston, If a company “feels like a good fit,” The last step of the process is ensuring New York and Basel. “We’re looking to Zioncheck said the next step was “openly the deals get off to a successful start. “We forge new partnerships and are there to trying to think of creative ways to struc- bring in – early in the negotiation – an rapidly move on any cutting-edge tech- ture win-win deals that meet both our alliance manager. So, a single point of nology that emerges,” Zioncheck said. partners’ needs and our needs.” contact that has all the context of the deal IV124405

©2018 Informa Business Information, Inc., an Informa company January 2020 | In Vivo | 29 ❚ R&D STRATEGY AstraZeneca’s Fredrickson On Its Cancer Ambitions

Just over a year ago, AstraZeneca at last returned to growth and set about a reorganization that placed oncology at the heart of its plans for continued success. In Vivo talked to the executive vice-president of its Oncology Business Unit David Fredrickson about how the company hopes to become a major cancer player.

BY ALEX SHIMMINGS

straZeneca PLC has been corresponding commercial unit. on a roll of late. Better “We specifically made a decision that than expected third quarter we want to focus on therapeutic area ex- financial results and strong cellence,” Fredrickson said. “What it takes showings at recent medi- to succeed in oncology is a different set of Acal meetings came during a second half capabilities, a different set of experiences of briskly paced positive Phase III data from what it takes to succeeds in respira- read-outs and approvals. tory and CVRM so we wanted an organiza- Much of the positive news flow has tion that allowed us to really be experts.” come from its oncology portfolio (see Ex- With the R&D and commercial oncology hibit 1), one of the firm’s three therapeutic units pursuing the same philosophy, he pillars, and one that is increasingly con- said, the two parts are working in tandem tributing revenues. AstraZeneca’s long- from discovery to market. As such, he and awaited return to growth, first seen in the Baselga are now “able to really think about third quarter of 2018, was fueled to a large our approach to redefining cancer care.” extent by swelling cancer drug sales. AstraZeneca is not alone in these Speaking to In Vivo, executive vice ambitions, of course. The growing can- president of AstraZeneca’s oncology unit cer market is lifting sales at more than David Fredrickson said this was an area one pharma firm: Johnson & Johnson, where the company has grand ambitions. Pfizer Inc. and AbbVie Inc. are just some “In 2017, oncology sales were just a little companies that also expect to see de- bit north of $4bn. In the first half of 2019, cent growth trajectories. Nevertheless, we delivered sales of $4bn, so in two analysts are noting something special years we have doubled the business,” he about AZ’s portfolio, with SVB Leerink said. “As we look forward over the next growth, means that the company’s describing it as “unparalleled in the couple of years, we absolutely believe product development efforts are no large pharmaceutical universe in terms that we should be doubling the business longer separated into early or late-stage of innovation and anticipated growth.” again.” It is well on its way: in 2015, about development but rather split into two 12% of AstraZeneca’s revenues were therapeutic area-focused R&D units Big Pharma Performances derived from oncology assets, whereas that are responsible for discovery right At present, the company sits in 13th place in the first three quarters of 2019, cancer through to late-stage development. The in the pharma top 20 companies (based drugs accounted for 37% or $6.39bn of second covers biopharmaceuticals and on 2018 total pharma sales), but in oncol- AZ’s sales. is made up of its cardiovascular, renal ogy terms, it already makes the top 10, Fredrickson’s further goal is to put Astra- and metabolism (CVRM), and respiratory coming in at eight with 2018 revenues of Zeneca among the top cancer companies therapy areas. These two R&D units are just over $6bn (see Exhibit 2). This leaves in the coming years. AstraZeneca’s aspira- each mirrored by a commercial unit. some way to go, though, before it begins tions in cancer are such that of its three The changes saw the departure of to trouble current leader Roche, which therapy areas, oncology was the only one some big names like CMO Sean Bohen racked up sales of $25.6bn in 2018 with to be given its own development unit upon and MedImmune head Bahija Jallal, but its trio of mega-blockbusters Herceptin the firm’s reorganization last January. the company brought on board noted (trastuzumab), Avastin (bevacizumab) The structural rejig, designed to oncologist José Baselga to lead the oncol- and Rituxan/MabThera (rituximab). position the big pharma for continued ogy R&D unit; Fredrickson heads up the (Roche, incidentally, will soon feel the

30 | In Vivo | January 2020 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com invivo.pharmaintelligence.informa.com R&D STRATEGY ❚

heat from Bristol-Myers Squibb Co. fol- Exhibit 1 lowing the latter’s recent acquisition of AstraZeneca’s Oncology Regulatory And Phase III News Flow Celgene Corp.) The stars of AstraZeneca’s portfolio – the DRUG DEVELOPMENT DATE third-generation EGFR inhibitor Tagrisso (osimertinib), the leading PARP inhibitor US filing granted priority review for first-line Lynparza (olaparib), the checkpoint in- Lynparza maintenance treatment with bevacizumab in 1/2020 hibitor Imfinzi (durvalumab), and the BTK advanced ovarian cancer. inhibitor Calquence (acalabrutinib) – have US accelerated approval for unresectable or been more than compensating for flagging metastatic HER2-positive breast cancer patients Enhertu 12/2019 revenues from its mainstays, Faslodex who have received two or more prior anti-HER2 (fulvestrant) and Iressa (gefitinib), and based regimens in the metastatic setting. the flat-lining older products, Arimidex (anastrozole), Casodex (bicalutamide) and US supplemental approval for first-line maintenance monotherapy for patients with Zoladex (goserelin). AstraZeneca is in the Lynparza 12/2019 germline BRCA-mutated metastatic pancreatic process of divesting its mature medicines cancer. to reallocate resources to the pipeline, including recently some commercial rights Imfinzi Chinese approval for unresectable Stage III NSCLC. 12/2019 to Arimidex and Casodex. ELEVATE-TN results in first-line chronic lymphocytic Its product stable was further stocked Calquence 12/2019 by the approval in the US as 2019 closed leukemia (CLL). of the antibody-drug conjugate Enfertu Chinese approval for first-line maintenance therapy Lynparza 12/2019 (trastuzumab deruxtecan, DS-8201), from in BRCA-mutated advanced ovarian cancer. the $6.9bn deal with Daiichi Sankyo last US priority review for small-cell lung cancer (SCLC) March. “[This deal was] an extraordinary Imfinzi 11/2019 opportunity and therefore we went to awarded. PDUFA date Q1 2020. extraordinary lengths in order to make it US FDA approval for CLL and small lymphocytic Calquence 11/2019 happen,” Fredrickson commented. leukemia for any line of treatment. Fredrickson said AstraZeneca’s recent run of success could be attributed to its Imfinzi and POSEIDON study showed the combination plus 10/2019 mantra: follow the science. “We have tremelimumab chemotherapy improved PFS in first-line NSCLC. scientific platforms where we believe we have the best and most innovative CASPIAN data presented showing use combined with standard chemotherapy gave a significant thinking taking place,” he said, referring Imfinzi 9/2019 27% reduction in death versus chemotherapy alone to its research into DNA damage repair, when given first-line for extensive-stage SCLC. immuno-oncology, tumor drivers and resistance, and, with the Daiichi Sankyo PROfound data in metastatic castration-resistant prostate cancer patients who have a mutation in deal, antibody-drug conjugates. Lynparza 9/2019 This way of thinking means the com- their homologous recombination repair genes and whose disease had progressed on prior treatment. pany lets research data, rather than target population size, dictate which particular FLAURA data in first-line treatment of adult patients indications are pursued. “We don’t start Tagrisso with locally advanced or metastatic epidermal 9/2019 first with a tumor type and say, ‘How are growth factor receptor (EGFR)-mutated NSCLC. we making sure we are able to find a drug in the most prevalent tumor types?’ – an PAOLA-1 PFS results from adding Lynparzato SoC Lynparza bevacizumab in first-line maintenance treatment of 9/2019 approach that certainly others will take,” women with advanced ovarian cancer. he explained. “What we are focused on is where can we dramatically improve out- Chinese approval for first-line treatment of EGFR- Tagrisso 9/2019 comes because we want to offer patients mutated NSCLC. step-change improvement in outcomes NEPTUNE missed OS primary endpoint compared not incremental improvements. I think Imfinzi plus with SoC chemo in previously untreated metastatic 8/2019 tremelimumab that that has really been a core tenet of NSCLC. the philosophy that we have: how do we really redefine cancer treatment?” Imfinzi US orphan drug status for SCLC. 7/2019 Within this, he said, are two compo- nents. “The first one is that we have set a really bold ambition to go into really early SOURCES: In Vivo; AstraZeneca; News Releases

©2018 Informa Business Information, Inc., an Informa company January 2020 | In Vivo | 31 ❚ R&D STRATEGY

stages of disease and the reason is that Exhibit 2 that is where the greatest opportunity is Top 10 Companies By 2018 Cancer Product Sales ($bn) for cure.” This, he continued, was also where the best outcomes for society and 27.78 for a sustainable commercial business were Roche most aligned with AstraZeneca’s ambition Celgene 13.65 to “eliminate cancer as a cause of death.” Moving to earlier stage disease will Novartis 13.43 require a new way of doing things. This 10.98 could be using novel trial endpoints and J&J new methods to find the right patients, BMS 10.31 for example, by looking at ctDNA [cir- culating tumor DNA] to determine who Merck & Co 8.24 would best respond to treatment at an Pzer 7.20 early stage. These new approaches will have reper- AstraZeneca 6.03 cussions down the line. Advances such as the use of ctDNA analysis are “certainly in- Eli Lilly 4.26 credibly exciting from a scientific perspec- AbbVie 3.93 tive,” but Fredrickson admitted that “we also need to be thinking today about how 0 5 10 15 20 25 30 we anticipate what that means for health SOURCE: In Vivo authority approvals. How do we anticipate what that means for reimbursement? How do we anticipate what that means for the medicine in biomarker-selected patients OS data still await. work that we need to be able to do com- with advanced pancreatic cancer. The Fredrickson said there was still much mercially in order to be able to take these limited patient population means that to be learned about the use of biomarkers novel endpoints, these new approaches to Lynparza will only realize sales of around such as TMB to find the patients who will clinical trial design, and make sure that $200m in pancreatic cancer out of total benefit most from immuno-oncology. De- in the real world they are going to work?” peak sales estimated at more than $5bn, spite the NEPTUNE setback, he said, “We In this challenge, he added, “having but analysts say it could have a “halo think that the science is very interesting the ability for José and me to be working effect,” reinforcing the drug’s status as and we have learned a lot more about together and have an entire organization the PARP of choice for oncologists – it all the biomarker that will help us as we that is able to think about how to maximize builds into the Lynparza story. continue to look at CTLA-4.” oncology is a real source of advantage.” But more than that, the approval was In the meantime, he will concentrate a vindication of AstraZeneca’s risky de- on wringing as much out of the portfolio Small, Targeted Populations cision to use progression-free survival as he can. “As I look at the next couple The second area where AZ is looking to as the endpoint in the pivotal study in of years ahead, my focus is on maximiz- “redefine” cancer therapy is for patients the face of the FDA’s avowed preference ing all of the life-cycle management that who are not doing well on current treat- for overall survival in pancreatic cancer. we’ve got to do around Lynparza, Imfinzi, ments or where they have few options Here, the small targeted population most Calquence and Tagrisso and obviously we left to them. “We have also a very ex- likely helped after the agency’s cancer are really excited about the opportunity plicit focus on relapsed patients and non- drugs advisory panel only narrowly voted to launch DS-8201 in the US. responders and how do we bring new in favor of the approval. “With five franchises – each of which therapies into those patient populations. The problem child has been tremeli- has the opportunity to be or is already a The only way you can do that is through mumab. A number of studies combin- multi-blockbuster – we feel quite good bold biomarker strategy, smart combina- ing the CTLA-4 inhibitor with its fellow that we’ve got a lot of the ingredients tions and bringing novel mechanisms of checkpoint inhibitor Imfinzi have missed to drive growth over the next couple of action to be able to address new targets their endpoints. These include MYSTIC years,” Fredrickson said. that can result in outcomes for patients.” and more recently last August NEPTUNE “If we stay on the trajectory that we Here, Lynparza’s December US approv- in previously untreated metastatic non- are on with the pipeline and if we stay al for use in a third tumor type, pancreatic small cell lung cancer in patients with a on the trajectory that we are on with our cancer, is a case in point. Based on the high tumor mutational burden (TMB), commercial organization, I think that we POLO study in a small (4-7%) subset of but the combination did achieve an will be well on the road to being one of patients harboring the germline BRCA unexpected win in the POSEIDON trial the top players in oncology in the years mutation, the label expansion makes where, used together with chemothera- to come.” Lynparza the first FDA-approved targeted py, it improved PFS in first-line NSCLC; IV124424

32 | In Vivo | January 2019 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com invivo.pharmaintelligence.informa.com R&D STRATEGY ❚

Global Regulatory and Compliance Insight for Fast Regulatory Approval

Successfully navigate the complex world of Pharmaceutical Regulatory and Compliance with access to worldwide intelligence for approved and pipeline drugs. Tracking product progress from submission to approval, our exclusive network of worldwide analysts and journalists cover critical areas of regulatory insight and analyse the implications of worldwide developments on your business. Anticipate challenges, minimize risks and maximize opportunities.

To fi nd out more, visit: www.pharmaintelligence.informa.com/ pink-sheet

©2018 Informa Business Information, Inc., an Informa company January 2020 | In Vivo | 33

JN2181 Pink Sheet Advert HBW US Letter.indd 1 2019/06/05 12:59 ❚ ON THE MOVE

❚ On the Move Recent executive appointments in the life sciences industry

❚ SCOTT BARRETT ❚ JOANNE BECK ❚ MONIQUE BOBADILLA ❚ JAMES HASSARD

COMPANY CHANGES

EXECUTIVE TO COMPANY NEW ROLE FROM COMPANY PREVIOUS ROLE EFFECTIVE DATE Judy Chou AbGenomics Chief Executive Bayer Senior Vice President, 1-Jan-20 International Inc Officer and Pharmaceuticals Global Head, Biotech President

Bruce Car Agios Chief Scientific Bristol-Myers Interim Head, Drug 6-Jan-20 Pharmaceuticals Officer Squibb Discovery

Jonathan Agios Chief Legal Officer Celgene Corp Executive Vice President, 3-Dec-19 Biller Pharmaceuticals General Counsel

Alex Howarth Akcea Chief Operating Lycera Corp President 7-Dec-19 Therapeutics Officer

Shehnaaz Alector Inc Chief Operating Theravance Senior Vice President, 11-Dec-19 Suliman Officer and Biopharma Corporate Development President and Strategy

Curtis L. Amphivena Chief Executive Parvus Chief Executive Officer and 2-Dec-19 Ruegg Therapeutics Inc Officer, President Therapeutics Inc President and Director

James Arrowhead Chief Commercial Coherus Senior Vice President, 6-Jan-20 Hassard Pharmaceuticals Officer BioSciences Marketing and Market Inc Access

Tomas BioArctic AB Chief Medical G. Keller Senior Consultant 1-Jan-20 Odergren Officer Consulting

Miguel Forte Bone Chief Executive Zelluna Chief Executive Officer 1-Jan-20 Therapeutics SA Officer Immunotherapy

Joanne Beck Boston Chief Operating Celgene Corp Executive Vice President, 19-Dec-19 Pharmaceuticals Officer Global Pharmaceutical Development and Operations

Christopher BrainsWay Ltd Chief Executive Dynatronics Corp Chief Executive Officer 1-Jan-20 von Jako Officer and President

34 | In Vivo | January 2020 invivo.pharmaintelligence.informa.com invivo.pharmaintelligence.informa.com ON THE MOVE ❚

Take an interactive look at recent executive-level company changes and  READ MORE promotions in the biopharma, medical device and diagnostics industries. ONLINE Visit: invivo.pharmaintelligence.informa.com

❚ STANLEY MUSIAL ❚ JAY NEWMARK ❚ CRAIG TOOMAN ❚ MARTIN WILLIAMS

COMPANY CHANGES

EXECUTIVE TO COMPANY NEW ROLE FROM COMPANY PREVIOUS ROLE EFFECTIVE DATE Eli Wallace BridgeBio Chief Scientific Peloton Chief Scientific Officer 9-Dec-19 Officer in Residence, Therapeutics Inc Oncology

Martin Caraway Chief Executive Yuma Executive Chairman 3-Dec-19 Williams Therapeutics Officer Therapeutics

Jay Newmark Clarus Chief Medical Genomic Health Senior Director, Medical 1-Dec-19 Therapeutics Inc Officer Affairs

Henrik C-RAD AB Chief Financial MSAB Chief Financial Officer 1-Mar-20 Bergentoft Officer

Shirley Zhao CStone General Manager, Bristol-Myers General Manager, China 7-Dec-19 Pharmaceuticals China and Head, Squibb Co Commercial

Monique Encoded Chief People and Genetech Inc SSF Global Product 18-Dec-19 Bobadilla Therapeutics Culture Officer Development and Global Product Strategy Human Resources Director

Franck EpicentRx Chief Financial Biotech Alliances Chief Executive Officer and 7-Dec-19 Brinkhaus Officer Founder

Gabriel M. Homology Chief Medical Avrobio Inc Vice President, Clinical 3-Dec-19 Cohn Medicines Inc Officer Lead

Scott Barrett Immuneering Chief Medical Incyte Global Medical 19-Dec-19 Corp Officer Pharmaceuticals Affairs Lead, Targeted Therapeutics

Marvin InspireMD Inc Chief Executive Integra Business Consultant 1-Jan-20 Slosman Officer LifeSciences

Sean Khozin Janssen Global Head, Data FDA Founding Director, 7-Dec-19 Research & Strategy INFORMED Development llc

January 2020 | In Vivo | 35 ❚ ON THE MOVE

COMPANY CHANGES

EXECUTIVE TO COMPANY NEW ROLE FROM COMPANY PREVIOUS ROLE EFFECTIVE DATE Elena JSC Olainfarm Chief Executive Veropharm General Manager 5-Dec-19 Bushberg Officer, Member of Management Board, JSC Olainfarm

Arnout Ploos Khondrion BV Chief Operating Novartis Senior Vice President, Head 9-Dec-19 van Amstel Officer and General Manager, Immunology, Hepatology and Dermatology

James Burns Locana Inc Chief Executive Casebia Chief Executive Officer, 10-Dec-19 Officer and Director Therapeutics President and Director

John Nektar Chief Commercial Pharmacyclics Chief Commercial Officer 3-Dec-19 Northcott Therapeutics Officer and Senior Vice President

Dean Sawyer Palo Alto Health Chief Executive Rx-Precision Chief Executive Officer 17-Dec-19 Sciences Inc Officer and President

Leila Alland PMV Chief Medical Affimed Chief Medical Officer 11-Dec-19 Pharmaceuticals Officer Inc

Craig Tooman Vyome Chief Operating Aratana Chief Executive Officer 7-Jan-20 Therapeutics Officer and Chief Therapeutics Financial Officer

Stanley Xenikos BV Chief Financial EryDel SPA Chief Financial Officer 2-Dec-19 Musial Officer and Chief Business Officer

PROMOTIONS

EXECUTIVE TO COMPANY NEW ROLE PREVIOUS ROLE EFFECTIVE DATE Jack Phillips Accelerate Chief Executive Officer Chief Operating Officer 1-Feb-20 Diagnostics Inc

Jean-Claude B. Braun Medical Chief Executive Officer and President 1-Jan-20 Dubacher Inc Chairman

Freda Lin Bayer AG President, Bayer Korea Managing Director and Country 1-Jan-20 Division Head, Bayer Taiwan

Siddharth Biocon Ltd Chief Executive Officer and Joint Chief Financial Officer 1-Dec-19 Mittal Managing Director

Tony Evans Cancer Therapeutics Chief Executive Officer and Chairman 1-Jul-20 CRC Chairman

Ryan Spencer Dynavax Chief Executive Officer and Senior Vice President, 16-Dec-19 Technologies Corp Director Commercial and Co-President

Jan Adams Grunenthal GmbH Chief Scientific Officer and Acting Chief Scientific Officer 1-Jan-20 Director

C. Frank Ionis Chief Scientific Officer and Senior Vice President, 1-Jan-20 Bennett Pharmaceuticals Inc Franchise Leader, Neurology Research and Franchise Leader, Drug Discovery Neurology Drug Discovery

Diane Gomez- Mentor Worldwide Worldwide President Vice President, Global Strategic 9-Dec-19 Thinnes llc Marketing and US Marketing

36 | In Vivo | January 2020 invivo.pharmaintelligence.informa.com invivo.pharmaintelligence.informa.com ON THE MOVE ❚

PROMOTIONS

EXECUTIVE TO COMPANY NEW ROLE PREVIOUS ROLE EFFECTIVE DATE Sven (Bill) Merus NV Chief Executive Officer, Director 31-Dec-19 Ante Lundberg President and Principal Financial Officer Annie C. Chen Nimbus Chief Medical Officer and Chief Medical Officer 17-Dec-19 Therapeutics President, Nimbus Lakshmi Inc Dustin Sjuts Revance Chief Commercial Officer, Head, Commercial, Aesthetics 2-Dec-19 Aesthetics and Therapeutics and Therapeutics Claudia Roche General Counsel Head, Legal, Diagnostics 1-Apr-20 Bockstiegel Robert M. Stemline Chief Commercial Officer Global Head, Commercial and 6-Dec-19 Francomano Therapeutics Inc Senior Vice President Frank DeRosa Translate Bio Chief Technology Officer Senior Vice President, Platform 12-Dec-19 Technology Namir Hassan Zelluna Chief Executive Officer Chief Scientific Officer 19-Dec-19 Immunotherapy AS

DIRECTORS EXECUTIVE TO COMPANY NEW ROLE EFFECTIVE DATE Kemal Malik Acceleron Pharma Inc Director 1-Jan-20 Ian Johnson Circassia Pharmaceuticals plc Executive Chairman 7-Dec-19 Beat In-Albon Evolva Holding SA Chairman 15-Apr-20 Scott St. Johnson Fisher & Paykel Healthcare Ltd Chairman 1-Aug-20

Wolfgang Kirsch Fresenius SE & Co KGaA Supervisory Board Member 1-Jan-20 Edmund P. Harrigan Incyte Corp Director 16-Dec-19 Hubert Joly Johnson & Johnson Director 5-Dec-19 Mark A. Weinberger Johnson & Johnson Director 5-Dec-19 Taiyin Yang Kodiak Sciences Director 19-Dec-19 Tony Hooper MannKind Corp Director 1-Jan-20 Sol Barer NexImmune Inc Chairman 16-Dec-19 Tatsuo Higuchi Otsuka Pharmaceutical Co Ltd Chairman 10-Mar-20 Iain Ross Silence Therapeutics Executive Chairman 1-Jan-20 Edwin M. Kania Vyriad Inc Chairman 11-Dec-19

ADVISORS

EXECUTIVE TO COMPANY NEW ROLE EFFECTIVE DATE Jeremy Pettus Diasome Pharmaceuticals Inc Chairman, Scientific Advisory Board 10-Dec-19 April Jasper Eyenovia Inc Scientific Advisory Board Member 19-Dec-19 Mark Bullimore Eyenovia Inc Scientific Advisory Board Member 19-Dec-19 Rebecca Auer Imugene Virotherapy Scientific Advisory Board Member 5-Dec-19 Joseph E. Bernardo Mobidiag Ltd Senior Strategic Advisor 10-Dec-19 Charles Hart RubrYc Therapeutics Inc Chairman, Scientific Advisory Board 4-Dec-19 Stephen Mayo RubrYc Therapeutics Inc Scientific Advisory Board Member 4-Dec-19

January 2020 | In Vivo | 37 ❚ DEAL-MAKING

Derived from Strategic Transactions, Informa’s premium source for tracking life sciences deal activity, the Deal-Making column is a ❚ Deal-Making survey of recent health care transactions listed by relevant industry segment – In Vitro Diagnostics, Medical Devices, Pharmaceuticals, and Research, Analytical Equipment and Supplies – and then Covering deals made December 2019 categorized by type – Acquisition, Alliance, or Financing. Strategic Transactions is updated daily with in-depth deal analysis, structural and financial terms, and links to SEC-filed contracts. For information about access please contact Customer Care at 888-670-8900 or [email protected]

❚ IN VITRO DIAGNOSTICS Seattle Genetics, Astellas ally with Bavarian Nordic sells PRV for $95m Merck in trial collaboration ALLIANCES Constellation nets $242.4m in CureVac and Genmab develop mRNA- public offering Veracyte gets rights to NanoString’s based antibody therapies diagnostics Follow-on nets $26m for Exicure Vyera gains exclusive US rights to FOPO nets $183.9m for CytoDyn’s HIV candidate Forty Seven ❚ MEDICAL DEVICES Global Blood Therapeutics enters Eisai to co-promote filgotinib in Japan $150m loan agreement; gets $75m with Gilead MERGERS & ACQUISITIONS up front J&J buys Verb Surgical Global Blood partners with Syros Public offering nets $272.4m for for sickle cell and beta thalassemia Immunomedics FINANCINGS therapies IVERIC bio nets $37.4m via follow-on OrthoPediatrics nets $60.2m via FOPO Hanmi gets rights to RAPT’s CCR4 antagonist for cancer Kodiak sells Baker Bros. royalty on net ViewRay closes $141m public sales of KSI301 stock sale Jazz gets US rights to PharmaMar’s SCLC candidate lurbinectedin Kodiak Sciences nets $298m via FOPO ❚ PHARMACEUTICALS Janssen Biotech gets rights to Public offering nets $48.6m for XBiotech’s bermekimab MEI Pharma MERGERS & ACQUISITIONS Neurocrine gains global license to Millendo nets $23.5m via FOPO Astellas pays $3bn in cash for Xenon’s XEN901 Nav1.6 inhibitor for Audentes epilepsy Momenta nets $212.6m through FOPO Neoleukin nets $70.7m via Astellas pays $120m up front for Onconova chooses Specialised public offering Xyphos Therapeutics to market rigosertib in Australia and New Zealand Chondrial, Zafgen reverse merge, Omeros nets $54.5m via FOPO forming Larimar to advance CCP drugs Pfizer gets global rights to Theravance Registered direct offering nets $4.65m for rare diseases JAK inhibitors for Onconova J&J buys Taris Biomedical Roche signs immunometabolism deal Relmada nets $108m through FOPO with Rheos Merck acquires precision medicine Revance nets $103.9m through company ArQule for $2.7bn Roche gets ex-US rights to Sarepta’s follow-on offering DMD gene therapy SRP9001 Sanofi buys Synthorx for $2.5bn Rocket Pharmaceuticals nets $80m SDP exercises option to acquire five Turnstone pens $1bn deal with Takeda through FOPO Roivant divisions; forms Sumitovant Scynexis nets $32.9m via FOPO to run them FINANCINGS TG Therapeutics completes $50m Abeona nets $97.2m via FOPO ALLIANCES registered direct offering Public offering nets $69m forAptose Acceleron, Fulcrum collaborate in the Ultragenyx sells Crysvita European royalty rights to Royalty Pharma pulmonary disease space Follow-on nets $117.5m for Ardelyx for $320m Alteogen licenses Hybrozyme platform Arrowhead nets $250.8m through Windtree nets $23m via PIPE to create subcutaneous biologics for FOPO undisclosed pharmaco Assembly Bio nets $117.5m via FOPO AskBio licenses Selecta’s ImmTOR platform to develop AAV gene Public offering nets $180.2m therapies for Pompe disease for Aurinia

38 | In Vivo | January 2020 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com invivo.pharmaintelligence.informa.com

------❚

| 39 Astel , and , and Genentech , DEAL-MAKING In Vivo | In Vivo January 2020 for up to $109.3m. $109.3m. to up for Ltd. Quethera Advanced Cellular Control through through Control Cellular Advanced -T cell candidate candidate cell -T convertibleCAR in 2010. Invest 2010. in Pharmaceuticals OSI ASTELLAS PHARMA INC. PHARMA ASTELLAS INC. BIOSCIENCES XYPHOS . In early December, Astellas Astellas December, . In early AvidBiotics the FDA in mid-2020 and an MAA in Europe in Europe an MAA and mid-2020 in the FDA most second Audentes’ 2020. in the H2 Pompe for AT845 is compound advanced Q3 in submitted The IND was disease. includes also pipeline The firm’s 2019. - mus Duchenne for programs preclinical ex studies (IND-enabling dystrophy cular myotonic for AT466 and 2020) Q1 in pected in 2020). expected (IND filing dystrophy focus fifth a adds deal the says Astellas drugs--which the firm--genetic for area immuno-oncology, regenerative, its joins neuro-muscular and immunotherapy, ac Astellas 2018 In businesses. medicine therapy gene ophthalmic-focused quired start-up As- represents acquisition Audentes The $3.5bn purchase its since largest tellas’ of Stanley Morgan Banks/Advisors: ment Centerview Inc.); Pharma (Astellas & Co. Inc.) Therapeutics (Audentes LLC Partners month, this acquisition second its In cancer- private acquiring is Inc. Pharma las Inc. Biosciences Xyphos biotech focused in $545m to up and front $120m up for (Dec.) payments. earn-out potential Xyphos two-year-old Post-transaction, - sub Astellas owned a wholly becomes Xyphos’ to attracted was Astellas sidiary. ( ACCEL is which Ligands) platform, Engineered cancer better new and create to designed and target, mobilize, can that therapies modulate, identify, to cells immune direct en- ACCEL the body. throughout cells and target and activity of control precise ables antigen chimeric universal Xyphos’ ing of -T convertibleCAR as known cell, (CAR)-T a powerful exploits The technology cell. involv pathway surveillance immune naturally are that receptors ing NKG2D within the types cell different on present killer natural including system immune has Xyphos some T-cells. and (NK) cells be to receptor natural the engineered - a bispe by turned-on is it until inactive protein. a MicAbody called antibody cific introduced, is protein When a MicAbody receptors inactive the to binds end one the while cell -T on the convertibleCAR on the malignant the target other binds -T the convertibleCAR activating thus cell Xyphos’ it. destroy aggressively to cell first studies in preclinical currently is XYP117 in 2021. the clinic enter to expected and focus a primary is immuno-oncology As combine to plans it Astellas, for area therapy cell its with technology Xyphos’ next-generation develop to capabilities executives Xyphos’ cells. high-function major at positions leadership held have Du- including firms biotech and pharma Eos Chiron, Merck, Pont Health Auris ; the company ; the company Medtronic and Elekta PHARMACEUTICALS MERGERS & ACQUISITIONS & MERGERS FINANCINGS ASTELLAS PHARMA INC. PHARMA ASTELLAS THERAPEUTICS INC. AUDENTES VIEWRAY INC. VIEWRAY ORTHOPEDIATRICS CORP. ORTHOPEDIATRICS operative care. Verb’s surgical system is is system surgical Verb’s care. operative - com will and in 2020 launch to expected . Surgical Intuitive leader market with pete bought Ethicon 2019 early In robotic flexible the Monarch of (developer in cash $3.4bn for platform) endoscope in earn-outs. $2.35bn to up and ❚ entered into non-binding memorandums memorandums non-binding into entered - collabora into enter to understanding of a 9.9% took firm. Elekta each with tions of the purchase through ViewRay in stake offering, public in the shares 11.5 million the MOU. (Dec.) with in connection Guggenheim Banks/Advisors: Investment Inc.; Co. & Oppenheimer LLC; Partners Co. & Piper Jaffray $60 per paying is Inc. Pharma Astellas acquire to in cash premium) (a 112% share firm Auden- therapy gene seven-year-old a total has The deal Therapeutics Inc. tes $3bn. (Dec.) of value equity Astellas’ combines The acquisition and capabilities, expertise, scientific AAV Audentes’ with resources global gene vector) viral (adeno-associated large-scale in-house technology, therapy in expertise and cGMP manufacturing, Au- development. drug neuromuscular I/II AT132 Phase is program lead dentes’ myopathy myotubular X-linked treating for neu- deadly and a rare is which (XLMTM), extreme causes that disease romuscular failure. respiratory and weakness muscle a BLA to submit to expects The company netted $141m through the through $141m netted Inc. ViewRay shares common million 47.8 of sale public The $3.13. at the overallotment) (including MRI-guided the MRIdian markets company the offering use will and system, radiation - con and expenditures capital for proceeds also could Funds R&D expenses. tinued relationships recently-announced support with netted $60.2m $60.2m netted Corp. OrthoPediatrics of offering public follow-on the through full (including shares common million 1.76 $36.50. at the overallotment) of exercise 50k an additional sold Stockholders the proceeds use will The company shares. for sets instrument and in implant invest to R&D for and customers its to consignment (Dec.) activities. marketing and sales and JMP LLC; BTIG Banks/Advisors: Investment Stifel Co.; & Piper Jaffray LLC; Securities Inc. Banks SunTrust Inc.; & Co. Nicolaus , ------Prosigna breast cancer cancer breast Prosigna lymphoma subtyping test. (Dec.) test. subtyping lymphoma on nCounter based classifier Envisia MEDICAL DEVICES MEDICAL VITROIN DIAGNOSTICS MERGERS & ACQUISITIONS & MERGERS ALLIANCES JOHNSON & JOHNSON & JOHNSON SURGICAL VERB INC. NANOSTRING TECHNOLOGIES INC. TECHNOLOGIES NANOSTRING INC. VERACYTE ❚ ❚ To expand its digital surgery platform, platform, surgery digital its expand To owner full acquiring is & Johnson Johnson Verb Surgical (Dec.) Inc. Surgical Verb of ship venture a joint in 2015 as created was Verb - Sci Life Verily and Ethicon J&J’s between Sciences). Google Life (formerly LLC ences the acquiring is J&J deal, current the Under Spe- Verily. from Verb of stake remaining disclosed. not were terms financial cific machine and robotics developing is Verb sur “democratizing” for tools learning sur connect to is goal The firm’s gery. platform surgical an end-to-end to geons planning, pre-operative with helping thus post- and making, decision intra-operative prognostic gene signature assay and Lym and assay signature gene prognostic licensed licensed Inc. Technologies NanoString to rights global exclusive Inc. Veracyte diagnostics commercialize and develop FLEX analysis system. nCounter on its NanoString’s to rights gets also Veracyte 510(k)-cleared phMark and front up $40m in cash paid Veracyte - com worth$10m of NanoString issuing is is NanoString shares). (376,732 stock mon commer $10m in receive to eligible also $3.5m, payments--$3.5m, milestone cial first, the of launch the $3m--upon and on the FLEX use for test third and second, - Vera collaboration the Through . System - nCounter the portfolio of expand cyte will tests. own its using diagnostics based ten NanoString offer will The company NanoString opportunities. job employees supply and manufacture will Weinberg Perella Banks/Advisors: ment Inc.) Technologies (NanoString Partners for use in idiopathic pulmonary fibrosis di- fibrosis pulmonary in idiopathic use for - classi swab a nasal and 2021, in agnosis following the diagnosis cancer for lung fier NanoStrong enables transaction The year. its of on the commercialization focus to Invest profiler. spatial digital GeoMx , and new tests developed developed new tests , and LymphMark on the use for partners or its Veracyte by The FDA-approved FLEX platform. nCounter - pro simultaneously can system nCounter - expres gene translate and measure, file, analytes multiple from signatures sion and medicine, translational research, for analyze can It use. diagnostic molecular 800 to up in RNA,targets DNA, protein or its offer globally to plans Veracyte genes. own company an Informa Inc., Information, Business ©2016 Informa ❚ DEAL-MAKING

announced it was paying $3m in cash to the potential for both patient need and being studied in Phase II dose expansion acquire seven-year-old gene therapy firm market opportunity within rare diseases; study. What makes it attractive to Merck Audentes Therapeutics. and the possibility for multiple assets, the is ARQ531’s ability to block both wild-type Zafgen board concluded that the combina- CHONDRIAL THERAPEUTICS INC. BTK and the C481S mutant form of the tion with Chondrial represents the best enzyme that is commonly associated with ZAFGEN INC. value creation prospect for the company. Chondrial Therapeutics Inc. and Zafgen Investment Banks/Advisors: MTS Health resistance to other BTK inhibitors, such as Inc. agreed to merge in a transaction Partners (Zafgen Inc.) AbbVie’s/J&J’s first-to-market Imbruvica resulting in a combined publicly traded (ibrutinib), which was approved in 2013 company named Larimar Therapeutics JOHNSON & JOHNSON for MCL; AstraZeneca’s Calquence (aca- Inc., which will take over Zafgen’s Nasdaq Janssen R&D LLC labrutinib), launched in 2017 for MCL and TARIS BIOMEDICAL LLC listing under a new stock symbol, be led gained an expanded indication for CLL in by Chondrial’s current president Carole Johnson & Johnson acquired Taris Bio- November 2019; and BeiGene’s Brukinsa Ben-Maimon, MD, and have a board con- medical LLC for an undisclosed sum. (Dec.) (zanubrutinib), approved for second-line sisting of four Chondrial and three Zafgen Taris is developing therapies for blad- MCL just last month. Other candidates directors. (Dec.) der diseases and cancer using its Taris Chondrial stockholders will receive newly drug delivery system which incorporates in ArQule’s cancer pipeline include AKT issued Zafgen common shares via a pri- a silicone-based device to enable the inhibitors ARQ092 (miransertib; in Phase vate placement, with Chondrial owning continuous release of medication into II for Proteus syndrome and Phase I for approximately 60%, and Zafgen the re- the bladder. The device is implanted via solid tumors) and ARQ751 (Phase I for mainder. Larimar will assume Chondrial’s a minimally invasive in-office procedure solid tumors with certain mutations) and focus on protein replacement therapies for using a catheter. The company’s lead FGFR inhibitor ARQ087 (derazantinib; in rare diseases. Chondrial’s lead program is candidate TAR200 (GemRIS) is in Phase I Phase II for biliary tract cancer). The ac- CTI1601, a frataxin (FXN) protein replace- for bladder cancer and provides continu- quisition further expands Merck’s existing ment therapy for Friedreich’s ataxia (FA), ous and controlled release of the chemo- oncology pipeline, adding more targeted a neuromuscular disease caused by a therapy gemcitabine into the bladder via genetic defect that results in abnormally the Taris device. Following the acquisition, candidates for hematological malignan- low amounts of FXN, a protein in the mi- Taris will continue having a research pres- cies. Investment Banks/Advisors: Bank of tochondria responsible for energy pro- ence in Massachusetts and becomes part America Merrill Lynch (Merck & Co. Inc.); duction. Chondrial originally in-licensed of Janssen R&D’s oncology therapeutic Centerview Partners LLC (ArQule Inc.) the compound under a 2017 alliance area. Under a late-2017 trial collaboration, from Indiana University and Wake Forest TAR200 is being studied in combination SANOFI University, which also provided related IP with Bristol-Myers Squibb’s Opdivo SYNTHORX INC. surrounding a carrier protein technology (nivolumab) in muscle-invasive bladder Sanofi will pay $68 per share (a 248% pre- that incorporates cell-penetrating pep- cancer patients who are scheduled for mium) to acquire Synthorx Inc. The deal tides (CPPs) capable of crossing both the radical cystectomy. Under a 2013 tie-up, has an enterprise value of $2.35bn and a cell and mitochondrial membranes; in the Taris and AstraZeneca are evaluating fully-diluted equity value of $2.5bn. (Dec.) case of CTI1601, to replace malfunctioning the feasibility of delivering AZ’s targeted FRX. Preclinical studies demonstrated therapies with the Taris system. AZ holds Synthorx uses its Expanded Genetic Al- promising results and a Phase I trial was an option to license resulting products. phabet technology to develop a differenti- recently initiated; topline data from this Taris raised $78m in its first four financing ated pipeline of cancer and autoimmune program are expected by the end of 2020. rounds and is backed by investors includ- disease treatments. The platform expands CTI1601 has both orphan drug (July 2017) ing Flagship Ventures, Polaris Ventures, the genetic code by adding a new X-Y DNA and fast track (December 2019) statuses RA Capital, Flybridge Capital Partners, and base pair to the two naturally occurring from the FDA, which has also granted Third Rock Ventures. base pairs to create optimized biologics rare pediatric disease designation (at the time of a potential future approval, MERCK & CO. INC. called Synthorins. The company’s lead this could qualify the company for a ARQULE INC. Synthorin candidate THOR707 is an IL-2 voucher redeemable for priority review Merck & Co. Inc. agreed to acquire cancer- variant that kills cancer cells by increas- of a subsequent marketing application). focused public biotech ArQule Inc. in a ing CD8+ T and NK cells without causing If approved, CTI1601 is projected to have transaction with a total equity value of vascular leak syndrome. Sanofi believes 12 years of market exclusivity and the $2.7bn. (Dec.) that the candidate has strong potential CPP-related IP is expected to be applicable Merck will pay $20 in cash per share (a in combination with other of its own im- 117% premium) for all outstanding ArQule to various other rare disease indications mune-oncology projects in development. beyond FA. Zafgen itself is a developer of shares. Founded in 1993, ArQule listed on methionine aminopeptidase 2 (MetAP2) Nasdaq in 1996 and has since amassed a The Big Pharma also looks forward to the inhibitors for both common and rare pipeline of oral kinase inhibitors headed access it gains to the Expanded Genetic metabolic diseases. Back in September up by lead candidate ARQ531, an oral Alphabet platform, which the company 2019, Zafgen began evaluating strategic Bruton’s tyrosine kinase (BTK) inhibitor acknowledges as being a strong tool both alternatives following preliminary in vivo that prevents B-cell receptor signaling independently and potentially in combina- animal study results indicating the com- critical for the survival and proliferation tion with its Nanobody technology for the pany did not expect a resolution regarding of leukemic cells in many B-cell malig- future development of biologics including a previous FDA clinical hold placed on its nancies, including chronic lymphocytic multi-specifics, drug conjugates, and lead compound ZGN1061, a methionine leukemia (CLL) and mantle cell lymphoma protein fusions. Synthorx was founded aminopeptidase 2 (MetAP2) inhibitor in (MCL). Concurrent with the acquisition, Phase II for Type II diabetes and Phase I ArQule released positive Phase I final in 2014 and went public via a $140m IPO for obesity. Because of its near-term mile- data on ARQ531, which demonstrated one year ago. Investment Banks/Advisors: stones (expected within 9-12 months post- efficacy in heavily pretreated refractory Morgan Stanley & Co. (Sanofi); Centerview transaction); strong scientific approach; CLL patients. The candidate is currently Partners LLC (Synthorx Inc.)

40 | In Vivo | January 2020 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com invivo.pharmaintelligence.informa.com

------❚

| 41 DEAL-MAKING In Vivo | In Vivo January 2020 ASKLEPIOS BIOPHARMACEUTICAL INC. BIOPHARMACEUTICAL ASKLEPIOS INC. BIOSCIENCES SELECTA about 4-5 hours, while subcutaneous subcutaneous while hours, 4-5 about shorter offers delivery (under-the-skin) - pro invasive a less times, administration biolog of absorption improved and cess, the unnamed granted has Alteogen ics. and development worldwide company - prod multiple to rights commercialization the Hybrozyme with in combination ucts front up $13m for in exchange technology - develop in specified $1.373bn to up and milestones. sales and ment, regulatory, and the clinical for responsible is Alteogen materials. ALTB4 the of supply commercial is in 2008, founded was which Alteogen, long-act areas: three the within focused conjugates, antibody-drug ing biobetters, also Alteogen biosimilars. antibody and to ATLB4 apply independently to plans candidates. biosimilar self-developed its proof-of-concept of the success Following 2019, August in announced studies (POC) (Ask Inc. BioPharmaceutical Asklepios exclusively option to its Bio) exercised - commercializa and development license ’s Inc. Biosciences Selecta to tion rights ImmTOR platform, tolerance immune nanopar biodegradable (antigen-specific immunomodulator the encapsulating ticle in adeno-associated use for rapamycin), for therapies gene (AAV)-based virus ly inherited rare, a disease, Pompe by marked disorder storage sosomal cardiac and respiratory, neuromuscular, (Dec.) dysfunction. to agreed partners the August, in Back to studies POC of the feasibility assess - in combina ImmTOR of the use validate methylmalonic for AAVs AskBio’s tion with disease) liver pediatric a (MMA; acidemia SEL302 preclinical on Selecta’s based the mitigate to ability its (evaluating capsid anti-AAV neutralizing of formation then de- would results Those antibodies). a with proceed would parties the if termine to pursue ImmTOR utilizing collaboration commercialization and the development agreed certain for therapies gene AAV of - dis genetic orphan and rare serious upon that agreement Under the current eases. supporting studies POC successful follows pay will AskBio advancement, program commer and development front, $7m up tiered plus $237m, to up of milestones cial single mid-to-high the in royalties sales all for be responsible will digits. AskBio a potential R&D for to related activities Selecta disease. Pompe for therapy gene - evi preclinical established already has its demonstrates that ImmTOR for dence immune AAV-specific induce to ability for potential supporting thus tolerance, therapy. gene receiving patients re-dosing (which platform therapy gene AskBio’s li- capsid AAV an extensive both includes line manufacturing cell Pro10 its and brary a pipeline generated already has process) - - Cytovant Cytovant Sinovant Sciences Sciences Sinovant technology, to to technology, Hybrozyme , lipid nanoparticle and ligand ligand and nanoparticle lipid , Arbutus (Chinese spec pharma); pharma); spec (Chinese Lysovant Lysovant and disorders); (metabolic ALLIANCES ALTEOGEN INC. ALTEOGEN ACCELERON PHARMA INC. PHARMA ACCELERON THERAPEUTICS INC. FULCRUM Dermavant (Dermavant vants: biopharma Roivant Genevant Ltd. (dermatology); Sciences Roivant between (50/50 Ltd. JV Sciences and RNA- for platforms delivery conjugate therapeutics); based Ltd. target therapies cell (dendritic Sciences Sciences Metavant receptors); ing T-cell Ltd. - dis infectious for Ltd. (biologics Sciences eases)) by 2024 as well as a right of first in interests ownership Roivant’s to refusal (neurological Ltd. Therapies Gene Axovant diseases). neuromuscular and granted an granted Inc. Alteogen biotech Korean company pharmaceutical undisclosed 10 global a top is says Alteogen (which - recom ALTB4 its use to a license player) enzyme, hyaluronidase human binant its as known - adminis subcutaneously multiple create (Dec.) biologics. tered - swap the domain involves Hybrozyme enzymes; similar structurally two of ping - mecha catalytic the inherent keeping the conformational improving but nism, the of stability thermal and flexibility hydrolyz temporarily By enzyme. target - Thera Fulcrum and Inc. Pharma Acceleron identify to up teaming are Inc. peutics the control to designed molecules small pathways in specific genes of expression of disease a pulmonary with associated (Dec.) interest. engine and product its use will Fulcrum to perform platform identification target in activities research and screening assay potential validate identifyto effort an and exclusive gets Acceleron targets. gene manufacture, develop, to rights worldwide pulmonary resulting commercialize and receive will Fulcrum therapies. disease in research- $18.5m to up front, $10m up in development $135m milestones, based can- a first for milestones regulatory and and in development $67.5m to up didate, - candi a second for milestones regulatory a to tied milestones sales in $145m date, - mile commercial in $72.5m product, first plus product, a second to related stones in the mid-single- royalties sales tiered (Strategic range low-double-digit to digit Fulcrum 4-29%). estimates Transactions R&D for reimbursement receive also will expertise its contributes Acceleron costs. signaling. superfamily in TGF-beta matrix, in the extracellular ing hyaluronan an from conversion facilitates Hybrozyme protein delivered intravenously otherwise - subcu convenient a more to therapeutic takes typically infusion IV route. taneous

- - Spirovant Spirovant , run , run Ltd. Biopharma Sumitovant - biopharmaceu Inc. Sciences Roivant (rare immunodeficiency diseases), diseases), immunodeficiency (rare (urinary disorders), and and disorders), (urinary ROIVANT SCIENCES INC. SCIENCES ROIVANT SUMITOMO CHEMICAL CO. CHEMICAL SUMITOMO by Roivant’s Myrtle Potter as CEO. (Dec.) CEO. as Potter Myrtle Roivant’s by a (following deal 2019 Under an October - the pre understanding of memorandum an alliance to agreed month), SDP vious (each divisions Roivant multiple involving pipelines development houses which of as well as focus) disease a specific within platforms technology Roivant’s to access selec asset pipeline (facilitates DrugOme development clinical accelerates and tion and analytics computational through (tech Innovation Digital and techniques) efficiency). workflow improve to nology these use will Sumitovant, through SDP, - devel pipeline support to technologies Sumitovant vants. five these of opment candidates, nine development have will GnRH III oral Phase Myovant’s including uterine for relugolix antagonist receptor a has it for which (an indication fibroids above (17% approval of likelihood 79% plans Myovant which for and average) (PRV) in voucher review a priority use to an- submission NDA its with conjunction cancer, prostate 2020), in early ticipated III Phase Urovant’s endometriosis; and agonist receptor adrenergic beta-3 oral (OAB); bladder overactive for vibegron this the FDA to submitted was an NDA occurring decision PDUFA a with month Altavant’s and 2020; 30, on December hydroxylase tryptophan II oral Phase for ethyl) RVT1201 (rodatristat inhibitor line top hypertension; arterial pulmonary Raising in Q2 2020. expected are results - pro the manufacturing about questions month declined this earlier the FDA cess, RVT802 III Phase Enzyvant’s approve to disease immune pediatric the rare for in a filing however, athymia, congenital also SDP year. next early expected is China as and Roivant in stake 11% an acquired the agreement, retains per the previous additional six to up acquire to options (gene therapies for cystic cystic for therapies (gene Ltd. Sciences a newly under operate fibrosis)--will - sub SDP owned wholly formed, 50.2% sidiary Altavant Sciences Inc. Sciences Altavant Ltd. Sciences Enzyvant Ltd. Sciences Myovant Ltd. Sciences Spirovant Sciences Ltd. Urovant Ltd. Co. Pharma Dainippon Sumitomo its exercise to in cash $3bn paid (SDP) acquire option to announced previously five five The vants). as (known divisions tical (rare Inc. Sciences Altavant companies-- Sciences Enzyvant diseases), respiratory Ltd. health Ltd. (women’s Sciences Myovant Sciences Urovant cancer), prostate and Ltd. Sumitomo Dainippon Pharma Co. Ltd. Co. Pharma Dainippon Sumitomo Ltd. Biopharma Sumitovant company an Informa Inc., Information, Business ©2016 Informa ❚ DEAL-MAKING

of clinical-stage, third-generation gene five years) to CureVac’s mRNA technology. years. It GBT exercises its option, the com- vectors. Combining Selecta’s ImmTOR If exercised, Genmab will fund all research pany could also pay up to $315m in option with AskBio’s AAV gene therapy platform and develop and sell resulting projects, exercise and total milestone payments per inhibits the immune response to the and would pay between $275m-$368m per candidate. Syros is eligible for mid-to-high vector. Integrating the two platforms is candidate in total milestones, plus mid- single digit sales royalties and holds onto expected to assist in achieving therapeu- single-digit to low-double-digit royalties. an option to co-promote the first marketed tic advantage in under-dosed patients CureVac holds onto an option to take part product in the US. The deal helps GBT (particularly pediatric patients) and in the development and/or commercializa- expand its blood disease pipeline. The provide a first-dose benefit by enhancing tion of one of the three projects. company recently celebrated the launch liver-directed transgene expression in pre- of its first product Oxbryta (voxelotor), the clinical models. The partnership’s goal is CYTODYN INC. only drug approved by the FDA that directly to rapidly advance new combination thera- VYERA PHARMACEUTICALS LLC inhibits sickle hemoglobin polymerization, pies through human proof-of-concept CytoDyn Inc. licensed Vyera Pharmaceu- the main cause of sickle cell disease. trial to validate potential for re-dosing in ticals LLC exclusive rights to market and patients with genetic diseases, with an distribute the HIV therapy leronlimab HANMI PHARMACEUTICAL CO. LTD. expectation to enter the clinic in 2020. (PRO140) in the US. (Dec.) RAPT THERAPEUTICS INC. CytoDyn will receive up to $500k up front RAPT Therapeutics Inc. granted Hanmi ASTELLAS PHARMA INC. and $87m in regulatory and sales mile- Pharmaceutical Co. Ltd. exclusive rights to MERCK & CO. INC. stones, plus a 50% royalty. Vyera will also co-develop and sell the CCR4 antagonist SEATTLE GENETICS INC. make a $4m equity investment in Cyto- FLX475 in South Korea, China, Taiwan, and Seattle Genetics Inc. and Astellas Pharma Dyn--13.11 million common shares and a Hong Kong. (Dec.) Inc. are teaming up with Merck & Co. Inc. warrant to purchase 6.56 million shares at RAPT gets $10m in an up-front and near- in a trial collaboration to evaluate the an exercise price of $0.30 per share. Cyto- term milestone payment, $48m in devel- combination of Seattle Genetics/Astellas’ Dyn will continue developing leronlimab opment milestones, and $60m for sales enfortumab vedotin and Merck’s Keytruda and is responsible for gaining FDA approval. achievements, plus double-digit royalties. (pembrolizumab) in patients with previ- It will supply Vyera with the product. Le- FLX475 is in Phase I/II trials targeting ously untreated metastatic urothelial ronlimab is an injectable humanized IgG4 “charged” tumors including virally-asso- cancer. (Dec.) anti-CCR5 monoclonal antibody currently ciated cancers, gastric cancer, non-small In September, the FDA accepted the BLA in pre-registration studies for HIV. It is also cell lung cancer, triple negative breast for enfortumab vedotin and granted in development for other indications includ- cancer, and head and neck cancers. Hanmi priority review for patients with locally ing cancer. CytoDyn acquired the candidate will support RAPT’s ongoing Phase I/II advanced or metastatic urothelial cancer from Progenics in mid-2012. trial and will also conduct its own Phase II who have received a PD-1/L1 inhibitor and study in Korea and China in gastric cancer EISAI CO. LTD. who have received a platinum-containing patients. RAPT (which went public via a GILEAD SCIENCES INC. chemotherapy in the neoadjuvant/ad- $33.5m US IPO last month) looks forward juvant, locally advanced, or metastatic Gilead Sciences Inc. and Eisai Co. Ltd. to gaining entrance to the Asian oncology setting. The PDUFA action date is an- entered into an agreement for the co- market through the deal with Hanmi. ticipated for mid-March 2020. Merck’s promotion in Japan of Gilead’s JAK1 inhibi- PD-1 antagonist Keytruda is marketed tor filgotinib, pending approval there for JAZZ PHARMACEUTICALS PLC for over a dozen solid and liquid tumors rheumatoid arthritis. (Dec.) PHARMAMAR SA including melanoma, NSCLC, head and Gilead licensed the candidate from Gala- PharmaMar SA granted Jazz Pharmaceuti- neck, lymphoma, colorectal, and other pagos in 2015, and the therapy is awaiting cals PLC exclusive rights to sell the small cancers. It is also being studied in nearly approval in the US, Europe, and Japan. In cell lung cancer therapy lurbinectedin in two dozen trials for additional cancer addition to RA, it is also in development the US once approved. The deal could be indications. Under the collaboration, the for ulcerative colitis, Crohn’s disease, pso- worth up to $1bn. (Dec.) three firms will conduct and fund a global riatic arthritis, uveitis, and small bowel Lurbinectedin was granted orphan drug registrational Phase III trial to be led by and fistulizing Crohn’s. Under terms of designation for SCLC in August 2018, and Seattle Genetics. The trial is expected to the collaboration with Eisai, Gilead retains earlier this month PharmaMar submitted commence in H1 2020. responsibility for manufacturing and mar- an NDA to the FDA for accelerated approval keting approval, while Eisai will distribute based on data from a Phase II basket trial. CUREVAC AG filgotinib in Japan for RA and potentially PharmaMar will carry out any remaining GENMAB AS other indications. regulatory activities and will also produce CureVac AG and Genmab AS partnered and supply the finished product to Jazz fol- GLOBAL BLOOD THERAPEUTICS INC. to discover and develop differentiated lowing approval. Jazz pays $200m up front; SYROS PHARMACEUTICALS INC. mRNA-based antibody therapeutics for $250m in regulatory milestones for acceler- cancer. (Dec.) Global Blood Therapeutics Inc. (GBT) and ated and/or full regulatory approval within The companies will combine CureVac’s Syros Pharmaceuticals Inc. penned a deal certain specified timeframes; $550m in mRNA technology with Genmab’s antibody for the discovery and development of new sales milestones; and tiered royalties rang- technologies to discover and develop sickle cell disease and beta thalassemia ing from the high-teens to 30%. mRNA-encoding antibodies. Genmab treatments. (Dec.) pays $10m up front and will make a €20m Under terms of the deal, Syros will use its JOHNSON & JOHNSON ($22.1m) equity investment in CureVac. An gene control platform to identify therapy Janssen Pharmaceutical Cos. initial project will be identified, for which targets and drug candidates that induce Janssen Biotech Inc. CureVac will fund a portion of overall costs fetal hemoglobin. GBT holds an option XBIOTECH INC. up to IND application. After that point, to license exclusive global development, Janssen Biotech Inc. has acquired exclu- Genmab will develop and commercialize manufacturing, and commercialization sive worldwide rights to XBiotech Inc.’s the candidate and will pay CureVac undis- rights to resulting projects. It pays $20m interleukin-1 alpha antagonist berme- closed milestones and royalties. Genmab up front and agreed to fund up to $40m in kimab in Phase II for atopic dermatitis and also gets three options (exercisable within preclinical research fees for at least three hidradenitis suppurativa. (Dec.)

42 | In Vivo | January 2020 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com Meddevicetracker: Medical Device Intelligence and Forecasts

Stay up-to-date and get a complete view of the continually evolving medtech landscape with access to real-time market intelligence on product and company developments across the medical devices, diagnostics and advanced delivery systems markets. Anticipate upcoming fi lings, clinical trials dates and data, and access market size information and expert forecasts all in one place, helping you assess the competition, track key events and make better-informed decisions.

To fi nd our more visit: ph armaintelligence.informa.com/ Meddevicetracker

JN2181 MDT Advert US Letter.indd 1 2019/06/04 17:44 ❚ DEAL-MAKING

For the rights, Janssen is paying $750m the other Nav1.6 or Nav1.2/1.6 inhibitors); Pfizer will pay Theravance $10m up front in cash up front and up to four milestone commercialization milestones up to $150m and up to $240m in development and payments of $150m each should it receive apiece for XEN901 and the three other com- sales milestones, in addition to sales certain commercial authorizations within pounds; tiered royalties on sales of XEN901 royalties. The licensed locally acting JAK a specified timeframe for a pharmaceuti- ranging from the low double-digits to mid- inhibitors can be rapidly metabolized, tar- cal product that contains bermekimab teens (10-16%) in the US and at slightly get validated pro-inflammatory pathways, and is for a non-dermatological indica- lower rates outside the US; tiered royal- and demonstrate skin-selective activity tion. XBiotech will retain its True Human ties on sales of the preclinical candidates with minimal systemic exposure. antibody discovery platform targeting ranging from the mid-single to low-double- IL-1 alpha to treat all non-dermatological digits (4-10%) in the US and at slightly RHEOS MEDICINES INC. diseases. It will use some of the proceeds lower rates outside the US; and for each ROCHE from the deal to develop next-generation research compound, a mid-single-digit to Rheos Medicines Inc. granted Roche ex- antibodies. XBiotech will manufacture a high-single digit (4-9%) percentage and a clusive global options to develop and sell bermekimab for use by Janssen in clini- tiered mid-single-digit (4-6%) percentage, therapies for conditions affected by im- cal trials in exchange for payments to be respectively. Under a three-year research munometabolism, including autoimmune paid in quarterly installments. In addition, collaboration that’s also part of the deal, and inflammatory diseases. The partners XBiotech will contract with Janssen to Neurocrine will fund all associated clini- may share US development and commer- provide clinical trial operation services to cal developments costs with a minimum cialization rights for some products. (Dec.) complete two ongoing Phase II studies of of 10 FTEs. Xenon will be responsible for Rheos, which started operations last year bermekimab in hidradenitis suppurativa certain preclinical and a portion of certain with $60m from Third Rock Ventures, and atopic dermatitis. Bermekimab is the near-term manufacturing costs and has an is responsible for exclusive research to only antibody targeting IL-1a currently in option to co-fund 50% of the US develop- identify novel immunometabolism targets the clinic and has the potential for supe- ment costs of XEN901 or another product that modify the fate or function of human rior efficacy and safety compared to the candidate in exchange for increased US immune cells, and is in charge of drug current standard of care. Research has royalties, capped at 20% of US net sales discovery. Roche pays $42.5m up front; shown that inhibition of IL-1a has poten- for XEN901. The current deal further boosts up to $90m for research and preclinical tial in treating a wide range of conditions Neurocrine’s CNS development pipeline; milestones; option fees; up to $660m in including skin, cardiovascular, rheuma- earlier this year it in-licensed Voyager’s development, regulatory, and sales mile- tological, and gastrointestinal diseases, investigational gene therapies VYAADC stones for all the programs; and tiered stroke, and cancer. (Phase II) for Parkinson’s disease and sales royalties. The Big Pharma will spend VYFXN01 (preclinical) for Friedrich’s ataxia. additional money if the companies split NEUROCRINE BIOSCIENCES INC. By offloading these assets, Xenon can shift US rights on certain candidates. Roche XENON PHARMACEUTICALS INC. focus to its later-stage epilepsy pipeline, already has top-selling immuno-inflam- Neurocrine Biosciences Inc. licensed which includes Phase II Kv7 potassium mation drugs in its portfolio, including exclusive worldwide rights to Xenon channel modulators XEN496 and XEN1101, Actemra and Rituxan. Its next potential Pharmaceuticals Inc.’s XEN901, a selec- while potentially extending its cash runway product in this therapy area could be sa- tive Nav1.6 sodium channel inhibitor into 2022, according to Xenon. tralizumab for neuromyelitis optica. The for epilepsy, and up to three other com- follow-on antibody to Actemra has been pounds. (Dec.) ONCONOVA THERAPEUTICS INC. filed in the US, EU, and Japan, and has a Xenon just last month completed a Phase SPECIALISED THERAPEUTICS 97% likelihood of approval, 10% above I trial of a pediatric-specific, granule formu- ASIA PTE. LTD. average. Regulatory clearances in all of lation of XEN901--including juvenile toxicol- Specialised Therapeutics Asia Pte. Ltd. these markets is expected in 2020. In ogy studies and dosing of healthy adult vol- licensed exclusive rights to commercialize another recent immunometabolism deal unteers in a PK study--to support its further rigosertib in Australia and New Zealand for of similar value, Eli Lilly teamed up with development in SCN8A developmental and Onconova Therapeutics Inc. (Dec.) ImmuNext for exclusive worldwide rights epileptic encephalopathy (SCN8A-DEE), Onconova stands to receive up to $30.4m to preclinical targets for $605m. an ultra-orphan pediatric indication, as in development, regulatory, and sales ROCHE well other epilepsies, including adult fo- milestones, plus tiered double-digit SAREPTA THERAPEUTICS INC. cal epilepsy. An IND filing to start a Phase royalties. Intravenous rigosertib is in II trial in SCN8A-DEE patients is expected Phase III trials in second-line higher-risk In its second significant gene therapy during Q1 2020. In addition to XEN901, myelodysplastic syndrome. Onconova has investment of 2019, Roche gained exclu- Neurocrine also gets exclusive rights to out-licensed rights in other territories in sive commercial rights outside of the US Xenon’s preclinical XEN393, XPC535, and preparation for the candidate’s approval. to Sarepta Therapeutics Inc.’s Phase I/II XPC391 (two of which will be selected SymBio has rights in Japan and Korea; gene therapy SRP9001 (AAVrh74.MHCK7. for further development), and another Pint Therapeutics in Latin America; HanX micro-dystrophin) for Duchenne muscular research-stage selective Nav1.6 or dual in China; and Knight Therapeutics in dystrophy, a rare neuromuscular disease. Nav1.2/1.6 inhibitor compound. In what the Canada. Specialised Therapeutics adds The deal comes just days after Roche fi- partners believe is the largest deal around rigosertib to an oncology pipeline that nally closed its acquisition of gene therapy a pre-Phase III epilepsy candidate to date, includes Abraxane (nanoparticle albumin- developer Spark Therapeutics after an- Neurocrine could pay up to $1.742bn: $50m bound paclitaxel), Nerlynx (nerlatinib); nouncing the transaction in January. (Dec.) up front ($30m in cash and $20m through Zepsyre (lurbinectedin), Yondelis (tra- Under the new agreement, Roche also the purchase of Xenon shares at $14.196 bectedin), Iclusig (ponatinib), and Aplidin received an option to license exclusive ex- (a 42% premium)); $25m ($11.25m in cash (plitidepsin). US rights to future Sarepta DMD products, and $13.75m payable through an equity including the following exon-skipping investment in Xenon at a 15% premium) PFIZER INC. therapies that target the dystrophin gene: upon the FDA’s acceptance of an IND for THERAVANCE BIOPHARMA INC. Exondys 51 (eteplirsen; launched for XEN901; up to $1.067.5bn in development Theravance Biopharma Inc. licensed DMD), Vyondys 53 (golodirsen; approved and regulatory milestones ($325m related Pfizer Inc. worldwide rights to preclinical in December 2019 for DMD), Phase III to XEN901 and up to $247.5m for each of pan-Janus kinase (JAK) inhibitors. (Dec.) casimersen, and Phase II SRP5051. Roche

44 | In Vivo | January 2020 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com invivo.pharmaintelligence.informa.com

- - - - - ❚

| 45 technology technology DEAL-MAKING In Vivo | In Vivo January 2020 (MVA-BN) for prevention of smallpox smallpox of prevention for (MVA-BN) ASSEMBLY BIOSCIENCES INC. BIOSCIENCES ASSEMBLY AS NORDIC BAVARIAN INC. PHARMACEUTICALS CONSTELLATION INC. EXICURE Investment Banks/Advisors: B. Riley FBR B. Riley Banks/Advisors: Investment Goldman & Co.; Fitzgerald Cantor Inc.; Piper Inc.; Co. & Jefferies & Co.; Sachs Inc. Co. & Baird W. Robert Co.; & Jaffray (developing Inc. Biosciences Assembly diseases and B hepatitis for therapies netted the microbiome) with associated offer public a follow-on through $117.5m at priced shares common ing 5.15 million buy to warrants pre-funded and $16.50 (Dec.) $16.499. at shares 2.42 million & Jefferies Banks/Advisors: Investment Baird W. Robert Ltd.; Bank Mizuho Inc.; Co. Co. & Blair William Leerink; SVB Inc.; Co. & undisclosed an AS sold Nordic Bavarian (PRV) Voucher Review a Priority company in PRV the got Nordic $95m. Bavarian for Jyn- of approval FDA upon 2019 September neos (Dec.) monkeypox. and & Jefferies Banks/Advisors: Investment Inc. Co. Inc. Pharmaceuticals Constellation drug discov cancer (epigenetics-based the public through $242.4m ery)netted (including common million 7.5 of offering Proceeds $34.50. at the overallotment) development continued towards go will III for Phase (approaching CPI0610 of CPI1205 (Phase in 2020), myelofibrosis castration-resistant metastatic II for I (Phase CPI0209 and cancer) prostate support also will and tumors), solid for net Constellation projects. stage earlier in placement a private $65m through ted (Dec.) October. & Co. Cowen Banks/Advisors: Investment Inc.; Co. & Jefferies & Co.; JP Morgan LLC; Inc. Banks SunTrust Markets; Capital RBC SNA its (using Inc. Exicure - immuno-on for therapeutics develop to - ge and diseases, inflammatory cology, through $25.85m netted disorders) netic 10 million of offering public a follow-on The each. $2.75 at priced shares common move to the funds use to plans company a through AST008 candidate cancer its arm a second initiate to trial; Ib/II Phase squa cutaneous in study Ib/II Phase its in an SNA develop to carcinoma; cell mous ataxia, Friedreich’s for candidate based advance and studies, IND-enabling initiate SNA a second develop I; to Phase into it and condition a neurology for candidate (Dec.) studies. IND-enabling initiate Chardan Banks/Advisors: Investment Partners Guggenheim Markets; Capital Ladenburg & Co.; Wainwright HC LLC; Inc. & Co. Thalmann - - FINANCINGS ARROWHEAD PHARMACEUTICALS INC. PHARMACEUTICALS ARROWHEAD APTOSE BIOSCIENCES INC. BIOSCIENCES APTOSE INC. ARDELYX ABEONA THERAPEUTICS THERAPEUTICS INC. ABEONA netted netted Inc. Pharmaceuticals Arrowhead of offering the follow-on through $250.8m the overallot (including shares 4.6 million a part use will The company $58. ment) at and R&D expenses fund to the proceeds of businesses, of acquisition the potential last Just technologies. and products, positive presented month, Arrowhead RNAi-based two on its data I topline Phase ARO-APOC3 candidates: cardiometabolic - fa and hypertriglyceridemia severe for and syndrome, chylomicronemia milial (including dyslipidemias for ARO-ANG3 - hypercholesterol familial homozygous (Dec.) diseases. metabolic and emia) netted $69m $69m netted Inc. Biosciences Aptose million 18.5 of offering a public through the overallot (including shares common cardiorenal for (therapeutics Inc. Ardelyx an through $117.5m netted diseases) 20 million of offering follow-on upsized - The com each. $6.25 at shares common ongoing support to the funds use will pany III tenapanor Phase its of trials clinical hyperphosphatemia of the treatment for disease kidney chronic with in patients and activities, regulatory for on dialysis, as well as commercialization, potential (Dec.) development. other pipeline Citigroup Banks/Advisors: Investment Co.; & Piper Jaffray LLC; & Co. Cowen Inc.; Leerink SVB (gene and cell cell and (gene Inc. Therapeutics Abeona follow-on in its $97.2m netted therapies) - com 32.38 million of offering public exercise the full (including mon shares and each $2.50 at the overallotment) of million 9.02 buy to warrants pre-funded warrants The pre-funded $2.50. at shares Great shareholder existing to sold were board two get will which Partners, Point (Dec.) seats. & Jefferies Banks/Advisors: Investment Leerink SVB Inc.; Co. developing is $4. The company ment) at and therapies cancer blood personalized clinical expand to the proceeds use will leu- lymphocytic (chronic CG806 for trials and lymphoma) non-Hodgkin’s and kemia leukemia myelogenous (acute APTO253 to and syndrome) myelodysplastic and - poten including other activities support or in-licensing acquisitions product tial (Dec.) agreements. Canaccord Banks/Advisors: Investment Inc.; & Co. Oppenheimer Inc.; Genuity Co. & Piper Jaffray didates; and sales royalties. Global costs costs Global royalties. sales and didates; basis. on a 50:50 shared be will profits and - - - in TAKEDA PHARMACEUTICAL CO. LTD. CO. PHARMACEUTICAL TAKEDA INC. BIOLOGICS TURNSTONE additionally received rights to certain IP certain to rights received additionally paid Roche in the US. SRP9001 exploit to make will and front up cash in $750m in Sarepta investment equity a $400m shares 2.5 million of the purchase through may Sarepta premium). (a 33% $158.59 at and in regulatory $1.73bn to up get also estimated royalties plus milestones, sales of in charge is Sarepta in the mid-teens. manufacturing and development clinical equally will the partners but build-out, the For costs. development global split which to DMD assets future additional will the company an option, holds Roche will and royalties, and milestones pay Nation- from Licensed expenses. share in 2017, (NCH) Hospital Children’s wide approval of likelihood 28% a has SRP9001 due to the average above 4% currently, disclosed results preliminary top-line patients four first the on 2018 June in vec of proof-of-concept providing treated, Takeda Phar Takeda and Inc. Biologics Turnstone tor expression. The candidate represents represents The candidate expression. tor in development program only Roche’s 2019, in November DMD presently; for of studies its discontinued the company fusion adnectin myostatin-inhibiting the BMS from (licensed RG6206 protein the program on the belief based 2017) clinical demonstrate to be able not would endpoint. primary the meet and benefit acting in 2019, a busy had itself Sarepta StrideBio with in deals role the licensee (limb- NCH and diseases) (neuromuscular and 2A), type dystrophy muscular girdle Myonexus acquire an option to exercising - dys muscular (limb-girdle Therapeutics Banks/Advisors: Investment trophies). & Stanley Morgan & Co.; Sachs Goldman Inc.) Therapeutics (Sarepta Co. potential a penned Ltd. Co. maceutical and the discovery surrounding $1bn deal im- virus-based vaccinia of development (Dec.) cancer. for munotherapies Turnstone’s is deal the of focus initial The (for RIVAL01 candidate preclinical lead project The TBIO6517). as to referred merly virus vaccinia on the company’s based is for been engineered has which platform, tumor and immune-stimulation enhanced large and oncolysis, potent selectivity, cell RIVAL01 capacity. carrying transgene backbone virus vaccinia the of consists IL- Flt3 ligand, for transgenes encoding antibody. anti-CTLA-4 and 12 cytokine, the when expressed are transgenes The in replicates and enters virus vaccinia global exclusive gets Takeda cells. cancer co-commercialize and co-develop to rights options licensing in addition to RIVAL01, could the partners that projects other for $120m in pay will The company discover. future and milestone, near-term up-front, $900m to up payments; investment equity - can licensed all across milestones in total company an Informa Inc., Information, Business ©2016 Informa ❚ DEAL-MAKING

FORTY SEVEN INC. Baker Bros. Advisors involving Kodiak’s OMEROS CORP. Forty Seven Inc. (immuno-oncology) netted KSI301. (Dec.) Omeros Corp. (developing therapies for $183.9m through a follow-on public offer- Investment Banks/Advisors: Goldman orphan indications targeting inflamma- ing of 5.59 million common shares (includ- Sachs & Co.; JP Morgan & Co. tion, complement-mediated diseases, ing the overallotment) at $35. The company CNS disorders, and immune-related dis- plans to use $70-75m of the proceeds to KODIAK SCIENCES INC. eases) netted $54.5m in an upsized public advanced lead candidate magrolimab Ophthalmic-focused Kodiak Sciences Inc. offering of 4.39 million common shares towards BLA filing (including funding of netted $298m in a follow-on offering of (including full exercise of the overallot- studies in myelodysplastic syndrome and 6.9 million common shares (including the ment) at $13.10 each. (Dec.) diffuse large B-cell lymphoma). Funds will overallotment) at $46 each. The company Investment Banks/Advisors: Cantor also support additional pipeline develop- will use some of the funds to move its Fitzgerald & Co. ment and research activities. (Dec.) KSI301 towards the BLA filing in retinal Investment Banks/Advisors: Credit Suisse vein occlusion and for sBLA submissions ONCONOVA THERAPEUTICS INC. Group; Guggenheim Partners LLC; Morgan (expected in 2022) for wet age-related Onconova Therapeutics Inc. (targeted Stanley & Co.; Oppenheimer & Co. Inc.; macular degeneration, diabetic macular small-molecule candidates for cancer) Roth Capital Partners edema (DME), and possibly diabetic netted $4.65m through a registered direct retinopathy without DME. Additional funds offering to two health care-focused institu- GLOBAL BLOOD THERAPEUTICS INC. will support development of additional tional investors of 13.88 million common Global Blood Therapeutics Inc. (GBT) en- pipeline candidates including KSI501 for shares at $0.36. Purchasers also received tered into a $150m loan agreement with DME and uveitis. Just one day prior to the five-year warrants to buy 6.9 million funds managed by Pharmakon Advisors. offering, Kodiak sold Baker Bros. a capped shares at $0.298, HC Wainwright was the The company drew down $75m immedi- 4.5% royalty on net sales of KSI301 in placement agent. Some of the proceeds ately and can access the remaining $75m exchange for $225m. (Dec.) will support an NDA filing for IV rigosertib at its option until December 31, 2020. The Investment Banks/Advisors: Chardan in second-line higher-risk myelodysplastic syndrome. (Dec.) loan bears interest at a rate of 7.0% plus Capital Markets; Goldman Sachs & Co.; LIBOR and matures in December 2025. The JP Morgan & Co.; Jefferies & Co. Inc.; Sun- Investment Banks/Advisors: HC Wain- money will help the company advanced Trust Banks Inc. wright & Co. its pipeline of treatments for sickle cell disease and other blood conditions, and MEI PHARMA INC. RELMADA THERAPEUTICS INC. will also support commercialization of MEI Pharma Inc. (oncology) netted Relmada Therapeutics Inc. (developing its recently approved sickle cell therapy $48.6m through a public offering of 32.3 psychiatric and neurological disorder Oxbryta (voxelotor). (Dec.) million common shares (including the treatments via the 505b2 regulatory path- IMMUNOMEDICS INC. overallotment) at $1.60. Funds will sup- way) netted $108m through the public Immunomedics Inc. (immunotherapies for port ongoing clinical development and sale of 3.8 million shares (including the cancer, autoimmune diseases, and other working capital. (Dec.) overallotment) at $30. The company will put proceeds toward R&D activities related serious conditions) netted $272.4m through Investment Banks/Advisors: Stifel Nico- the public offering of 16.4 million common to lead candidate REL1017 (d-methadone), laus & Co. Inc.; Wells Fargo Securities LLC shares (including the overallotment) at an oral NMDA receptor antagonist in $17.50. The money is primarily earmarked MILLENDO THERAPEUTICS INC. Phase III for major depressive disorder (MDD)--an indication for which it has an for the upcoming commercial launch (once Millendo Therapeutics Inc. (therapies 18% likelihood of approval (6% above approved) of the metastatic triple-negative for endocrine diseases) netted $23.5m average)--and also in development for ad- breast cancer treatment sacituzumab govite- through a follow-on public offering of 4.17 can in the US. Funds will also support ongo- ditional neurological indications. A Phase million common shares at $6 each to help III trial in treatment-resistant depression ing pipeline development, manufacturing, support pipeline development. (Dec.) and corporate needs. (Dec.) is expected to begin in 2H 2020. Relmada Investment Banks/Advisors: Citigroup also has three other 505b2 candidates in Investment Banks/Advisors: Bank of Inc.; SVB Leerink America Merrill Lynch; Cowen & Co. LLC; its CNS-focused pipeline. (Dec.) Goldman Sachs & Co.; Jefferies & Co. Inc. MOMENTA PHARMACEUTICALS INC. Investment Banks/Advisors: Guggenheim Partners LLC; Jefferies & Co. Inc.; SVB Leerink IVERIC BIO INC. Momenta Pharmaceuticals Inc. netted $212.6m through the public offering of Ophthalmic-focused IVERIC bio Inc. (for- REVANCE THERAPEUTICS INC. 14.5 million shares at $15.50. The com- merly Ophthotech) netted $37.4m through Revance Therapeutics Inc. netted $103.9m pany will use the proceeds to fund pipeline a follow-on public offering of 6.25 million through the public offering of 6.5 million development. Lead candidate M710, a common shares priced at $4 each and shares at $17. The company will use the proposed biosimilar to Eylea (aflibercept), pre-funded warrants to purchase 3.75 mil- proceeds to fund the commercialization lion shares at $3.99. The company plans is in Phase III (in collaboration with Mylan of its DAXI (formerly RT002; daxibotu- to use the proceeds for ongoing clinical under a 2016 deal) for wet age-related linumtoxinA injection). Just last month, development of Zimura for geographic macular degeneration, macular edema Revance filed a BLA with the FDA in the atrophy secondary to dry age-related following retinal vein occlusion, diabetic moderate-to-severe glabellar (frown) line macular degeneration, and for additional macular edema, and diabetic retinopathy. indication (for which the candidate has a development of its gene therapies and Momenta also has nipocalimab (M281), 99% likelihood of approval, 10% above HtrA1 inhibitor program. (Dec.) an anti-FcRn antibody, in Phase II for my- average). A PDUFA decision is expected asthenia gravis, hemolytic disease of the Investment Banks/Advisors: Cowen & Co. in November 2020. DAXI is also in Phase fetus and newborn, and warm antibody LLC; Wedbush PacGrow Life Sciences III for cervical dystonia, with a 57% likeli- hemolytic anemia. (Dec.) hood of approval, 5% above average, in KODIAK SCIENCES INC. Investment Banks/Advisors: Goldman that indication. (Dec.) Ophthalmic-focused Kodiak Sciences Sachs & Co.; JP Morgan & Co.; Stifel Nico- Investment Banks/Advisors: Cowen & Co. Inc. entered a royalty agreement with laus & Co. Inc. LLC; Guggenheim Partners LLC; Needham

46 | In Vivo | January 2020 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com Pink Sheet & Scrip MARKETING SOLUTIONS

How long will it take your sales team to reach 42,000 senior decision makers in pharma companies globally?

Let us demonstrate how we can do this and show you ROI now!

BRANDING | THOUGHT LEADERSHIP | LEAD GENERATION

CHRISTOPHER KEELING Phone: +44 203 377 3183 Email: [email protected]

Marketing SolutionsIdeaAD_PinkScrip1906_Letter.indd 1 10/17/2019 11:34:17 AM ❚ DEAL-MAKING

& Co. Inc.; Piper Jaffray & Co.; Stifel Nico- laus & Co. Inc. editors editorial advisory board ROCKET PHARMACEUTICALS INC. Lucie Ellis Brian Chapman Rocket Pharmaceuticals Inc. (gene thera- Executive Editor ZS Associates, Partner pies for rare diseases) netted $79.9m in Ben Comer Benjamin Comer a public offering of 3.82 million shares Pharma Editor PwC, Senior Manager at $22.25. The company will use the pro- Health Research Institute ceeds to support further development of Ashley Yeo Medtech Editor its pipeline of multi-platform gene thera- Don Creighton ICON, Global Head of Pricing & Market Access pies (including ex vivo lentiviral (LVV) and Amanda Micklus in vivo adeno-associated virus vectors) for Principal Analyst Sara Jane Demy Demy Colton, CEO rare diseases and to accelerate manufac- Andrea Charles turing capabilities. Concurrent with the Custom Content Editor Deborah Dunsire, MD financing, Rocket announced positive Regina Paleski William Looney H. Lundbeck, President & CEO preliminary efficacy data from its Phase I/ Contributing Editors Barbara Freischem II trial of RPL201, a potential LVV therapy European Biopharmaceutical Enterprises for leukocyte adhesion deficiency-I. (Dec.) Executive Director Investment Banks/Advisors: Cowen & Co. director, medtrack & strategic transactions content Les Funtleyder E Squared Capital Management LLC; Evercore Partners; JP Morgan & Co.; Patricia Giglio LifeSci Capital LLC Health Care Portfolio Manager deals analysts Terry Hisey SCYNEXIS INC. Beth Detuzzi, Deanna Kamienski Deloitte, Senior Principal, Life Science Anti-infectives developer Scynexis Inc. Maureen Riordan netted $32.9m through a follow-on offer- Annlisa Jenkins PlaqueTec, CEO ing of 38.9 million common shares priced head of publication design Ken Kaitin, PhD at $0.90 each. The company also issued Gayle Rembold Furbert warrants to purchase another 38.9 million Tufts Center for the Study of Drug Development, Director shares exercisable at $1.10. Scynexis’ senior designer Janet Haniak lead candidate is Phase III ibrexafungerp Harris Kaplan for invasive fungal infections caused by designers Red Team Associates, Managing Partner Debi Robinson, Jean Marie Smith, Candida, Aspergillus and Pneumocystis Ellen Licking Paul Wilkinson species. (Dec.) EY, Senior Analyst, Global Life Sciences Investment Banks/Advisors: Aegis Capital Julie Locklear Corp.; HC Wainwright & Co.; Maxim Group head of editorial ops (pharma) Managing Partner, Genesis Research LLC; WBB Securities LLC Karen Coleman Roger Longman TG THERAPEUTICS INC. head of content Real Endpoints, Chairman Mike Ward TG Therapeutics Inc. (treatments for B- Dan McIntyre cell cancers and autoimmune diseases) advertising Publick House, Partner grossed $50m through a registered direct Christopher Keeling Ranjini Prithviraj DIA Publications offering to one biotech-focused institu- subscriptions Senior Managing Editor/Associate Director tional investor of 5.4 million common Dan Simmons, Shinbo Hidenaga shares at $9.20 (a 5% discount). (Dec.) managing director Michael Ringel, PhD BCG, Senior Partner and Global Topic Leader Phil Jarvis ULTRAGENYX PHARMACEUTICAL INC. Research and Product Development Ultragenyx Pharmaceutical Inc. (devel- Kenneth Schultz, MD oping treatments for rare and ultra-rare editorial office Trethera Corporation, Chairman and CEO genetic diseases) sold to Royalty Pharma 605 Third Avenue, Floor 20-22 for $320m royalty rights due to Ultragenyx Jack Wong New York, NY 10158 Allergan, Associate VP, Regulatory Affairs, from its partner Kyowa Kirin for net sales invivo.pharmaintelligence.informa.com Asia Pacific, Middle East & Africa of Crysvita (burosumab; approved in Eu- rope for X-linked hypophosphatemia) in customer service Nadim Yared the EU, UK, and Switzerland. (Dec.) [email protected] CVRx, President & CEO Investment Banks/Advisors: J. Wood Capi- tal Advisors; Perella Weinberg Partners IN VIVO: [ISSN 2160-9861] is published monthly, except for the combined July/August issue, by Informa Business Intelligence, Inc., 605 Third Avenue, Floor 20-22, New York, NY 10158. WINDTREE THERAPEUTICS INC. US Toll-Free: +1 888 670 8900 | US Toll: +1 908 547 2200 | UK & Europe: +44 (20) 337 73737 Windtree Therapeutics Inc. (therapeutics Australia: +61 2 8705 6907 | Japan: +81 3 6273 4260 and devices for cardiovascular and pul- Office of publication, The Sheridan Group, 66 Peter Parley Row, Berlin, CT 06037. monary diseases) netted $23m through Postmaster: Send address changes to Informa Business Intelligence, 605 Third Avenue, a private placement of 8.75 million com- Floor 20-22, New York, NY 10158. mon shares at $3.02 (a 20% discount) to © 2020 by Informa Business Intelligence, Inc., an Informa company. institutional investors. The company also All rights reserved. issued five-year warrants to purchase 4.38 No part of this publication may be reproduced in any form or incorporated into any information million shares exercisable at $4.03. (Dec.) retrieval system without the written permission of the copyright owner.

48 | In Vivo | January 2020 invivo.pharmamedtechbi.com invivo.pharmaintelligence.informa.com