Combination Strategies A Common ASH 2016 Preview Genentech On Cancer Thread In NASH R&D Scrip has selected 10 of the most Fong talks about Genentech’s latest Intercept continues to lead the race, exciting data readouts you shouldn’t deal and why it is predicting success but some analysts think Gilead is miss at this year’s American Society for this time around for making up ground (p4) Hematology (p14) products (p17)

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Scripscrip.pharmamedtechbi.com Pharma intelligence | informa cant slowing in cognitive decline among people with mild dementia due to Al- zheimer’s disease who were treated with solanezumab versus placebo. The primary endpoint was measured by the Alzheim- er’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog). Lilly changed the primary endpoint of the study earlier this year to the single cognitive assessment from the original co-primary endpoint that measured cognition and function. Some investors took the change as a sign that the company was concerned about a weak outcome. The trial results, including many second- ary clinical endpoints, favored solanezumab, T.Dallas but the magnitudes of treatment differenc- es were small, Lilly confirmed. Shutterstock: Shutterstock: The company will not pursue a regulatory submission for solanezumab and will work with investigators to conclude the open- Lilly’s Solanezumab Fails, But The label extensions for all three Phase III trials. Lilly will evaluate the data further to deter- mine the impact on development plans for Surprise Would Have Been Success solanezumab and other Alzheimer’s drugs JESSICA MERRILL [email protected] in the pipeline. The firm plans to present more findings from the study on Dec. 8 dur- The Phase III failure of the Alzheimer’s shadow over the field of research.Lilly’s ing the Clinical Trials on Alzheimer’s Disease treatment was largely expected, but is stock opened 15% lower at $64.34 on the (CTAD) meeting. nonetheless a disappointment for the dis- news, as some investors had bought into While the news isn’t an enormous sur- ease and for the anti-amyloid field, cast- the stock ahead of the catalyst in the event prise, it still is a disappointment. There was ing a shadow over other therapies in de- the data were positive, which would have hope that by targeting patients earlier in velopment, including Lilly’s own pipeline. resulted in substantial upside. Analysts and the course of their disease, and by confirm- long-term investors generally considered ing the presence of amyloid pathology via li Lilly & Co.’s high-profile anti-amyloid Lilly’s attempt to run a refined Phase III trial PET screening or cerebrospinal fluid testing, treatment solanezumab failed a third testing solanezumab to be a high-risk bet, EXPEDITION3 would yield a different result EPhase III trial, EXPEDITION3, even given that the drug failed two prior Phase from the two prior trials, which failed in 2012. though it was conducted in patients with III trials, EXPEDITION and EXPEDITION2, and Despite the risks, Lilly went on to initiate the milder Alzheimer’s disease and relied on a because of the high number of Alzheimer’s third trial in 2013 after a pre-specified pooled biomarker to test patients for amyloid. The drugs that have failed in late-stage trials. analysis showed a statistically significant im- trial failure, announced Nov. 23, was largely Lilly said EXPEDITION3 did not meet the provement in patients with mild disease. expected, but nonetheless casts another primary endpoint, a statistically signifi- CONTINUED ON PAGE 7

BROUGHT TO YOU BY THE EDITORS OF PHARMASIA NEWS, START-UP AND SCRIP INTELLIGENCE IN THIS ISSUE Genentech sees promise and opportunity in the cancer vaccine space – Intercept continues to lead the historically a tricky race to get the first drug approved development area for NASH with Ocaliva 4 17

COVER / Lilly’s Solanezumab Fails, But The Surprise Would from the editor Have Been Success [email protected] 3 Purdue Hints At Large Acquisition In Coming Weeks 4 Combination Strategies A Common Thread In NASH R&D Lilly’s turkey came early this year. The news on Nov. 6 GSK Strategy Chief: No Major M&A Likely In 2017 23 that solanezumab had flunked its final trial was a bit like finding out you didn’t get the Maserati you’d 7 GSK’s Nucala Shows Promise In A Rare Systemic Vasculitis requested for Christmas – not a surprise, but sad all 8 Novo Nordisk ‘Caught Short’ the same. Lilly’s share price is now down about 20% By Lantus Exclusion since the beginning of this year, and it has lost 11.6% 9 Juno Stresses Differences Between Its CAR-Ts of its value since Nov. 22. As JCAR015 Trial Put On Hold Again The amyloid hypothesis is the gift that keeps on 10 R&D Bites taking away. People don’t exactly expect it to deliver the goods, but if it did it would be fantastic. Plenty 11 Chiesi Takes Aim At Next-Generation Eosinophilic Asthma of firms are still plugging away at it, and each time it Therapy disappoints they all feel the blow. 12 Industry’s Achievements Lauded At 12th Annual Biogen, with in Phase III for Alz- Scrip Awards heimer’s, has slipped 4.8% since Nov. 22, while AC 14 Expert View: ASH 2016 Preview: Immune and MorphoSys – partnered with Roche Don’t Miss These 10 Presentations for and , respectively 16 Business Bulletin – are down 13.4% and 7.3%, respectively. Informa Pharma Intelligence’s Pharmaprojects database 17 Genentech Oncology Director Talks Cancer Vaccine lists around 400 candidates in active development Challenges for Alzheimer’s, with the precursor 18 Novartis Buys Selexys As Competitors Stumble In protein the leading target. Will there ever be a Ma- Sickle Cell serati among the turkeys? 18 Allergan Up For Alzheimer’s Challenge With Chase Buy 19 Amid Brexit Chaos, UK PM Promises More R&D Funding, Lower Taxes, And Other Pro-Innovation Measures 20 Policy & Regulation Briefs exclusive online content 21 Stockwatch: The TIGER That Came To Lilly 22 Pipeline Watch Freshly Appointed Auspherix CEO Highlights 23 Appointments New Antibiotic Class Dr Neil Miller, the recently-appointed CEO of UK-based biotech Auspherix, talks to Scrip about the company’s new class of antibiotics and how it plans to help address the worldwide antimicrobial resistance crisis. http://bit.ly/2gyrMAf

F-Star Business Chief On Denali Deal, Potential F-Star Delta Spinout Jane Dancer, chief business officer at F-star – a Cambridge, UK- based biotech – chats to Mike Ward, global director of content for Informa Pharma Intelligence, on the sidelines of the recent BIO-Europe partnering conference in Cologne, Germany. @scripnews /scripintelligence http://bit.ly/2fE134w

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Purdue Hints At Large Acquisition In Coming Weeks Purdue Pharma’s business development director and head of medical affairs talk to Scrip about the company’s hunt for new drugs to add to its portfolio outside of the opioid pain therapy space and how it is preparing for generic erosion and increasing pricing pressures in the US. LUCIE ELLIS [email protected]

urdue Pharma LP hinted on the sidelines of the BIO-Europe pain area so well. We can bring in these programs and develop partnering conference earlier this month that a significant ac- them quickly because we have the regulatory expertise: we Pquisition announcement will be made before the end of 2016, know how to manage the hurdles and the clinical requirements which will see the company expand its R&D to a new therapy area in order to get a product approved,” she said. outside of opioid pain treatments. Kathryn Gregory, executive director of licensing and business DRUG PRICING CONCERNS development at Purdue, told Scrip that the company is look- Looking at the growing drug pricing pressures worldwide, Pur- ing for the right opportunity and is hopeful to “announce a few due’s head of medical affairs, strategic research, Tracy Mayne, things” towards the end of this year. “We are looking from very highlighted that new measures for interpreting the value of early-stage, innovative, non-opioid, non-NSAID (nonsteroidal medicines, particularly pain therapies, are needed worldwide. anti-inflammatory drug) pain products all the way through to “There is a revolution in the US and it is focused on the develop- anything on the market that is a good fit in terms of our com- ment of value frameworks.” He noted that there is currently “a mercial sales force,” Gregory said. huge effort going on by a number of different entities” to talk She also noted the company has been looking for “special- about disease-specific value frameworks in the US. “We need to ty-driven types of opportunities” in the CNS space. Purdue has define the value of each drug very much within the context of an interest in movement disorders and epilepsy indications it thinks will sit in the CNS space adjacent to its current pain port- folio. However, Gregory noted that notoriously complicated and risky CNS conditions like Alzheimer’s disease are too much of a stretch for Purdue at this time. Purdue’s ideal suitor would have a marketed product but a pipeline with room for growth. “We’re looking for more of a cor- nerstone property,” Gregory said. “It’s not just having a marketed product; we’re also interested in looking at the capability of the pipeline and building out a portfolio. We are looking for a sus- tainable platform and a sustainable business.” Purdue has a budget of up to $2.5bn for a potential acquisi- tion, though Gregory noted the company will consider a num- ber of purchases around a new “anchor product” if it cannot find everything it desires for a fresh portfolio line all under one roof. Purdue’s attempts to diversify away from opioid pain drugs were kick-started last year when the company struck a partner-

ship with Eisai Co. Ltd. for Lemborexant, an insomnia therapy. Mizin Roman Shutterstock: Phase III clinical trials for Lemborexant, a dual orexin receptor an- tagonist, launched earlier in 2016. Gregory highlighted that the company will investigate other potential indications for this prod- its specific disease,” he said. “Alzheimer’s is a great example, [a uct under its partnership with Eisai – the drug is already in Phase II value framework] could mean the return of cognition scales or trials for excessive sleepiness associated with medical conditions. it could be a measure for the burden relief on caregivers – but In terms of increasing competition for its current pain portfo- both of those assessments would be very different than mea- lio in the US, Purdue’s business development head said, “While sures for the next arthritis drug.” we see a lot of generic competition in the opioid space, Purdue In Europe, Mayne highlighted that health technology apprais- has an excellent commercial organization that is really able to al bodies, such as NICE which operates in England and Wales, manage this situation appropriately and is able to maintain a need to update their systems. “Look at a body like NICE and it’s healthy business. Our evergreening is bringing innovation to cost per quality adjusted life year measure; that was a great tool the marketplace.” 25 years ago but we realize things have changed,” he said. “A However, Gregory added that the company is ready to quickly drug that reduces pain has a very different value proposition to move new pain products through development to maintain its say a rheumatoid arthritis drug that increases physical function lead on the US market. “Obviously we are looking for new prod- and those value benefits need to be recognized.” ucts where we feel we can differentiate because we know the Published online 22 November 2016

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Combination Strategies A Common Thread In NASH R&D Intercept continues to lead the non-alcoholic steatohepatitis race, but some analysts think Gilead is making up ground; data presented at AASLD shows those two, along with Allergan/Tobira and Bristol, are jockeying to produce combination regimens for the unmet medical need. JOSEPH HAAS [email protected]

ith hepatitis C on the decline, non-alcoholic steatohepatitis Wis becoming the focus of liver disease R&D. While Intercept Pharmaceu- ticals Inc. and Genfit SA have the early lead in drug development, recent deal- making by Allergan PLC and Bristol-Myers Squibb Co., as well as a reshuffled strategy at Gilead Sciences Inc., appear to have the competition in flux. Intercept continues to lead the race to get the first drug approved for non-alcoholic ste- atohepatitis (NASH) with Ocaliva – but, not for the first time, Tobira Therapeutics Inc. (ac- Bristol’s Michael Burgess Tobira’s Laurent Fischer quired by Allergan in September) is arguing Squibb Co. Bristol-Myers Source: PLC Allergan Source: that being first to market won’t be as impor- tant as figuring out and delivering the best liver diseases is on NASH driven by a goal of report out during the first half of 2017. FGF21 combination of mechanisms to address the addressing all-purpose cirrhosis, he said. has already shown in Phase II in diabetes that complex liver/metabolic disease. “Our real driver is those patients who have it upregulates adiponectin, which Burgess Those and other companies presented more severe disease, [fibrosis scores of] F3-F4,” said is closely related to fibrotic activity. data during the American Association for the Burgess said in an interview. Bristol is aiming Although not currently being investigated Study of Liver Diseases (AASLD) conference for a portfolio that targets F3-F4 NASH and in NASH, PRM-151 attacks a common mech- Nov. 11-15 on their NASH pipelines and talk- all-cause fibrosis, and for drugs that work as anism of fibrosis, so it could be applied to a ed about combination and biomarker strate- monotherapy, but also could be combined combination strategy, he said. Bristol also is gies. It all remains up for grabs now as Inter- for a more effective cocktail, he explained. working on preclinical candidates that target cept’s Ocaliva (obeticholic acid) and Genfit’s Nitto Denko will complete an ongoing LPA1, which Burgess said could address fibro- elafibranor have advanced into Phase III, with five-week Phase Ib study under its agree- sis and the inflammatory effects of NASH. Allergan/Tobira’s cenicriviroc right behind ment with Bristol, but the US-based big them, slated to enter pivotal studies in 2017. pharma already is planning the protocol for SAFETY WILL BE A KEY Bristol announced itself as a significant a Phase II trial that will launch early next year CONSIDERATION competitor in the space on the eve of the when Bristol takes over clinical development At Intercept, the primary focus is on bring- AASLD meeting, paying $100m up front to of the HSP47 molecule. ing its bile acid analog Ocaliva through license worldwide rights to a Phase Ib can- PRM-151, part of a 2015 option deal to Phase III in NASH, but the company is look- didate, ND-L02-s0201, which targets heat acquire privately held Promedior Inc. and ing ahead to a combo strategy of its own, shock protein 47 (HSP47) from Nitto Denko PEF-FGF21, a candidate Bristol has optimized CEO Mark Pruzanski said during AASLD. Corp. Bristol already had the Phase II can- since its licensure from Ambrx Inc. fill out Pruzanski sees several advantages for Oca- didate PEG-FGF21 for NASH, as well as the what Bristol hopes will be a comprehensive liva – its potential to be the first to market in recombinant human pentraxin-2 protein combination strategy in NASH. NASH, previous approval in another liver indi- candidate PRM-151, currently in Phase II “If we look at it from a strategy point of cation and a substantial safety database – as in myelofibrosis and idiopathic pulmonary view, we believe that in patients with ad- well as the validation inherent in the fact that fibrosis, which gives it the potential to es- vanced fibrosis, you need to target both [the] several other companies, including Gilead tablish an in-house three-drug regimen for fibrotic component and the underlying in- and Novartis AG, are developing FXR ago- the disease. sult,” Burgess noted. nists for NASH. Michael Burgess, Bristol’s head of cardio- Bristol has mouse-model data suggest- “I think imitation is the highest form vascular, immunoscience, fibrosis and ge- ing that FGF21 could serve a dual purpose, of flattery,” he said in an interview. “What netically defined disease development, told addressing the metabolic syndrome that we’ve seen is that FXR is now considered a Scrip the Nov. 10 deal furthers the company’s underlies NASH as well addressing fibrosis di- validated target and any company looking long-time interest in fibrosis, with a focus on rectly, he added. The compound is in a 75-pa- to stake out a serious claim on the NASH liver and lung disease. The primary focus in tient Phase II study in NASH, which should space needs an anchor FXR agonist in its

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armamentarium. We certainly agree with tients with the most advanced disease, but evolve more like HIV than hepatitis C, be- that.” Intercept’s R&D centers on bile acid for patients with earlier-stage disease, who cause of the differing nature of the diseases. analogs, and Pruzanski thinks human FXR are expected to take the drug for a long pe- NASH development should benefit from the compounds will prove to offer a better safe- riod of time, ideally you want to go all-oral,” subsiding competition in HCV drug develop- ty and tolerability profile than the synthetic he said. “But there are oral GLP-1 analogs or ment, he pointed out, because a large clinical versions others are working on. receptor agonists that might be interesting.” infrastructure of liver treatment centers is al- “I’ve long maintained that a natural com- Tobira presented one-year biopsy data ready primed to participate in NASH studies. pound analog should be inherently safer in from patients in its Phase IIb CENTAUR study “I think it’s going to be more like HIV, where chronic administration than a purely syn- of cenicriviroc (CVC), showing that twice as the patient will require multiple therapies thetic molecule,” he said. “So far, from a track many patients who received the study drug that are complementary, but because this is record standpoint, that hypothesis has been achieved a one-stage improvement in their going to be chronic, lifelong treatment, the proven correct and there are no less than four fibrosis scores compared to those on pla- winners will be the companies that can put other synthetic FXR agonists that either didn’t cebo. Tobira CEO Laurent Fischer pointed out together fixed-dose combinations,” he said. make it into the clinic or made it to Phase I or that the 289-patient study enrolled only pa- The challenge will be to create simple early Phase II and have blown up.” tients with liver disease at the F2 or F3 stages. and safe regimens for patients who are Partly due to its development in PBC, Oca- Showing this improvement is important, already taking medicine for other related liva has already been dosed in more 1,600 because fibrosis is linked to clinical out- conditions such diabetes, hypertension clinical study participants, which Pruzanski comes and progression to cirrhosis, he said. and high cholesterol. thinks provides some sense of how the drug The data give CVC solid ground as it moves Fischer noted that CVC demonstrated a will fare as a chronic long-term therapy. He into Phase III next year. That level of improve- safety profile no different than placebo in the predicts competitors will have to measure up ment in fibrosis score has not been seen af- Phase IIb study. It also can be dosed once- in terms of safety data. ter one year of treatment with a NASH candi- daily and has a long half-life, which should “In PBC alone, we submitted an NDA with date before, he added. benefit the goal of patient compliance. 675 patient years of exposure,” he noted. “We The study is continuing for a second year, Gilead, which has added NASH candi- have a cohort of PBC patients who’ve been with another biopsy after two years of treat- dates to its pipeline recently with a series of on Ocaliva for more than five years. There’s ment, and Fischer expects to see additional smaller targeted deals, may be a rising force not been any discernible safety signal with benefit then. in the space, but the company is starting the drug. The side-effect profile of OCA is over somewhat after abandoning its most very well characterized and that is a big ad- ALLERGAN, GILEAD advanced candidate for NASH, the LOXL2- vantage. And until and unless a similar safety COMBINATION STRATEGIES targed antibody simtuzumab. For the firm database is amassed for any other FXR ago- UNDERWAY that has dominated the HCV competition, nist or any other molecule being advanced Fischer said he and his team will lead liver the primary focus now turns to selonsertib in NASH, the jury is out.” drug development at Allergan, which paid (GS-4997), a Phase II inhibitor of apoptosis In terms of a combination strategy, Inter- nearly $1.7bn in a buyout of Tobira an- signal-regulating kinase 1 (ASK1). cept presented preclinical data on a second nounced in September. The combined Gilead reported data at AASLD from a proprietary candidate, INT-767, a dual agonist companies already have a NASH combina- study testing selonsertib in NASH patients of FXR and PGR5, at AASLD. It is completing tion therapy strategy underway with the with fibrosis scores of F2 and F3. Two arms a Phase I study in healthy volunteers, after DPP-4 inhibitor evogliptin, cross-licensed tested the drug in tandem with simtuzumab, which Intercept will decide whether to ad- from South Korea’s Dong-A Pharmaceutical but data demonstrated that the antibody did vance it as a candidate for NASH, PBC or both. Co. Ltd. in April, he noted. In tandem with not provide an additive effect, and a cohort testing simtuzumab monotherapy yielded Pruzanski said INT-767 is a more potent acquiring Tobira, Allergan also brought in unspectacular results. Selonsertib demon- agonist of FXR than Ocaliva, and has looked the preclinical FXR agonist AKN-083 with its strated anti-fibrotic activity after 24 weeks of better than its predecessor in animal models $50m purchase of Akarna Therapeutics Inc. treatment in the first study to assess results of both liver and non-liver disease. TGR5 is a in September. not only with liver biopsy, but also with non- dedicated bile acid receptor involved primar- Under the partnership with Dong-A, To- invasive tests such as magnetic resonance ily in energy metabolism, the exec said. bira obtained rights to develop and market a elastography (MRE). An 18 mg dose of sel- Intercept is also looking to add other combination of CVC and evogliptin in North onsertib produced an improvement of one mechanisms to its NASH pipeline, he said, America, Europe and Australia, while the stage or greater in fibrosis score in 43% of whether through internal R&D or business Korean firm gets rights to the combo in its patients (13/30), while a 6 mg dose met that development. One area Pruzanski finds home market, where evogliptin is approved endpoint in 30% of patients (8/27). promising is GLP-1. The problem is that most for diabetes as Suganon. Published online 21 November 2016 GLP-1 analogs that have reached market or “We’re beginning to build a large pipeline are in development – such as established of NASH products, because we anticipate diabetes drugs Byetta/Bydureon (exenatide) that treatment of NASH will take a combi- View Preclinical data for INT-767, and Victoza (liraglutide) – are dosed subcu- nation of at least two drugs, probably more, a dual agonist of FXR and PRG5 here: taneously or intravenously. very much like hep C and HIV,” Fischer said. http://bit.ly/2gntqWq “I think that might ultimately work in pa- Overall, Fischer thinks the NASH space will scrip.pharmamedtechbi.com 2 December 2016 | Scrip intelligence | 5 HEADLINE NEWS

GSK Strategy Chief: No Major M&A Likely In 2017 STEN STOVALL [email protected]

GSK expects further consolidation among rivals in 2017 but its “From time to time the stars align. So down the track I would see own focus will remain internal, as it keeps integrating assets other opportunities and we’ll take them but I’ll leave it to Emma to out- acquired by its product swap with Novartis and as its new CEO line next year. She’s going through the program now, understanding takes corporate control. the opportunities,” Redfern said. The strategy head does not think the CEO-designate’s lack of an R&D laxoSmithKline PLC is unlikely to partake in any big M&A or postgraduate science background will hinder Ms. Walmsley in trying plays for the time being as it prepares for a new CEO and to improve R&D returns; rather it should allow her to assess GSK’s in- Gcontinues to bed down and integrate assets acquired by its novative approach with fresh eyes. product swap with Novartis AG, its chief of strategy told Scrip at a “A lot of the big decisions revolve around R&D. One reason why recent industry conference. Emma was chosen is partly great leadership skills, partly her great per- GSK’s complex, three-part transaction with Novartis, first announced formance focus which reflects her coming from the consumer busi- in April 2014, leaves the British drug maker with a better balanced port- ness where you have to be very customer orientated,” Redfern said. folio centered on , consumer health, respiratory and HIV medi- “The board feels Emma has the best chance of being the best leader cines. The transition is still settling, so the subject of M&A was not seen of all the businesses including pharma. And it’s interesting, she’s been as greatly relevant to the GSK executives who participated at this year’s around the management team for a few years but has the advantage FT Global Pharmaceutical and Biotechnology Conference in London of coming in fresh and can just ask questions of science and she’s on Nov. 16 and 17. spending most of her time on pharma R&D right now and is really thinking that through.” TRUMP-FED M&A FRENZY? Redfern, a chartered accountant by training who has led GSK’s new But David Redfern, GSK’s chief strategy officer, did say the surprise US business development strategy since 2008, said R&D will remain at the election result of a future Trump Administration would likely lead to a center of GSK operations under the new CEO. US tax “holiday” which would further fuel sector consolidation. “Ultimately we’re an innovative pharma company. It’s in our “Overall I do think there’s likely to be quite a bit of M&A next year. DNA. We spend £3bn a year and have 10,000 to 11,000 people in The only thing that’s not clear is just HOW big it gets,” Redfern said. “Do R&D. In the last few years some 25% of our pharma and vaccines people go after big targets like Bristol-Myers Squibb Co. , Inc. , business came from products that were launched three years Biogen Inc. - who knows! Everyone’s got issues - and opportunities,” he ago or less.” said rhetorically. “We’ll also see more innovation in the consumer business – it’s a “I do think that it will lead to more capital being spent. And buying different type of innovation obviously but bringing new formulations, innovation in particular. I don’t think there will be M&A to drive diversi- new packaging, new customer insights.” fication. It’s possible, but less likely. What I think you’ll see is more capital being deployed to buy innovation and efforts to buy growth across DPU R&D APPROACH SET TO STAY the industry,” Redfern said. Redfern also sees the company’s R&D approach continuing based on discovery performance units (DPUs) which was an initiative de- GSK TO “SIT OUT” BIG M&A DANCE signed by Dr. Moncef Slaoui, GSK’s vaccines chief and former head But that frenzy is not likely to see GSK participation. of R&D, who is retiring from the company in June 2017. The DPUs “We’re not currently discussing M&A here, largely because we’ve re- replaced the group’s previous R&D activities, deconstructing them cently done it and we’re busy integrating,” Redfern told Scrip on the into 38 focused and accountable DPUs and transforming GSK’s late- meeting’s sidelines. stage pipeline, which currently has more than 30 Phase III programs Another restraining factor is the imminent arrival of Emma Walms- compared with fewer than 10 in 2006. ley, head of GlaxoSmithKline PLC’s consumer division, as the successor “The DPU model is working well and I wouldn’t expect radical to Sir Andrew Witty, who has been CEO there since 2008. Ms. Walmsley change to the DPUs. It’s really about how the medicines emerge will be moving there from her current role as CEO of GSK’s Consumer from the DPUs and there’s a lot of Phase I and Phase II data coming Healthcare division. She has been a member of GSK’s corporate execu- in 2017 and we’ll then ask what’s best to take from that point, which tive team since 2011. will be the key question,” said Redfern who has also been chair of Asked whether Ms. Walmsley, who takes over the GSK reins on Apr. the HIV partnership, ViiV Healthcare Ltd since 2011. ViiV was set up 1, would take a more acquisitive M&A approach, Redfern shrugged in 2009 by combining the HIV management expertise of GSK and and said “It’s far too early to say what Emma is going to do as CEO. Pfizer Inc. The duo was joined three years later by Japanese pharma We continue to do early research deals and I’m sure that will continue. group Shionogi & Co. Ltd. And on potential divestments of legacy tail assets, from time to time “I spend around 50% of my time on that company because it’s there’s a deal that just makes sense,” he said, without elaborating other grown so big and within that role I spend way more time on the than to cite as an example GSK’s sale earlier this year of around half of R&D part than the commercial part. A lot of the big decisions revolve its 12.4% stake in South Africa’s largest listed pharma company Aspen around R&D,” he said. Pharmacare Holdings Ltd. Published online 21 November 2016

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CONTINUED FROM COVER ab and solanezumab, such as dose, trial There is evidence that the accumulation design and the antibody itself. GSK’s Nucala of amyloid plaque deposits in the brain con- “We believe investors will not complete- Shows Promise tributes to Alzheimer’s, but the pathway has ly discount the value of aducanumab,” continued to confound drug makers as a Porges said. In A Rare therapeutic target. Biogen’s stock opened 7.6% lower Nov. 23 at $293.82, though it made up ground dur- Systemic WHAT DOES FAILURE MEAN ing the day. Merck was mainly flat. FOR OTHERS? Vasculitis Two other high-profile drugs are in late- FOR LILLY, A CHANCE TO MOVE GlaxoSmithKline PLC plans to sub- stage development for Alzheimer’s, and FORWARD AND TAKE STOCK IN mit approval applications next year investors will wonder what the results of ALZHEIMER’S for the use of Nucala (mepolizumab) EXPEDITION3 might mean for those inves- For Lilly, the news could represent a chance in patients with eosinophilic granu- tigational drugs: Merck & Co. Inc.’s small to clean the slate and move forward, as it lomatosis with polyangiitis (EGPA), molecule selective beta secretase (BACE1) heads out of an extended period of signifi- after the IL-5 antagonist MAb met inhibitor verubecestat and Biogen Inc.’s adu- cant patent expirations. The company has its endpoints in a pivotal Phase III canumab, a targeting several new drugs and near-term pipeline study that is part of a collaboration beta amyloid. products to drive growth, like Trulicity (dula- between GSK and the US National Analysts were mixed about what the re- Institute of Allergy and Infectious sults might mean for other drugs in devel- glutide) for type 2 diabetes and Taltz (ixeki- Diseases on developing drugs for rare opment and the broader amyloid hypothe- zumab) for psoriasis, as well as up and com- diseases. The Phase III study, dubbed sis. Some like Bernstein Research analyst Tim ers like the CDK4/6 inhibitor abemaciclib for MEA115921, is the first double-blind Anderson advised caution about transfer- breast cancer and the JAK1/JAK2 inhibitor placebo-controlled trial to be con- ring the results of EXPEDITION3 onto other baricitinib for rheumatoid arthritis. ducted in EGPA, an extremely rare drugs. condition, and gaining an approval “While Lilly’s, Biogen’s and Merck’s drugs ‘Driven by new product in this patient population should all target the same protein, they all do it dif- launches, we continue to help Nucala stand out among a ferently enough that there should not be clutch of new drugs being developed much of a read-through from one drug to expect to grow average for eosinophilic conditions. Nucala the other,” he said. “In the case of Lilly, we’ve annual revenue by at least was approved for marketing in the said for a long time that they may have giv- EU in December 2015 as an add-on en too low of a dose, which could impact 5% between 2015 and treatment for severe refractory eo- results. Lilly never seemed to have a great sinophilic asthma in adult patients, answer for why they picked the solanezum- 2020.’ – Incoming Lilly CEO and in the US in November 2015 as ab dose they did.” David Ricks add-on maintenance treatment of Credit Suisse analyst Vamil Divan agreed patients with severe asthma aged 12 in a same-day note. “Given sola did appear years and older, with an eosinophilic to have a modest impact on cognition Incoming CEO David Ricks sought to as- phenotype. It has also been approved and some secondary clinical endpoints, sure investors that the company remains for marketing in Canada, Australia, we are not ready to dismiss the amyloid on track. “Lilly has strong growth prospects Japan, Switzerland, Chile, South Ko- hypothesis at this time, but remain cau- without solanezumab,” he said. “Driven by rea and Taiwan. Analysts at Informa’s tious on the likelihood of success for any Datamonitor Healthcare expect only of these pipeline opportunities in this new product launches, we continue to ex- a limited uptake for Nucala in 2016, high-risk area.” pect to grow average annual revenue by at with sales in the US, Japan and the However, Baird Equity Research’s Brian least 5% between 2015 and 2020.” top five EU markets forecast at just Skorney sounded an alarm, noting, “Today’s Nonetheless, the EXPEDITION3 fail- over $100m in 2016, rising to $600m failure comes pretty close to a nail in the cof- ure is a step back for Lilly’s ambitions in in 2020. But competition to Nucala is fin for the…amyloid hypothesis.” Alzheimer’s. The company is investing already increasing: Teva Pharmaceuti- Leerink analyst Geoffrey Porges said heavily in the field with the hope of being cal Industries Ltd.’s IL-5 antagonist that “this is a serious blow” for Biogen and the leading drug developer in the area. MAb, Cinqaero (reslizumab; Cinqair other companies developing Alzheimer’s Lilly has a broad portfolio of Alzheimer’s in the US) was approved for eosino- therapies. If all of the value of aducanum- drugs in clinical development that work philic asthma earlier this year in the ab were removed from Biogen’s valuation through an array of mechanisms and the US and Europe, and a third MAb, in Leerink’s model, Porges forecast that firm has suggested that it might be com- AstraZeneca PLC’s benralizumab, is the company’s stock would be reduced in bination approaches that will eventually in Phase III clinical studies. value by $37, or 10%. Still, he pointed to yield therapeutic benefits. material differences between aducanum- Published online 23 November 2016 [email protected], 23 Nov 2016 scrip.pharmamedtechbi.com 2 December 2016 | Scrip intelligence | 7 HEADLINE NEWS

Novo Nordisk ‘Caught Short’ Sanofi/Novo Nordisk In Head- By Lantus Exclusion To-Head Novo Nordisk says it was caught by surprise when US pharmacy benefit managers decided to exclude Sanofi’s basal insulin Lantus and downgrade Diabetes Combo its own Levemir from formularies in favor of Eli Lilly’s soon-to-be launched biosimilar Basaglar. Novo had been hoping for more time to secure some of Approvals Lantus’ US market share with its new diabetes product Tresiba, but now Sanofi and Novo Nordisk – which are bat- accepts that will not happen. tling to shore up their diabetes franchises in SUKAINA VIRJI [email protected] the face of biosimilar competition – have si- multaneously garnered US approval for new he diabetes market has been an show positive results in a major cardio- combination products to treat the disease. area of significant pushback from vascular outcomes trial (CVOT) in type However, analysts expect the two companies T payers and greater demands for re- 2 patients at high risk of CV disease. In to adopt different pricing strategies. bates, putting pressure on sales. Novo Nor- the SUSTAIN-6 trial, semaglutide demon- The US FDA has simultaneously disk AS has been one of the most signifi- strated a 26% risk reduction compared approved two combinations of a basal cant casualties, and cut its growth forecast with placebo. insulin and a GLP-1 receptor agonist for 2017 last month. Victoza demonstrated CV benefit in the from Sanofi and Novo Nordisk AS. “People have said, ‘but you knew the bio- LEADER trial earlier this year. Sanofi’sSoliqua (insulin glargine similar was coming,’” said Novo Nordisk’s IR The SGLT2 inhibitor empagliflozin (Jard- [Lantus] and lixisenatide) and Novo manager Melanie Raouzeos at the Jefferies iance, Boehringer Ingelheim GMBH/Eli Lilly Nordisk’s Xultophy (insulin degludec Healthcare conference in London on Nov. & Co.) was the first to show a reduction in [Tresiba] and liraglutide [Victoza]), 16-17. “We did know it was coming, but we CV death in the EMPA-REG trial. both once-daily treatments, have been didn’t expect that the PBMs would be so approved for adults with type 2 diabetes aggressive about accepting it. We thought ANOTHER THREAT inadequately controlled by basal insulin it would be launched and then take its time Aside from diabetes, Novo Nordisk’s hemo- or GLP-1 receptor agonists. to be accepted.” philia business faces a significant threat. Both combos are expected to be Novo Nordisk’s basal insulin Levemir (in- Competition is expected shortly in launched early in 2017 and will be sold sulin detemir) has always lagged behind the form of Roche’s late-stage promis- at a discount to the combined price of Sanofi’s Lantus (insulin glargine) in sales ing bispecific antibody for hemophilia the component products. ($2.68bn in 2015 versus Lantus’ $6.98bn), A, emicizumab (ACE910), which is being “We expect Sanofi to adopt a sig- likely because of its comparatively late touted as a future blockbuster. Emici- nificantly different pricing strategy market entry. zumab, given once-weekly subcutane- versus Novo and position the combo With Lantus going off patent, both com- ously, has demonstrated prophylactic ef- as a ‘Lantus Plus’, just a small price panies developed new drugs to shore up ficacy for people with severe hemophilia premium to Lantus,” said Credit their diabetes franchises. Sanofi’s Toujeo A, regardless of the presence of Factor Suisse analysts in a note dated Nov. (insulin degludec) was approved by FDA in VIII inhibitor antibodies (which develop 22. “Xultophy is already available in February 2015 and Novo Nordisk’s Tresiba in around 30% of hemophilia A patients), the UK and in this market Novo has (insulin glargine) in September 2015. How- potentially streamlining treatment of this priced it as a premium product, effec- ever, these have arguably modest benefits condition. tively a 20% discount to the sum of its over their predecessors. Currently, patients who develop in- components Victoza and Levemir. This “Tresiba has had good market access, hibitor antibodies are treated with bypass makes sense as Novo does not want to but we were forced to give higher rebates agents such as Novo Nordisk’s NovoSeven cannibalise its existing monotherapy [than planned]. Biosimilar Lantus left us and Shire PLC’s Feiba. revenue from both franchises. In with no choice,” said Raouzeos. Tresiba has If approved, “50% of NovoSeven’s sales contrast, Sanofi’s GLP-1 Adlyxin has been taking market share from Lantus and are at risk,” said Novo Nordisk’s Raouzeos. negligible sales for GLP-1 mono and “cannibalizing Levemir,” she added. Sales in 2015 were around $1.5bn. the standalone efficacy of it means its However, despite $3bn in cash on its potential is limited.” SEMAGLUTIDE PROMISE balance sheet and no debt, Novo Nordisk [email protected], 22 Nov 2016 Novo Nordisk has said previously it plans will not be adding “new legs” to its busi- to file its Victoza (liraglutide) follow-on ness, said Raouzeos. “In terms of business product, semaglutide, in the US by the development, we’re interested in add- CLICK end of 2016. ons or adjacent activity, but all M&A will Read full story at: Raouzeos noted that semaglutide was be modest.” http://bit.ly/2gRsoFr recently the second GLP-1 agonist to Published online 22 November 2016

8 | Scrip intelligence | 2 December 2016 © Informa UK Ltd 2016 HEADLINE NEWS

Juno Stresses Differences Between Its CAR-Ts As JCAR015 Trial Put On Hold Again Juno stressed structural differences, safety record and potential of its JCAR017 CAR-T therapy during a Nov. 23 call about the disappointing hold on its ROCKET ALL study for JCAR015 – the second clinical hold for the company’s most advanced development program.

EMILY HAYES [email protected]

uno Therapeutics Inc. is stressing the Chief medical officer Mark Gilbert said tory domain, JCAR017 and JCAR014 have a structural differences between the chi- during the Nov. 23 call that removing fluda- 4-1BB domain. Jmeric receptor T-cell therapies rabine from the preconditioning regimen The kinetics of T-cell expansion with a in its pipeline after two fatalities caused it was the right response following the deaths 4-1BB costimulatory domain is slower and to put the brakes on a study of JCAR015 in reported this summer, but noted that the “probably provides an improved tolerabil- adult acute lymphoblastic leukemia. company had not expected this would en- ity profile” relative to a CD-28 co-stimulato- Juno announced the voluntary hold on tirely eliminate the risk of neurotoxicity or ry domain, Gilbert said. the Phase II ROCKET in relapsed . “I do think we understand that there is a and refractory ALL on Nov. 23, noting that “Unfortunately, it is clear now that fluda- strong correlation with the rapid expansion two patients died from cerebral edema. rabine is not the sole cause (or any cause) of CAR T cells in these patients that seems The news followed a prior clinical hold on of the cerebral edema, although officials in to correlate directly with them developing the trial after three patients – and later a the call were adamant that the removal of cerebral edema,” Gilbert said. fourth – died from similar adverse events, the chemotherapy did lessen the toxicity The type of viral vector also differs in but the company blamed the deaths at of the treatment,” Biomedtracker analyst that JCAR017 and JCAR014 have a retro- that time on the use of fludarabine in a Robert Jeng commented in a note. viral vector, versus a lentiviral vector for preconditioning chemotherapy regimen. CEO Hans Bishop said during the Nov. 23 JCAR015. JCAR015 targets CD19 in B-cell malig- call that going forward all options are on the Bishop said that the company expects nancies. The company said that develop- table for JCAR015, including continuing the FDA will look at JCAR015 and JCAR017 as ment of another anti-CD19 candidate – study with a modified protocol, beginning “entirely separate products” and that the JCAR017 – is not affected and pointed out a new study and terminating the program. company continues to be “optimistic about differences between the candidates dur- “I think it’s important to say we see a its goal of launching JCAR017 in NHL as ing a Nov. 23 investor call. likely path forward for JCAR015 in ALL, but early as 2018,” Bishop said. FDA had placed a clinical hold on Juno’s it’s just too early right now to speak to that Biomedtracker analyst Jeng, however, ROCKET study this summer after three pa- with regards to the actual risk/benefit pro- concluded that the execs remained “stub- tients with cerebral edema died and re- file, and that’s what we are primarily going bornly optimistic and even defiant” in the quired the company to submit a revised to judge this on,” Gilbert said, face of patient deaths. patient consent form, trial protocol and Juno execs stressed that the company re- “This is quite a major setback for not only investigator brochure. mains encouraged by both the efficacy and JCAR015 but for the Juno pipeline and per- Juno’s position was that the deaths tolerability it is seeing for JCAR017 across haps the entire CAR-T class. It is simply not were caused by the use of fludarabine in a range of ongoing trials in pediatric ALL, clear how much of the severe neurotoxic- a preconditioning cyclophosphamide che- adult ALL, NHL and CLL. ity is construct-specific or a characteristic motherapy regimen and the agency lifted The candidates are different in a number of this still relatively new and complex class the hold on research after the company re- of ways that could affect safety profiles. of therapy,” Jeng commented. vised the protocol to stop using that agent. Whereas JCAR015 has a CD28 co-stimula- Published online 23 November 2016

Comparison Of CAR-T Programs

SPONSOR PROGRAM VECTOR TARGET CO-STIMULATORY DOMAIN INDICATIONS

Novartis CTL019 Lentivirus CD19 4-1BB DLBCL, ALL KITE KTE-C19 y-retrovirus CD19 CD28 DLBCL, PMBCL, TFL MCL, ALL, FL, CLL Juno JCAR015 y-retrovirus CD19 CD28 Adult ALL JCAR014 lentivirus CD19 4-1BB NHL, adult ALL, CLL JCAR017 lentivirus CD19 4-1BB Pediatric ALL, adult NHL Bluebird BB121 lentivirus BCMA 4-1BB Multiple myeloma Source: Gena Wang, Jefferies analyst note, July 8, 2016

scrip.pharmamedtechbi.com 2 December 2016 | Scrip intelligence | 9 R&D BITES

Nearing Finish Line, HCV Race Focuses On Pfizer’s Avelumab Poised For Speedy Review By FDA Salvage Therapy Pfizer Inc. and Merck KGAA’s PD-L1 inhibitor avelumab appears on track Change was in the air at the American to be the fourth anti-PD-1/L1 antibody to reach the market and the first Association for the Study of Liver Dis- for metastatic Merkel cell carcinoma. The companies announced Nov. 29 eases meeting held in Boston between that a BLA for avelumab was accepted for priority review for the treatment Nov. 11-15 and not just because of the of metastatic MCC, positioning the cancer for FDA ap- recent US election results. The shifting proval in the first part of 2017. Avelumab is the cornerstone of Pfizer’s drug development focus in liver diseas- strategy to become a leader in the field of immuno-oncology and getting es from the hepatitis C virus (HCV) to the drug on the market next year is an important catalyst for the initiative. non-alcoholic steatohepatitis (NASH) Pfizer is studying avelumab in dozens of clinical trials in as many as 15 in- is palpable, with market-leader Gilead dications, including gastric, ovarian, renal and . The company’s Sciences Inc. recently stating that its lat- long-term focus is on combinations involving avelumab as a backbone, the est Phase III, three-drug combination area in which Pfizer believes it can catch up to immuno-oncology leaders regimen probably signals the end of its like Merck & Co. Inc., Bristol-Myers Squibb Co. and Roche. Pfizer has said R&D work in HCV. Still, Gilead and its it expects to have a total of 10 IO assets in clinical development by the two closest pursuers in HCV – Merck & end of the year. The FDA has approved three other PD-1/L1 inhibitors and Co. Inc. and AbbVie Inc. – unveiled data multiple new indications for the treatments under the six-month review for their next-generation direct-acting clock established for priority reviews. Opdivo, Merck’s Keytruda (pem- antiviral (DAA) combination regimens brolizumab), and Roche’s Tecentriq (atezolizumab) are the first PD-1/L1 in Boston, and each company is work- inhibitors to reach the market. ing to produce eye-opening data in one [email protected], 29 Nov 2016 of the few remaining challenges in the space – salvage therapy, that is curing HCV-infected patients who’ve failed a previous round of therapy with a DAA eight weeks in treatment-naïve patients product is administered to protect the regimen. Elsewhere, Merck is trying to against Epclusa for 12 weeks in POLA- body against infection. Green Cross’s build a case for treating injectable drug RIS-2 and 3. POLARIS-2 was open to all BLA, filed in November 2015, was in- users who have HCV as a means to ad- genotypes whereas POLARIS-3 focused tended to secure approval for the treat- dress the greatest risk for new infections on genotype 3-infected individuals with ment of primary immunodeficiency dis- and as a possible pathway to eradicating compensated cirrhosis, an area the com- eases (PID), a class of inherited genetic the virus. And AbbVie has completed pany cites as one of the greatest remain- disorders that cause an individual to year one of a five-year effort to collect ing unmet needs in HCV. Gilead found, have a deficient or absent immune sys- liver outcomes data for HCV patients however, that 12 weeks of Epclusa was as tem. IVIG-SN demonstrated positive re- cured with its DAA regimens. Gilead efficacious or more so than eight weeks sults in a Phase III study in patients with plans to file a pan-genotypic triple regi- of sof/vel/vox in both of these studies. PID, meeting its primary endpoint of no men containing the nucleoside poly- acute serious bacterial infections. These [email protected], 24 Nov 2016 merase inhibitor Sovaldi (sofosbuvir), results, included in the submission, were its second-generation NS5A inhibitor well beyond the requirement specified velpatasvir and the investigational pro- in FDA guidance of no more than one tease inhibitor voxilaprevir for approval US Approval Delay For acute serious bacterial infection per in the US by the end of 2016. Sovaldi Green Cross patient-year. The FDA has asked Green also is a component of Harvoni with the Cross to submit additional data on man- first-generation NS5A inhibitor ledipas- The US FDA has issued a complete re- ufacturing processes, but hasn’t raised vir and it is combined with velpatasvir in sponse letter (CRL) on Green Cross any issues with the product’s efficacy or Epclusa. Gilead presented data during Corp.’s biologics license application safety, the company stressed. “We now AASLD from its four Phase III POLA- for I.V.-Globulin SN (IVIG-SN), a hu- have a very clear idea about the remain- RIS studies for the three-drug regimen, man immunoglobulin G for intrave- ing process to obtain the final approval,” also known as sof/vel/vox, showing sus- nous administration, which although said E. C. Huh, president of Green Cross, tained virologic response (SVR) rates set to delay an approval is not expected in a statement. “We will complete the ap- for salvage patients in the 96%-97% by analysts to exact a serious toll on the proval process without setbacks and beef range in the POLARIS-1 and 4 trials. South Korean company’s North Ameri- up our US sales and marketing strategy.” Gilead compared the regimen dosed for can business plans. The plasma-derived [email protected], 24 Nov 2016

10 | Scrip intelligence | 2 December 2016 © Informa UK Ltd 2016 HEADLINE NEWS

Chiesi Takes Aim At Next-Generation Eosinophilic Asthma Therapy JOHN DAVIS [email protected]

Chiesi may be coming late to the development of eosinophilic mithKline PLC. AstraZeneca’s benralizumab is in Phase III clinical asthma therapies, but there are certain advantages associated studies, and is expected to be dosed every eight weeks, while with acquisition target Atopix Therapeutics’ potential products GlaxoSmithKline’s Nucala (mepolizumab) and Teva Pharmaceu- that could strengthen the specialty pharma’s already significant tical Industries Ltd.’s Cinqaero (reslizumab; Cinqair in the US) are presence in the asthma market. administered every four weeks and already marketed. Informa Pharma Intelligence’s database Biomedtracker lists he privately-held European mid-sized pharmaceutical com- the handful of companies that are developing CRTh2-antago- pany Chiesi Farmaceutici SPA is hoping an orally active small nists as follows: Tmolecule being developed by acquisition target Atopix Ther- apeutics Ltd. for eosinophilic asthma will trump the more advanced Selected CRTh2 Antagonists In Development injectable monoclonal antibodies in development for the condition, or already marketed by competitors. COMPANY PRODUCT STAGE OF DEVELOPMENT Chiesi is to acquire the UK based Atopix for an amount that fevipiprant Novartis AG Phase III could exceed €75m ($80m), the Parma, Italy-based company (QAW039) announced Nov. 11. Atopix’s major asset is the oral CRTh2 an- Pulmagen Therapeutics ADC3680 Phase II tagonist, OC459, that is in Phase II proof-of-concept studies (Asthma) Ltd. in patients with severe asthma and persistent airway eosino- Merck & Co. Inc. MK-1029 Phase II philia despite treatment with high-dose corticosteroids. Atopix Panmira Pharmaceuticals also has a back-up compound, ATX2417, that has completed a AM211 Phase I LLC Phase I study. Array BioPharma Inc. ARRY-502 program on hold The Oxford company has been backed by experienced biotech Boehringer Ingelheim VC firms including SR One, Wellington Partners, SV Life Sciences AP768 program on hold and MPM Capital. GMBH Chiesi is taking on OC459 despite the compound’s failure earlier Source: Biomedtracker. this year in moderate to severe atopic dermatitis; Atopix reported in February 2016 that a Phase II study had found no benefit as- Analysts at Datamonitor Healthcare estimate that the asthma sociated with OC459 in patients with atopic dermatitis, compared market could reach $20.8bn by 2024, a compound annual growth with placebo. However, that study did show the compound was rate of 4.7%, because of the high cost of the biologic therapies that generally well tolerated, and provided insight into the mode of are targeting severe persistent uncontrolled asthma. The market action of OC459, Atopix said. CRTH2 antagonists may have no should grow despite the advent of generic versions of commonly activity in atopic dermatitis but the CRTH2 pathway is active in used inhalers, they note. eosinophilic asthma, Atopix’s executive chair Tim Edwards com- Chiesi has a major interest in respiratory drugs, with its asthma mented at the time. inhaler Foster (beclomethasone plus formoterol) accounting for The chemoattractant receptor-homologous molecule (CRTH2) more than 30% of its total revenues. Also in its research pipeline receptor is found on TH2 lymphocytes, basophils and eosinophils, is a triple combination inhaler, which in September 2016 was and its ligand is thought to be prostaglandin D2 released from mast submitted for approval to the EMA for the treatment of chronic cells. The pathway is involved in allergic responses that include eo- obstructive pulmonary disease. It contains beclomethasone, for- sinophilic airway inflammation, with eosinophilic disease being moterol fumarate and glycopyrronium bromide. more severe than non-eosinophilic disease, and associated with The Italian company has previously taken part in M&A to asthma exacerbations and hospitalization. achieve its aims: it acquired Cary, North Carolina-based Cor- The potential of Atopix’s products in eosinophilic asthma is be- nerstone Therapeutics Inc. in 2013 for $252m to establish a US ing backed by Chiesi’s vice president and head of R&D, Paolo Chiesi, base, and to extend its respiratory portfolio. Also in 2013, Chiesi who believes OC459’s patient-friendly oral dosage form may also bought Denmark’s Zymenex AS for its Phase III enzyme replace- be significantly more cost-effective than other therapies in the ment therapy for alpha-mannosidosis, velmanase alfa, to boost clinical setting. its rare diseases portfolio. Still, Chiesi will find itself up against big pharma companies in Chiesi’s turnover reached €1.467bn in 2015, 80% of which came the eosinophilic asthma field like Novartis AG and Merck & Co. from outside Italy and up by 9.4% on turnover in 2014. Sales of Inc., that are currently developing CRTH2 antagonists, as well the Foster inhaler reached €492m. Net income in 2015 amounted as companies developing injectable monoclonal antibodies for to €228m. eosinophilic asthma that include AstraZeneca PLC and GlaxoS- Published online 21 November 2016 scrip.pharmamedtechbi.com 2 December 2016 | Scrip intelligence | 11 HEADLINE NEWS

Industry’s Achievements Lauded At 12th Annual Scrip Awards The world’s political tectonic plates may be shifting, but this has done little to undermine the achievements of the pharma, biotech and allied industries over the past year, and on Nov. 30 we celebrated the best of these at the 12th annual Scrip Awards in London. n a lavish ceremony presented by the proved anti-CD38 antibody in multiple my- DEALS, DEALS, DEALS broadcaster Jeremy Vine, Scrip rewarded eloma transformed Genmab … into a player,” The Best Partnership Alliance (sponsored Iexcellence across the whole range of said the judges. by INC Research) recognizes the impor- business activities. The Award for Best Company in an tance of pharmaceutical and/or biotech The Scrip Awards categories range from Emerging Market (sponsored by ICON) companies working together to develop those that reward the broader achieve- went to Mundipharma Singapore. new medicines. This year the trophy went to ments of companies, to those for innovation Mundipharma’s independent associated AstraZeneca and Human Longevity for their in deal making, advances in R&D and the companies are privately owned entities cov- long-term genomic partnership which aims more personal accomplishments of teams ering the world’s pharmaceutical markets. to harness the power of genomic informa- and individuals. Mundipharma consistently delivers high tion to propel the discovery and develop- Overall, Genmab was the big winner of quality products and in 2016 broke ground ment of novel medicines. The companies the night, receiving two trophies, but the on its Betadine manufacturing and R&D fa- hope their partnership will drive new drug loudest applause went to this year’s Lifetime cility in Singapore, an important strategic target and biomarker identification to select Achievement Award recipient, Dr. Raymond move and one that will enable it to respond patients who can respond to treatment, and F. Schinazi. quickly to regional health crises. believe it could change the way clinical trials The judges were impressed by its growth are designed. COMPANIES in sales and its deals that have strengthened “The impact on our industry and patient The first of the awards that celebrate compa- its position. outcomes if this alliance achieves its goals ny successes, PPD’s Pharma Company of The award for Best Contract Research Or- are immeasurable,” the judges said. ganization was this year split into two cat- the Year Award (sponsored by PPD), went The Licensing Deal of the Year (spon- egories to separate the full-service providers to Shire. The winner of this special award is sored by Worldwide Clinical Trials) award from those smaller CROs that provide niche chosen each year by Scrip’s senior edito- celebrates the licensing transactions that services to their clients. rial team, based on a variety of key metrics, are vital both in helping to keep pharma’s The winner of the Best Contract Re- including its financial performance in 2015, pipelines replenished and in generating in- search Organization – Full-service pro- strategic advances, progress in the emerging come for smaller firms. viders was QuintilesIMS, which enjoyed a markets, and advances in the drug pipeline. The winner Galapagos received an up- busy qualifying year, with the creation with Scrip was impressed by Shire’s perfor- front payment of $725m consisting of a Quest Diagnostics of the world’s second- mance since its planned merger with Ab- license fee of $300m and a $425m equity largest clinical trials laboratories, Q2 Solu- bVie was called off in October 2014. It has investment from its deal with Gilead to de- tions, to provide precision medicine enabled produced consistent growth, increased its velop the JAK1-selective product filgotinib by genomics and companion diagnostics. It R&D spend and acquired Baxalta to take a also announced the merger with IMS Health for the treatment of rheumatoid arthritis leadership position in rare diseases. This con- to create a new type of CRO, one that spans and other inflammatory diseases, in a boost tinued progress leaves it poised to enter the the clinical-commercial continuum. to Gilead’s inflammation R&D portfolio. top 20 pharma companies worldwide by The judges described the entry as “out- “Hugely valuable strategically to Gala- pharma sales next year. standing”, noting QuintilesIMS’ impressive pagos given that the asset had been re- The always-competitive WuXi AppTec record of involvement in development of turned only a few months previously, yet Biotech Company of the Year Award best-selling products. “The new mega-struc- within three months it had found another (sponsored by WuXi AppTec) went to ture offers interesting potential for 2017.” big partner in Gilead and at much better Genmab. The Award for Best Contract Research financial terms,” the judges said. “For Gilead, Genmab’s business achievements over Organization for those companies that it’s a decent addition to their portfolio in an the period led to a third year of profitabil- provide niche services went to Altascienc- important market.” ity and a significant increase in its valua- es Clinical Research. Altasciences offers The award for Financing Deal of the tion. The company received EU and US ap- comprehensive Phase I/II drug develop- Year (sponsored by EBD Group) went to proval for its first-in-class CD38 antibody ment including the full array of required Immunocore for its series A financing. Darzalex, plus expanded US approval for support services. It has improved its range Totalling $320m, this was the largest pri- Arzerra, and entered into a new collabo- of services to meet sponsors’ expanding vate financing in the life sciences ever in Eu- ration with Novo Nordisk for its DuoBody needs, leading to the development of rope and second largest globally in the sector. bispecific antibody technology. specialized offerings, and the judges also The oversubscribed round included some of “The deal with Janssen on their now-ap- noted its strong social media strategy. the most highly regarded institutions in the

12 | Scrip intelligence | 2 December 2016 © Informa UK Ltd 2016 HEADLINE NEWS

healthcare sector and provided the company triggers and disburses payments to investi- in the development program. The judges with financial security to advance its ImmTAC gators in real-time. It removes the need for described it as an outstanding product that technology platform and other initiatives. time-consuming, error-prone payment pro- “clearly addresses a major medical need for The judges said, “This financing stood out cesses that can damage relationships with a large number of poor people”. … due to its sheer scale and the impressive study sites, reducing turnover rates with a The inaugurual Community Partnership amount raised.” process that is as automated as payroll. of the Year (sponsored by Medidata) award The judges said this was a huge chal- seeks to acknowledge the numerous ways in PEOPLE SKILLS lenge across industry and that the technol- which pharma and biotech companies give For those awards that look at individual and ogy brought great benefits for streamlining back to the wider community, and the judg- team achievement, the award for Manage- transparency reporting requirements. es awarded it to GlaxoSmithKline’s Newborn ment Team of the Year (sponsored by The trophy for Best Technological De- Survival Project in India. India has the highest CRF Health) went to Genmab’s Core Lead- velopment in Clinical Trials –patient-fo- newborn death rate in the world, accounting ership Team. cused went to AiCure’s artificial intelligence for 27% fatalities with the first 28 days of birth, This team’s most notable achievement in DOT smartphone app. mostly from treatable conditions. GSK’s CSR the qualifying year was the swift approval for AiCure technology is a new approach to project works with community volunteers to Darzalex (daratumumab) for multiple myelo- artificial intelligence that uses AI to visu- improve the continuum of care for newborns ma with Janssen, marking Genmab’s second ally confirm medication ingestion on smart- and is estimated to save 6,000 lives each year. marketed antibody. This came alongside its phones. The platform was developed to au- The judges described it as excellent: “Keep on broader goal of building the company into tomate directly observed therapy (DOT), the doing and expanding it.” a sustainable business and ensuring the cre- gold standard in monitoring and maximiz- ation of a robust pipeline and future product ing adherence, by visually identifying the LIFETIME ACHIEVEMENT opportunities. “They have taken Genmab to patient, the drug, and the act of ingestion. The biggest winner of the night was the the next level,” the judges decided. The judges said it was an “impressive Lifetime Achievement Award recipient Dr. Meanwhile, Allergan’s president and CEO technology” noting that lack of compliance Raymond F. Schinazi, who is recognized Brent Saunders won Executive of the Year was a huge issue for trials and can dramati- as one of the most influential persons in the (sponsored by Lachman Consultants). cally impact study results. life science sector. Through a year of enormous change for Al- QuintilesIMS’ Clinical Advance of the A world leader in nucleoside chemistry, lergan, Saunders has led the company with Year Award (sponsored by QuintilesIMS) Schinazi is best known for his pioneering a decisive and direct vision. Seeing ahead went to Summit Therapeutics for its Phase work on HIV, HBV and HCV drugs, includ- of changing marketplace and environment II CoDIFy study of ridinilazole in Clostridium ing stavudine, lamivudine, emtricitabine, conditions, his approach was powered by a difficile infection. telbivudine, and most recently sofosbuvir deep commitment to customers, patients The Phase II CoDify study suggests that (Sovaldi). More than 94% of HIV-infected in- and driving innovation to overcome unmet ridinilazone has the potential to become a dividuals in the US on combination therapy healthcare needs. front-line treatment in the management of C. take at least one of the drugs he invented. The judges described him as “an out- difficile infection, an unmet medical need. It He is the Frances Winship Walters Profes- standing, inspirational leader with a proven exceeded its primary endpoint showing su- sor of Pediatrics and Director of the Labora- track record prior to becoming CEO at Aller- periority against current standard of care van- tory of Biochemical Pharmacology at Emory gan, and (in the period under review) effec- comycin and met key secondary endpoints tively and efficiently bringing two organisa- showing its promise in reducing recurrence University and co-Director of the HIV Cure tions together.” rates, a key clinical challenge. Scientific Working Group for the NIH-spon- The judges said this was an outstanding sored Emory University Center for AIDS Re- R&D MARCHES ON study for a much-needed new therapy. “The search. Dr. Schinazi has authored over 500 Developing new drugs is the lifeblood of findings represent an important leap forward peer-reviewed papers and seven books and the industry and the trophies in this area in prevention of recurrent infections from C holds over 100 issued US patents, which show novelty across the R&D process. diff. The market for such a treatment is huge.” have resulted in 15 New Drug Applications. The perennially popular Best Technologi- HUYA Bioscience International’s After 35 years of service, Dr. Schinazi cal Development in Clinical Trials was split Best New Drug Award (sponsored by retired from the Department of Veterans into two this year, with categories rewarding HUYA Bioscience International) went Affairs with his latest position as Senior Re- advances that are focused on helping spon- to Sanofi Pasteur’s Dengvaxia (tetravalent search Career Scientist. He is the recipient sors, and those designed to ease the lives of dengue vaccine). of numerous awards including the 2015 clinical trial participants. Dengvaxia is the first vaccine against William S. Middleton Award from the De- Best Technological Development in dengue, a disease that affects 390 million partment of Veterans Affairs which is the Clinical Trials – Sponsor-focused went to people each year. It is indicated to prevent highest honor for outstanding achieve- Medidata Solutions’ Medidata Payments. dengue caused by all four of the virus sero- ment in biomedical research. Medidata Payments in the first end-to- types and is the culmination of over two de- Dr. Schinazi was appointed to the Glob- end site payment technology, an EDC-driv- cades of scientific innovation and collabo- al Virus Network (GVN) Executive Commit- en solution that automatically calculates, ration, with 40,000 volunteers participating tee in 2016. scrip.pharmamedtechbi.com 2 December 2016 | Scrip intelligence | 13 EXPERT VIEW

ASH 2016 Preview: Don’t Miss These 10 Presentations A CAR-T late breaker from Kite Pharma and sickle cell disease updates from recently acquired Oklahoma biotech, Selxys, lead Scrip’s handpicked top 10 data presentations you shouldn’t miss at this year’s American Society for Hematology annual meeting, held in San Diego, Dec. 2-6.

LUCIE ELLIS [email protected]

he American Society for Hematolo- University of Iowa Specialized Programs of presented on Dec. 4 during the ASH an- gy’s annual meeting kicks off on Dec. Research Excellence (SPORE). nual meeting. T 2; to get you ready for attending this Despite KTE-C19’s initial strong perfor- The day before Kite’s late-breaking abstract year’s meeting or to help you know what to mance in refractory DLBCL patients, con- announcement, Novartis acted on a 2012 lookout for online, Scrip has selected 10 of cerns have been raised over patient deaths option agreement to purchase Oklahoma the most exciting data readouts expected at in the ZUMA-1 study and analysts at ASH will City-based Selexys for up to $665m in up- the San Diego-based event. be looking for further insights into adverse front, acquisition and milestone payments. Kite Pharma Inc. has managed to overtake events seen in the Phase II study. There have been several recent failures of Selexys Pharmaceuticals Corp. as the most Datamonitor Healthcare analysts Dustin potential sickle cell therapies at late stages of anticipated company to present data at ASH Phan told Scrip: “These data demonstrate development. In September, a second Phase 2016, as the former will discuss pivotal data promising efficacy and suggest that KTE-C19 III study of Mast Therapeutics Inc.’s vepolox- for its CAR-T therapy, KTE-C19, during the could achieve accelerated approval if the six- amer failed to show that it reduced the dura- late-breaking abstract session on the last day month response rate is as strong as the three- tion of VOC compared with placebo, and the of the meeting. Prior to Kite’s late-breaker an- month response rate data already reported.” company said it was thinking of terminating nouncement on Nov. 22, conference attend- Nonetheless, Phan noted there continue all clinical development of the product. A ees and analysts had been excited to see to be concerns regarding the two patient week earlier, Emmaus Life Sciences Inc. found data for Selexys’ sickle cell disease therapy, deaths on trial due to cytokine release syn- the submission of just a single Phase III study as Novartis AG recently decided to act on its drome (CRS). While such adverse events are a in its US NDA for pharmaceutical grade L-glu- 2012 option to acquire the smaller company known side effect of CAR-T therapy, Kite has tamine to treat sickle cell disease was being – a deal worth up to $665m. stated they will continue to analyze the data questioned by the FDA. The agency would for predictors of toxicity. prefer data from two Phase III studies. As such 1. CAR-T QUESTIONS FOR KITE The data presented at ASH will be from analysts will be eagerly awaiting Selexys’ data, Kite will present data from an interim analy- an analysis of 93 patients with at least one which is expected to be positive following sis of the pivotal ZUMA-1 trial of its chimeric month of follow-up at cutoff. The larger pa- Novartis’s buyout announcement. antigen receptor (CAR) T-cell therapy, KTE- tient population compared with the last SelG1 is based on the concept that block- C19, in patients with refractory aggressive data release will hopefully provide additional ing P-selectin – an adhesion molecule that non-Hodgkin’s lymphoma (NHL). The com- insight into the drug’s efficacy and safety in causes cells to stick together – may help pany previously released interim topline DLBCL. “While these data are impressive thus avert VOC in sickle cell patients. Current treat- results from the ZUMA-1 trial in September far, KTE-C19 will need to continue to demon- ment for sickle cell anemia is usually aimed at 2016. This topline analysis from Kite’s Phase strate durability of response to gain the confi- avoiding crises, relieving symptoms and pre- II trial revealed that refractory diffuse large dence of regulatory bodies,” Phan said. venting complications. marrow trans- B-cell lymphoma (DLBCL) patients treated Additionally at ASH, data from another co- plant offers the only potential cure. with KTE-C19 exhibited an overall response hort of ZUMA-1 containing transformed fol- rate of 76% and a complete response rate of licular lymphoma (TFL) and primary medias- 3. CAR-T RIVALRY HEATS UP 47%. While the ORR and CRR fell to 39% and tinal B-cell lymphoma (PMBCL) patients will Competing with Kite’s KTE-C19, Novartis is 33% at three months, respectively, these be presented. Results thus far are “similarly also due to present first data from its Phase II data are still impressive compared to the promising” in this cohort, Phan said, with an registrational trial for CAR-T therapy CTL019 23% ORR and 8% CRR exhibited by refracto- ORR of 91% and a CRR of 73% (both fall to in pediatric and young adult patients with ry DLBCL patients in the SCHOLAR-1 study. 64% at three months). However, this interim relapsed/refractory acute lymphoblastic SCHOLAR-1 (Retrospective Non-Hodgkin analysis only contains 11 patients. leukemia (ALL). CTL019 was previously Lymphoma Research) is a retrospective granted Breakthrough Therapy designation analysis of patients with chemo-refractory 2. WHAT HAS NOVARTIS by the FDA in July 2014 for this treatment DLBCL looking at data from Phase III stud- ACQUIRED WITH SELEXYS BUY? setting and also received a PRIME designa- ies from the Canadian Cancer Trials Group Phase II data for Selexys’ SelG1, an anti-P- tion from the European Medicines Agency and LYSARC (CORAL Study) and large retro- selectin antibody being evaluated for the in June 2016. spective databases including from the MD reduction of vaso-occlusive crises (VOC) Data for CTL-019 continue to demonstrate Anderson Cancer Center, Mayo Clinic and in patients with sickle cell disease, will be clinical activity in refractory pediatric ALL

14 | Scrip intelligence | 2 December 2016 © Informa UK Ltd 2016 EXPERT VIEW

patients but, similarly to KTE-C19, safety and neoplasm (BPDCN). According to the avail- date and analysts will be looking for explana- toxicity concerns have been raised for CTL- able ASH abstract (#342), SL-401 achieved tions at ASH. Roche is relying on Gazyva to 019 related to CRS. Approximately 82% of an impressive 86% ORR in 29 patients in this replace revenues from the increasingly bio- patients thus far in this Phase II trial have ex- study. Stemline won a Breakthrough Therapy similared rituximab. perienced CRS, with as many as 44% of those designation for SL-401 in the US in August Gazyva is already on the market as a treat- patients requiring anti-cytokine therapy. Fur- this year based on previously reported Phase ment for CLL and follicular lymphoma, the thermore, two early deaths occurred prior to II data in BPDCN patients. most common type of indolent NHL – the initial disease assessment, one due to disease Stemline will also be presenting early latter of which it only gained approval for ear- progression and one due to intracranial hem- SL-401 data at ASH from ongoing Phase II lier this year. orrhage, while an additional two patients studies in AML patients and patients with failed to respond. “CTL-019 will likely have to myeloproliferative neoplasms. SL-401 is a re- 8. PHASE III GALLIUM STUDY demonstrate impressive efficacy while man- combinantly expressed com- Roche will also present first Phase III data aging safety and toxicity if Novartis continues prised of human IL3 conjugated to diphthe- for Gazyva from the GALLIUM study, in pa- to seek a rapid approval,” Phan told Scrip. ria toxin. The drug is designed to target the tients with previously untreated follicular IL-3 receptor which is highly expressed on lymphoma. 4. ABBVIE’S UPDATES ON some cancer stem cells. The drug is already approved in the sec- VENCLEXTA COMBO ond-line follicular lymphoma setting, but Preliminary data will be presented at the 6. WILL CTI’S PERSIST-2 STUDY Roche will be hoping for strong data for meeting from a Phase II trial investigating MEET CO-ENDPOINT? Gazyva as a first-line treatment in order to the safety and efficacy of Roche/AbbVie CTI BioPharma Corp. will present full Phase III gain a label extension. Currently Rituxan is Inc.’s Venclexta (venetoclax) in combination data for pacritinib from the PERSIST-2 study, the first-line standard of care therapy for fol- with Rituxan (rituximab) with or without which is testing the drug in patients with licular lymphoma; Roche will be aiming to bendamustine for patients with relapsed/ myelofibrosis and thrombocytopenia (less transfer patients over to its follow-on product as more biosimilar rituximab products reach refractory follicular lymphoma. Biomed- than 100,000 platelets per microliter), who the market. tracker analysts have noted that preclinical are considered to have a shortened median and early clinical data suggest the addition survival time compared with myelofibrosis 9. IMBRUVICA DATA FOR of Venclexta to Rituxan with or without patients with normal platelet counts. 2017 FILING bendamustine may improve response over CTI BioPharma released topline data from AbbVie will present Phase II data for Rituxan or chemotherapy alone. AbbVie will the PERSIST-2 study in August this year; pre- Imbruvica (ibrutinib) during the late-breaker hope to see these positive effects repeated liminary efficacy analysis showed pacritinib session at ASH. The company is hoping for in this larger study. therapy was associated with a significant a label extension for its approved cancer During ASH, AbbVie and Roche will also response rate in spleen volume reduction, a therapy into chronic graft-versus-host dis- be presenting Phase I safety data for Ven- co-primary endpoint. However, the drug did ease on the back of this data. A filing for clexta as a monotherapy for relapsed/refrac- not meet the second co-primary endpoint of Imbruvica in this indication is anticipated in tory multiple myeloma. Venetoclax – which a greater than 50% reduction in total symp- the first half of 2017. AbbVie will also show a targets the protein B-cell lymphoma 2 (BCL- tom score (TSS), although it was approaching host of Imbruvica data in NHL, including the 2) – has been impressing ASH attendees in marginal significance (p = 0.0791). Phase II DAWN study in follicular lymphoma. recent years in chronic lymphatic leukemia The fate of pacritinib is also critical for (CLL), displaying strong potency even in Shire PLC, which has a licensing agreement 10. REVLIMID PHASE III hard-to-treat patients with 17p deletions. to jointly commercialize pacritinib in the US UPDATES However, in that indication potency has with CTI BioPharma and has exclusive com- Celgene Corp. is presenting over 300 ab- been a double-edged sword as the oral mercialization rights for all indications out- stracts at ASH this year, including data from agent was also associated with life-threat- side the US. three Phase III studies of Revlimid (lenalido- ening tumor lysis syndrome in its early days mide) in NHL and CLL. Leerink analysts high- of development. AbbVie and Roche will 7. PHASE III GOYA STUDY lighted in a Nov. 23 note, titled 2016 ASH be hoping to avoid a similar situation with Among the large number of presentations Preview And Itinerary Planner, that “while not Phase I studies in multiple myeloma. expected from Roche at this year’s meeting, registration-enabling, the non-Hodgkin’s lym- Venclexta was approved for CLL in the Phase III data from the failed GOYA study phoma MAGNIFY data will offer evidence for US and Europe in April and October this for Gazyva (obinutuzumab) or Rituxan plus potential success in the pivotal Revlimid trials year, respectively. CHOP in patients with previously untreated in follicular lympohma (RELEVANCE and AUG- DLBCL will be discussed. MENT) that are expected to read out in 2017.” 5. STEMLINE TO PRESENTS Genentech Inc., a Roche company, an- Leerink analysts added that the CLL CON- MULTIPLE PHASE II TRIALS nounced earlier this year that the GOYA study TINUUM data being presented at ASH will FOR SL-401 did not meet its primary progression-free inform the advancement of Celgene’s next Stemline Therapeutics Inc. will present updat- survival endpoint compared to Rituxan plus generation immunomodulatory drug, CC- ed results from the ongoing Phase II trial for CHOP chemotherapy (R-CHOP). Few details 122, in this indication. SL-401 in blastic plasmacytoid dendritic cell from the failed study have been released to Published online 24 November 2016 scrip.pharmamedtechbi.com 2 December 2016 | Scrip intelligence | 15 BUSINESS BULLETIN

Kymab Keeps Cash Coming In With $100m Led By Baxter Divests Serum Business In Chinese Investors Turkey Business Rejig Kymab Ltd. has raised $100 million in a Global healthcare company Baxter International Inc. has completed the Series C financing led by new investors alignment of its local business in Turkey with the global separation of its ORI Healthcare Fund L.P. and includ- operations by selling a portfolio of serum products to ing Shenzhen Hepalink Pharmaceutical domestic firm Kocak Farma. Licenses and brands in the serum product Co. Ltd. both of China. Existing share- portfolio currently belonging to the US firm’s operating arm, a 50/50 joint holders Wellcome Trust, Bill & Melinda venture with leading company Eczacibasi Ilac Pazarlama AS known as Ec- Gates Foundation, Malin Corporation zacibasi Baxter, will be divested to Kocak by the end of the year, along with plc, CF Woodford Equity Income Fund production and other factory equipment. The JV will cease production in and Woodford Patient Capital plc also this area, meaning layoffs for around 500 employees and other workers. participated. CEO David Chiswell told No figures have been disclosed about the value of the divestment or other Scrip the company planned to have five arrangements. With a market share of almost 60%, Eczacibasi Baxter has programs in clinical testing by 2019 with been a dominant force in the serum business in Turkey for over 50 years, a pipeline of products in four main ar- and Kocak is therefore gaining a strong portfolio. Hakan Kocak, the Turk- eas: immuno-oncology, autoimmunity, ish firm’s CEO and general manager, underlined that the transfer would hematology and infectious disease. Ac- help his company to grow and also bring new technology. “Serum is a stra- cording to Chiswell, the first program – tegically important product. We will act responsibly and increase produc- which will enter the clinic next year – is tion, providing easier access for Turkish patients to these products,” he an antibody against the OX40 ligand. declared. At the same time - in line with the global spin off of the Baxalta “If you antagonize it then you prevent Inc. business in mid-2015 - the biopharmaceutical products of Eczacibasi T cells prolonging an immune response, Baxter will be transferred to a new equally owned JV with Eczacibasi, Ec- it’s like tuning it down. In theory you could go for any T cell driven autoim- zacibasi Baxalta. mune disease. We’re initially targeting Ahmet Sevindik, 24 Nov 2016 GvHD because that’s a disease in which you know when the immune response starts: when you do the transplant. We’ll pany Celon Pharma SA is aiming to But some time ago, Celon forecast have a poster at ASH with some very ex- have three of its own investigational that the cash flow it generates from citing data of our antibody in a primate innovative products in the clinic in the development and sale of generics, model of GvHD.” The next program to 2017, spearheading a strategic move and EU research funds for develop- enter the clinic will be in immune-oncol- towards the development of innova- ing innovative products, would still ogy “but we’re not disclosing the target tive pharmaceutical products. The ex- need an injection of capital to sup- for that.” Despite a very successful fund- pansionary strategy is part of a plan port a move into innovative products. raising history, Kymab’s $100m Series C drawn up several years ago. “We knew A further consideration supporting adds to $120m in Series A and B funds, we would need extra capital around this path forwards was the increas- Chiswell said: “If those five programs are about now to invest in research pro- ingly competitive nature of the gener- successful we’ll need even more money. jects and help fund the initiation ics market, Wieczorek noted. In the We will obviously have to find develop- of clinical trials for our innovative IPO, Celon raised PLN245m ($63m) ment partners. But the good thing about being well financed is we can get partners products,” said president and major from offering 13 million newly issued when we have data, when a partnership is shareholder, Maciej Wieczorek, in an B series shares to institutional inves- worth more to us. The plan is take these interview with Scrip. Currently, Celon tors and two million B series shares to programs forward until we get proof of markets a mix of branded and generic individual investors, representing 33% concept data and then seek partners.” products, including the respiratory of the company and 25% of the voting [email protected], 24 Nov 2016 agent Salmex (fluticasone plus salmet- shares. Wieczorek remained Celon’s erol) and the anticancer Aromek (letro- majority shareholder and president zole). The Polish company also en- of the management board after the Poland’s Celon Pharma tered into collaborations with India’s IPO. The company is the first with a Lupin Ltd. and Glenmark Pharmaceu- full suite of pharmaceutical activities Pursues Innovation ticals Ltd. in 2015 involving the mar- – R&D, manufacturing and market- Having raised just over $60m in an keting of a generic version of Glaxo- ing – to be listed on the Warsaw Stock IPO on the Warsaw Stock Exchange in SmithKline PLC’s Seretide (fluticasone Exchange. October, the 14-year-old Polish com- plus salmeterol) in various countries. [email protected], 24 Nov 2016

16 | Scrip intelligence | 2 December 2016 © Informa UK Ltd 2016 HEADLINE NEWS

Genentech Oncology Director Talks Cancer Vaccine Challenges LUCIE ELLIS [email protected]

Peter Fong, associate director of oncol- “Every single patient is going to have because of the latter company’s manufactur- ogy business development at Genentech their tumor sequenced and based on the ing know how. – a division of Roche – talks to Scrip about sequence information we’ll have this vac- Roche has a vast immuno-oncology port- the company’s latest deal with BioNTech cine made on an individual basis,” Fong said. folio, including a number of compounds in in oncology vaccines and why Genentech However, he highlighted that this person- clinical development and the first PD-L1 in- is predicting success this time around for alized vaccine approach has its challenges. hibitor to reach the market, Tecentriq (atezoli- more cancer vaccine products, especially “Clearly when you’re making a therapeutic zumab), which is approved for use in bladder when used in combination with newer that’s individual for every single patient cancer and non-small cell lung cancer. immunotherapy options. you’re going to have logistical issues that However, Genentech still sees promise you have to plan for,” he said. and opportunity in the cancer vaccine space A patient being treated with one of – historically a tricky development area. Most Genentech, a division of Roche, and pri- approaches to cancer vaccines have been vately held BioNtech’s cancer vaccines unsuccessful due to difficulties identifying will have to undergo a tumor resection the correct cancer targets, or , to or biopsy, the tissue will then be sent to vaccinate against; but there has been a new a sequencing center where whole se- wave of interest for use in conjunction with quencing would be performed, based on cancer as cancer vaccines that genetic information mutations will could prime the immune system to seek spe- be identified along with new antigens, cific molecular targets. these will be ranked and a mRNA vaccine Fong said Genentech was interested in created specific to that tumor. The treat- vaccine development because “despite the ment must then be shipped back to the great promise of the checkpoint inhibitors patient after formulation and injected. you’re still going to have a limited response “It’s an individualized approach; you are depending on the patient population and the tumor type. This idea that you can take Peter Fong not taking the same antibody and giving it to lots of different patients, you’re tak- the brakes off the immune system with ing lots of different patients and making checkpoint inhibitors is super exciting,” he enentech Inc.’s potential $310m a unique vaccine for each of them,” Fong said. “However, we want to do more than (€278m) deal with messenger RNA said. He highlighted manufacturing and that. We also want to tell the immune Gcompany BioNTech AG is not a typi- commercialization as prime challenges for system where to go. When you vaccinate cal end license deal, Peter Fong, associate the two companies to work through. Also, a patient you’re actually telling the T-cells director of oncology business development from a regulatory standpoint, Fong noted where the tumor is.” at Genentech, told Scrip at the recent BIO- that this was a new therapeutic approach Genentech and BioNTech will start their Europe partnering conference, held in Co- requiring a different regulatory pathway. mRNA vaccine development collaboration logne, Germany. Fong told Scrip that Genentech’s prepa- by looking at potential combinations of Te- Genentech’s deal with BioNTech is “a ration for these challenges began before it centriq and a vaccine candidate. “Tecentriq situation where both parties are going to even signed the deal with BioNTech. “This has already been developed as a mono-ther- fund development of the product equally kind of preparation really starts in the dili- apy so we’re really just adding the vaccine on and also share in the profits,” he said. Fong gence phase before you sign the deal,” he top of something that’s already approved in also highlighted that the technology “is said. “Once you start going into diligence two indications; we’re not starting both of certainly not your typical monoclonal an- with a potential partner you’re thinking them from scratch,” Fong said. tibody or small molecule.” Genentech and through a lot of the issues you are going to Fong expects the first patient to be treated BioNtech are jointly developing cancer have to solve with that company. Also for a with an mRNA vaccine in combination with vaccines based on BioNTech’s capabilities deal like this you have to have so much align- Tecentriq in 2017. Published online 24 November 2016 in the design, formulation, manufacturing ment and communication internally - all of and clinical testing of individualized neo- our respective stakeholders were involved antigen-based mRNA vaccines, combined in the process and we have discussed these Peter Fong Chats To Mike Ward at with Genentech’s cancer immunotherapy, challenges.” Fong said that one of the reasons BIO-Europe Partnering Meeting here: diagnostic, manufacturing and commer- Genentech decided to partner with BioN- http://bit.ly/2gByHtW cial expertise. Tech in the personalized vaccines space was

scrip.pharmamedtechbi.com 2 December 2016 | Scrip intelligence | 17 HEADLINE NEWS

Novartis Buys Selexys As Allergan Up For Alzheimer’s Competitors Stumble In Sickle Cell Challenge With SUKAINA VIRJI [email protected] Chase Buy Novartis has exercised its option to symptoms and preventing complications. Allergan is paying $125m for Chase acquire Selexys in a deal worth up to Bone marrow transplant offers the only po- Pharmaceuticals and its Alzheimer’s disease $665m, following data from the Phase tential cure. candidate CPC-201 that has completed II SUSTAIN trial of SelG1 in sickle cell dis- Phase II testing. The modest upfront reflects ease. The move follows several recent TOUGH AREA the Phase III graveyard that Alzheimer’s dis- failures in the space. There have been several recent failures ease represents. Chase is led by two former of potential sickle cell therapies at a late Allergan executives. stage of development. In September, a ovartis AG has acquired US biotech Allergan PLC has acquired Chase second Phase III study of Mast Therapeu- Selexys Pharmaceuticals Corp., Pharmaceuticals Corp. for an upfront tics Inc.’s vepoloxamer failed to show that Nwhich has a sickle cell disease treat- payment of $125m plus potential regu- ment in Phase II development, for up to it reduced the duration of VOC compared latory and commercial milestones of $665m in upfront, acquisition and mile- with placebo, and the company said it was up to $875m to Chase’s shareholders. stone payments. thinking of terminating all clinical devel- These include India’s Cipla Ltd., which The terms of the deal were agreed in opment of the product. held a 16.7% stake in the firm. 2012 when Novartis obtained an exclu- A week earlier, Emmaus Life Sciences Inc. Chase’s lead compound, CPC-201, sive option to buy the Oklahoma City- found the submission of just a single Phase is a patent-protected combination based firm. III study in its US NDA for pharmaceutical of the most commonly prescribed The company’s SelG1, an anti-P-selectin grade L-glutamine to treat sickle cell dis- acetylcholinesterase inhibitor done- antibody, is being evaluated for the reduc- ease was being questioned by the FDA. pezil and the peripherally acting tion of vaso-occlusive pain crises in patients The agency would prefer data from two cholinergic blocker solifenacin with sickle cell disease (SCD) in the Phase II Phase III studies. (which is already approved to treat SUSTAIN study. Results from the study are be- A review of Informa Pharma’s R&D pipe- overactive bladder). ing presented at the American Society of He- line database, Pharmaprojects, indicates AChEIs have been shown to im- matology (ASH) annual meeting on Dec. 4. that Pfizer Inc. and its partner GlycoMi- prove cognition in Alzheimer’s disease “Sickle cell disease affects millions of metics Inc. have one of the few potential patients but dosing is limited by side people around the world and there are therapeutics for sickle cell disease at an effects including diarrhea, nausea and limited therapies available for treatment advanced stage of clinical development – vomiting. of vaso-occlusive pain crises,” said Bruno Pfizer started a Phase III study of the syn- In Phase II testing of CPC-201, 29 out Strigini, CEO of Novartis Oncology. “With thetic glycomimetic molecule, rivipansel, of 33 patients (88%) reached 40 mg/day this acquisition, Novartis is able to leverage back in June 2015. The RESET (rivipansel: of donepezil (maximum dose allowed), its leadership in hematology research to evaluating safety, efficacy and time to dis- without experiencing dose-limiting advance development of a potential new charge) study is evaluating the treatment adverse events. Allergan believes that treatment option for patients.” of VOC in hospitalized patients aged six Chase’s next-generation formulation SCD is a hereditary blood disorder char- years or older. Rivipansel is designed to in- offers the possibility of better dos- acterized by sickle-shaped red blood cells. hibit all three types of selectin involved in ing with the potential for improved It is a life-long disease with many forms cell adhesion. cognition and function in Alzheimer’s that can range in clinical severity from as- Daiichi Sankyo Co. Ltd.’s marketed plate- disease patients. ymptomatic to life-threatening. Vaso-oc- let anti-aggregant Effient (prasugrel) has Chase recently completed an end of clusive crises (VOC), or pain crises, are the been submitted for the additional indica- Phase II meeting with the US FDA and major reason for healthcare encounters in tion, use in pediatric sickle cell disease, in based on feedback from the agency, SCD and occur episodically when sickle- some markets. Allergan intends to advance CPC-201 shaped red blood cells block blood flow Karolinska Development portfolio com- into a single Phase III registration study through blood vessels. pany Modus Therapeutics (which recently in 2017. SelG1 is based on the concept that changed its name from Dilaforette) is in [email protected], 23 Nov 2016 blocking P-selectin – an adhesion mol- Phase II with its potential sickle cell prod- ecule that causes cells to stick together uct, sevuparin. – may help avert vaso-occlusive crises in Selexys raised a $23 million Series A CLICK sickle cell patients. round led by MPM Capital concurrent with Read full story at: Current treatment for sickle cell anemia the option agreement in 2012. http://bit.ly/2fxhkgk is usually aimed at avoiding crises, relieving Publised online 21 November 2016

18 | Scrip intelligence | 2 December 2016 © Informa UK Ltd 2016 HEADLINE NEWS

Amid Brexit Chaos, UK PM Promises More R&D Funding, Lower Taxes, And Other Pro-Innovation Measures The UK prime minister has promised more government R&D funding and other incentives in an attempt to reassure businesses worried by the uncertainty created by the Brexit vote. The move comes shortly before the Chancellor’s autumn statement and the next meeting of the UK EU Life Sciences Steering Group.

IAN SCHOFIELD [email protected]

n a move intended to reassure science-based companies amid the across the various R&D sectors. Martin Turner, policy and projects chaos caused by the UK Brexit vote, the UK prime minister There- manager at the UK BioIndustry Association, said “we look forward Isa May has announced that the government is to invest an extra to hearing in greater detail in the autumn statement and beyond £2bn year into R&D by 2020 and to establish an Industrial Strategy how this funding will impact on the sector.” Challenge Fund for priority technologies as part of what she called a For Ed Corbett, engagement manager at pharma strategy consul- “modern, ambitious industry strategy.” tants Novasecta, the announcement represented “a small step to- Addressing the annual conference of the Confederation of Brit- wards calming UK pharma/biotech nerves” following the Brexit vote. ish Industry, May said she would also commit to the UK having the “If I were a pharmaceutical or biotech CEO in the UK I would cau- lowest corporation tax among the G20 group of countries. The tax tiously welcome this,” he said, although he added that “how the is already scheduled to fall to 17% by 2020 and suggestions are that funding will be allocated and what will be used as a model is very it could be reduced still further, possibly to 15% or lower. unclear.” He suggested to Scrip that it might mimic the EU’s Horizon Also on the cards is a review of the R&D tax credit, which has 2020 research funding program, to which the UK could lose access already been shown to stimulate additional investment in the UK. if it leaves the single market. But he pointed out that Horizon 2020 The Treasury is to look at how to make this support “even more ef- “is worth €80bn versus £2bn.” fective” to ensure that the UK continues to actively encourage in- Similarly, he said that the UK figure was “significantly smaller than novation, May told the conference. the £26bn the US government invests in the National Institutes of She added that a Patient Capital Review would be launched to Health every year, and therefore may not make the UK as competi- help companies secure the longer-term investment they need to tive as hoped. This, combined with outstanding uncertainty on free transform ideas into business, and that the small business innova- movement of people, upon which pharma/biotech depends, will tion research initiative would also be reviewed. mean that the UK¹s position as a global leader in life science re- Her speech came in advance of the autumn statement to be deliv- search is by no means guaranteed.” ered by Chancellor Philip Hammond on Nov. 23, when he is expected The government position, he said, “reflects the general uncer- to announce measures for tackling issues such as the high level of UK tainty of Brexit. It is nice mood music but we need to know how government debt, the possibility of slowing economic growth, and a and when it will be allocated.” likely rise in inflation following the plunge in the value of the pound. The Association of the British Pharmaceutical Industry and the AUTUMN STATEMENT AND BREXIT BioIndustry Association both said they welcomed the extra R&D The Chancellor’s autumn statement will coincide with the next funding promised by the prime minister as well as the government’s meeting of the UK EU Life Sciences Steering Group, which is trying to pledge to support and invest in science and technology innovation. assess the impact of Brexit on the life science sector. The meeting is Mike Thompson, the ABPI’s chief executive, said: “As we look expected to look at ways of mitigating the effects of a UK departure ahead to the autumn statement on Wednesday, reports today of an in key areas like commercial and trade, regulatory convergence, and extra £2bn of funding a year for the sector will help to ensure this movement of people. becomes a reality. This is hugely welcome and will be well received Corbett, whose firm has interviewed key heads of pharma and by everybody involved in UK life sciences.” biotech firms about the impact of the UK leaving the EU, said that BioIndustry Association CEO Steve Bates said it was “fantastic to senior leaders in EU-headquartered companies “have said that be- see this government showing an understanding of what is impor- cause of the general uncertainty they are holding off on short-term tant to life science businesses.” While the continued commitment investment decisions.” A key issue raised, he said, was the move- to R&D was welcome, he said, “for us the focus on improving the ment of people. “One member of our panel of CEOs said that ‘com- R&D tax credit regime, the focus on patient capital, and the review panies and our people are very rattled’.” of the small business research initiative are crucial and very wel- The uncertainty has been compounded after the international come. The UK is becoming the location from which the global lead- trade secretary, Liam Fox, told Labour MP Daniel Zeichner that he ing life science businesses of the future will grow.” did not agree that the UK needed to remain part of a Europe-wide regulatory system. HOW WILL IT BE USED? This chimes with fears expressed by many in business that the UK Quite how the R&D funding promised by the prime minister will ben- is heading for a so-called “hard” Brexit, with full withdrawal from the efit the biopharmaceutical industry is unclear, though, as she gave single market and the EU customs union. no details in her speech as to how the funding would be spread Published online 21 November 2016

scrip.pharmamedtechbi.com 2 December 2016 | Scrip intelligence | 19 POLICY & REGULATION BRIEFS

NICE Backs Imbruvica In CLL On Price Cut Despite Outcome Expanded US Approval Set To Take Uncertainties Janssen’s Darzalex Higher The UK’s National Institute for The US FDA has approved Janssen Biotech Inc.’s Darzalex (daratumum- Health and Care Excellence has re- ab, licensed from Genmab AS) in combination with lenalidomide (Celgene versed its earlier stance on Johnson Corp.’s Revlimid) and dexamethasone, or bortezomib (Velcade) and dexa- & Johnson /AbbVie Inc.’s blockbuster methasone, for the treatment of patients with multiple myeloma who have chronic lymphocytic leukemia drug received at least one prior therapy. This go-ahead for second-line use brings Imbruvica (Ibrutinib) and now pro- the anti-CD38 monoclonal forward in the treatment arc for this disease. visionally backs its use to treat some Darzalex was first approved in the US, rather earlier than expected, almost patients with chronic lymphocytic leu- exactly a year ago to treat patients with multiple myeloma who have re- kemia (CLL) routinely on the publicly ceived at least three prior lines of therapy, including a proteasome inhibitor funded National Health Service after (PI) and an immunomodulatory agent (IMiD), or who are double-refrac- receiving more input on the drug and tory to a PI and IMiD. That US approval was followed by one in the EU a promised price cut. In June, NICE is- in April under an accelerated procedure for relapsed or refractory disease. sued draft guidance rejecting the drug The new supplemental approval – which was based on the open-label Phase for treating pre-treated patients with III CASTOR and POLLUX studies – comes three months after a supple- CLL, and asked the drug’s makers to mental sBLA was submitted to the FDA in August 2016. Darzalex received put forward a case for including it on FDA Breakthrough Therapy Designation for this indication in July 2016. England’s new Cancer Drug Fund for It puts Darzalex on a more equal footing to its rival monoclonal Empliciti those with genetic changes. But J&J’s (elotuzumab) from AbbVie Inc., which was approved in the US shortly after corporate entity in Europe Janssen Darzalex received its first approval there, but for earlier-line use in combina- Inc. declined to do so, saying there tion with Revlimid and dexamethasome in patients who have received one were already observational data avail- to three therapies. Empliciti is a SLAMF7 (signalling lymphocyte activation able for this group, and that collecting molecule family member 7) protein inhibitor. further data through the CDF would [email protected], 22 Nov 2016 not address the uncertainty in this population. Instead the drug’s mak- ers offered an undisclosed price dis- count, which NICE concluded made Inc.’s Rituxan (rituximab), have poor the European Medicines Agency. The the therapy cost effective. The orally prognoses and very little treatment PRIME program is aimed at accelerat- administered therapy had only previ- options,” said Datamonitor Health- ing the regulatory process for prom- ously been available through the Can- care analyst Dominique Fontanilla. ising investigational medicines that cer Drugs Fund despite patients with [email protected], 25 Nov 2016 could offer patients benefits in disease this type of leukemia being difficult areas where there are no treatments, to treat and having limited treatment or which might offer a major thera- options. Some existing treatments for Sage Therapeutics On PRIME, peutic advantage over existing treat- the disease can also cause severe side ments. The news came after Sage-547 effects. But the promised cost cut to Partnerships and Pricing For won Breakthrough Therapy Designa- the NHS means Imbruvica is now rec- Its PPD First tion for the treatment of PPD in Sep- ommended in revised draft guidance tember. The designations were based SAGE Therapeutics Inc.’s Sage-547 is as a routine option for people with on results from a Phase II placebo- on track to become the first ever phar- CLL who have had treatment before, controlled 202A study of Sage-547 in or who have genetic changes known maceutical indicated for postpartum severe PPD. Datamonitor healthcare as 17p deletion or TP53 mutation. Up depression. It has won PRIME desig- analysist Maha Elsayed says that the to one in 10 adults with chronic lym- nation from the European Medicines PRIME and FDA Breakthrough desig- phocytic leukemia have a form of can- Agency and Breakthrough Therapy nations underscore the urgent need for cer with such genetic changes, which Designation for the treatment of PPD treatment options for these patients. makes their disease progress quicker from the US FDA. Jeff Jonas, the com- She points out that there are no drugs and more difficult to treat. “Patients pany’s CEO, speaks to Scrip about specifically designed for women with with relapsed/refractory CLL who are what when it expects to launch, what PPD and that the main forms of treat- not suitable for chemo-immunothera- it wants from a partner and what it ment are psychotherapy or classic anti- pies, such as regimens which include might charge. Sage has announced depressant meds. the standard-of-care Roche /Biogen it has won PRIME designation from [email protected], 25 Nov 2016

20 | Scrip intelligence | 2 December 2016 © Informa UK Ltd 2016 STOCKWATCH

The TIGER That Came To Lilly The reasons behind Lilly’s latest clinical failure had much less to do with the indication and more to do with repeating the past mistakes of Inspire and Sunesis. Unfortunately, that same die has already been cast for the trials of Biogen and Ophthotech that are due to report imminently. ANDY SMITH

n 2008 I remember arguing with my colleagues at the time about being the fairest. At the other end of the spectrum, those from the results of a ‘positive’ clinical trial that I felt had effectively failed Leerink Partners and Morgan Stanley promoted a rose-tinted view Iand whose results were unlikely to be reproducible. Even eight of the latest failure of the amyloid hypothesis in AD as it related to years later tiny effect sizes and high p-values seem not to be a barrier a very similar antibody (aducanumab) and early AD patient popu- to the progression of drugs in small or needy patient populations. lation in Phase III development at Biogen Inc. Despite this quar- Thankfully these types of results are frequently the harbingers of ul- terbacking Biogen’s share price did fall over 6% in sympathy on timate clinical, regulatory or commercial failure and with one down the day of Lilly’s announcement, but even that fall did not convey and two to go before the year-end there is probably much more risk the fact that with aducanumab Biogen is committing an almost than reward for the sector. carbon-copy of the solanezumab faux pas. Biogen initially presented interim Phase Ib data for aducanumab THE TIGER (formerly BIIB037) back in 2014 that showed some interesting ef- In 2008 when Inspire Pharmaceuticals Inc. announced the ‘posi- fects in small groups of early AD patients but without a convinc- tive’ results of its TIGER-1 Phase III clinical trial of denufosol in 332 ing dose-response and with worrying safety signals. Before the cystic fibrosis patients its stock price soared, opening up 75% as full Phase I dataset was released Biogen announced its move into investors raised their hopes for the second Phase III TIGER-2 study Phase III without conducting any Phase II studies and the CMO and ultimate approval of a blockbuster drug. To my cynical eye a unloaded $10m worth of Biogen stock. When a fuller data set on p-value of 0.047 in one primary endpoint and the failure in the aducanumab Phase I studies was presented in 2015 the linear re- other key endpoint of exacerbations – which the FDA more re- lationship between the product’s safety and efficacy had declined cently favors – were important warning signs. When Inspire then so much that the announcement contributed to a 25% fall in Bio- announced changes to the protocol of the TIGER-2 study, the fail- gen’s stock. ure of denufosol was cemented for me. In TIGER-2 the treatment The fact that they share the same target and early AD patient period was doubled from 24 to 48 weeks, the target enrolment population as EXPEDITION3 make me think that the aducanumab was increased from 350 to 450 patients and the enrolment criteria Phase III studies are destined to fail when they report later this year. were modified to include less severe patients. The chopping and Of course, there is always the possibility for a Lilly-inspired data changing of clinical trial protocols has been a key fault line that has mine in order to find a small retrospectively defined subset and a run through the subsequent and failed clinical studies of Sunesis hitherto unknown and unvalidated endpoint on which a ‘positive’ Pharmaceuticals Inc. and last week, Eli Lilly & Co. adjective could be applied in the trial announcement. Just as TIGER-2 failed, Lilly reported the widely anticipated third Phase III EXPEDITON3 results of solanezumab in Alzheimer’s dis- OPHTHOTECH ease (AD) last week, unveiling a comprehensive failure that sent With Ophthotech Corp.’s Phase III trial results for its anti-PDGF apa- the company’s stock price down about 11% on the day of the an- tamer Fovista (pegpleranib) also expected before the end of the year, nouncement. Like TIGER-2, the EXPEDITION3 protocol had been and coming a few months after the Phase III failure of Regeneron changed from the previous two failed Phase III studies in order to Pharmaceuticals Inc.’s – an antibody against the same tar- magnify a small, retrospectively defined treatment effect that, in get in the same patient population as Fovista – Fovista also has all the the end, turned out not to exist. potential for failure but a ‘positive’ announcement. Solanezumab’s failure has less to do with the AD indication and I have predicted the clinical trial failures of Circassia Pharmaceu- much more to do with the baloney sold to Lilly’s management by ticals PLC and Lilly so far this year and the reasons for those failures the senior vice presidents of R&D so that they could stay in their can be extended to other companies replicating their mistakes and jobs and collect bonuses after the failures of first two EXPEDITION set to report hotly anticipated Phase III data before the year-end. Phase III studies in 2012. The fall-out from the failure of EXPEDITION3 With the share price of Lilly joining those of AstraZeneca PLC and therefore has ramifications not just for any other disease-modifying Novartis AG at their 52-week lows this week, it may be time to sell drug intervention aimed against amyloid-beta in AD, but any other in November (instead of May) and go away. company where failure is rewarded with an opportunity to repeat Published online 28 November 2016 past mistakes. Andy Smith gives an investor’s view on life science companies. He has BIOGEN been lead fund manager for four life science–specific funds, including Investment bank analysts had mixed responses to solanezumab’s 3i Bioscience, International Biotechnology and the AXA Framlington failure, with perhaps those from UBS – reducing their share price, Biotech Fund, and was awarded the techMark Technology Fund Man- removing $1.1bn in sales and maintaining their neutral rating – ager of the year for 2007.

scrip.pharmamedtechbi.com 2 December 2016 | Scrip intelligence | 21 PIPELINE WATCH

Scrip’s weekly Pipeline Watch tabulates the most recently reported late-stage, Phase III clinical trial developments for the more than 10,000 CLICK drug candidates under active research worldwide. To see changes to the Visit the Pipeline Watch webpage at progress of product candidates further back in the development pipeline, scrip.pharmamedtechbi.com for all and a table of the week’s product approvals, please visit our Pipeline the week’s changes to the industry’s R&D pipeline Watch webpage at scrip.pharmamedtechbi.com.

Selected clinical trial developments for the week 18–24 November 2016

LEAD COMPANY/PARTNER COMPOUND INDICATION COMMENTS Phase III Suspended solanezumab (beta amyloid EXPEDITION3; primary endpoint Eli Lilly & Co. mild Alzheimer’s disease targeted MAb) not met. ischemic stroke (post stroke MILESTONE; efficacy not sufficient Acorda Therapeutics Inc. Ampyra (dalfampridine) walking difficulties) in this additional indication. Qapzola (apaziquone) intervesical Enrolment halted, a new smaller Spectrum Pharmaceuticals Inc. bladder cancer instillation study to start. Phase III Results Published Xtampa ER (oxycodone) tamper Online Nov. 10 in the journal, Collegium Pharmaceutical Inc. chronic pain resistant Drugs. Phase III Completed prevention of recurrent venous EINSTEIN CHOICE; Johnson & Johnson/Bayer AG Xarelto (rivaroxaban) thromboembolism Evaluating a reduced dose. Phase III Interim/Top-line Results Met primary and secondary eosinophilic granulomatosis with GlaxoSmithKline PLC Nucala (mepolizumab) endpoints, filings for the new polyangiitis indication next year. Well tolerated in children, Omidria (phenylephrine and Omeros Corp. ocular inflammation in an FDA-required post-marketing ketorolac) inj study. AcelRx Pharmaceuticals Inc. ARX-04 (sublingual sufentanil) moderate to severe pain Effective and well tolerated. Phase III Initiated DIVERSITY; triggers $50m Gilead Sciences Inc./lGalapagos NV filgotinib Crohn’s disease milestone for Galapagos. Astellas Pharma Inc. gilteritinib acute myelogenous leukemia As maintenance therapy. CheckMate743; with iplimumab Bristol-Myers Squibb Co. Opdivo (nivolumab) mesothelioma as first line therapy. non-squamous non-small cell lung Innovent Biologics Inc. IBI305 (biosimilar ) In China. cancer (NSCLC) SymBio Pharmaceuticals Ltd./The SyB P-1501 (Ionsys; transdermal pain In Japan. Medicines Co. fentanyl) Phase III Announced EAGLE, KESTREL; partial head and neck squamous cell AstraZeneca PLC durvalumab clinical hold lifted by FDA, carcinoma enrolment resumes. Source: Biomedtracker

22 | Scrip intelligence | 2 December 2016 © Informa UK Ltd 2016 APPOINTMENTS

Gamida Cell, a company focused on Wellcome. Most recently, Millls was ex- John Wayne Cancer Institute and Gene cancer and orphan genetic diseases, ecutive vice president, development and Therapy Laboratories. has appointed Julian Adams chair of its chief medical officer at Acadia. He cur- board of directors. Adams brings over 30 rently serves as a visiting professor at the Industry veteran David Rodman has joined years’ experience to the company and is Centre for Age Related Diseases, Institute the biopharma company miRagen Thera- president of research and development of Psychiatry, Psychology and Neurosci- peutics Inc. as executive vice president at Infinity Pharmaceuticals. Before Infinity, ence, King’s College London. of research and development. With more Adams was the senior vice president of than 25 years of experience, Rodman is an drug discovery and development at Mil- Myovant Sciences Ltd., a company fo- elected member of the American Society lennium Pharmaceuticals. cused on women’s health disease and for Clinical Investigation and was named a other endocrine-related disorders, has ap- fellow and established investigator of the Paul Hayes, group finance director of The pointed Terrie Curran to its board of direc- American Heart Association. Before miRa- Vitec Group Plc., has been appointed Con- tors as an independent director. Curran is gen, Rodman was vice president of clinical sort Medical Plc.’s group chief financial president of worldwide markets for the in- development at Vertex Pharmaceuticals officer (CFO). Hayes will succeed Richard flammation and immunology portfolio at Inc. and before this, he was executive direc- Cotton and join the company as CFO and Celgene Corporation. Previously, she was tor, respiratory translational medicine at the an executive director on the board in May, senior vice president and general manager Novartis Institutes for biomedical research. 2017. Previously, Hayes was group financial of women’s health and endocrinology at controller at Signet Jewellers Ltd. (formerly Merck & Co. Inc. Richard Malamut has joined CNS fo- Signet Group Plc) and before this, he held a cused, Avanir Pharmaceuticals Inc., as senior director role at RHM Plc. Paragon Bioservices, a manufacturer senior vice president, research and de- of , vaccines and viral velopment, and chief medical officer. Be- Addex Therapeutics, a company fo- vectors, has appointed John Conner sen- fore Avanir, Malamut was the senior vice cused on neurological disorders, has ior vice president of GMP manufacturing. president of global clinical development appointed Roger G. Mills to the newly Conner is a biotech operation executive, at Teva Pharmaceutical Industries Ltd. Pre- created position of chief medical officer. who most recently was senior vice presi- viously, he held roles working in pain, psy- Mills has gained over 25 years of biop- dent of Cytovance Biologics. Before this, chiatry and neurodegenerative diseases harma experience at various companies he was associate director, technical sup- at Bristol-Myers Squibb and AstraZeneca, including Acadia Pharmaceuticals, Pfizer, port of CancerVax Corporation and he as well as consulting for Avanir, Schwarz Gilead Sciences, Abbott Laboratories and also held management positions at the Bioscience and Shire Pharmaceuticals.

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scrip.pharmamedtechbi.com 2 December 2016 | Scrip intelligence | 23 Pharma intelligence

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