GSK's Big Reveal

3 August 2018 No. 3916

Scripscrip.pharmaintelligence.informa.com Pharma intelligence | informa at Genentech Inc. (Also see “GSK Bags Bar- ron As R&D Boss As Vallance Joins UK Govern- ment” - Scrip, 8 Nov, 2017.) With a budding early immuno-oncology pipeline, Walmsley clearly has her eye on establishing GSK as an important player in the space. The event in London was Barron’s first opportunity to present his R&D strategy and coincided with the company’s second quarter sales and earnings release. “This is an ideal time to be thinking about reinventing R&D, because we are doing well. We are growing,” Barron said.

PILLARS FOR INNOVATION Investors have been eager to hear from the R&D legend, but with few near-term catalysts or big changes to the late-stage pipeline, they may be underwhelmed by the update. Barron, meanwhile, is focused on deliver- GSK’s Big Reveal: ing scientific and cultural changes that will yield breakthroughs over the long-term. An R&D Overhaul Poised To Yield He talked about a time horizon of 2021 to 2026, and he talked more high-level, rather than specifics, about incentives needed to Long-Term Cultural Change drive innovation, the technologies that can JESSICA MERRILL [email protected] help improve clinical trial success, and cultural changes. He said science, technology laxoSmithKline PLC CEO Emma pharma R&D – is that investors will need to and culture are the three pillars needed to Walmsley may have spelled out the be patient to see GSK deliver on its promise drive innovation, and all three must be in Gbig pharma’s R&D turnaround plan of innovation. GSK does not have a wealth place to be successful. best while introducing the company’s new of late-stage drugs in the pipeline and GSK’s focus will be on developing Chief Scientific Officer and President-R&D despite delivering advancements in core breakthrough medicines, rather than Hal Barron to the stage during an investor areas like respiratory disease and HIV re- incrementally beneficial ones. As he ex- event July 25. cently, the company has fallen well behind plained it, “ones that are going to be very “His job is to transform our pipeline and rivals in important areas like oncology and transformative, ones that don’t stop after reignite GSK’s reputation as an innovator,” immunology, where it’s clear Barron plans the first indication, ones that have a broad she said. “That is going to take some time, to course correct. lifecycle and ones that when they help, but I can assure you he is already having Walmsley recruited Barron to GSK late they help in a fundamental way.” He said an impact.” last year to reinvent the company’s phar- the company would be more agonistic to Indeed, the big takeaway from the meet- maceutical R&D, with an eye toward build- therapy area and go where the science ing – the first in which Barron addressed ing in oncology. It was a big coup given his leads, underpinned by genetics. investors at length about his plans for legacy in cancer as the former head of R&D CONTINUED ON PAGE 7

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Abbvie’s Orilissa Approved Leadership Perspective Pricing Debate Pricing strategy aims to enable Silence Therapeutics exec explains why Pfizer’s CEO is notably optimistic access to endometriosis drug this is a key moment for the company about potential US policy changes (p15) and the RNAi space (p17) (p21) IN THIS ISSUE

from the editor [email protected]

The presentation of 18-month Phase II data for Biogen/ fect); the companies’ adaptive trial design including a new Eisai’s anti-amyloid-beta protofibril antibody BAN2401 Eisai-designed composite scale for measuring clinical out- generated the biggest buzz at the Alzheimer’s Association comes in Alzheimer’s; lack of clarity over the link between International Conference last week (see p9). changing levels of amyloid plaque in the brain and clini- But enthusiasm for the results was more a reflection of cal outcomes; and, more fundamentally, the fact that the the context of repeated confusion and failure in the field trial has yet to be published and peer reviewed. of Alzheimer’s R&D (and indeed the previous lackluster Meanwhile, second-quarter results season has been 12-month data in this very trial), than a ringing endorse- marked by changes at the top, with Gilead announcing ment of this particular drug candidate. And Biogen reeled the impending departure of CEO John Milligan and chair back from pre-presentation hints that the drug might be John Martin (p8), new R&D head Hal Barron dominating headed for a speedy FDA review on the basis of the Phase GSK’s Q2 call (p1), Amgen announcing the retirement of II results as skeptics raised their voices. Various factors cry R&D chief Sean Harper and commercial head Anthony out for caution and further analysis – including the nu- Hooper and Bristol-Myers Squibb revealing that commer- merical imbalance of carriers of the APOE4 genetic risk cial head Murdo Gordon is to replace Hooper at Amgen factor for Alzheimer’s (far higher in the placebo group (see Scrip online for these latter two articles.) than in the highest treatment dose that showed most ef-

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exclusive online content inside: COVER / GSK’s Big Reveal: An R&D Overhaul Poised To Yield Hemlibra Effect Is Muted At Shire - For Now Long-Term Cultural Change https://bit.ly/2v2l13q Hemlibra has taken a bite out of Shire’s FEIBA sales, but 4 AstraZeneca’s Oncology Business Delivers, Edging Toward compensatory boosts in other areas of the business helped CV/Metabolic As Top Contributor CEO Ørnskov keep the business ticking over while awaiting the finalization of Takeda’s takeover. 5 First-Line Chemo Combo Data Help Merck’s Keytruda Power Past Opdivo Buoyant Biotech Funding Environment Directly 8 Milligan’s Retirement Means New CEO For New Gilead Impacts CRO Q2s https://bit.ly/2vn9Lhq 9 Biogen, Eisai Report BAN2401 Seemingly Positive In The contract services industry is reaping the rewards of a Alzheimer’s; Others Skeptical resilient biotech funding environment, re-accelerating growth in the sector. 12 UCB Looks To Its Next Wave Of Innovative Products

First-Line Chemo Combo Data Help Merck’s Keytruda 13 Chugai Explores New Tech In Strategic Push For Innovation Power Past Opdivo https://bit.ly/2ApgX2f 14 AbbVie HCV Revenue Surprises Again, But Falloff Is Coming Keytruda sales are soaring on first-line lung cancer use, but with many new filings and approvals, Merck tells its second-quarter 15 AbbVie Prices Oral Endometriosis Drug Orilissa In Value earnings call it’s just the beginning. Range, Focusing On Access

Bristol Touts Opdivo’s Stability – And Diversity – 17 Interview: Silence Therapeutics’ Chair On Why Keeping In Strong Q2 Quiet Has Done The Biotech No Favors https://bit.ly/2v6YfXr The recently launched Opdivo/Yervoy combination already has 20 Innovation Critical As Japan Pharma Faces Continued a leading position in first-line kidney cancer in the US – with a Pricing Pressures 30% share of new patients – but has been rejected in Europe. 21 Pfizer’s CEO Is Bullish On Rebate Changes That Could Sanofi Top UK Exec Plans For Hard Brexit, Power New Launches Blasts ‘Poor Access’ To New Drugs https://bit.ly/2KikHCC 22 Pipeline Watch The managing director for Sanofi in the UK says clinical trials there will become less likely in future if access to innovative 23 Lysosomal Storage Disorders: Azafaros Takes Aim drugs doesn’t improve, causing comparative standards of care At Small Molecules to deteriorate. 23 Appointments Harper, Hooper Exit As Amgen Revenues Rise https://bit.ly/2O0qAGM Amgen revealed better-than-expected second quarter earnings July 26 and said its R&D and commercial heads Sean Harper and Anthony Hooper are retiring. Harper, who’s getting involved with start-ups, is being replaced from within by David Reese; Bristol’s Murdo Gordon will take over for Hooper. @PharmaScrip /scripintelligence

/scripintelligence /scripintelligence

scrip.pharmaintelligence.informa.com 3 August 2018 | Scrip | 3 Q2 UPDATE: ONCOLOGY

AstraZeneca’s Oncology Business Delivers, Edging Toward CV/Metabolic As Top Contributor JESSICA MERRILL [email protected]

straZeneca PLC may soon be most recognized as an oncology compa- Any. The UK pharma’s oncology port- “There is not just one product folio is its dominant growth driver and will soon edge out the other two business units driving our growth. It is really – cardiovascular/metabolic and respiratory – in terms of revenue contribution. an engine that is powered by Powered by a notable 44% revenue growth in the second quarter, oncology multiple products.” sales outpaced respiratory sales and nar- CEO Pascal Soriot rowed the gap significantly with CV/metabolic. Oncology generated $1.43bn in the quarter, representing 29% of AstraZeneca’s revenues – a significant jump from 2017, growth,” he said. “It is really an engine that is parza with Merck & Co. Inc. under a 2017 when oncology accounted for 20% of rev- powered by multiple products.” collaboration. Most of sales came from use enues. Sales of respiratory products grew Investors appear to be warming to As- in ovarian cancer, Fredrickson said, though 12% to $1.23bn in the quarter, representing traZeneca’s story. The company’s stock hit Lynparza was recently approved in the 24% of sales. Under pressure from generic a 52-week high of $38.73 on the positive US for treatment of patients with BRCA- competition to Crestor (rosuvastatin), CV/ earnings news. mutated breast cancer. Lynparza has so far metabolic sales declined 9% to $1.62bn, or Deutsche Bank analyst Richard Parkes said maintained commercial leadership in the 32% of the company’s sales. the quarter was encouraging. “Overall solid PARP space. results and good performance of the key The other drug investors are watching SORIOT’S LONG GAME drivers should reassure over the return to closely is the PD-L1 inhibitor Imfinizi, which Building AstraZeneca into a big oncology growth. AstraZeneca is our top EU pharma remains well behind the PD-1 blockbust- player has been CEO Pascal Soriot’s ambi- pick,” he said. ers like Merck’s Keytruda (pembrolizumab) tion, though the company still has its work BMO Capital Markets analyst Alex Arfaei and Bristol-Myers Squibb Co.’s Opdivo cut out for it when it comes to turning new said, “The strong ramp-up of launch prod- (nivolumab). As the fifth to market PD-1/ cancer drugs like the PARP inhibitor Lynpar- ucts and effective management of mature L1 inhibitor, Imfinzi generated $122m in the za (olaparib), the PD-L1 blocker Imfinzi (dur- products should allow AstraZeneca to meet quarter, but it has a bit of a niche to focus valumab) and the BTK inhibitor Calquence its reaffirmed 2018 guidance.” on. Imfinzi is the only PD-1/L1 inhibitor ap- (acalabrutinib) into blockbusters. proved for Stage III NSCLC in patients whose Nonetheless, Soriot took a moment to CANCER SALES ADD UP disease has not progressed on concurrent applaud AstraZeneca’s turnaround initiative AstraZeneca Exec VP and Global Head- chemotherapy, though three other check- during the company’s second quarter sales Oncology Business Unit Dave Frederickson point inhibitors are approved for Stage IV and earnings call July 26. talked to Scrip in June about the compa- NSCLC that has spread and which is more “The strategy we have been pursuing ny’s oncology growth drivers and expan- frequently diagnosed. the last four or five years is starting to bear sion plans. (Also see “AstraZeneca Looks To Outside of oncology, AstraZeneca is hop- fruit,” he said. “There is still a lot of hard work Deliver On Its Promises In Oncology” - Scrip, ing the IL-5 inhibitor Fasenra (benralizumab) ahead of us, but the new products are start- 26 Jun, 2018.) for eosinophilic asthma will be a big new re- ing to have an impact on our plan.” AstraZeneca’s top-selling cancer drug is spiratory growth driver. The drug generated The company’s consolidated revenues the third-generation EGFR inhibitor Tagris- $65m in the first quarter, after launching in grew 2% to $5.16bn in the second quarter, so (osimertinib), which generated $422m late 2017. Severe asthma is a small subset of and Soriot said he expected to see the mo- in the second quarter, reflecting growth the broader asthma market, however, and mentum build in the second half of the year of 82%, driven by use in second-line non- GlaxoSmithKline PLC’s Nucala (reslizum- and that AstraZeneca is on track to reach its small lung cancer in patients with T790M- ab) has a head start. (Also see “Severe Asthma goal of returning to product sales growth in mutations and a new indication that Market Snapshot: A Competitive Therapy 2018. Core EPS declined 21%, however, but came in April in first-line EGFR-mutated Area That Will Test Payers’ Influence” - Scrip, both sales and earnings were ahead of ana- lung cancer. 23 May, 2018.) Nucala generated £141m in lyst consensus estimates. Lynparza generated $150m, though As- the second quarter. “There is not just one product driving our traZeneca shares profits on sales of Lyn- Published online 26 July 2018

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First-Line Chemo Combo Data Help Merck’s Keytruda Power Past Opdivo EMILY HAYES [email protected]

erck & Co. Inc. says that its Key- truda is now capturing two-thirds Mof new first and second-line lung cancer patients in the US – a 20% increase in share since April – helping the PD-1 inhibitor power past Bristol-Myers Squibb Co.’s competing Opdivo in the second quarter. Merck reported second quarter sales on July 27, including $1.67bn in Keytruda (pembrolizumab) sales, whereas Bristol’s competing PD-1 inhibitor Opdivo (nivolumab) had sales of $1.63bn in the same period. In the US, about 60% to 65% of Keytruda sales derive from lung cancer, 15% from melanoma, 5% in bladder, 5% in microsat- ellite instability-high cancer, and the rest from all other indications, Adam Schechter, in squamous first-line NSCLC at the Ameri- Merck’s Schechter told the earnings call president of global human health at Mer- can Society of Clinical Oncology (ASCO) that the Keytruda/chemo combo has been ck, said during a same-day earnings call. meeting in June. (Also see “Roche, Bristol On well received and that excluding patients Schechter didn’t provide specific numbers The Defensive After Merck’s Lung Cancer Wins with EGFR and ALK mutations, Keytruda ex-US, but said most of the revenue in Eu- At ASCO” - Scrip, 6 Jun, 2018.) A filing for that is getting roughly two-thirds of new lung rope and Japan is coming from lung can- use is under review with the FDA, with an cancer patients. This includes Keytruda as cer, with melanoma as the clear second- Oct. 30 action date. (Also see “Merck’s Stellar a monotherapy and in combination with largest contributor. Keytruda Squamous Lung Cancer Data Re- chemotherapy in first- and second-line in- Keytruda was the first PD-1 inhibitor to fute Naysayers” - Scrip, 23 May, 2018.) dications, Merck clarified after the call. The step on the global stage, winning its first US Lung cancer specialists at ASCO reaf- two-thirds share of new patients represents FDA approval in relapsed metastatic mela- firmed the importance of the gold standard about a 20-point increase in share versus noma in September 2014. Bristol’s Opdivo of overall survival, and aside from Merck, what the company saw prior to the AACR was approved in December of that year for none of the other PD-1/L1 sponsors have meeting, Schechter said, adding that he ex- the same indication. Keytruda had a slight demonstrated a benefit for OS in first-line pects continued substantial adoption in this lead in sales at first, but by the third quar- lung cancer to date. indication throughout the rest of the year. ter the drugs were on the market Opdivo had caught up, and went on to win the first Sales Of PD-1/L1 Inhibitors non-small cell lung cancer (NSCLC) approval 1800 and has by far dominated the PD-1/L1 landscape since (see graph). 1600

Keytruda, however, has been catching up. 1400 (Also see “ Merck’s Keytruda Keeps Nipping At 1200 Opdivo’s Heels” - Scrip, 1 May, 2018.) Data from the KEYNOTE-189 study showing that Key- 1000

truda with chemo has a survival benefit over ) 800 m $ chemo alone in first-line non-squamous ( NSCLC regardless of PD-L1 expression were 600 presented at the American Association for 400 Cancer Research (AACR) annual meeting in 200 April with great fanfare. (Also see “Merck’s Key- truda Enjoys Clean Sweep In Lung Cancer, At 0 Bristol’s Expense” - Scrip, 17 Apr, 2018.) Merck -200 went on to present positive overall survival 4Q14 1Q15 2Q15 3Q15 4Q15 1Q16 2Q16 3Q16 4Q16 1Q17 2Q17 3Q17 4Q17 1Q18 2Q18 data for the Keytruda-chemo combination Bristol's Opdivo Merck's Keytruda Roche's Tecentriq AstraZeneca's Imﬁnzi

scrip.pharmaintelligence.informa.com 3 August 2018 | Scrip | 5 Q2 UPDATE: ONCOLOGY

Keytruda is approved as a monotherapy for first-line lung cancer MERCK’S Q2 KEY PRODUCT REVENUES with PD-L1 expression over 50% and in combination with chemo for Drug Actual sales vs. Consensus all comers in first-line NSCLC. No other PD-1/L1 inhibitors are yet ap- Expectation proved for first-line metastatic NSCLC. Keytruda is also approved as a monotherapy in second-line metastatic NSCLC. Keytruda (pembrolizumab) $1.67bn (Cons: $1.64bn) During its earnings call on July 26, Bristol said that it expects IO Zepatier (elbasvir/grazoprevir) $113m (Cons: $117m) penetration in first-line lung cancer in the US will accelerate in 2018, Januvia/Janumet (sitagliptin) $1.53bn (ConsL $1.5bn%) reaching 70% to 75% by the end of the year, and that there will still Zetia (ezetimibe) $381m (Cons: $247m) be 25% to 30% on chemotherapy and eligible for a PD-L1 inhibitor in second-line NSCLC. Vytorin (simvastatin) $155m (Cons: $158m) In addition to overtaking Opdivo, Keytruda is overshadowing other Remicade (infliximab) $157m (Cons: $153m) approved PD-1/L1 inhibitors that came to the market later. Roche Gardasil (human papillomavirus $603m (Cons: $603) reported CHF320m ($321m) in sales for the PD-L1 inhibitor Tecentriq 9-valent vaccine, recombinant) (atezolizumab) for the first half of this year. AstraZeneca PLC reported Isentress (raltegravir) $305m (Cons: $261m) $122m for Imfinzi (durvalumab), also a PD-L1 inhibitor, in the second quarter. Pfizer Inc. and partner Merck KGAA have not reported sec- Nasonex (mometasone furorate) $81m (Cons: $71m) ond quarter earnings yet for their PD-L1 inhibitor Bavencio (avelumab), Singulair (Montelukast sodium) $185m ( Cons: $178m) first approved for the rare skin cancer Merkel cell carcinoma in March Cozaar/Hyzaar $125m (Cons: $116m) 2017 and soon after also cleared for bladder cancer, so it is not clear (losartan potassium) whether it has gotten off the ground yet. (Also see “Pfizer’s Avelumab Zostavax (Zoster vaccine) $44m (Cons: $71m) Makes Its Debut, In Rare Form Of Skin Cancer” - Scrip, 23 Mar, 2017.) Cubicin (daptomycin) $94m (Cons: $1.06bn) Merck was asked during its call about its strategy in pursuing approval for Keytruda in Stage III lung cancer, in light of AstraZeneca’s Animal Health $1.09bn (Cons: $1.06bn) success as the first PD-1/L1 inhibitor cleared in that segment. (Also Source: I. Hilliker, Jefferies see “AstraZeneca’s Imfinzi Scores First Early Lung Cancer Approval” - , 16 Feb, 2018.) Merck Research Laboratories President Roger Perlmut- survival compared with the cetuximab and the chemo backbone. ter noted that Merck has some data for Keytruda in non-metastatic However, it has not yet demonstrated a significant improvement for lung cancer and the company expects that there “will be additional progression-free survival, the co-primary endpoint, but the study data that will come forward in the months and years ahead that will continues. Merck said the results will be submitted to regulatory au- permit a specific indication,” but he declined to comment on regula- thorities worldwide and presented at n upcoming medical meeting. tory strategy. Keytruda received accelerated approval for treatment of recurrent or metastatic HNSCC with disease progression on or after platinum- KEYTRUDA FOUNDATION FOR containing chemotherapy in August 2016. However, in July 2017, MULTI INDICATIONS Merck announced that the drug failed to show a survival benefit over Like Bristol in its second-quarter earnings report, Merck stressed Key- investigator’s choice of chemotherapy in the KEYNOTE-040 study of truda’s breadth, which it noted is now FDA approved in 12 indica- recurrent or metastatic disease. (Also see “Merck’s Keytruda Gets Ben- tions across eight tumor types and similarly approved in multiple efit Of Doubt, Despite Failing in Head & Neck” - Scrip, 24 Jul, 2017.) indications across tumor types in countries around the world. Merck Perlmutter said that numerous approvals and filings are “really just announced approval on July 26 for Keytruda in second-line meta- the beginning of what will be a very robust period of evaluation for static melanoma in China. Bristol’s Opdivo was approved for second- Keytruda in both combination therapy and monotherapy settings.” line NSCLC with no EGFR or ALK mutations in China in June. (Also More than 100 abstracts related to Keytruda were presented at the see “Opdivo Approval Opens China I-O Doors But Pricing Key” - Scrip, ASCO meeting, the exec noted. “Many of these represented progress 18 Jun, 2018.) reports that we expect will yield data supportive of registration in the Supplemental biologic license applications (sBLAs) are now not too distant future, including for the treatment of small-cell lung under FDA review for Keytruda in advanced hepatocellular carci- cancer and renal cell carcinoma,” he said. noma and adjuvant melanoma, with user fee dates of Nov. 9 and And in the future, the company expects data supporting use in Feb. 16, respectively. breast and prostate cancers, he said. Pathological complete response Positive Phase II data were reported for small cell lung cancer in the results for Keytruda as a neoadjuvant therapy in I-SPY trials of early KEYNOTE-158 study at this year’s ASCO meeting. breast cancer were very impressive, he pointed out. (Also see “Merck’s The company also reported positive results on July 25 from an in- Keytruda Offers Hope And Risk In Early Breast Cancer” - Scrip, 6 Jun, terim analysis for Keytruda as a monotherapy in patients with PD-L1 2017.) Keytruda is being studied for neoadjuvant and adjuvant use expression in the pivotal Phase III KEYNOTE-048 study of first-line or in the Phase III KEYNOTE-522 study of triple-negative breast cancer. metastatic squamous cell carcinoma of the head and neck (SCCHN Perlmutter said that going forward, he is very enthusiastic about or HNSCC). The study compared Keytruda monotherapy or Keytruda where that could lead. with platinum-based chemotherapy and the 5-FU regimen against Schechter added that the company is excited to get into this mar- Eli Lilly & Co.’s Erbitux (cetuximab) with the same backbone chemo ket and already is calling on those physicians through its partnership regimen. Keytruda monotherapy was associated with longer overall with AstraZeneca on the PARP inhibitor Lynparza (olaparib), which

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recently was approved for BRCA-mutated metastatic breast cancer. $71m, and the cholesterol drug Zetia (ezetimibe) with $226m ver- (Also see “Lynparza Gets First Mover Advantage In BRCA-Positive Breast sus consensus of $247m, Jefferies analyst Ian Hilliker said in a July Cancer” - Scrip, 15 Jan, 2018.) 27 note (see table ). “So we are ready to launch with Keytruda as soon as the data Still, concerns remain about whether Merck is too dependent on would be available and the indication available,” Schechter said. Keytruda. During the call, Credit Suisse’s Divan asked what is holding the company back from more aggressive deal-making and business A GOOD QUARTER FOR MERCK development. Keytruda’s success came with the backdrop of a good quarter. CEO Kenneth Frazier said Merck is “actively looking for the best op- Overall the company reported worldwide sales of $10.5bn in the portunities across all kinds of structures, including acquisitions and second quarter, up 1% year-over-year and beating consensus of partnerships, collaborations and licensing.” Over the past few years, $10.3bn. Merck narrowed its full-year revenue range to between some deals didn’t pan out, either because the target was not a will- $42bn and $42.8bn. ing seller or because competition for that asset made the price un- “Expectations were high coming into the quarter, but we think tenable based on Merck’s assumptions, the exec said. these results should still be well received and allow for continued There also generally has been a dearth of M&A across the indus- confidence in the story and upside in the stock as we move into try recently as significant investment has flowed into small biotechs, 2H18, when we should see additional upside as the Keytruda rollout reducing their need to sell right now in order to fund development into first-line lung cancer continues,” Credit Suisse analyst Vamil Divan programs. said in a July 27 note. “But I want to assure you that augmenting our pipeline through Sales of Keytruda and most of the company’s other key drugs business development, nevertheless, remains an important priority, were above consensus, helping offset the few misses for Zostavax and so we’ll continue to scour the landscape carefully,” Frazier said. (Zoster vaccine), which had sales of $44m versus consensus of Published online 29 July 2018

CONTINUED FROM COVER higher than the investment in 2016. has five targets it is exploring under the pro- “Sometimes we may have taken mol- The company has 40 new molecular en- gram with Adaptimmune. The company’s ecules and pushed them towards a disease tities in the clinical pipeline, with late-stage early oncology portfolio also includes an because of where they were therapeutical- opportunities including two treatments ICOS agonist, a OXO40 inhibitor, a poten- ly discovered,” he explained. “Had we had for HIV, dolutegravir/lamivudine and car- tial first-in-class PRMT5 inhibitor and a BET a disease-agnostic approach, even further boteravir/ripilvirine, and the company’s inhibitor. complimented by human genetics, that most advanced oncology treatment, a po- As Barron put it, “Any of the cancer things might not have been the first indication.” tential first-in-class, anti-BCMA antibody- can go from not-so-wow to wow pretty Barron did come to the meeting with drug conjugate in pivotal trials for multiple quickly.” one tangible piece of news for investors, myeloma. The R&D overview overshadowed an a collaboration with the genetics leader Certainly, Barron made it clear he encouraging second quarter financial per- 23andMe Inc. focused on using genetic doesn’t believe more is better. He quoted formance, in which consolidated revenue data to develop new medicines. GSK made former Apple CEO Steve Jobs as saying, increased 4% to £7.3bn, pharma sales in- a $300m equity investment in exchange “Innovation is saying no to thousands of creased 1% to £4.2bn and vaccines in- for a four-year collaboration to work with things.” Barron added, “This is the kind of creased 16% to £1.3bn. Vaccine sales bene- 23andme exclusively for drug target dis- culture that I would love to have at GSK fited from the launch of the shingles vaccine covery programs. R&D.” Programs should be swiftly killed af- Shingrix, which GSK is now expected to de- ter Phase II if they don’t show an effect, he liver sales of £600m-£650m in 2018, its first RESTRUCTURING TO SUPPORT said, but also noted Phase II studies need full year on the market. MORE R&D INVESTMENT to be appropriately powered to yield a The strong launch of Shingrix and a delay GSK also unveiled a strategy for investing strong signal. in the launch of a substitutable generic ver- more in R&D. The company unveiled a new Barron did highlight a few promising sion of GSK’s big asthma drug Advair led the restructuring program focused on improv- programs in addition to BCMA, which has company to raise its financial expectations ing supply chain and reducing administra- shown notable efficacy in heavily pre-treat- to the year. The company expects adjusted tive costs. The program is expected to yield ed multiple myeloma patients and has been EPS to grow 7%-10% in 2018 as long as a annual savings of around £400m by 2021, prioritized for development. He also talked substitutable generic continues to be de- savings that will be redirected to R&D in- about potential in cell therapy through layed. If one launches by Oct. 1, that growth vestment and commercial support for new GSK’s collaboration with Adaptimmune would be more like 4%-7%. Mylan NV re- launches. The program is expected to cost Therapeutics PLC and noted, “We think we ceived a complete response letter from the £1.7bn until 2021. can do this better than maybe anyone.” FDA for its generic version of Advair in June. Walmsley declined to say by how much He pointed to GSK ‘794, a TCR T-cell ther- (Also see “Branded Advair Breathes Another GSK would increase R&D investment direct- apy targeting the NY-ESO peptide that is in Day; Mylan Says A CRL Is On The Way For A ly, however. The company spent £4.48bn development for sarcoma but could have Generic” - Scrip, 13 Jun, 2018.) on R&D, or 14.8% of revenue, in 2017, 19% broader utility in other solid tumors. GSK Published online 25 July 2018

scrip.pharmaintelligence.informa.com 3 August 2018 | Scrip | 7 C-SUITE CHANGE

Milligan’s Retirement Means New CEO For New Gilead JOSEPH HAAS [email protected] MARY JO LAFFLER [email protected]

hile Gilead Sciences Inc. post- are resources to continue investing in the ed solid financials during the pipeline. W second quarter, the surprise an- Milligan will stay in his current role while nouncement that President and CEO John the board conducts a CEO search. Milligan is stepping down at the end of As for the qualities the industry should ex- 2018 shifted focus from the company’s past pect in his successor, Milligan listed areas of performance to its path forward. expertise that he said are not his strengths: Chairman John Martin also announced “I think the next leader should be somebody during Gilead’s July 25 second quarter earn- who brings expertise – scientific, commer- ings investor call that he will step down from cial or other – into new opportunities for his role at Gilead when Milligan’s successor us to grow, for example, people who have takes over. Milligan succeeded Martin in the launched products into new markets such CEO role in early 2016; both have been with as we’re doing [in] NASH or people who re- Gilead since 1990. ally know how to compete in the oncology In that time, the company has grown into John Milligan area where I have less experience,” he said. “I a dominant force in antivirals, both for HIV think we are looking for a new leader who and hepatitis C, and demonstrated excel- believed the company needed a new thera- will bring new ideas, a previous history and lence in building portfolios and pursuing peutic direction to restore growth. (Also see experiences we don’t have, and one who lifecycle management in competitive fields. “Gilead Cites ‘More Sophisticated’ Process As will take the baton from me and move it As the HCV market and HIV portfolio have Pressure For A Major Deal Increases” - Scrip, 20 forward.” matured, there has been significant pressure Mar, 2017.) In a same-day note, Jefferies analyst Mi- for Gilead to diversify. and It’s biggest step Gilead has followed up on the Kite ac- chael Yee questioned whether a “New Gil- in a new direction came with the $11.9bn quisition with similar immuno-oncology ead” is coming. He said the move seemed acquisition last August of Kite Pharma Inc., deals around cell therapy platforms, in- driven by the board of directors “to invigo- just before the approval of its chimeric anti- cluding transactions involving Cell De- rate the company and to bring on fresh gen receptor T-cell (CAR-T) therapy Yescarta sign Labs Inc., Sangamo Therapeutics leadership to turn Gilead from pharma-like (axicabtagene ciloleucel). (Also see “What’s Inc. and Gadeta BV. to more biotech-like.” Gilead Getting From Kite For Nearly $12bn?” The transition likely brings short-term un- Also see “Gilead Acquisition Of Cell - Scrip, 29 Aug, 2017.) • certainty for investors, especially until the But now, delivering on that strategic shift Design: The Next Logical Step” - Scrip, 8 new CEO is named, Yee added. “We think will be the new CEO’s challenge. Dec, 2017. the good news is a ‘new’ future will hope- Gilead has had a meteoric rise on the fully lead to more pipeline, more bold steps, • Also see “Gilead Partners With Sangamo backs of the hepatitis C direct-acting anti- more aggressive [business development] virals, with total sales for that business esti- For Gene Editing As It Builds Up Kite’s Cell and a chance for [profit and earnings] ex- mated to surpass $111bn. Milligan took over Therapy Platform” - Scrip, 22 Feb, 2018. pansion and stock appreciation,” he wrote. from Martin in late January 2016, around the Gilead gave a promising pipeline update • Also see “Deal Watch: Gilead Contin- time that Merck’s competing HCV combina- for one of the bolder moves it has made, ues To Add To IO Armamentarium In tion Zepatier (elbasvir/grazoprevir) came with the NASH candidate selonsertib. The to market at a deep discount compared to Collaboration With Gadeta” - Scrip, 20 company expects Phase III data in the first Gilead’s dominant HCV franchise headed by Jul, 2018. half of 2019 and possible regulatory filings Harvoni (sofosbuvir/ledipasvir) and Sovaldi “Now that the company is on solid foot- in mid-2019, which means Gilead could (sofosbuvir). ing for the future, the board and I have claim first place in the race to bring a NASH The decline in Gilead’s HCV fortunes agreed it is a good time to turn the reigns drug to market. continued through 2016, leading to a Feb- over to a new leader,” Milligan told the July Quarterly sales were largely as expected, ruary 2017 decision in which Gilead split 25 earnings call. He added that he thinks with Yescarta continuing its growth trajec- sales guidance for HCV from the rest of its Gilead will move forward from a position tory, solid growth for the HIV franchise and portfolio and offered clear projections of a of “tremendous strength” with a growing a plateau in the hepatitis C business, which sustained downturn for the HCV franchise. HIV franchise and an “industry-leading cell has been in decline. (Also see “As Gilead Seeks Milligan oversaw a rumor-heavy period therapy program,” plus its late-stage pipeline New CEO, Second Quarter Shows Stability” - where Gilead was the center of consistent assets in inflammation and non-alcoholic Scrip, 25 Jul, 2018.) M&A speculation as analysts and investors steatohepatitis (NASH). He noted there also Published online 25 July 2018

8 | Scrip | 3 August 2018 © Informa UK Ltd 2018 RESEARCH & DEVELOPMENT

Biogen, Eisai Report BAN2401 Seemingly Positive In Alzheimer’s; Others Skeptical MANDY JACKSON [email protected]

iogen Inc. and Eisai Co. Ltd. reported that the highest dose of BAN2401 significantly cleared amyloid from the brain and Bimproved cognition in patients with mild Alzheimer’s disease, but questions remain about the exclusion of certain individuals from the high dose arm and whether that confounded the results from the large Phase II trial. Reflecting some investor uncertainties over the data, Biogen’s stock declined by more than 11% in after-hours trading after Eisai Chief Medical Officer Lynn Kramer reported the much-anticipated detailed results at 18 months from the 856-patient Study 201, presented on July 25 as a late-breaking oral presentation at the Alzheim- er’s Association International Conference (AAIC) in Chicago. In Tokyo, Eisai’s share price also was strongly down in mid-after- noon trading, falling by a similar percentage as investors digested the new data. Results for the amyloid-beta protofibril-targeting antibody were largely in line with expectations following the top-line data re- leased recently, which generated huge interest in the Alzheimer’s community and around the validity of the amyloid hypotheses, which is that accumulations of the protein contribute to the development of the disease. One exception was the new disclosure that patients who carried Analysts seemed to agree that the the APOE4 gene – associated with early onset of Alzheimer’s disease and rapid decline – were excluded from the high-dose BAN2401 APOE4 carrier versus non-carrier group at the request of ex-US regulators. analysis is most important and that no

DEBATE OVER APOE4 ROLE conclusions can be drawn about the APOE4 carriers tend to experience amyloid-related imaging abnor- BAN2401 data until that is done. malities (ARIA) at higher rates than non-carriers, which was the case in the BAN2401 study. However, there was some debate during Biogen’s same-day call with analysts and investors about whether APOE4 carriers have a worse response to treatment. with mild cognitive impairment. If so, the higher dose of BAN2401 would perform better than pla- Analysts seemed to agree that the APOE4 carrier versus non-carri- cebo and the lower doses, because that arm of the trial had fewer er analysis is most important and that no conclusions can be drawn APOE4 carriers. about the BAN2401 data until that is done. Biogen Vice President of Clinical Development Samantha Budd Evercore ISI analyst Umer Raffat looked at other studies to see if Haeberlein argued during the company’s call that APOE4 status has APOE4 status impacted drug efficacy and had mixed findings, but an impact on the age of Alzheimer’s disease onset, but not on the he said the BAN2401 effect on cognition may be large enough efficacy of treatment. that even with APOE4 patients in the mix the results could still Haeberlein noted that amyloid was cleared from patients’ brains be significant. in a dose-dependent manner, according to PET scans, which would lead her to believe that APOE4 status did not play a role in BAN2401’s AMYLOID CLEARING’S LINK TO COGNITIVE effect on cognitive decline. BENEFITS DEPENDS ON ANALYSIS Biogen Executive Vice President and Chief Medical Officer Al- Biogen and Eisai reported earlier in July in the top-line results that fred Sandrock added that the APOE4 carrier versus non-carrier BAN2401 at its highest dose provided statistically significant reduc- subgroup analysis probably will be the first subgroup analysis that tions in amyloid plaques and slowed the rate of cognitive decline Biogen and Eisai will conduct, and those data would be shared as in the large Phase II trial, which enrolled patients with mild cogni- soon as possible. tive impairment (MCI) due to Alzheimer’s disease or mild Alzheimer’s The second subgroup analysis, he said later in the call, probably with confirmed amyloid pathology in the brain. will look at prodromal (pre-symptomatic) patients versus those BAN2401, which targets amyloid beta protofibrils by selectively

scrip.pharmaintelligence.informa.com 3 August 2018 | Scrip | 9 RESEARCH & DEVELOPMENT

binding to and neutralizing soluble, toxic amyloid beta aggregates, A Mixed Effects Model with Repeated Measures (MMRM) as- was originated by Swedish bioventure BioArctic and acquired glob- sessment showed a mean reduction in amyloid load of 70 units ally by Eisai in late 2007, then brought under the 2014 multi-asset (p<0.0001). PET scans also showed that 81% of patients treated Alzheimer’s drug development partnership with Biogen. with the highest BAN2401 dose converted from amyloid positive to Eisai’s strategic alliance with Biogen in Alzheimer’s dates back to amyloid negative at 18 months, which reached significance with a p 2014. As well as BAN2401 and the beta amyloid-targeting antibody value of <0.0001. aducanumab, this includes the Eisai BACE (beta-site amyloid precur- In addition, an analysis against predefined clinical endpoints at sor protein) inhibitor elenbecestat and a Biogen anti-tau antibody. 18 months confirmed a slowing in cognitive decline from baseline The firms will co-promote any marketed drugs under the alliance based on ADCOMS, which was dose-dependent. At the highest dose in major markets, and for BAN2401 (and elenbecestat), they are this was 30% versus placebo (p=0.034), but a statistically significant equally splitting overall costs including R&D expenses, with Eisai to slowing of decline was seen on ADCOMS as early as six months book sales for both drugs and profits to be shared equally. (p<0.05), and at 12 months (p<0.05). Biogen suggested on July 24, the day before the AAIC presenta- Bayesian analysis of ADCOMS at 12 months gave an estimated tion, that the company and its partner may be able to pursue ac- probability that the highest dose slowed clinical decline more than celerated approval in the US based on the Phase II results, but noted placebo of 98%.

COGNITION EFFECTS MIXED The data presented on July 25 Biogen noted in its call that that, given BAN2401’s mode of action, there is a “complex relationship between plasma exposures and don’t make the possibility of what’s going on in the brain – Cmax is important to achieve.” But in terms of effect on cognition, Biogen and Eisai reported approval ahead of Phase III data dose-dependent effects via two out of three secondary endpoints. The highest BAN2401 dose showed a 30% slowing in clinical de- any clearer given the APOE4-related cline as assessed by ADCOMS compared with placebo at 18 months concerns. (p=0.034), and statistically significant slowing also was observed at six months (p<0.05) and 12 months (p<0.05). Also, the highest BAN2401 dose slowed clinical decline by 47% such a decision depends on future discussions with the FDA. (Also compared to placebo at 18 months, according to the Alzheimer’s see “Enthusiasm Builds For Biogen’s BAN2401 In Alzheimer’s, But SMA Disease Assessment Scale-cognitive subscale (ADAS-Cog; p=0.017). Gene Therapy Hits A Snag” - Scrip, 24 Jul, 2018.) However, the slowing in cognitive decline from baseline as as- The data presented on July 25 don’t make the possibility of ap- sessed by Clinical Dementia Rating Sum of Boxes (CDR-SB) was not proval ahead of Phase III data any clearer given the APOE4-related statistically significant, though the companies said there was a dose- concerns. Some analysts have already said that a further large ran- dependent slowing in cognitive decline from baseline, in excess of domized Phase III study with a pre-specified endpoint appears nec- the pre-specified difference of 25% over the course of the study, and essary, but this has yet to be confirmed by Eisai or Biogen. reaching 26% at 18 months for the highest dose versus placebo (the Patients were treated with 2.5 mg/kg of BAN 2401 every two weeks, decline in the latter being in line with earlier research). 5 mg/kg once-monthly, 5 mg/kg bi-weekly, 10 mg/kg monthly, 10 mg/ Dose-dependent increases in amyloid-beta levels were observed kg bi-weekly or placebo. A Bayesian adaptive randomization trial design in cerebrospinal fluid (p<0.0001 at the highest dose at 18 months), meant that patients could be randomized into treatment arms with a and there was a statistically significant reduction in total tau levels higher likelihood of efficacy after interim assessments of the data. against placebo in both of the 10mg/kg dose regimens (p<0.05). That meant that there were 247 patients in the placebo arm, 52 in the 2.5 mg/kg bi-weekly arm, 51 in the 5 mg/kg monthly arm, 92 ARIA, INFUSION REACTIONS MOST COMMON treated with 5 mg/kg bi-weekly, 253 in the 10 mg/kg monthly arm ADVERSE EVENTS and 161 in the 10 mg/kg bi-weekly arm. Biogen and Eisai said their drug “demonstrated an acceptable toler- The primary endpoint was a Bayesian assessment at 12 months of ability profile through 18 months of study drug administration.” The the likelihood of success in terms of the Alzheimer’s Disease Com- treatment-related adverse event rate was 26.5% for the placebo arm, posite Score (ADCOMS), which was not statistically significant at any 53.4% for the 10 mg/kg monthly treatment arm and 47.2% for the 10 dose. An 80% chance of providing a 25% slowing in ADCOMS was mg/kg bi-weekly treatment arm. needed, but the highest dose of BAN2401 achieved only a 64% likeli- Serious adverse event rates were 17.6% for the placebo arm, hood of meeting the 25% threshold. 12.3% for the 10 mg/kg monthly arm and 15.5% for the 10 mg/ However, at the 18 month stage, Biogen and Eisai reported at AAIC kg bi-weekly arm. that the reduction of accumulated amyloid plaques in the brain was ARIA and infusion-related reactions were the most common treat- statistically significant at all doses. These were measured using stan- ment-related adverse events, and there was a 9.9% rate of ARIA with dardized PET (positron emission tomography), and scans of patients edema (ARIA-E) at the highest BAN2401 dose, but ARIA-E did not oc- treated with the highest dose of BAN2401 (10 mg/kg bi-weekly) and cur in more than 10% of patients in any of the treatment arms. assessed by the Centiloid scale showed an observed mean reduction However, the rate of ARIA-E in APOE4 carriers was 14.6% at the from 74.5 at baseline to 5.5 at 18 months (no p-value was reported). highest dose; all patients with MRI-confirmed ARIA-E were discontin-

10 | Scrip | 3 August 2018 © Informa UK Ltd 2018 RESEARCH & DEVELOPMENT

ued from the study. Concerns around safety related to ARIA meant esis without Phase III results showing that reducing amyloid plaques that regulators wanted to limit number of patients in the high-dose in the brain will result in a slowing of Alzheimer’s disease progression. group who were carriers. The amyloid hypothesis has yet to be proven in a Phase III trial, despite many efforts, but Biogen and Eisai remain confident in this APOE4 STATUS MAY OR MAY NOT BE AN approach via BAN2401, the Phase III BACE inhibitor elenbecestat for EFFICACY PREDICTOR which Phase II results were presented at AAIC, the anti-amyloid agent “Confounding the data, the proportion of subjects in the 10mg/kg aducanumab with Phase III results expected in 2020 and other pro- [bi-weekly] arm that were APOE4+ was substantially lower than the grams. placebo arm and other dose groups, which may have impacted the “I find these Phase II [BAN2401] data unconvincing as patients on baseline rates of cognitive decline between the various arms and lower doses did numerically worse than those on placebo, and only contributed to the appearance of benefit compared to placebo,” the highest dose, tested in 161 patients, met the primary endpoint. Leerink analyst Geoffrey Porges wrote in a July 25 note. Unfortunately, promising Phase II data often do not play out in Phase The percentage of patients who carried the APOE4 gene was just III trials,” Fulton said. 30% in the highest dose arm and 70% to 91% in all other arms in the “I understand why Biogen/Eisai would want to race for FDA ap- Phase II study. proval based on these results as replicating the statistically significant “The reason behind this difference in patient enrollment was due benefit for the highest tested dose in a large Phase III trial is far from to a request from health authorities outside of the US that APOE4+ a sure bet,” she continued. subjects be removed from the highest dose arm and randomized “The companies are likely banking on the FDA being swayed by solely to the other lower doses of BAN2401 or placebo,” Porges said. the extremely high unmet need in AD, acute public awareness and Haeberlein said during Biogen’s call that data to date for the alli- lack of disease-modifying therapies.” ance’s Phase III study with aducanumab had not shown a connection Biogen’s CMO Sandrock stood by BAN2401 as proof of the amyloid between APOE4 status and treatment efficacy. hypothesis, however, noting that it’s important to attack “more ag- Evercore ISI’s Raffat noted that aducanumab results show that gregated forms [of amyloid plaques] with the right antibody and the APOE4 carriers may do slightly worse on amyloid-reducing therapy right approach.” than non-carriers, but the difference in cognitive decline may not be He noted that the very next step would be to have discussions with enough to make an anti-amyloid drug ineffective. regulators, because there is a “range of possibilities here” on how to pro- The analyst also looked at data from a 1,901-patient Phase III study ceed. “Colleagues at Eisai are talking about additional trials,” he added. for Merck’s BACE inhibitor verubecestat, which appeared to show Leerink’s Porges wrote that BAN2401 largely lived up to expecta- that non-carriers had worse efficacy than APOE4 carriers. tions, but more data are needed to confirm efficacy observed to date. The forthcoming analysis of APOE4 carriers versus non-carriers “The results presented today have exceeded the Street’s expecta- may or may not settle the debate related to BAN2401, however, with- tions on ADCOMS, but do not provide confirmatory evidence that out a large Phase III dataset. BAN2401 had a meaningful benefit on standard cognitive measures “Is APOE4 confounding results? We’ll find that out soon,” Biogen’s due to the differences in baseline patient characteristics across the Sandrock said. arms,” the analyst wrote. “We do believe the data today is supportive of the amyloid hy- AMYLOID DOUBTS REMAIN REGARDLESS OF pothesis, but continue to believe that aducanumab remains Biogen’s APOE4 SUBANALYSIS most valuable asset in this indication.” Datamonitor Healthcare analyst Zara Fulton told Scrip that the With contributions from Ian Haydock in Tokyo. BAN2401 data were unconvincing in terms of the amyloid hypoth- Published online 26 July 2018

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scrip.pharmaintelligence.informa.com 3 August 2018 | Scrip | 11 R&D STRATEGY

UCB Looks To Its Next Wave Of Innovative Products JOHN DAVIS [email protected]

he sales growth of UCB Group’s five core products is allowing the Brus- Tsels, Belgium-based company to invest and prepare for the launch of its next wave of new products, and to support the early clinical-stage development of potential therapies which include an anti-tau antibody, UCB0107, and a potential myasthenia gravis therapy, rozanolixizumab. However, work on one clinical-stage candidate, the potential Sjogren’s syndrome therapy, seletalisib, has been halted internally because of the need to prioritize other agents, the company said during its 2018 half-year results briefing on July 26. Seletalisib has produced positive results in early-stage clinical studies in Sjogren’s syndrome and activated PI3K delta syndrome, and no new safety signals were observed, UCB noted. Novel products closest to Phase IIb results are expected in the first half We are “pleased with the maturation of of 2020 for padsevonil in the treatment of the pipeline, with two products, romo- the market include the highly drug-resistant epilepsy. sozumab and midazolam nasal spray (for potential osteoporosis acute repetitive seizures) in the final phases NEW PRODUCT WAVE of development, bimekizumab progressing therapy Evenity, which Novel products closest to the market in- well in Phase III in three different indications, was resubmitted in clude the potential osteoporosis therapy, and two products in Phase II (padsevonil Evenity (romosozumab), which was resub- and rozanolixizumab),” reported UCB CEO the US by UCB and its mitted for US approval earlier this month Jean-Christophe Tellier. by UCB and its partner Amgen Inc. for use Bernstein analysts concurred. “The sec- partner Amgen for use in in postmenopausal women at high risk of ond half will be weaker but the pipeline postmenopausal women fracture. is progressing nicely,” they commented. Phase III studies of bimekizumab in mod- In addition to its pipeline, UCB has been at high risk of fracture. erate to severe psoriasis were started dur- strengthening its business development ing the first half of 2018, with two of those and deal making activities. involving active comparators, ustekinumab and adalimumab, with results expected by REDUCING TAU SPREAD the end of 2019. A Phase IIIb study compar- UCB0107 has been designed to block the which has produced positive results in a ing bimekizumab with secukinumab was spreading of “tau seeds” from dying neu- Phase IIb proof-of-concept study for the started in June. rones, a UCB executive noted. These small treatment of IgG auto-antibody-mediated And Phase III studies of bimekizumab for aggregates of tau infect other neurones disease. Subcutanous rozanolixizumab has psoriatic arthritis and ankylosing spondylo- and induce the formation of tau oligomers potential in the treatment of myasthenia arthrosis are expected to start in the fourth and neurofibrillary tangles. UCB0107 has gravis (MG), immune thrombocytopenia quarter of 2018. been specifically developed to prevent the (IP) and chronic inflammatory demyelinat- In the first half of 2018, UCB recorded rev- spread of tau seeds from human material, ing polyneuropathy (CIDP), and results in enues of €2.27bn (+2%, or +6% at constant and this second-generation anti-tau anti- MG and IP are expected during the second exchange rates (CER)), driven by Cimzia (cer- body was reported to be progressing well in half of 2018. A registration study in the first tolizumab pegol), Vimpat (lacosamide), Kep- Phase I studies; it has potential for the treat- of these conditions could start in the first pra (levetiracetam), Briviact (brivaracetam) ment of progressive supranuclear palsy and quarter of 2019. and Neupro (rotigotine), which had com- Alzheimer’s disease, delaying or stopping A further compound, dapirolizumab bined net sales of €1.8bn (+3%, or +12% at their progression, the company said. pegol, is in Phase II studies for systemic lu- CER) in the 2018 first half. UCB’s profits to- Another early-stage clinical compound pus erythematosus, with Phase IIb results taled €551m (+28%) in the half. is the anti-FcRn antibody, rozanolixizumab, expected in the fourth quarter of 2018. Published online 27 July 2018

12 | Scrip | 3 August 2018 © Informa UK Ltd 2018 R&D STRATEGY

Chugai Explores New Tech In Strategic Push For Innovation IAN HAYDOCK [email protected]

hugai Pharmaceutical Co. Ltd. is taking steps to explore net of Things (IoT, referring to a network of connected devices) and new potentially disruptive technologies and strengthen its artificial intelligence (AI), and how they may be applied to the large CR&D infrastructure in a strategic pursuit of innovation, as it amounts of data generated in the life science/pharma, including in seeks to think more broadly about the products and services it could both the clinical/non-clinical fields and information from devices. potentially provide beyond pharmaceuticals. PFN was founded in 2014 to focus on novel technology appli- The Japanese firm, majority owned by Swiss parent Roche, is cations in areas including biotech/healthcare, transportation, and building out its antibody discovery activities in Singapore, investi- manufacturing, and has developed an open source, deep learning gating potential applications of artificial intelligence, and expanding framework, Chainer, and related distributed (“edge-heavy”) data pro- early-stage production process capabilities as part of the moves. cessing methods. New CEO Tatsuro Kosaka told Scrip in an interview earlier this year The hope under the Chugai tie-up is to apply data analysis tech- that Chugai was planning in general to think much more about nologies in the R&D and value chain across discovery, development “around the pill” and “beyond the pill” in areas such as genomic medi- and manufacturing, to generate new insights and value, improve in- cine, given his prediction that “destructive technologies will greatly novation and productivity, and better meet medical needs. change our society.” Chugai’s Foundation Medicine Inc. unit, which is now being set up as an independent division, this March filed for the approval in Japan SINGAPORE ANTIBODY EXPANSION of a broad genomic profiling assay for solid tumors, as part of the In the first of the new moves, all unveiled at the time of its second company’s push into Personalized Healthcare. An expedited review quarter results, the company will expand its Chugai Pharmabody Re- of the product was granted in May. search subsidiary in Singapore, established in 2012 to focus on the In the last of the newly announced moves to support innovation, discovery of novel targeted antibody drugs and related proprietary Chugai is to construct a JPY4.5bn, 4,925sq m building at its Ukima engineering technology. Research Laboratories in Tokyo, to bolster process development for Guaranteed funding for the facility has been extended for a further small and “middle” molecule high-potency active ingredients. five years, with Chugai to invest a total of SGD282m ($207m) over the Aimed at the early development of processes for investigational 2022-26 period. drugs, from early stage through to commercial scale, the facility is Located in the major Biopolis biocluster, the life of the wholly due to start operations in January 2020. owned subsidiary - chaired by renowned UK cancer researcher Sir David Lane - had already been extended for five years from 2016 and SOLID Q2 GROWTH then again for the same period, with total investment now set to The changes came as Chugai, 59.9% owned by Roche, reported a 13% reach SGD476m in the 2012-21 timeframe. rise in revenues in the fiscal first half ended June 30 to JPY285.1bn, Chugai Pharmabody will work with the company’s Kamakura and with operating profit surging 41% to JPY66.6bn and net income ris- Fuji Gotemba research sites in Japan to develop its expertise, and ing to JPY49.0bn (+34%). expects its workforce to reach around 125 by 2026. Oncology again led the way, and although sales in this segment The site has already contributed to the development of several fell slightly due to the general April reimbursement price cuts in Ja- novel pipeline antibodies, including SKY 59 (RG6107) and ERY974. pan, Japanese sales of top product Avastin (bevacizumab) were up The former, an anti-C5 recycling antibody licensed to Roche, is now 3% to JPY45.4bn in the six months. in a Phase I/II multinational study for paroxysmal nocturnal hemo- The overall figures were also boosted in part by first-quarter globinuria. gains from the transfer of a portfolio of long-listed older products ERY974, in Phase I for solid tumors, is a bispecific antibody target- in Japan to Teva-affiliated generic firm Taiyo Pharmaceutical ing Glypican-3/CD3. Industry Co. Ltd.. Although Chugai did not mention any such support, Singapore’s Chugai has so far left its full-year forecast unchanged, and is ex- Economic Development Board typically provides a range of attrac- pecting a core operating profit of JPY71.6bn (+66%) on revenues of tive incentives to invest in and conduct life science research in the JPY285.1bn (+53%) for the 12 months to December 31. city state, such as administrative and facilities support and possible From the editors of PharmAsia News. tax measures. Published online 30 July 2018

TECH-DRIVEN DRUG DISCOVERY CLICK Separately, Chugai has invested JPY700m ($6.3m) in a third-party al- Go to Scrip online for the full array of our location of shares in Preferred Networks (PFN), as part of a new part- in-depth analyses and insights drawn from nership agreement with the Tokyo-based technology company. this quarter’s biopharma earning reports. The companies will look jointly at new technologies such as Inter-

scrip.pharmaintelligence.informa.com 3 August 2018 | Scrip | 13 Q2 UPDATE

AbbVie HCV Revenue Surprises Again, But Falloff Is Coming JOSEPH HAAS [email protected]

s AbbVie Inc. continues to report Humira growth and investors con- Atinue to worry about biosimilar competition, the Chicago-area pharma offered a surprise when it presented its second quarter earnings: a better-than-expected performance for the hepatitis C franchise, bringing it on par with rival Gilead Sciences Inc.. Overviewing its second quarter financials July 27, AbbVie reported that its HCV franchise, led by Mavyret (glecaprevir/pi- brentasvir), yielded global sales of $973m, up more than 100% from second-quarter 2017. During the first quarter, the franchise brought in $919m, 61% higher than consensus estimates of $572m, but the company talked down HCV’s longer-term prospects. (Also see “HCV Sales Drive Ab- bVie’s Great Quarter, But Gains Won’t Last” - Scrip, 26 Apr, 2018.) Now, AbbVie is still pre- strong leadership positions in other major team anticipates a much more gradual and dicting some decline in HCV – both in the markets, including Japan, Germany, Spain stable decline in HCV sales going forward,” US and in Japan – but is also admitting and Italy, “based on its compelling clinical he added. the immediate future for the franchise is profile and our commercial execution.” During its July 27 second quarter earn- hard to predict. ings call, Merck & Co. Inc. revealed that its HCV totaled $422m in net sales in the US ABBVIE RISES WHILE GILEAD two-drug HCV combo Zepatier (elbasvir/ for the quarter, with ex-US sales reaching CONTINUES TO FALL grazoprevir) brought in $113m during April, $551m – both numbers more than 100% Mavyret’s ascendancy occurs in the context May and June, slightly below consensus increases year-over-year. Mavyret, the first of significant HCV revenue slippage by Gil- expectations of $117m, making the New oral, pan-genotypic eight-week regimen ead, once the dominant leader in the space. Jersey pharma a distant third-place player for HCV, generated a significant majority During its second quarter earnings call on in HCV. of the franchise’s sales with $932m. (Also July 25, the Foster City, Calif., firm – which Gonzalez said AbbVie still expects a bit see “AbbVie’s Mavyret Is First 8-Week Pan- has pivoted focus recently to immuno- of a step-down in HCV revenues during Genotypic Combination For HCV” - Scrip, 3 oncology and HIV – reported $1bn in sales the quarter, due to market factors in Japan Aug, 2017.) Chief Financial Officer William for its three-product HCV franchise, basically and the US. But, he added, the pharma had Chase told the investor call that given level with the prior quarter’s total of $1.05bn. expected those factors to impact HCV sales Mavyret’s momentum, AbbVie is now in- (Also see “As Gilead Seeks New CEO, Second during the second quarter and instead fran- creasing its projected full-year 2018 HCV Quarter Shows Stability” - Scrip, 25 Jul, 2018.) chise sales grew. AbbVie projects third-quar- sales to more than $3.5bn. That total still was down substantially from ter HCV revenue of $850m, which would be That puts AbbVie largely even with HCV $2.9bn in the second quarter of 2017, and a 13% decline sequentially. leader Gilead, which projected full-year Gilead has been frank during recent quar- In Japan, Mavyret is being used to treat HCV sales of $3.5bn-$4bn at the start of terly calls that HCV is a declining franchise, patients who failed previous therapy on an the year. both domestically and internationally. (Also all-oral DAAl regimen, a number AbbVie ex- “The pace of Mavyret’s uptake continues see “Gilead Admits It Needs M&A To Resume pected to decline during the second quar- to exceed expectations, driven by strong Growth, But Stays Quiet” - Scrip, 8 Feb, 2017.) ter. “I can’t tell you that there’s perfect data in market share performance globally as well Leerink Partners analyst Geoffrey Porges Japan on how many of those patients there as higher treatment volumes from ware- noted July 26 that Gilead’s second-quarter are, but we had forecasted that that would housed [direct-acting antiviral] failure pa- performance, a 4% sequential decline in go down somewhat in the second quarter tients in certain markets,” Chase said. HCV revenue, was the lowest quarterly de- and will continue to go down in third and CEO Rick Gonzalez touted that Mavyret cline it had seen in HCV since the fourth fourth quarter,” Gonzalez explained. “It didn’t has a “market-leading position in the US” and quarter of 2016. “Gilead’s management go down as much as we had assumed in the

second quarter. It did go down some, but it more patients despite the curative impact adalimumab biosimilars will launch this Oc- didn’t go down as much as we assumed. We of the drug,” the analyst concluded July 27. tober in Europe and quickly put significant are assuming another step function down pressure on Humira’s EU sales. “We expect of those patients in third and fourth quarter.” HUMIRA GROWTH UNABATED, European biosimilars to erode AbbVie’s In the US, AbbVie had anticipated de- IMBRUVICA’S RISE CONTINUES Humira sales at an annual rate close to the creasing patient starts – one of the primary Overall, AbbVie’s quarter offered more of the mid-20% rate seen with Remicade (John- factors in the sharp drop-off in revenue for consistent drumbeat of Humira (adalimum- son & Johnson’s infliximab)] when it faced Gilead’s HCV products – but that hasn’t yet ab) growth, progress with the cancer fran- biosimilar competition in Europe,” he said. occurred as greatly as projected. “It’s a simi- chise of Imbruvica (ibrutinib) and Venclexta “Additionally, we continue to model an at- lar phenomenon as we were seeing patient (venetoclax), and the potential of two Phase risk launch of a US Humira biosimilar by late volumes higher than we would have ex- III Humira successors, upadacitinib and ri- 2020, likely by Pfizer Inc., which has shown pected,” the CEO said. “Again, we had pro- sankizumab. The pharma also pointed to a willingness to launch at-risk in the past jected that they would come down some- the recent approval of Orlissa (elagolix) for with its Remicade biosimilar Inflectra launch what in second quarter. We didn’t see that endometriosis as part of its strategy to man- in 2016.” come down. We are projecting some reduc- age the impact of direct biosimilar competi- On the topic of possible drug pricing tion in patient volumes in the third and the tion to Humira. policy changes in the US, Gonzalez offered fourth quarter. We’ll have to see how that AbbVie posted second quarter global a wide-ranging answer which culminated plays out, but that’s the basic difference.” revenue of nearly $8.3bn, up 17.1% over with him pointing out that while there aren’t Even if AbbVie begins to see HCV sales the second quarter of 2017. Humira totaled many specifics yet on Trump’s blueprint fall off beginning this quarter, Morningstar nearly $5.2bn for the quarter, $3.5bn in the for addressing health care costs, “when we analyst Damien Conover predicts steady US (up 10%) and $1.7bn internationally (up looked at the framework, at least for AbbVie’s and substantial annual revenue for the fran- 4.4%). Imbruvica posted $850m in global business … there were probably more posi- chise in the near-term. “We expect AbbVie’s sales, a nearly 60% increase, with US sales of tives than there were negatives based on the hepatitis C platform to support over $3bn $693m, up 31% year-over-year. kinds of products that we have.” annually for several years based on reaching Morningstar’s Conover predicted that Published online 29 July 2018 AbbVie Prices Oral Endometriosis Drug Orilissa In Value Range, Focusing On Access EMILY HAYES [email protected]

bbVie Inc. says it set the price tag mineral density, hence the higher dose is for its newly US FDA approved oral The ICER pricing review intended for a shorter period of use. Aendometriosis pain drug Orilissa at about $850 per month, with a view to- group said that the ABBVIE PRICES TO OPTIMIZE ward enabling patient access when the launch price, which ACCESS product launches in retail pharmacies in Commenting on the $844.87 per month early August. amounts to $10,138 price tag, before rebates or discounts, About one in 10 women of reproductive per year, falls within the company told Scrip that it has been age have the condition, which can cause thoughtful and responsible in its ap- debilitating pelvic pain. Furthermore, the the annual value-based proach to pricing in order “to optimize number of women in North America aged patient access.” 15 to 49 with endometriosis is set to grow price benchmark range The Institute for Clinical and Economic from 8.2m in 2017 to 8.5m in 2025 (world- its experts established Review (ICER) commented that the launch wide, from 188m to 196.6m worldwide), price, which amounts to $10,138 per year, according to Datamonitor Healthcare for the treatment in a falls within the annual value-based price projections. June report. benchmark range its experts established On July 24 the FDA approved two doses for the treatment in a June report: $8,800- of Orilissa (elagolix) for moderate-to-severe $12,800. endometriosis pain – a 150 mg once daily ICER explained that its value-based dose for use up to 24 months and a 200 mg price benchmark reflects the hypothetical twice daily dose cleared for use up to six price for a prescription drug that aligns months. The oral gonadotropin releasing with the clinical benefits patients receive hormone (GnRH) antagonist is associated from that treatment. with a dose-dependent decrease in bone- However, the independent health scrip.pharmaintelligence.informa.com 3 August 2018 | Scrip | 15 NEW PRODUCT APPROVAL

technology assessment organization San Diego, Calif-based Neurocrine Bio- endometriosis that supported the filing of said when releasing the report that that sciences Inc. originally developed elagolix the drug. The trials showed Orilissa was as- while the drug was efficacious in trials of as an alternative to injectable GnRH an- sociated with significantly higher response women with endometriosis, “treatment tagonists and outlicensed exclusive world- rates for reducing menstrual pain and non- still could potentially challenge short- wide rights to AbbVie in 2010 in a deal menstrual pain after three and six month, term budgets given the large number of worth $75m upfront and another $500m relative to placebo. women affected by endometriosis.” in development, regulatory and commer- The filing for elagolix had priority review Despite the favorable preliminary cost- cial milestones, plus sales royalties. AbbVie and a decision was initially expected in April. effectiveness findings, ICER concluded, is solely managing commercialization However, the agency extended the review “only about 26% of women with endome- At its peak, Lupron had sales of about period by three months until August to review liver function data. Liver safety has also been a big post-approval concern in a European Union safety review of Gedeon Richter PLC/Allergan PLC’s selective progesterone receptor modulator Esmya (ulipristal acetate), which was initially authorized for use in treating abnormal bleeding in women with uterine fibroids in that region in 2012. (Also see “Liver Damage Worries Lead To Further EU Restric- tions On Richter’s Esmya “ - Pink Sheet, 21 May, 2018.) That drug is also under review for the same indication in the US; the decision date for the filing was extended from May to August. FDA labeling for elagolix includes a warning about dose-dependent liver en- zyme elevations along with dose- and duration-dependent decreases in bone mineral density that may not be com- Elagolix is also in Phase III development for pletely reversible, reduced ability to rec- ognize pregnancy, suicidal ideation and treating heavy bleeding associated with uterine mood disorders, and reduced efficacy for estrogen-containing contraceptives. fibroids. Updated Phase III data are expected “Most common adverse reactions (>5%) in clinical trials included hot flushes and in the fourth quarter, followed by a filing in 2019. night sweats, headache, nausea, insomnia, amenorrhea, anxiety, arthralgia, depression- related adverse reactions and mood changes,” labeling advises. triosis-related pain could be treated before $4.5bn for the treatment of male cancer, but Elagolix is also in Phase III development spending crossed ICER’s potential budget only $100m in endometriosis, Neurocrine for treating heavy bleeding associated with impact threshold of $915 million per year.” CEO and founder Kevin Gorman told Scrip. uterine fibroids. (Also see “AbbVie’s Got A Lupron had big downsides for patients, who Competitive Edge With Elagolix For Women NEED FOR NEW TREATMENT are typically young and of reproductive age, With Uterine Fibroids” - Scrip, 21 Feb, 2018.) OPTIONS in that it would send them straight into Updated Phase III data are expected in the Traditional treatment options have in- menopause, with symptoms like hot flashes fourth quarter, followed by a filing in 2019. cluded nonsteroidal anti-inflammatory and night sweats, and the bone loss was Other oral GnRH antagonists in the pipe- drugs (NSAIDS) and oral contraceptives. “devastating,” he said. “The drug was never line include relugolix, from the Allergan/ AbbVie’s injectable GnRH antagonist Lu- embraced for endometriosis.” Roivant Sciences GMBH-backed wom- pron (leuprolide), now available as a ge- The oral elagolix was designed to lower en’s health startup Myovant, which is in neric, and other subcutaneously delivered estrogen enough to work on endometrial Phase III for uterine fibroids, endometriosis drugs in the same class have also been lesions and dramatically reduce pain, but to and prostate cancer, and linzagolix, from available for endometriosis, but are asso- be much better tolerated, he explained. ObsEva SA/Kissei Pharmaceutical Co. ciated with amenorrhea and loss of bone AbbVie funded two identical pivotal Ltd., which is in Phase III for uterine fibroids mineral density. Lupron is also approved studies of almost 1,700 women with and Phase IIb for endometriosis. for prostate cancer. moderate-to-severe pain associated with Published online 24 July 2018

Interview: Silence Therapeutics’ Chair On Why Keeping Quiet Has Done The Biotech No Favors JO SHORTHOUSE [email protected]

his is a key moment in time, says Having been at big pharma for a large part combination of access to capital through Annalisa Jenkins, executive chair of her career, Jenkins is clearly still enthused new investors in Europe and the US, and Tof Silence Therapeutics PLC, for about the nimble nature of the biotech and business development deals. both the company and the interfering the ability to follow the science. “We have a “We’re sitting at the moment with a valu- RNA (RNAi) space, likening it to the devel- platform that can reasonably quickly iden- ation on AIM of about $160m. Dicerna and opment of antibody technology several tify a target, create a series of candidates Arrowhead are sitting north of $500m in years ago. and move them through an engine of dis- the US and of course, we all know that Al- The crux of the science lies at the abil- covery to candidate selection within about nynam is multiple billions. I do not believe ity of RNA interference to inhibit gene ex- 9 to 12 months, including early phase in vivo that those relative valuations actually reflect pression by neutralizing targeted mRNA pharmacology,” she explains. “And then with the fundamental value that sits within those molecules. The space is hotting up, with that data in hand, we can make choices as companies,” she says. “I don’t think that the Alnylam Pharmaceuticals Inc.’s selec- to whether we want to move that internally inherent, fundamental value within our tive RNAi agent, patisiran, expected to be or we want to partner.” The company has portfolios across Arrowhead and Silence is reach the market for the treatment of hAT- just recently identified three new targets that much different and yet, they’re north TR amyloidosis in the near future. (Also see and programs that are moving through that of $500m valuation and we’re sitting at “Alnylam Set For Transformation As Patisiran internal engine. $150m.” The lack of liquidity in AIM is obvi- Nears Market With Data Upgrade” - Scrip, 25 While there is an ability to flex in the ously a frustration for Jenkins, as is, ironically, Apr, 2018.) If approved this will herald the preclinical discovery to candidate selec- the prior silence of the company before she next phase of growth and evolution of the tion, the manufacturing aspect is more of a joined the board. sector, and Jenkins believes that Silence challenge. Jenkins says the company needs One of the reasons why ex-Zealand CEO can play a key role on the growth of the to “clarify” its manufacturing strategy. It will David Horn Solomon has been chosen as RNAi industry. be investing in the area and deciding what the company’s new chief executive is his it wants to build in-house and what it will previous strong relationship with investors, IN THE CLINIC look to do through third parties. But this is the banks, and with the capital markets. Silence’s lead program is SLN124, which just one of the many strategies Jenkins has “He’s also credible because of his very robust seeks to target and silence the repressor of had to navigate at her relatively short time academic background, so, he’s able to trans- hepcidin, a protein which lies at the center at the company. late that science and medicine through to of iron metabolism in the body, in order the capital markets, and I think that’s go- to upregulate it. The company is now pro- GETTING TO KNOW YOU ing to be extremely important for the next gressing towards filing a Clinical Trial Au- Having spent the past 10 months as non- phase of growth of the company.” thorization (CTA) and expects to be dosing executive chair getting to the know the Jenkins likens Silence to a “hidden gem. patients in 2019. It is currently working in inner workings of the genetic medicine It was almost as if nobody had heard about beta thalassemia and myelodysplastic syn- company, its programs, investors and man- us, and when they did hear about us, it was drome and exploring the potential for mov- agement team, her priority is clear; to un- really to talk about the Alnylam litigation,” ing this molecule into hemochromatosis, a lock the value of the company’s platform she explains. genetically-based disease of iron overload. It as the wider sector strides on. Priority num- is also working on a next generation version ber one has been to transition to become a LITIGATION AND LEGACY of that molecule using novel technology drug development company with an end- The patent fight was started by former CEO coming out of its lab. to-end R&D model, she explains, and prior- Ali Mortazavi. In 2017, it launched legal ac- It is also proceeding preclinically in alco- ity number two is to ensure the company tion stating that Alnylam and The Medicines hol abuse. This area will come under review is well capitalized. Company. The various claims to be heard over the summer, Jenkins confirms. “We She believes the AIM-listed company is at the trial in December 2018 will include a will be moving it forward and looking for a fundamentally undervalued. “I think it’s fair decision on the infringement of one of Si- partner along the way, and so it has the po- to say that today, in the UK, the AIM listing lence’s European patents by patisiran. tential to dose patients next year but I think does not work well for companies of our size “Success for us would be an injunction that largely depends on the strategy that we and shape, and stage. And therefore, that and damages for past infringement and come up with,” she says. An area Jenkins is doesn’t create the opportunity at this point the recognition of the foundational chemi- excited about is metabolism. A target is yet for the right amount of liquidity for bringing cal modifications that were invented by our to be decided upon but there will be an- the right investors into the company,” she Berlin scientists many years ago,” Jenkins ex- nouncements in the second half of this year. says. The company is now looking at the plains. “When I joined the company most of

scrip.pharmaintelligence.informa.com 3 August 2018 | Scrip | 17 LEADERSHIP PERSPECTIVE

the media, and the analysts, thought of our “And so, I came back [to the UK] with the company as the company that was suing Al- goal to do two things. One was to secure a nylam,” she says, but she hopes to turn those couple of chair roles of significant compa- perceptions around with the industry and nies in the UK and show that a woman can its observers looking on Silence as a drug survive and fly, and create value, in that role. development company with a platform and And I also came back to help a number of a long legacy. “Part of our strategy, like any the British companies be connected with company, will seek to uphold our patent po- talented women who could also take their sition and pursue those that wish to use our role whether that be as a CEO or as a C-suite inventions. But it’s not core to our story, it’s to help drive those forward.” just part of our story.” The court case will be Jenkins’ lessons in leadership were im- heard in the UK in December, and a decision printed on her from an early age while is expected in January 2019. serving in the Royal Navy. “I learnt the im- Jenkins came to the company in Octo- portance of valuing everybody equally; I ber 2017, a veteran of R&D, having worked learnt the importance of teams, I learnt at Bristol-Myers Squibb Co. and Merck the importance of grace under fire. And I Serono SA after leaving the British Navy. learnt the importance of basically having Latterly she had left big pharma to try her a plan, being decisive, getting on and get- hand at the corporate side of biotech. She ting stuff done. And I learnt that through launched from her global R&D head role to military leadership.” become CEO of Dimension Therapeutics “I learnt how to Jenkins was the first female physician to Inc., and chairs the boards of Cell Medica operate as a woman serve on the frontline at war in 1991 with Ltd., Vium, and Cocoon Biotech. She is also the Mine Sweeper Squadron in the North- CEO of PlaqueTech, a company that looks in a man’s world ern part of the Gulf. The most important for novel biomarkers and inflammatory part of her experience, she recalls, was be- pathways in cardiovascular disease. and I learnt how ing the only woman serving at sea with a As a former R&D leader, Jenkins is pas- to operate in an squadron of 700 men while under fire. “I sionate about protecting science. “I believe often say that was the best preparation for it all starts as a science, the quality of sci- environment of what I subsequently have had to experience, having the focus on unmet medical ence in the pharmaceutical industry, be- needs and how to benefit patients. And conflict.” cause I learnt how to operate as a woman then building the team and raising the – Annalisa Jenkins in a man’s world and I learnt how to oper- money that allows you to execute on that,” ate in an environment of conflict.” she says. “I also believe that the bedrock of our industry, an innovative biopharma sec- OPPORTUNITIES tor, depends on the ability to translate those Jenkins characterizes the RNAi space as discoveries and inventions into patents that “graduating”. While still in a relatively early basically create the market. And I believe phase, there is a huge amount of opportu- that my position is entirely consistent with nity to come as new targets are identified. [that of] the president and chairman of BIO, While the field still has relatively few players, the premier industry association led by John there is an increasing number of non-gene Maraganore.” Maraganore is, of course, presi- therapy companies that want to access the dent and CEO of Alnylam. “RNAi toolbox”. And there are not that many companies that can allow larger firms ac- OPERATING IN A MAN’S WORLD be successfully executed,” she explains. cess to that. While Jenkins is emphatic about the pro- The UK’s biotech sector is in a much “I think that what you’re going to see is tecting her scientists works, she also does worse state than in the US, in terms of fe- a number of the mid- to large-cap com- not shy away from conflict or difficult male leadership, she believes. “There are ac- panies looking for opportunities for part- decisions. She decided to move back to tually no more than one or two board chairs nerships and collaborations, and access to the UK from the US because of the “enor- in the biotech sector that are women. There RNAi platforms, and I believe that Silence is mous opportunity” in the health, life sci- are very few female CEOs and in fact there going to be able to play a role in that,” she ence, and biotech sectors in the UK as the are very few C-suite women. And I will tell says. “There’s going to be generation three, second pillar of the UK industrial strategy you that it’s not a lack of pipeline, it’s just and there’s going to be generation four. And post-Brexit. “It’s absolutely clear that this that women in the UK have found it tre- we fully intend to be front and centre of the is a major opportunity and that the [UK] mendously challenging to make their way next phase of evolution and innovation in government has articulated this and I through to chief exec and board positions,” the space.” would like to help make sure that that can she opines. Published online 25 July 2018

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