15 December 2017 No. 3884

Scripscrip.pharmaintelligence.informa.com Pharma intelligence | informa Kymriah (tisagenlecleucel) and Gilead Sciences Inc.’s Yescarta (axicabtagene ciloleucel) for certain blood cancers – and Spark’s gene therapy Luxturna appears poised for approval in the near-term for a rare form of blindness, physicians are anxious to see more treatments that can move the bar closer to a cure. Investors too are rewarding drugs that can deliver the promise of big advances. Wall Street’s reaction to data presented at ASH also shows how important early clinical trial data in even a handful of patients can be a huge catalyst for companies working to bring big breakthroughs to small patient populations. Bluebird bio was handsomely re- warded by Wall Street after presenting Shutterstock: Ervin-Edward Shutterstock: positive data on multiple fronts. The com- pany’s LentiGlobin gene therapy helped patients with transfusion-dependent An ASH That Moves The Ball – β-thalassemia (TDT) achieve freedom from chronic transfusions in a Phase I/II study. The company also presented posi- And The Ticker Price tive updated results from a Phase I trial of JESSICA MERRILL [email protected] bb2121, an anti-B-cell maturation anti- gen (BCMA) CAR-T cell therapy partnered n a year of notable advances in blood can- 29.4% to open at $221.55 and Blueprint with Celgene Corp., in 21 patients with cer and gene therapy, the American Soci- Medicines Corp.’s stock gained 24.6% to relapsed/refractory multiple myeloma. In Iety of Hematology (ASH) annual meeting open at $89.54. another announcement, Phase I data in Dec. 9-12 presented the opportunity for Meanwhile, Spark Therapeutics Inc.’s two patients treated with sickle cell dis- drug companies to showcase their latest ad- stock fell 35.9% to $46.99 as investors re- ease confirmed the benefits of a refined vances. Big news on potentially paradigm- acted negatively to data in hemophilia manufacturing process for LentiGlobin changing medicines were rewarded as A and Syros Pharmaceuticals Inc. fell gene therapy in that therapeutic space. investors clung on for a soaring ride, while 48% to $6.42 on underwhelming results “BLUE’s impressive updates at ASH – Wall Street’s reaction to less-than-stellar of an ongoing Phase II trial of its first- across the board – are at the upper end news coming out of ASH was about as blus- in-class retinoic acid receptor alpha in of our expectations, which bodes well tery as the December snowstorm that hit acute myeloid leukemia and myelodys- for the outlook of the company,” Leerink Atlanta on the opening day. plastic syndrome. analyst Michael Schmidt said in a Dec. 11 Biotech stocks relying on the success The most attention at ASH was around research note. of one or two late-stage products experi- gene and CAR-T therapies, although there Celgene also benefited from the positive data on BCMA, along with marginally posi- enced big stock fluctuations on Monday were incremental updates in many areas. tive data on the CAR-T therapy JCAR017 morning after the busy weekend of data Now that the first CAR-T drugs have been releases. bluebird bio Inc.’s stock jumped approved by the FDA – Novartis AG’s CONTINUED ON PAGE 7

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Advances At ASH Brexit Breakthrough Stock Scan Celgene, Spark, Biomarin and others UK life sciences pact to the fore Generics fluctuated in November report progress in Atlanta (p1-7) as negotiations proceed (p10-11) (p16-17) IN THIS ISSUE

from the editor [email protected]

This year’s American Society of Hematology annual meet- gene therapies for diseases including hemophilia, beta ing was a fantastic showcase for therapeutic progress in thalassemia sickle cell disease were also presented to ac- very serious diseases. The diversity of the advances in claim: Emily Hayes has the lowdown on BioMarin and diseases like hemophilia, blood cancers and beta thalas- Spark Therapeutics’ hemophilia data (p6). semia presented at the meeting is testament to the huge Meanwhile, early data on the use of checkpoint in- commitment of biopharma companies and academic re- hibitors in blood cancers, both as monotherapy and in search institutes to seek solutions for medical problems combination, suggests products like Merck’s Keytruda that once seemed impossibly difficult to address. and Bristol-Myers Squibb’s Opdivo will soon extend In a year that has seen the FDA approve the first their dominion from solid to liquid tumors. chimeric antigen receptor T-cell, or CAR-T, therapies Next week we’ll have more from the meeting, includ- targeting the CD19 antigen to treat leukemia and lym- ing analysis of the broader prospects for Roche and phoma, additional CAR-T progress was highlighted, AbbVie’s Venclexta following the lauded MURANO including for investigational CAR-T treatments target- study in chronic lymphocytic leukemia, and details of ing the B-cell maturation antigen (BCMA) for myelo- Ablynx’s HERCULES data, which are expected to lead ma. See p4 for Mandy Jackson’s in-depth analysis of the to approval for caplacizumab in acquired thrombotic progress of Celgene’s CAR-T programs partnered with thrombocytopenic purpura. Can’t wait until next Fri- bluebird bio and Juno Therapeutics. Successful trials of day? Read them online today!

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EDITORS IN CHIEF Ian Schofield EDITORIAL OFFICE Eleanor Malone (Europe) Vibha Sharma Christchurch Court Denise Peterson (US) Joanne Shorthouse 10-15 Newgate Street Ian Haydock (Asia) Sten Stovall London, EC1A 7AZ US CUSTOMER SERVICES EXECUTIVE EDITORS Michael Cipriano Tel: +44 (0)20 7017 5540 COMMERCIAL Derrick Gingery or (US) Toll Free: 1 800 997 3892 Alexandra Shimmings (Europe) Joseph Haas Email: clientservices@ Mary Jo Laffler (US) Emily Hayes pharma.informa.com Mandy Jackson POLICY AND REGULATORY Cathy Kelly TO SUBSCRIBE, VISIT Maureen Kenny (Europe) Jessica Merrill scrip.pharmaintelligence.informa.com Nielsen Hobbs (US) Brenda Sandburg TO ADVERTISE, CONTACT Bridget Silverman [email protected] EUROPE Sue Sutter Neena Brizmohun Francesca Bruce ASIA John Davis Anju Ghangurde Lucie Ellis Ying Huang All stock images in this publication Kevin Grogan Jung Won Shin courtesy of www.shutterstock.com John Hodgson Brian Yang unless otherwise stated

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2 | Scrip | 15 December 2017 © Informa UK Ltd 2017 20

Moeller Talks Consolidation Blood Rivals Robotic Pills 20 6 Are Coming 13

exclusive online content inside: Roche Powers Forward With First-Line Tecentriq In COVER / An ASH That Moves The Ball – And The Ticker Price Advanced NSCLC http://bit.ly/2l8KI0l 4 Celgene’s CAR-T Leadership Goals Advance At ASH 2017 The actual data on the clinically meaningful effect on PFS of the triple combination of Tecentriq, Avastin and chemotherapy on 6 Spark Plots Rebound For Hemophilia A Gene Therapy, previously untreated advanced NSCLC patients in the IMpower150 As Rival Biomarin Surges study have now been presented at a scientific meeting, and suggest that Roche could be a significant competitor in the large 8 Pharma ‘All-Stars’ Talk Hot Topics At Forbes Summit NSCLC market in the not too distant future. 9 Gilead Acquisition Of Cell Design: The Next Logical Step Novartis’ Kisqali Impresses In Premenopausal Breast Cancer As Market Crowds 10 Pharma Lauds Brexit ‘Breakthrough’ http://bit.ly/2BF9YSy Updated data from the MONALEESA-7 study shows the extent 11 Sir John Bell: UK Life Science Pact Essential of its progression-free survival benefit in premenopausal women with advanced breast cancer; supplemental filings are planned. 12 Sage’s Depression Therapy Shows ‘Dramatic’ Effect Lilly Plumbs Data To Differentiate CDK4/6 13 Shire Explores Robotic Pill Potential For Hemophilia Inhibitor Verzenio http://bit.ly/2Acqzcb 14 Hisun-Pfizer Split: What Went Wrong And What Next? Lilly highlighted five prognostic factors at SABCS that may be linked to high Verzenio response. As the third CDK4/6 inhibitor 16 Stock Scan November 2017: Generics Get Volatile on the US market, the company needs to differentiate its breast cancer drug from Pfizer’s Ibrance and Novartis’s Kisqali. 18 Arix Shepherds Atox $30m Funding Amid High Hopes Start-Up Obsidian Gets $49.5m To Determine How For Start-up’s Lead Asset And When To Activate CAR-T Cells http://bit.ly/2z37JpH 20 Joerg Moeller, Bayer Development Chief, Obsidian CEO Michael Gilman described the company’s On R&D Consolidation technology – which allows CAR-T cells and other therapies to be activated by available small molecule drugs – as being able 22 Pipeline Watch to modulate the effective yet toxic therapies by dialing down, turning up or shutting off the treatments as needed. 23 Shanghai: J&J’s First Innovation Site Outside N America

Oncolytics After 2017 Refresh: New CEO Makes New 23 Appointments Year Resolutions http://bit.ly/2z418eO 2018 will be a year of change for Calgary, Canada-based Oncolytics Biotech, according to its CEO Dr. Matt Coffey. After switching gears to focus on metastatic breast cancer as the lead indication for its oncolytic virus-based drug candidate Reolysin, the biotech is ready to enter Phase III and step-up its clinical and commercial activities.

Deal Watch http://bit.ly/2jxvIbL Astellas builds on a 2013 collaboration by acquiring Mitobridge. Ardelyx is partnering with Kyowa Hakko Kirin to bring tenapanor to market in Japan. Meanwhile, Depomed, Xoma and Bristol all @PharmaScrip /scripintelligence offload programs before the end of the year. /scripintelligence /scripintelligence

scrip.pharmaintelligence.informa.com 15 December 2017 | Scrip | 3 ASH MEETING

Celgene’s CAR-T Leadership Goals Advance At ASH 2017 MANDY JACKSON [email protected]

elgene Corp. hit a double whammy at the American Society able disease,” Frankel said. “These are patients that have gone into the of Hematology (ASH) meeting running Dec. 9-12 in Atlanta, Phase I trial that otherwise would’ve gone into hospice.” CGa. via partners bluebird bio Inc. and Juno Therapeutics Jefferies analyst Michael Yee wrote in a Dec. 10 note that the Inc. that could help the company meet its goal of becoming a leader bb2121 data were “the most remarkable data at ASH this year (hard in chimeric antigen receptor T cell (CAR-T) therapies. to beat 94% response rate and 56% CR rate).” He predicted that “there Bluebird and Celgene reported new data for bb2121 showing will be rising Street enthusiasm for bluebird’s bb2121 CAR-T myelo- strong, durable response rates in relapsed and refractory multiple ma drug now and this is going to help turn some of the sentiment myeloma as the Phase I clinical trial for their CAR-T therapy targeting around on Celgene.” B cell maturation antigen (BCMA) progresses. Juno and Celgene also Yee said bb2121 could generate $1bn to $2bn in annual sales, reported durable responses in diffuse large B cell lymphoma (DLBCL) especially if Celgene and bluebird can move their therapy into and highlighted what appears to be a relatively good safety profile earlier lines of treatment, and the analyst indicated that investors for JCAR017, their CAR-T candidate against CD19, that the companies have not modeled those kinds of sales for the product candidate. hope will amount to a best-in-class product versus the two approved Data for the CAR-T therapy last wowed Celgene and bluebird CD19-targeting CAR-T therapies. investors at the American Society of Clinical Oncology (ASCO) Celgene has had various interests in cell therapies for a while, but meeting in June. (Also see “Bluebird Flies On 100% Response Rate was not involved in CAR-T until after Novartis AG, Kite Pharma Inc. For Anti-BCMA CAR-T” Scrip, 6 Jun, 2017.) (now owned by Gilead Sciences Inc.) and Juno began to generate “Based upon these encouraging data, it’s ethical to explore use in excitement for their novel CD19-targeting therapies. The bluebird earlier lines of therapy,” Frankel said. partnership for bb2121 targeting BCMA allows Celgene to combine Any upside to bb2121 estimates would be a big bonus for Celgene its investment in regenerative medicine with its expertise in multiple investors, especially, after a recent mix of wins and losses for part- myeloma, seeking a first-in-class position for that CAR-T therapy. nered and internally developed assets. (Also see “Celgene’s Partnered Celgene’s top-selling product Revlimid (lenalidomide) is the lead- Pipeline Delivers Successes And Setbacks” Scrip, 21 Nov, 2017.) The com- ing brand-name multiple myeloma therapy and the cornerstone pany’s stock took a hit in October when Celgene ended development of many multiple myeloma treatment regimens, so it makes sense of mongersen (GED-0301) for Crohn’s disease, casting doubt on the for Celgene to bring its first CAR-T therapy forward in that disease. If drug’s ulcerative colitis program. (Also see “Celgene IBD Pipeline In Ques- bb2121 is successful in a pivotal trial that began earlier this month, it tion As Mongersen Crohn’s Disease Trial Ends” Scrip, 20 Oct, 2017.) Shares could be the first-ever marketed BCMA-targeting CAR-T therapy and fell further when Otezla (apremilast) failed to live up to sales estimates further diversify the company’s multiple myeloma portfolio beyond in the third quarter. (Also see “Celgene Admits It Screwed Up Otezla Esti- the blockbuster Revlimid. mates; Investors Lose Confidence” Scrip, 26 Oct, 2017.) However, Celgene closed up 1.8% at $108 per share on Dec. 11 ‘UNPRECEDENTED DATA SET’ based on the positive efficacy and relative safety reported for bb2121 Results from the first 21 patients in the ongoing Phase I trial for at ASH. Partner bluebird, which also had positive updates in sickle bb2121 – all heavily pre-treated multiple myeloma patients with a cell disease and beta thalassemia at the meeting for its gene therapy median of seven prior lines of therapy – were presented at ASH on LentiGlobin, surged 17.9% to $201.80. Dec. 10. Dosing ranged from 50m cells to 800m cells at infusion, ad- ministered after a pre-conditioning chemotherapy regimen of cyclo- TOLERABILITY ADDS TO POSITIVE EFFICACY phosphamide and fludarabine. Safety has been a difficult issue for CAR-T therapies with the blast With a median 40 weeks of follow-up, 17 out of 18 patients (94%) of reengineered T cells causing cytokine release syndrome (CRS) in treated with bb2121 dosed at 150m, 450m or 800m cells achieved many patients. Severe neurotoxicity also has been a concern, leading an objective response; 16 out of 18 had a very good partial response to deaths in studies conducted by Kite and Juno. (Also see “Too Sick (VGPR; 89%) and 10 out of 18 had a complete response (CR; 56%). For CAR-T? Kite Reports Cerebral Edema Death” Scrip, 8 May, 2017.) Nine out of 10 patients evaluable for minimal residual disease (MRD) But while Celgene and bluebird reported 15 out of 21 patients status were MRD negative. Median progression-free survival (PFS) (71%) experienced CRS, most cases were Grade 1 or 2 with only has not been reached, but PFS at six months was 81% and at nine two cases of Grade 3 CRS (9%). Roche’s Interleukin-6 (IL-6) inhibi- months was 71%. tor Actemra (tocilizumab), which was approved alongside Novar- “This is a really an unprecedented data set in the breadth of the tis’ Kymriah (tisagenlecleucel) in August to treat CAR-T-related CRS, response, the depth of response and the durability in patients who was administered to four bb2121-treated patients and another pa- have exhausted all of the available treatment options,” Stan Frankel, tient was treated with steroids, causing CRS symptoms to subside Celgene corporate vice president, head of immuno-oncology, clini- within 24 hours. cal research and development, said in an interview with Scrip. There was one case of Grade 4 neurotoxicity at the dose of “We have been lucky over the last decade to have multiple new 450m cells, but the symptoms – including cerebral edema and agents that have taken survival in multiple myeloma from a median subarachnoid hemorrhage – were in a patient with high tumor of two years and have gotten it to eight years, and it’s still an incur- burden and a prior subarachnoid hemorrhage. The companies

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said the neurotoxicity was managed and the patient maintained of Kite-developed Yescarta in relapsed or refractory large B-cell lym- her response to bb2121. phoma, including DLBCL, in October. (Also see “Gilead/Kite Pricing For The FDA granted a breakthrough therapy designation for bb2121 Yescarta Undercuts Novartis’s CAR-T Kymriah” Scrip, 18 Oct, 2017.) and the multiple myeloma treatment has been deemed eligible for Juno was in a position to be competitive with those two products, the European Medicines Agency’s (EMA’s) priority medicines (PRIME) but the company and Celgene decided earlier this year to discon- scheme; both programs allow for expedited review of treatments for tinue development of JCAR015 based on neurotoxicity concerns, diseases with unmet needs. including five deaths from cerebral edema. (Also see “Juno Ends Celgene and Bluebird have taken bb2121 dosed at 150m to 300m JCAR015 Development In ALL, Cementing Third Place CAR-T Position” cells in a single infusion into a Phase II pivotal trial known as KarMMa, Scrip, 1 Mar, 2017.) JCAR017, on the other hand, may be so safe that it which could have its first set of preliminary data available by the ASH can be administered as an outpatient therapy. (Also see “CAR-T To Go: meeting in December 2018 in San Diego, Frankel said. Juno Sees JCAR017 As Safer, Suited For Outpatients” Scrip, 2 Nov, 2017.) That 80-patient trial will look at bb2121 as a fourth-line therapy, Data for the next-generation CAR-T therapy, now also known as since patients must be relapsed or refractory after at least three prior lisocabtagene maraleucel, were presented on Dec. 11 at ASH from lines of therapy, including immunomodulatory agents, proteasome the Phase I TRANSCEND trial in relapsed or refractory non-Hodgkin’s inhibitors and a CD38 inhibitor. Objective response rate (ORR) is the lymphoma (NHL). The study includes a pivotal cohort in DLBCL that primary endpoint. could support approval. “Celgene and Bluebird have announced they are moving the An analysis of safety across 91 DLBCL patients revealed 32 people product forward aggressively,” Bernstein analyst Aaron (Ronny) Gal experienced CRS of any grade (35%), but only one case of severe CRS said in a Dec. 11 report. “Celgene has indicated they expect they can (1%). There were 17 reports of neurotoxicity of any grade (19%), in- get approval by 2020. We suspect this indicates it will take 6 months cluding 11 cases of severe neurotoxicity (12%). The other most com- to a year to complete recruitment, and the company (and regulators) mon treatment-emergent adverse events were neutropenia, ane- will want at least 6 months of runout from the last patient to show mia, fatigue, thrombocytopenia, nausea and diarrhea. convincing durability (in addition to the strong response rate).” In terms of efficacy, for 19 patients treated with dose level 2 (100m Future studies will look at earlier lines of therapy, including a cells) the ORR was 74% (14 out of 19 patients) at three months with Phase III head-to-head trial starting in 2018 in the third-line setting a 68% CR (13/19). Seven out of 14 patients that were assessed at six versus the combination of Celgene’s Pomalyst (pomalidomide), months had a CR (50%). Sixteen of 20 patients (80%) across doses Johnson & Johnson’s Darzalex (daratumumab) and dexametha- who had a CR at three months still had a CR at six months; 11 out of sone in patients who’ve previously been treated with Revlimid and 12 (92%) who had a CR at six months maintained their response until a proteasome inhibitor. the data cutoff for the ASH analysis. “The primary endpoint of this study is PFS. With Pomalyst/dara/ Frankel described the JCAR17 data as “equally impressive” com- dex showing approximately nine months of progression free sur- pared with the bb2121 results with “deep and durable” and an “ad- vival in the 3rd or later line population, we suspect this could set equate safety profile.” Based on feedback from clinicians about using up bb2121 for approval in this population in the ~2021 timeframe,” the Novartis and Gilead/Kite products, he added, “we’re convinced Bernstein’s Gal wrote. the safety profile is unique” with the possibility some patients could BCMA is an important target in multiple myeloma for Celgene. The be treated on an outpatient basis. company plans to file an investigational new drug (IND) application Celgene committed $1bn up front in 2015 to partner with Juno with the FDA by the end of 2017 for a BCMA-targeting bispecific an- on the development of CAR-T and other therapies for cancer and au- tibody known as CC-93629 and it will file an IND in 2018 for an an- toimmune diseases. (Also see “Celgene shows CAR-T confidence with tibody-drug conjugate against the target in partnership with Sutro $1bn Juno investment” Scrip, 30 Jun, 2015.) Celgene exercised its first Biopharma Inc. option under the agreement in 2016 to develop and commercialize President and Chief Operating Officer Scott Smith noted dur- Juno’s CD19 program outside of North America and China, and it will ing Celgene’s Dec. 10 investor event at ASH that “because of how start a global trial for JCAR017 in DLBCL in 2018. strongly we feel about this target, it’s important for us to build differ- Juno has a preclinical candidate targeting BCMA and an early ent approaches and different modalities and different ways to get at Phase I CAR-T therapy against the multiple myeloma target, both of this particular target. So we don’t look at [the bispecific antibody] as which were presented at ASH, but those assets are not part of the backup. We look at it as a campaign in BCMA in multiple myeloma.” Celgene collaboration. When asked during Celgene’s Dec. 10 investor event at ASH JUNO PROGRAM EXPANDS CAR-T GOALS whether Celgene might renegotiate with Juno to gain US rights to JCAR017 with Juno is outside of Celgene’s multiple myeloma territo- JCAR017, however, President of Hematology and Oncology Nadim ry, but well within its hematology franchise. The company hopes that Ahmed hinted that the company might be interested in expanding it will offer both good efficacy and improved safety compared with its interest in Juno’s lead CAR-T candidate to further the big biotech’s Novartis’ Kymriah and Gilead/Kite’s Yescarta (axicabtagene ciloleucel) cell therapy goals. “Of course, currently we have actually less rights, as well as Juno’s prior CD19-targeting candidate JCAR015. but as I stated earlier, we have a very clear strategic ambition to be Novartis won US FDA approval at the end of August for Kymriah in leaders in cellular therapy,” Ahmed said. In prior comments, he noted relapsed or refractory pediatric acute lymphoblastic leukemia (ALL). that Celgene intends to be a leader in CAR-T therapies via more than (Also see “Novartis Beats CAR-T Competitors To The Pricing Punch With one program – both multiple myeloma and lymphoma. Kymriah Approval” Scrip, 31 Aug, 2017.) That was followed by approval Published online 12 December 2017 scrip.pharmaintelligence.informa.com 15 December 2017 | Scrip | 5 ASH MEETING

Spark Plots Rebound For Hemophilia A Gene Therapy, As Rival Biomarin Surges EMILY HAYES [email protected]

BMO Capital Markets analyst Matthew described the long-lasting results as “ex- Luchini said in a Dec. 11 note that the prob- citing” and said gene therapy for hemo- ability of success for SPK-8011 has dropped philia A, which is six times more common from 45% to 20% and that the results could than hemophilia B, is “seen as the ulti- mean a delay in the launch of one year to mate grail.” 2022, increasing Biomarin’s lead time. The landmark studies reported Spark’s he- However, president and co-founder Kath- mophilia B therapy SPK-9011 and Biomarin’s erine High told Scrip after the news broke: valoctocogene roxaparvovec are “leading “I do not like to prognosticate, but I do not the way to a cure for hemophilia,” van den think anything presented today would l Berg wrote. change the timeline.” Spark hit a major bump in the road, The company believes it has a product however, when it came to data for its SPK- with a competitive profile and just needs to 8011 in hemophilia A presented at ASH nail down the right dose. Dec. 11. Co-founder and CEO Jeffrey Marazzo said The company reported that four weeks Shutterstock: TAW4 Shutterstock: during a Dec. 11 investor call that “while after infusion, there was a 100% drop in the factor levels are not yet where we’d like the annualized bleeding rate (a mean of 0 park Therapeutics Inc. went into them to be, we have a potent vector and a down from 5.5) and a 98% drop in the use the American Society of Hematol- product candidate that works at generating of Factor VIII to a mean of 1.2 annualized Sogy annual meeting with its hemo- therapeutic levels at low doses.” infusions, down from 57.8. No serious ad- philia A gene therapy SPK-8011 looking well “Our remaining work is to optimize the verse events have been observed to date, matched against close competitor valoc- efficacy that we are seeing and we are con- Spark said. tocogene roxaparvovec (BMN 270) from fident that we have the technology product But the variability of levels of Factor BioMarin Pharmaceutical Inc., but was candidate and team to do so,” the exec said. VIII reported for patients was very disap- soon flattened by data that raised questions pointing. about consistency of response and com- LEADING THE WAY TO A CURE Data were presented for two doses. mercialization timelines. Spark’s Factor IX hemophilia B candidate The minimum Factor VIII activity level the Spark’s SPK-8011 (Spark200) has a novel SPK-9001, partnered with Pfizer Inc., per- company is looking for is 12% of normal bio-engineered adeno-associated viral formed well in an early study published in and the range should be within 50%-90%. (AAV) vector that encapsulates the human the New England Journal of Medicine on Levels too low threaten efficacy and lev- Factor VIII gene under the control of a liver- Dec. 6, just prior to the meeting. As of Nov. els that are too high pose a risk of throm- specific promoter for the treatment of he- 29, the annualized bleeding rate in 11 pa- bosis. High commented that 50% is the mophilia A. tients was reduced by 97% and the annual- “sweet spot.” The American Society of Hematology ized infusion rate was reduced by 99%. The Two participants had a dose of 5 x 1011 (ASH) meeting, held this year in Atlanta from mean steady-state Factor IX activity level 12 vector genomes (vg)/kg body weight. Dec. 9-12, proved to be pivotal for gene weeks after a single infusion was 36% of nor- One had sustained Factory VIII activity therapies in hemophilia. mal, the range being 15% to 78%. An edi- level after 12 weeks of 10% – the range Results presented at the meeting for SPK- torial accompanying the study results sug- was 7% to 11%. In the second, the Factor 8011 in hemophilia A at the meeting were gested that a cure may be in sight. VIII level as of data cut-off was 37% but disappointing, though there were positive Positive long-term results for BioMarin the mean after 12 weeks was 16% (with a elements. Data from a Phase I/II dose escala- Pharmaceutical Inc’s AAV vector Factor VIII range of 6% to 37%). tion study presented Dec. 11 at the meeting gene therapy valoctocogene roxaparvovec Two additional participants had a dose for a very small patient sample – four pa- (formerly BMN 270) in severe hemophilia A of 1 x 1012 vector genomes (vg)/kg body tients – showed excellent clinical outcomes, were published by Savita Rangarajan, of the weight and their sustained Factor VIII activ- but results were variable when it came to Hampshire Hospitals NHS Foundation Trust ity levels were 9% (range of 7% to 12%) and the Factor VIII activity and did not meet in- in Basingstoke, UK, in the NEJM on Dec. 10. 13% (7% to 24%) of normal, respectively, as vestor expectations. In an editorial accompanying the Bio- of the data cut-off. The company’s stock price tumbled on marin results, H. Marijke van den Berg, of Three more patients have been infused news of the data, closing by almost 35% to the PedNet Hemophilia Research Foun- but data will not be available until the $47.72 on Dec. 11. dation in the Netherlands, and colleagues second or third quarter of 2018 – one had

6 | Scrip | 15 December 2017 © Informa UK Ltd 2017 ASH MEETING

a dose of 1 x 1012 vector genomes (vg)/kg Spark will continue its dose-ranging work The 4e13 vg/kg dose has consistently body weight dose and two had a higher until it establishes the right regimen for demonstrated weaker FVIII production dose of 2 x1012 vector genomes (vg)/kg Phase III. Per the protocol of the Phase I/II compared to the 6e13 vg/kg dose, but body weight. study, the company may test up to 10 pa- could facilitate a larger market share for the “To date, none of the seven infused par- tients for each dose. product, said Leerink Swann analyst Joseph ticipants has reported a serious adverse The goal in the next few months is to Schwartz in a Dec. 10 note. Optionality in event, including no Factor VIII inhibitors, no enroll and study enough subjects to make doses should be appealing to different pa- thrombotic events and no Factor VIII activity a decision what dose to take forward to tient segments of the market, the analyst levels that may increase risk of thrombosis,” Phase III, but the company does not expect explained. the company reported. it will need to go above the three doses in In a NEJM editorial accompanying the Jefferies analyst Michael Yee observed in a development. data, van den Berg commented that “al- Dec. 11 note that the variability in response though the obtained levels are impressive, kinetics was unexpected – one patient had BIOMARIN RISES the large variation among patients needs a level of 5% but “spiked up to 20-25%, then Biomarin’s valoctocogene roxaparvovec clarification.” went back down below 10%.” The data also fared well amid comparisons with Spark, “Will it be possible to predict who can be shows that it takes longer than expected but its data also drew some scrutiny. treated with lower doses? Can a precondi- time to reach eventual plateau, “suggesting The company released updated data at tioning regimen reduce the vector dose?” we need more time to figure out the overall the ASH meeting for two doses – 6e13 vg/ she asked. profile of the drug.” kg (n=7) up to 78 weeks and 4e13 vg/kg Meanwhile, Biomarin is gearing up for BMO Capital Markets’ Luchini commented (n=3) up to 48 weeks. Phase III. The company plans to start two that the data did not reflect a dose response “Although median FVIII levels of 90% at pivotal trials soon as part of the Phase III for the higher vs. the lower dose. week-78 for the high dose (6e13) and 49% GENEr8 program testing each dose – 6e13 “Intra-patient variability was also high, at week-48 for the mid-dose (4e13) remain vg/kg and 4e13 vg/kg. with one patient’s FVIII levels ranging from within 50-90% of normal, which we consid- Schwartz commented that the latest data ~2% to ~12% and one other from ~2% to er to be ideal, investor focus remains on the support BioMarin’s decision to pursue both ~27%,” he noted. outliers,” BMO Capital Markets Ian Somaiya dose levels. Longer term therapy has been associated commented in a Dec. 11 note. On Dec. 11, BioMarin stock closed up by with a plateau. In the group on the higher dose, the 7.46% to $88.11. The cause of the variability has not been mean Factor VIII level was 90% of normal, Published online 12 December 2017 determined. During Spark’s call, clinicians but the range was from 50% to 120%, So- explained that Factor VIII level is not typically maiya noted. Levels over 100% are associ- measured in hemophilia patients on Factor ated with risk for thrombotic events. Spark’s Hemophilia B Gene Therapy SPK9001 VIII treatment unless they are bleeding, and The therapy was also well tolerated across Packs A Punch And Saves Big Bucks: it is unclear what should be expected fol- all doses tested and no patients developed http://bit.ly/2jwIIhN lowing gene therapy. inhibitors or dropped out, BioMarin reported.

CONTINUED FROM COVER BioMarin Pharmaceutical Inc. edged trial testing its gene therapy SPK-8011 presented by another partner, Juno Thera- out Spark in the race to bring a potential in hemophilia A patients Dec. 11, show- peutics Inc. Celgene’s stock opened on one-time cure to patients with hemophilia ing they reduced their overall annual- Dec. 11 3.8% higher at $110.07, before set- A (see story on p6). BioMarin’s stock gained ized bleeding rate after week four by tling down mid-day. Juno investors seemed 9% to open Dec. 11 at $89.49, boosted by 100%, but there was considerable vari- unmoved, with the stock moving down positive data from a Phase I/II trial testing ability among the level of Factor VIII that 11.8% in mid-day trading. the gene therapy valoctocogene roxaparv- was achieved, raising questions in the Blueprint Medicines, meanwhile, soared ovec in patients with hemophilia A. minds of investors. Data from an ongo- on early data from the dose-escalation por- Data from the three patients with the ing Phase I/II trial of SPK-9001 for the tion of an ongoing Phase I clinical trial of longest follow-up at week 48 had Factor treatment of hemophilia B looked solid, avapritinib, a KIT and PDGFRα inhibitor for VIII activity levels in or near the normal but hemophilia A represents the larger advanced systemic mastocytosis (SM). Al- range and zero bleeding events after four commercial opportunity. Hemophilia A though the data were from just 32 patients weeks. BioMarin plans to begin enrolling occurs about six times more often than treated with avapritinib, the results were en- Phase III studies by the end of the year. The hemophilia B. couraging: an overall response rate of 72% data were published in the New England Regardless of the results presented at and a disease-control rate of 100% in patients Journal of Medicine Dec. 9, along with a ASH, these programs have many more evaluable for response. With the positive re- glowing editorial, highlighting the work as milestones to hit in the road to approval, so sults in hand, Blueprint said it plans to engage a potential cure for hemophilia A. there are likely to be plenty more stock hic- global regulatory authorities in the first half of Spark also released positive data on cups along the way. 2018 on input for a registration pathway. the first four patients from a Phase I/II Published online 11 December 2017 scrip.pharmaintelligence.informa.com 15 December 2017 | Scrip | 7 HEADLINE NEWS

Pharma ‘All-Stars’ Talk Hot Topics At Forbes Summit JESSICA MERRILL [email protected]

ive of industry’s top leaders took the stage together at the Saunders defended his decision, claiming that the IPR challenges are Forbes Healthcare Summit in New York on Nov. 30 to discuss unfair because they act as double-jeopardy with federal court patent Fsome of the most pressing issues facing the industry, and as challenges under Hatch-Waxman. “I don’t think it is desperation,” he said. usual during what is billed as “the pharma all-stars” panel, there was “The current system is a flawed system. If you want to debate the IP kinship, discord and a few fireworks. system that would be a more substantive debate,” he said to Schleifer. This year, there was also a poignant moment when a cancer Nonetheless, most of the panelists agreed with motivation behind patient in the audience stood up and asked a question of the five Allergan’s deal, if not exactly the tactic. “I agree as a matter of policy chief executives that sucked the air out of the room and reminded with the double jeopardy issue,” Frazier acknowledged. everyone that despite all of the issues – drug prices, taxes, patent Amidst the lively debate, panelists and attendees were drawn protection, stock prices, commercial successes, mega-flops – there back to reality by an audience member who stood up to ask a ques- are plenty of reasons to keep investing in pharmaceutical drug de- tion that was essentially, “I have a rare cancer; What can you do for velopment. me?” With all of the positive developments going on in the oncol- This year’s pharma all-star lineup included Merck & Co. Inc. CEO ogy field, he wanted to know what drug companies can do for Kenneth Frazier, Pfizer Inc. CEO Ian Read, Allergan PLC CEO Brent smaller subsets of patients with rare cancers, where the commercial Saunders, Eli Lilly & Co. CEO David Ricks and Regeneron Pharma- opportunity might be smaller. ceuticals Inc. CEO Len Schleifer. The moment was a reminder of what is at stake when it comes to drug development and the critical nature of the work beyond the ADMINISTRATION ‘DOES VALUE THIS INDUSTRY’ drug pricing and policy debates. The question also hung in the room After a year that started with the President of the United States call- as realities like blockbuster sales and R&D investment sunk in. ing out the drug industry for “getting away with murder,” the panel- Schleifer acknowledged the challenges. “You do have to have a re- ists appeared to agree that industry’s anxiety around the potential ward,” he said. “You are spending billions and billions of dollars. There for more government involvement in drug pricing has tempered. has to be a reward system that incentivizes.” (Also see “Trump Throws Pharma A Curve Ball On The Third Day Of J.P. But Pfizer’s Read sought to assure him that drug makers are willing Morgan” Scrip, 12 Jan, 2017.) The industry has had a mixed relation- to study rarer cancers. He pointed to the company’s ALK1/ROS1 tyro- ship with President Trump at different points during the year, but the sine kinase inhibitor lorlatinib in development for a rare lung cancer panelists appeared largely pleased with the appointments of former with ALK and ROS1 mutations. colleague Alex Azar as Health & Human Services Secretary and Scott “We develop those drugs,” he said, noting that Pfizer will often do- Gottlieb as FDA Commissioner. nate the drug to independent scientists investigating a specific area. Ricks, who previously worked with Azar at Lilly, said he didn’t hear “They come to us and say, ‘I want to run this trial in 30 patients, will you any unexpected issues arise during the recent Senate confirmation donate the drug?’ And we do, once we review the scientific rationale. I hearing. “I didn’t hear anything particularly new,” he said. “I do think think there is adequate access in those kinds of precision drugs.” the new commissioner of the FDA has put into action some things Lilly’s Ricks said flexibility at FDA to allow the use of earlier data to that can improve and are improving the environment,” he added. support indications for rare and urgent diseases is also a positive step Merck’s Frazier had a positive tone about the White House, even toward developing medicines for rarer cancers. “I would say we need after he personally became the target of a Trump tweet after he that in other therapy areas,” he said. stepped down from the president’s American Jobs Advisory Council in August. ‘WE ARE IN THE MIDST OF A MARKET EXPERIMENT’ “I think this administration does value this industry,” Frazier said. “I In the end, all five CEOs largely agreed the industry is in the midst of think [Trump] got across to us that he was not trying to fundamen- change, both in the commercial market when it comes to drug pric- tally kill innovation, so I think that is a very positive thing.” ing and the payer environment, and when it comes to the science. He added, “Our relationship with the government doesn’t trouble “I think we are in the midst of a market experiment,”Schleifer said, me at the moment.” referencing the current attempts by pharma companies and payers to use new methods to tie the cost of drugs to the value they deliver. ‘IT MADE US LOOK BAD’ He pointed to the launch of Regeneron’s Dupixent (dupilumab) for The fireworks came when Allergan’s recent deal with the Saint Re- atopic dermatitis as an example, where the company, with its partner gis Mohawk Tribe to circumvent the inter partes review (IPR) system Sanofi, tried to price the drug reasonably for a biologic in the hopes came up. Allergan drew a lot of criticism for the deal, aimed at pro- of securing broader access. tecting the intellectual property for Restasis, while Saunders has also “We expect them to reward us, not because we are such good been a vocal critic of some of the industry’s pricing practices. guys … but because it is in their own self-interest,” he said. Schleifer, who has a reputation for straight talk, told Saunders the But Read countered that argument. He said the incentives in the move reflected poorly on the entire industry. “I think it made us look insurance market need to be better realigned to long-term health bad,” he said to Saunders. “It makes you look desperate. … I think outcomes to broaden market access to drugs. you’d be better off trying to invent a new drug.” Published online 8 December 2017

8 | Scrip | 15 December 2017 © Informa UK Ltd 2017 HEADLINE NEWS

Gilead Acquisition Of Cell Design: The Next Logical Step JOSEPH HAAS [email protected]

ilead Sciences Inc.’s acquisition of and chief medical officer, now are under the ated, according to the company. The technol- privately held Cell Design Labs Inc. Gilead umbrella.) ogy splits a CAR-T construct into two separate, Gseemed almost preordained follow- Gilead’s primary interest in Cell Design inactive molecular components, where they ing its $11.9bn buyout of CAR-T specialist seems to be about applying the synNOTCH wait in an “off” state until introduction of a Kite Pharma Inc. back in October, and mar- platform – which can enable T-cell thera- small molecule therapy brings them together ket analysts expect the deep-pocketed spe- pies to detect new molecular targets and – thereby “closing the switch” – to become ac- cialty firm to continue making bolt-on deals turn on genes – to its future CAR-T and TCR tive and seek out and eliminate cancer cells. to advance its expertise and capabilities in (T-cell receptor) therapies, the exec added. Cell Design has been focusing on one immuno-oncology. The existing Kite/Cell Design partnership marketed small molecule. Although At- Gilead announced a structured buyout applies the THROTTLE platform to a preclini- wood declined to specify what molecule valued at approximately $567m for the Em- cal acute myeloid leukemia (AML) candidate that is, he said a broad selection of mole- eryville, Calif.-based Cell Design on Dec. 7, that Atwood said is making steady progress cules can be used and the firm has a handful bringing in its synNOTCH gene expression towards the clinic, perhaps arriving in 2019. of backups to move into the clinic. and THROTTLE switch technology platforms. Atwood said integration planning is Cell Design’s founders realized from the Kite was already partnered with Cell Design slated to begin shortly and continue into start that their technology likely would be to apply the THROTTLE “on-off switch” tech- January, and that Cell Design executives will widely applicable, more broadly than their nology to a preclinical chimeric antigen begin meeting with Gilead and Kite during small company could bring about on its own, receptor T-cell (CAR-T) therapy and Cell De- the American Society of Hematology con- Atwood noted. That resulted in the partner- sign Co-founder and CEO Brian Atwood told ference in Atlanta Dec. 9-12. Whether Cell ship with Kite, which had been talking with Scrip that the platform also could be applied Design is to become a Gilead subsidiary and Cell Design’s scientific founder Wendell Lim, to a next-generation version of Kite’s recent- whether Atwood and his team will be stay- a University of California scientist, for several ly approved Yescarta. ing on is to be determined, he added. Cell years before Cell Design’s inception in 2015. The second chimeric antigen receptor T- Design, which has no other partnerships Kite was among the investors in Cell Design’s cell (CAR-T) therapy on the market, Yescarta outside of Kite to resolve, has been advanc- $28.4m Series A financing. (axicabtagene ciloleucel) obtained US FDA ing three proprietary preclinical programs: “It was really a great relationship right approval Oct. 18 for relapsed or refractory a lead candidate in multiple myeloma and from the beginning and led us through to large B-cell lymphoma, just weeks after Gil- two others in prostate and liver cancer. where we are today,” Atwood said. “We see ead’s acquisition of Kite. “As we went through our discussions and the technologies combined with what Kite’s Kite holds a 12.2% ownership stake in diligence with the Gilead team, a big part of doing – which is much broader than Yescar- Cell Design. The anticipated total value of what they’re interested in is our other tech- ta – and what Gilead has been doing in the $567m for the transaction includes a $125m nology platform synNOTCH,” Atwood said. “So, past 10 years in cancer as a way to get this upfront payment to Cell Design’s sharehold- really, they bought us for this kind of broad technology out and make it work in a lot of ers and up to $322m in milestone payments technology platform and its applicability to different cancer indications.” tied to development and approval mile- CAR-T therapeutics in a broad for manner for stones. The other $70m in the perceived liquid tumors as well as solid tumors. We’d ex- ESTABLISHING LEADERSHIP deal price reflects Kite’s ownership in Cell pect both technologies to be applied broadly.” Analysts were uniformly impressed with Gil- Design, although Gilead won’t actually be The synNOTCH technology works by re- ead’s latest transaction. Michael Yee of Jef- paying itself that amount to complete the engineering the naturally occurring Notch feries Equity Research said the Cell Design transaction, Atwood noted. receptor and placing the resulting con- technology can help improve or enhance Despite the existing relationship between structs into a patient’s immune cells, en- the programs acquired via the Kite pur- Gilead and Kite, Atwood, also a managing abling those cells to be programmed. When chase. “We are positive on the demonstrated partner at Versant Ventures, said he had no the programmed cell binds with its targeted investment to CAR-T and believe this is a prior inkling of the August deal combining cancer cell, it will trigger one or more spe- ‘long-term’ investment to build a cancer cell those two companies. cific molecular activities, Cell Design says, in- therapy platform over the next five years,” he “There were rumors that Gilead had inter- cluding local modulation of tumor defense wrote in a Dec. 7 note. est in several cancer companies, including mechanisms, drug delivery to induce a cus- Yee predicted that Gilead might next look Kite, but the [Kite executives] that I’m most tomized cytokine profile and supercharge to bring in gene-editing technology through in touch with who are on our board, David the immune system, and long-term protec- some sort of deal. That type of technology Chang and Arie Belldegrun, never talked tion of cancer recurrence by encouraging could enable Gilead to fine-tune and control to me about this stuff,” Atwood said. “For T-cells to differentiate into specific subtypes. T-cell therapeutics “from all angles,” he added, us, the interactions [with Gilead] really only THROTTLE enables CAR-T cells to be turned pointing to Sangamo Therapeutics Inc. as occurred after the closing of the deal.” (Bell- on and off repeatedly, potentially making one potential partner or buyout prospect. degrun and Chang, respectively Kite’s CEO them both more effective and better toler- Published online 10 December 2017

scrip.pharmaintelligence.informa.com 15 December 2017 | Scrip | 9 BREXIT

Pharma Lauds Brexit ‘Breakthrough’ IAN SCHOFIELD [email protected]

ews that “sufficient progress” has The announcement came at the end of end up in situation where we can’t supply.” been made for the Brexit nego- a week that saw ABPI CEO Mike Thompson One committee member asked: “Why Ntiations to move on to phase two and several other pharma executives outline can’t we simply manufacture more of what has been given a cautious welcome by UK some of their more pressing concerns at a we need ourselves?” Thompson pointed out pharma firms, although concerns remain hearing of the House of Commons’ business, that the industry does not have the capability over the need for some form of continuing energy and industrial strategy committee, to manufacture all the medicines it needs in regulatory alignment between the UK and which is conducting an inquiry into the im- the UK. As for constructing more production the EU as well as a transition period of at pact of Brexit on the pharmaceutical industry. facilities, he noted that a manufacturing plant least two years after Brexit. Key among these concerns is the impact “costs tens, sometimes hundreds of millions The Association of the British Pharmaceu- of Brexit on the movement of medicines. of pounds” and that “no one” is going to build tical Industry said that the progress made The witnesses were asked about the impor- new manufacturing plants in the UK which on citizens’ rights in phase one of the talks tance of the EU to the UK in terms of trade in “at current values with the devaluation of the was “particularly welcome news for phar- medicines and vaccines, and how the avail- pound is 2.3% of the global market.” maceutical companies and our employees,” ability of medicines might be affected by Building such plants “would not make and that to “provide certainty to everyone, the possible imposition of tariff and non-tar- economic sense,” Thompson said. “I don’t we hope this is swiftly agreed.” iff barriers. Thompson said that the value of think its practical and it would also mean But it stressed that it was “crucial” that the both imports from and exports to the EU of costs would have to go up dramatically.” regulation and supply of medicines for UK pharmaceuticals is about £30bn. 44% of the and EU patients were now prioritized in the UK pharmaceutical industry’s exports go to BATCH RELEASE negotiations. “A cooperation agreement the EU, with about 45 million packs leaving Another major concern is batch release – spe- between the UK and the EU on medicines UK shores every month and 37 million packs cifically the requirement under EU law that is the best way to ensure that there is no coming the other way, he added. companies have a batch release site in an EU disruption to 500m patients receiving the “The reason for that is in a sense that this member state if the products are for distribu- medicines that they need,” the association industry has made the most of being in the tion in the EU, and the fact that companies said. It also called for a “single-step fixed- single market and we have very integrated without EU facilities will have to build them. term transition period” that allows compa- supply chains across the whole of the conti- GlaxoSmithKline PLC announced earlier nies to make any necessary changes to the nent.” Thompson said, noting that “for us the this year that it was planning to build some supply chain. “Protecting public health in most critical issue at this moment in time is testing sites in continental Europe because the UK and Europe must be a priority.” the delay issue.” of this requirement. Thompson told the The BioIndustry Association also wel- If the UK does pull out of the EU single committee that in the absence of some comed the agreement and called for a tran- market and customs union, industry fears form of regulatory cooperation framework sition period to ensure medicines supply these supply routes will be disrupted, caus- between the UK and the EU after Brexit, “es- was not affected. ing delays at borders and to patient access sentially GSK would not be able to supply its Noting the agreement’s proposal to en- to medicines. The ABPI said in its written medicines manufactured in the UK to other sure “continuity in the availability of goods submission to the committee that if trade EU member states if it hadn’t got that facil- placed on the market” under EU law before between the UK and EU were to be subject ity built. So they are going to spend tens of Brexit, the BIA’s CEO, Steve Bates, said: “My to customs duties, import VAT and border millions of pounds to set up that capability.” initial reading of the ‘goods on the market’ controls (import/export declarations and in- Paul Fleming, technical director of the Brit- proposals is that it should enable medici- spections/goods testing), “this would cause ish Generic Medicines Association, agreed. nal products that have been tested and re- significant disruption to the supply chain for The time taken to establish testing facilities leased prior to the Brexit date (which may medicines.” Particularly affected would be means that “people are changing their be- well now be later than March 2019) to be time- and temperature-sensitive products, havior” – either thinking about building new freely available in the EU, even if that test- including gene therapy medicines. facilities, “which would be the ultimate and ing and release is carried out in the UK and Thompson said this was “not an issue of most costly approach,” or making “new com- the goods are shipped to other EU countries UK patients versus EU patients, this is about mercial arrangements,” Fleming said. This pro- after the UK withdraws.” patients across all Europe. Everybody is go- cess can take “at least 12 months, typically 18 This, Bates said, was “important detail for ing to lose out here. At one level, we say or up to 24 months.” global companies deciding how, and cru- surely everyone will understand that and we On top of the costs of building new facili- cially when, to progress existing Brexit con- will not end up in that position,” but the scale ties, companies will essentially be duplicat- tingency plans.” He also hoped the propos- of the challenge facing those who are nego- ing batch release testing for the UK and the als on citizens’ rights would “enable people tiating the arrangements could mean that EU, and this will entail much additional ex- to better plan their life science careers with “somehow these things could get missed, pense for companies with only UK sites. their families.” the officials can’t cope with it, and we could Published online 10 December 2017

10 | Scrip | 15 December 2017 © Informa UK Ltd 2017 BREXIT

Sir John Bell: UK Life Science Pact Essential STEN STOVALL [email protected]

ritain’s life sciences industry has ing medicines and healthcare technology. agencies in the UK has been a bit too missed the innovation boat twice in Concerns over Brexit and its long-term im- slanted towards keeping things ‘fair’ while Brecent years due to risk aversion and pact on the economy make that even more assembling all the possible experts at once. a plodding mindset, but the government’s imperative, he said. Well the experts bring with them a very sub- just-unveiled industrial strategy to boost the “What we’re trying to do is create a sus- stantial problem and that is the perceived sector offers a once-in-a-lifetime opportu- tainable innovation cycle that starts with wisdom of what is right and what is wrong. nity to undo the damage. our great universities – discovery programs That was the message from Sir John Bell, like the one that Merck is bringing to the NHS: DARPA POTENTIAL? Regius Professor of Medicine at University of UK, work their way through clinical devel- “The DARPA model is very interesting be- Oxford, who played a key role in formulating opment, work their way through manufac- cause they avoid experts like the plague. the Life Sciences Sector Deal, unveiled on turing – but to complete the circle, the best And they work very hard to try to create Dec. 6 and which the UK government says innovations have got to be adopted. And novel approaches to really novel problems. will be ‘transformative’. that’s where there’s a break in the cycle. The I don’t think we do that very well,” said Bell, NHS needs to think how it will adopt the in- who is a Canadian-British immunologist ‘ADAPT OR DIE’ novations much more effectively,” he told and geneticist. The pact will involve long-term partnership the House of Lords committee. “DARPA has an in-built procurement with the government, backed by private “If you’re talking about a sustainable sys- model which went straight back into de- sector co-investment. It brings together tem, but if you don’t have that whole circle fense which meant that when they dis- commitments and investments into the UK working, then industry will question it, and covered satellites they were immediately by 25 global organizations from across the probably back away.” deployed for defense purposes, the same life sciences sector, including a major injec- He said history shows the UK approach for GPS. But don’t forget, we have a massive tion by Merck & Co. Inc.’s European entity to life sciences innovation isn’t working, and industry that could procure innovation of a Merck Sharp & Dohme Ltd. (MSD) and by needs urgent change. new kind – it’s called the NHS,” Bell said. GlaxoSmithKline PLC, unveiled as votes He noted that Prime Minister Theresa of confidence in the new strategy. OPPORTUNITIES MISSED May on Nov. 20 said she wanted to see an Giving evidence beforehand to the UK’s “We completely missed immuno-oncology. increase in the level of investment in R&D, House of Lords Science and Technology Probably the biggest breakthrough in on- from 1.7% to 2.4% of GDP by 2027. This Committee on Dec. 5, Bell predicted that cology in 50 years was the use of the im- could mean around £80bn of additional “we will see more of those investments in mune system. The UK had no play in immu- investment in advanced technology in the the not-too-distant future, and they’ll be no-oncology.” next decade. Bell in his evidence to the very significant ones in discovery science in He said another transformative innova- House of Lords Science and Technology the UK. They’ll be parked close to academic tion that Britain missed out on was gene- Committee on Dec. 5 said, “I’m really confi- science; they’ll work together and hopefully editing. dent we’ll get to 2.4% of GDP on R&D. But it create value. They’ll hopefully put the pat- “Every country in the western world was will rely on the Treasury helping us.” ents in the patent box; and hopefully they’ll involved in the CRISPR-cas9 innovation ex- He said a joined up, well-funded and in- manufacture things here.” cept one, the UK,” he said. novation-hungry British life sciences sector He was speaking after MSD said it would could lead the way in future, if all went well. build a state-of-the-art life sciences R&D fa- RISK AVERSION “One of the ideas that has come out of the cility in London, creating around 950 jobs. He said that although the UK has an excel- braining storming for this is what healthcare And GSK said on Dec. 5 it was investing lent science base, “we don’t do high-risk sci- will look like 20 years from now. Pharma £40m fresh funds into its previously an- ence. And one of the ways the Americans companies would love to explore for exam- nounced effort to generate genetic sequenc- have ‘won’ is that they do high-risk science.” ple the issue of what early diagnosis means ing data from the UK Biobank, the world’s He used the US Defense Advanced Research in terms of running a healthcare system,” he most comprehensive health resource. GSK’s Projects Agency, also known as DARPA, to il- said. For that to be effective though, current new commitment will support the sequenc- lustrate the point. spending programs need to be re-evaluat- ing of data from all 500,000 volunteer par- “DARPA research programs are all about ed and changes made. ticipants, beyond the first 50,000 subset an- using brand new technologies to address Published online 8 December 2017 nounced by the company earlier in 2017. brand new missions – not using recycled Bell said the two moves were in response technology to address old missions. It’s new to the life sciences sector deal and that technology for new missions.” RWE and Clinical Trials To Take Center Stage In they underscored that the UK needs to “The way we’ve gone about the distri- UK Sector Deal Prospects: become more innovative, joined-up, and bution of life sciences funding of research http://bit.ly/2C8JBBR much more willing to take risks in develop- in both the charities and the government

scrip.pharmaintelligence.informa.com 15 December 2017 | Scrip | 11 RESEARCH & DEVELOPMENT

Sage’s Depression Therapy Shows ‘Dramatic’ Effect MANDY JACKSON [email protected]

age Therapeutics Inc. CEO Jeff Jonas is so impressed with his Remission rates at weeks four and six were 52% and 45% for the company’s oral depression drug candidate SAGE-217 based on SAGE-217-treated patients and 28% and 33% for the placebo group SPhase II results reported on Dec. 7 that even without Phase III (p=0.0221 at week 4; not statistically significant at week 6). data to back up the small mid-stage study he’s willing to say that the “Although no head-to-head comparison was performed, officials efficacy seen to date supports first-line treatment. in the accompanying call suggested that SSRIs show a remission rate Investors also were enthusiastic, sending the company’s stock of around 25%-30% and only after 6-8 weeks. Thus, it is not unreason- up 70% to close at $156.27 after Sage reported that patients able to consider whether SAGE-217 could be targeted as a new front- who were treated with its oral GABA-A receptor modulator had a line standard of care for MDD,” Biomedtracker analysts said. statistically significant mean reduction in Hamilton Rating Scale In terms of safety, there were no serious or severe adverse events for Depression (HAM-D) scores of 17.6 points at day 15 versus a and no deaths. mean reduction of 10.7 points for patients who received a pla- cebo (p<0.0001). Nearly two-thirds of SAGE-217-treated patients PHASE III PLANS DEPEND ON FDA FEEDBACK were deemed to be in remission at the 15-day mark and statisti- Sage did not disclose its Phase III strategy, which it will discuss cally significant efficacy was observed two weeks after patients’ with the FDA now that it has the positive Phase II results in hand. last dose. SAGE-217 was granted a fast track designation earlier this year and Jonas said in an interview with Scrip that the rapid onset of efficacy the company was asked about a potential accelerated filing for – observed as early as day two – as well as the remission rate, durable the MDD indication. Jonas deflected such speculation – at least in responses and general tolerability of SAGE-217 “is obviously distinct MDD – because the large size of the patient population (about 16m from both the conventional therapies as well as some of the newer people in the US) is likely to require larger, longer studies to vet the fast-acting therapies.” drug’s safety. He said the efficacy is so different from available therapies, which However, the company left the door open for an accelerated fil- can take weeks or months to improve depression symptoms, that ing in postpartum depression (PPD). Sage said it has increased the “people are going to have to clear their minds of the conventional size of its ongoing Phase II study for SAGE-217, but did not provide approach to treating depression if we’re successful” in Phase III. any details about that. Jonas noted during the company’s same-day Informa Pharma Intelligence service Biomedtracker noted in its conference call with investors that Sage believes a smaller proof-of- Dec. 7 analysis of Sage’s Phase II study that the company already has concept study in PPD is no longer necessary given the efficacy seen shown efficacy in Phase III for the SAGE-217 mechanism of action. for the GABA-A modulation mechanism of action in the brexanolone Sage plans to submit its intravenously administered GABA-A modu- and SAGE-217 MDD studies. lator brexanolone for US FDA approval to treat postpartum depres- Importantly, the CEO said multiple times during the company’s sion based on positive Phase III data reported almost a month ago. call, there was no difference in response to SAGE-217 when the “The company has already shown success in this novel class of overall Phase II data were compared to various subgroups of pa- GABA-A modulators with brexanolone, but SAGE-217 is even more tients in the MDD study, demonstrating consistent efficacy across important as a potential once-daily oral formulation,” the Biomed- the entire population. tracker analysis said. “Our approach will be to [develop] this for the general popula- tion of MDD regardless of whether they’re characterized as moder- TWO WEEKS TREATMENT, SIX WEEKS ASSESSMENT ate or severe or [treatment-]resistant or not,” Jonas said during the The Phase II clinical trial enrolled 89 people with moderate to severe company’s call. “We believe that this is a novel mechanism that may major depressive disorder (MDD), including those on background approach depression in a way that no one’s done before and … that selective serotonin reuptake inhibitor (SSRI) therapy, who were allows us to anticipate, or at least think about, the opportunity for this treated with 30 mg of SAGE-217 or a placebo nightly with food for as true first-line therapy.” two weeks. HAM-D scores were between 22 and 33 at baseline, or a Leerink analyst Paul Matteis offered a positive take on the SAGE- median of 25.2 in the SAGE-217 arm (n=45) and 25.7 in the placebo 217 results in MDD, but was not as optimistic about the drug’s place arm (n=44). in the treatment paradigm as Sage’s CEO. Remission at day 15, defined as a HAM-D score of 7 or less, was “Given the large effect size seen at two weeks, which is we see as dif- achieved by 64% of patients treated with SAGE-217 and 23% who ferentiated from other depression therapies, we now model usage for received a placebo (p=0.0005). Other secondary endpoints also were SAGE-217 in the second and third-line setting versus only fourth-line positive at day 15 (p<0.002). previously,” Matteis wrote in a Dec. 7 note. “In turn, our ~$3.4bn gross The mean reductions from baseline in HAM-D scores at week four sales opportunity in 2025 may seem large for a Phase II asset (and it is – two weeks after the two-week treatment period – were 15.6 points additionally risk-adjusted); however it’s worth noting that prior SSRI/ in the SAGE-217 arm and 11.9 in the placebo arm (p=0.0243). The SRNIs such as Zoloft, Effexor, Lexapro and Cymbalta all generated be- mean HAM-D reduction of 15 points in the drug arm was numeri- tween $2bn-$5bn in peak sales in what were fairly crowded branded cally, but not significantly, better than the 13-point reduction in the categories (multiple drugs approved with the same mechanism).” placebo arm at week six. Published online 7 December 2017

12 | Scrip | 15 December 2017 © Informa UK Ltd 2017 RESEARCH & DEVELOPMENT

Shire Explores Robotic Pill Potential For Hemophilia KEVIN GROGAN [email protected]

hire PLC has teamed up with robotic pill specialist Rani Thera- agulation complex) was the only therapy approved for prophylactic peutics LLC to investigate an oral option for hemophilia pa- treatment of hemophilia A with inhibitors. However, competition Stients that could transform the treatment pathway for sufferers arrived across the Atlantic last month with the approval of Roche’s of the bleeding disorder and replace injections. Hemlibra (emicizumab). Although the Rani pact is very much an early-stage collabora- tion, Shire will be hoping that it can help shore up its leading posi- tion in the hemophilia space, one of the challenges for its recently- appointed R&D chief Andreas Busch. Also no oral therapies exist for the disease, but the benefits of having a pill in terms of improving patient compliance, outcomes and quality of life are evident. (Also see “Shire Tempts Busch From Bayer As It Eyes Top Spot In Rare Dis- eases” Scrip, 1 Dec, 2017.) Datamonitor Healthcare analyst Daniel Chancellor told Scrip that “the idea of a simple-to-swallow pill that is able to provide comparable bleeding control to current therapies would be hugely attractive.” He added that it would be “arguably a bigger advance than gene therapies, because the barrier to treatment would be so low [and] would basically fulfil any target product profile that you could design.” Chancellor said that “obviously the challenge lies in the technol- Shutterstock: patpitchaya Shutterstock: ogy, but I expect strong patient demand if it can match the pharma- cokinetic profile of current long-acting recombinant FVIII therapies.” The collaboration will involve research on the use of the Rani Pill He added that “I expect there will always be a place for intravenous technology for the oral delivery of Factor VIII therapy for patients with injections for acute bleeds, but again this may depend on the PK pro- hemophilia A. The approach that the California-based biotech has file of a pill.” developed for the delivery of large molecules such as peptides, pro- As for Rani, Chancellor said that the company “certainly looks like teins and antibodies, which currently have to be injected or infused, one to watch.” Founded in 2012 after being spun out of InCube Labs, centers around a capsule that delivers an intestinal injection without its ‘robotic’ pill is being developed to convert injectables, such as TNF- exposing medication to digestive enzymes. alpha inhibitors, interleukin antibodies, basal insulin and basal insulin Rani noted that once the capsule is consumed, it stays protected and GLP-1 analogs into oral pills, and has attracted the attention of until it enters the small intestine and delivers medication into the in- a couple of other big pharma players. (Also see “Rani raises cash for testinal wall. Since the intestines do not have sharp pain receptors, ‘holy grail’ of oral formulations for biologics” Scrip, 30 Aug, 2013.) the intestinal delivery is expected to be pain free. Rani entered into a collaboration in 2015 with Novartis AG to The collaboration gives Shire an exclusive option to negotiate a evaluate its drug delivery platform with selected biologics in the license to develop and commercialize the technology for delivery Swiss major’s portfolio. This was followed by a metabolic disease pact of FVIII therapy following feasibility studies. No financial details were signed with AstraZeneca PLC in 2016 and both of those big phar- disclosed but Shire has also made an equity investment into Rani. mas have taken stakes in the company. Fritz Scheiflinger, head of global research at Shire, said in a state- Rani also has the backing of Alphabet’s Google Ventures arm and a ment that the firm’s “in-depth scientific expertise and leadership po- recent $39m Series D financing brings the total raised to date to over sition in hemophilia and Rani’s deep experience in engineering and $100m. David Pyott, a director and former CEO at Allergan PLC, said material science, we are excited by the potential of this partnership in a statement announcing the Shire pact that “Rani has the potential to reduce the chronic burden of hemophilia on patients’ everyday to disrupt the industry with its innovative approach to delivering bio- lives by researching an oral option to deliver FVIII to patients.” logics orally [and] the hemophilia market is an excellent application Shire has the world’s largest hemophilia franchise following its ac- of Rani’s technology.” quisition of Baxalta Inc. and until recently Feiba (anti-inhibitor co- Published online 6 December 2017

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scrip.pharmaintelligence.informa.com 15 December 2017 | Scrip | 13 STRATEGY

Hisun-Pfizer Split: What Went Wrong And What Next? YING HUANG [email protected]

wo weeks after suspension of trad- and tazobactam), Pristiq (desvenlafaxine), cere Pharmaceutical Group. The two ing, Zhejiang Hisun Pharmaceuti- Celebrex (celecoxib) and Dynastat (parecox- companies forged a JV in 2011 with a focus T cal Co. Ltd. officially addressed -en ib sodium injection). (Also see “Pfizer Looks on developing branded generic drugs in quiries from the Shanghai Stock Exchange To Ramp Up Branded Generics Via MOU With China. Merck contributed its diabetes block- regarding the split-up of the Hisun-Pfizer China’s Hisun” Scrip, 2 Jun, 2011.) buster Januvia, its now-off-patent statin Pharmaceuticals Co. Ltd. joint venture. To date, most products have not made drug Zocor and cardio medicine Cozaar to On Nov. 29 Hisun revealed the new any solid progress; the JV has only complet- the JV. As part of Merck’s overall restructur- framework agreement with Pfizer Inc. on ed transfer for local sub-packing and manu- ing, it handed over control of the JV to Sim- the ongoing product technology transfer, facturing of Caduet and Minocin. Hisun also cere in 2015. which could potentially accelerate the lo- has in-licensed the rights of Dynastat to “The continued unequal investments were cal development for nine branded generics develop a generic version and filed a drug one of the reasons that the Merck-Simcere JV licensed from the latter, while the venture application with China FDA. was unwanted by MSD,” Chen explained. and Pfizer will maintain a collaborative com- mercial partnership. Hisun said that Pfizer’s sale of 49% stake ‘AstraZeneca, MSD and GlaxoSmith­Kline have all to Sapphire I Holdings Limited is a strate- made deals with Chinese pharmas, contract sales gic imperative based on its global consid- erations and priorities. After a three-year organizations­ or distributors’ lock-in period, Hisun gave up the preemp- tive rights to purchase the shares in order to protect the interest of investors and A production line is, however, under She explained that in general, multina- reduce the impact on the JV and Hisun’s construction for Tazocin, a single product tional pharmas in China are rationalizing own operations. that contributed greatly to Hisun’s revenue their investments towards their innovative After Pfizer’s exit, production localization raking in CNY308m ($46.56m) in 2014. But pipelines and finding outsourced partners and product supply will be carried out un- since 2015, the supply of Tazocin had de- for their long-established branded gener- der a new framework that was signed on creased by 90%, as a result of which Hisun ics, called off-patent originators in China. Nov. 10 between Pfizer and the venture and saw a 95.6% drop in its net profit year-on- “AstraZeneca PLC, MSD and GlaxoS- includes the intellectual property license year. Pfizer paid Hisun a total of $25m as mithKline PLC have all made these deals agreement, technology transfer agreement compensation for the supply shortage of with Chinese pharmas, contract sales or- and supply agreement for nine products. Tazocin in 2016. ganizations (CSOs) or distributors.” The new framework clearly set outs a sev- According to Pfizer’s SEC filing for the third However, in the case of Hisun-Pfizer en-year time frame for the venture to finish quarter 2017, the company determined the reasons for the breakup could be the technology transfer, during which Pfizer that it had other-than-temporary declines more complicated. A company source will continue to supply those products for a in the value of Hisun Pfizer last year, which with knowledge of the matter told Scrip smooth transition. recognized a loss of $211m for the first nine that the “big thing” was the delivery prob- The secretary of the board at Hisun said in months of 2016, primarily as a result of an lem of the Tazocin active pharmaceutical a response that the new agreement is actu- increase in risk due to the continued slow- ingredients (API), which accounted for ally a continuation of the previous one, but down in the Chinese economy and changes almost 20-30% of Hisun’s revenue. The the specific timetable for localization can in the expected timing and number of new unavailability really made people at Hisun subsequently accelerate product develop- product introductions by the JV. Pfizer noted “angry”, the source said. ment at the new venture. that it would evaluate strategic alternatives At the same time, Pfizer was concerned with Hisun for carrying the investment. about Hisun getting warning letters and REASONS BEHIND THE SPLIT-UP “I expect that Pfizer’s China business plan its quality issues, the source added. In Sep- Pfizer and Hisun launched the JV in 2012 does not anticipate the losses and contin- tember 2015, Hisun received a warning let- in Hangzhou city to develop, manufacture ued investments the JV requires,” Helen ter from the US FDA and was put on import and commercialize off-patent pharmaceuti- Chen, head of China practice and Asia life alert for 15 APIs. The warning letter came cal products, including 10 products licensed sciences at L.E.K Consulting, told Scrip. just three months after a quarantine request from Pfizer, such as Caduet (amlodipine “As established multinational pharmas from Health Canada for a similar problem besylate/atorvastatin calcium), Glucotrol in China are now measured on both the caused by data integrity concerns. XL (glipizide), Minocin (minocycline), Ra- top and bottom line, it’s no longer just rev- The conflicts were also due to “political” is- pamune (sirolimus), Solu-Medrol (methyl- enue growth.” sues between Hisun and the JV. “All the vice prednisolone sodium succinate), Medrol Similarly, Chen cited the example of the presidents were envious of the performance (methylprednisolone), Tazocin (piperacillin split between Merck & Co. Inc. and Sim- of the JV. And Hisun-Pfizer was under a very

14 | Scrip | 15 December 2017 © Informa UK Ltd 2017 STRATEGY

different benefit plan than Hisun,” the source Forming JVs with domestic companies is known for its traditional Chinese medicine continued. “But these are small things that was a way for multinationals to tap a wider and a generic of Viagra, Jinge. Li said Guang- just added up.” market in China, but it did not always have zhou Pharma is awaiting approvals for some happy endings. Teva drugs in China as well. (Also see “China HISUN MOVING ON Besides the Hisun-Pfizer and Simcere- Generic Sildenafil Market Growing But Chal- Hisun said the exit of Pfizer would not MSD breakups, Bayer AG also expressed lenges Ahead” Scrip, 27 Aug, 2015.) have a significant impact on its business; difficulties in merging the OTC business Teva acquired Ivax Pharmaceuticals it will keep the exclusive rights to those with Dihon Pharmaceutical Group Co. Inc. years ago, through which it gained 50% products in China and Pfizer is not enti- Ltd.. The company told investors last year shares in Kunming Baker Norton Pharma- tled to sell them in this territory. During that it was experiencing “stronger business ceutical Co. Ltd., a JV between Kunming the process of setting up the timetable, disruption than anticipated during the inte- Pharmaceutical Factory and Ivax. But Kun- the two companies worked together to gration of Merck Consumer Care and Dihon ming Pharma purchased 49% of the shares evaluate the possibilities of changes at in China” as it wrestles with lower-than-ex- back in 2015, leaving Teva with only the re- different APIs production sites for the next pected growth for its consumer care busi- maining 1% in the JV. five years, and formulated response mea- ness in emerging markets. (Also see “Game That said, the rumored Teva-Guangzhou sures accordingly. Of Thrones: Bayer Looks To Lead China’s OTC Pharma JV could be significant. “The 2018 To ensure the transfer is completed in Market” Scrip, 5 May, 2014.) Generics Quality and Efficacy Evaluation time, the two partners also formed a spe- deadline will shake up the market, given cial team with experienced members from OTHER BREAK-UPS that generics still represent the majority in various departments, including produc- Sanofi and Minsheng Pharmaceutical China,” L.E.K.’s Chen said. tion, technology, supply chain, registration formed a JV focusing on vitamin and mineral “This could be a good time for a foreign and commercialization, to conduct project supplements in 2010 to expand reach in Chi- company like Teva to make a play for the investigation, technology transfer and per- na’s consumer-drug market. But the marriage China market. First generics is aligned with sonnel training with detailed plans. ended in Jan. 2017, as Minsheng bought innovation in China’s regulatory framework Meanwhile, Sapphire’s investment came back 60% shares of the JV from Sanofi. – they are eligible for expedited CFDA re- from a $4bn fund called Hillhouse Fund III, However, the breakup with Minsheng views and are often in the same provincial L. P., under management of Hillhouse Capi- didn’t stop Sanofi seeking a new Chi- tender category as the originators.” tal Group. Hisun said Hillhouse also made nese partner. In Dec. 2016, Sanofi inked But overall, Chen predicts that China is efforts to help production localization a framework agreement with China Re- more likely to see more innovative rather through tech-transfer. Hillhouse’s invest- sources Sanjiu Medical and Pharmaceuti- than generic JVs. ment portfolio covers healthcare and medi- cal to establish a strategic partnership to “China’s policy direction is towards in- cal services, which could bring complemen- jointly explore the opportunities in the novation, and pharma is no exception. Just tary and synergistic effects for Hisun. A few consumer healthcare market in China. look at the ‘Made in China 2025’ goals.” high-profile investments that Hillhouse has The strategic partnership involves the The trend, in fact, is already visible. Kite made include BeiGene (Beijing) Co. Ltd.’s formation of the JV company which will Pharma Inc. and Shanghai Fosun Phar- $97m financing and WuXi PharmaTech focus initially on pediatric and gyneco- maceutical Group Co. Ltd. announced a Inc.’s $3.3bn go-private deal. (Also see “Wuxi logical OTC products. JV in Jan. 2017 to develop, manufacture and PharmaTech Pushing Ahead with $3bn Go- Back in 2016, the Japanese ophthalmic commercialize axicabtagene ciloleucel in Private Deal” Scrip, 28 Aug, 2015.) care company Santen Pharmaceutical Co. China with the option to include additional Hisun noted that at the current stage, the Ltd. and the state-owned Chongqing Kerui products, including two T cell receptor (TCR) two partners have no follow-up plans yet to Pharmaceutical Group signed a multi-year product candidates from Kite. establish more collaborations. collaboration under which they established AstraZeneca recently established a new In a previous response to the Shanghai a manufacturing joint venture in Chongq- drug development JV with a state-backed Stock Exchange’s enquiry regarding wheth- ing to develop generic lines in various areas private equity firm Future Industry Invest- er the company lacks in-house developed including infection and glaucoma. (Also see ment Fund (FIIF) in Nov. The new com- products and is heavily dependent on Tazo- “Santen JV To Become China’s ‘Largest Oph- pany called Dizal Pharmaceutical is equally cin, Hisun outlined its ambitions to develop thalmic Site’” Scrip, 22 Mar, 2016.) owned by the two parties. new drugs for growth. It claimed to have Tsumura & Co. also entered a JV agree- Under the deal, AstraZeneca will transfer built 45 technology platforms, 12 of which ment with Shanghai Traditional Chinese the R&D capabilities of its Innovation Center are for developing innovative pharmaceu- Medicine Co., Ltd., a subsidiary of Shanghai China to the JV, including exclusive rights ticals for treating hyperlipidemia, cancer, Pharmaceuticals Holding Co. Ltd., to de- to three preclinical drugs in oncology, car- hyperglycemia, Alzheimer’s, fatty-liver and velop Chinese medicine compound granules. diovascular and metabolic diseases and the hepatitis C. In 2016, it has received 66 ap- Most recently, the chairman of Guang- respiratory segment, while FIIF will provide provals for clinical trials, including approvals zhou Pharma Chuyuan Li said in an inter- funding and expertise in establishing strate- for innovative drugs and biologics. (Also see view with Bloomberg that Teva Pharma- gic partnerships in China. “Nascent Deal Helps Hisun Advance Innova- ceutical Industries Ltd. is pursuing a joint Published online 10 December 2017 tion Goals” Scrip, 2 Aug, 2016.) venture with his company. The Chinese firm From the editors of PharmAsia News. scrip.pharmaintelligence.informa.com 15 December 2017 | Scrip | 15 STOCK SCAN

Stock Scan November 2017: Generics Get Volatile JOHN HODGSON [email protected]

ach month Scrip looks at the previ- Big Pharma* Stock Trading Trends - November ous month’s fallers and risers among Ethe stocks of the world’s top 50 public drug companies. Overall, November saw market value -31% +40% shrinkage in pharma with average stock Biggest monthly gainer, generics player Valeant Biggest faller of the month - generics player values among the top 50 companies declin- as fresh drug approval halts it decline Mallinckrodt, as it issued Q3 results ing 1% during November 2017. Specialty pharma stocks declined an average of 2%, dragged down by 10-11% falls at Regen- eron Pharmaceuticals Inc. and Alexion -2% +$2,550 Pharmaceuticals Inc. Regeneron was The average decline in stock value across Winnings from daily pharma bets starting with hit by the failure of its combination treat- specialty pharma companies a $1,000 stake ... ments in diabetic macular edema and wet *Top 50 Companies By Annual Prescription Drug Sales macular degeneration and the implication that might have for the continuation of its ophthalmic franchises with Eylea abliber- Springing surprises on investors seems up 60% over the first nine months of 2016 cept). (Also see “As Regeneron Worries Rise like a bad idea because it is often impossible – good news, one would have thought. But On Eylea Combo Failure, Eyes Turn To PAN- to know how markets will react to news. investors must have been expecting more: ORAMA” Scrip, 27 Nov, 2017.) Alexion’s stock Otsuka Pharmaceutical Co. Ltd., for in- Lundbeck’s stock value fell 17% amidst was downgraded by two analysts because stance, saw profits eroded further by loss of seasonal grouchiness about the paucity of concerns about continued sales growth exclusivity on its anti-psychotic drug, Abilify of growth amongst the Danish company’s and the market took note. (aripiprazole), and yet its stock rose over 5% newer products. But it was the sheer range of perfor- in November as investors found reassurance Stock market investors seem particu- mances amongst generics companies that in the company’s rising revenue. It may also larly unsure about what is going on in caught the eye. While Valeant Pharmaceu- have helped that the FDA approved Otsu- the generics space and how it is going to ticals International Inc., Endo Interna- ka’s compliance-enhancing ‘digital’ version work out. tional PLC and Teva Pharmaceutical In- of Abilify, complete with ingestible sensor. Most strikingly, they penalized dustries Ltd. each ended several months’ of (Also see “First ‘Digital Medicine’ Approved, Mallinckrodt heavily (the stock was down stock price decline and became the biggest Slow Rollout Planned” Medtech Insight, 15 30.1% in the month) when its Q3 results risers during November, Mallinckrodt PLC, Nov, 2017.) emerged on November 7 (see the plum- Lupin Pharmaceuticals Inc., Fresenius Lundbeck Inc. went the other way: the meting stock graph in Winners and Losers Kabi AG and Hikma Pharmaceuticals PLC company reported nine-months revenue in November). The company had missed occupied four of the five worst-performing up 12% and core operating and net profits revenue forecasts on Acthar gel, a reposi- positions. It is clear that communication of sales and earnings expectations from biopharma Why Stocks Changed Monthly Monthly companies and the public part of their in- Company What happened Company What happened rise fall vestor base is a continuing problem: as in Approval of Vyzulta for Disappointing Q3 previous months, reporting of quarterly Q3 Valeant 40.7% glaucoma and positive Q3 Mallinckrodt -30.1% results amidst threat of results (parameters that companies monitor revenue and earnings payer tightening Better-than-expected Q3 Receives double FDA Endo 17.2% Lupin -20.5% closely and over which companies have a earnings facilities warning measure of full control) shifted stock values Strong Q3 but new drug Teva 9.2% Gradual recovery over month Lundbeck -16.9% sales disappoint more often and by bigger amounts than Positive phase III news in factors subject to external influence, such Roche 7.7% hemophilia and lung cancer Disappointing Q3 (NSCLC) results followed by Fresenius -15.5% as clinical trial outcomes and regulatory analyst (UBS) Continuation of top downgrade mid-month intervention. (Also see “Quarterly Reporting: AbbVie 6.2% performance during past three months Revised down Hikma Investor Reality Check Or Pharma Communi- -11.5% expectations for Pharmaceuticals Q3 profits hit by Abilify LOE generics business cation Gap?” Scrip, 1 Nov, 2017.) Otsuka 5.1% but, reassuringly, revenues Over half of the biggest stock rises or falls up 3.3% Investors see Regeneron -10.9% challenges across seen in November can be attributed to new company's portfolio information revealed in quarterly reporting Analysts downgrade the Alexion -10.3% (see tables in Why Stocks Changed, below). stock serially

16 | Scrip | 15 December 2017 © Informa UK Ltd 2017 STOCK SCAN

Winners and Losers In November Pushback Underpins Mallinckrodt’s Disap- pointing Q3 Results” Scrip, 7 Nov, 2017.) Hover over legend to highlight a company. Y axis shows price relative to start of month. However, at the beginning of the month Losers investors also devalued Teva, Endo and Vale- 110 ant (by 5.4%, 6.7% and 18.6%, respectively) before earnings and other news reversed

100 that judgement (see Winners). This hesitancy among investors has its roots in the uncertainties currently infecting 90 generics drugs producers. Without the mo- nopoly protection afforded to the branded 80 and specialty sectors of pharma, pressures Relative price on pricing from competition are being ex-

70 acerbated by bulk buyers (especially gov- ernmental payers) seeking better deals. Pricing pressures have driven M&A activity 60 as a means to cost-efficient manufacturing and distribution and that, in turn, has driven 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 higher levels of financial debt. Debt is less 01/1 02/1 03/1 06/1 07/1 08/1 09/1 10/1 13/1 14/1 15/1 16/1 17/1 20/1 21/1 22/1 23/1 24/1 27/1 28/1 29/1 30/1 31/10/2017 Mallinckrodt Lupin Lundbeck Fresenius Hikma Pharmaceuticals tolerated by investors now than at the time Regeneron Alexion Dr Reddy GSK Astellas AstraZeneca when other investors lent the companies the money. Winners On top of this, a number of generics com- 160 panies are caught up – or rumored to be caught up – in investigations led by the US Department of Justice into collusion in price 140 fixing. (Also see “ Generic Price-Fixing Lawsuit Grows As More Companies, Two Executives Named Defendants” Scrip, 31 Oct, 2017.) 120 A measure of investor uncertainty is the

Relative price volatility of generics stocks prices.

100 During the past few months, the magni- tude of stock price fluctuation for generics companies within top 50 pharma has been 80 higher than that for companies in the spe- cialty or branded groups – an indicator that

1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 1/2017 there are long-term uncertainties in the 01/1 02/1 03/1 06/1 07/1 08/1 09/1 10/1 13/1 14/1 15/1 16/1 17/1 20/1 21/1 22/1 23/1 24/1 27/1 28/1 29/1 30/1 31/10/2017 market. (Also see “Stock Scan October: Ge- Valeant Endo Teva Roche AbbVie Otsuka nerics Pull Pharma Down” Scrip, 6 Nov, 2017.) *Top 50 Companies By Annual Prescription Drug Sales In November the level of price fluctuation for generics firms rose markedly, while that of other large pharmaceutical companies was reduced. tory corticotropin injection product for were down compared to the equivalent Wild stock price fluctuations, of course, multiple sclerosis and infantile spasms quarter of 2016, as were its major generic provide fertile ground for day traders – if you that represents over half of the compa- compounds. CEO Mark Trudeau blamed can guess which way the wind is blowing. ny’s specialty sales. Indeed, sales of all but a growing trend of unfilled prescriptions Published online 8 December 2017 one of the company’s specialty products for some of the decline. (Also see “Payer

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scrip.pharmaintelligence.informa.com 15 December 2017 | Scrip | 17 FINANCING

Arix Shepherds Atox $30m Funding Amid High Hopes For Start-up’s Lead Asset STEN STOVALL [email protected]

ate-stage clinical biotech Atox Bio Inc. tibodies are really ‘on/off’ switches – they particular case, the fact is that Atox are tar- told Scrip its successful $30m Series F can either turn on immune systems like geting an orphan indication in NSTI with rel- Lfinancing gave it adequate funding to they’re doing in immuno-oncology or turn tecimod, which already has some interest- progress lead therapeutic candidate reltec- off the immune system like they do in in ing clinical data behind it regarding efficacy imod in Phase III for necrotizing soft tissue inflammatory diseases such as RA and pso- and safety.” infections and Phase II in acute kidney injury, riasis. But none of those approaches are ap- With its equity stake in Atox, Arix has met and that further indications will also be tar- propriate for patients with infections.” its self-set target to have 12 Arix group busi- geted for the asset. “Using a short peptide like reltecimod re- nesses by the end of 2017 – a goal set in The funding round, completed Dec. 4, ally allows us to modulate the immune sys- February when the group floated on the was led by Arix Bioscience PLC, which di- tem in a similar way to as using a dimmer on London stock market. rectly invested $8m and will now place one a light switch,” he explained. “We set out then to have a balance of ear- of its directors on the Atox board to help the “If we’re successful we’ll be the first and ly and late stage companies and this with start-up accelerate its development plans. only product to be developed for NSTI. Pa- a Phase III asset fits in to the late stage cat- Arix’s equity stake in Atox brings its overall tients with this disease really have nothing egory, being potentially less than two years portfolio to 12 companies since the life sci- right now to take for it.” away from registration.” ences operating group listed on the London Data from the Phase III study in NSTI are “It also fits with our strategy because of its Stock market in February. likely in the first half of 2019. A Phase II study innovative novel mechanism and because is also planned with Reltecimod for acute it’s in a very significant area of clinical need ATOX BRINGS ARIX LATE kidney injury (AKI) with read-out likely in the – and like with our other companies, it has STAGE ASSET second half of 2019, Teleman said. a team of experienced entrepreneurs who Atox is developing novel immune modu- Going forward, Atox will trial reltec- have done this successfully before.” lators for critically ill patients with severe imod for multiple indications. “These ex- He said that in the long term there was infections. Its main asset reltecimod is a tend to severe infections and to some potential for Atox’s main drug to be used in novel peptide that binds to the CD28 co- other pathological conditions that are sepsis. “Sepsis is perhaps the biggest clini- stimulatory receptor to modulate the host’s not necessarily infection-sourced, such as cal need that there is currently. Given the immune response to severe infections. severe pancreatitis and severe influenza,” mechanism of this drug, that is the future Atox is conducting a Phase III clinical Teleman said. potential for this product,” Tobin said. study of reltecimod in the US for pa- Arix will meanwhile continue to expand tients with necrotizing soft tissue infec- ARIX WILL KEEP EXPANDING its portfolio. tions (NSTI), and will start a Phase II clini- ITS PORTFOLIO “There’s no plan to slow down. We have cal study for acute kidney injury (AKI) in Jonathan Tobin, an Arix director who will deals that are actively in diligence or term 2018. Reltecimod has orphan drug status join Atox’s board, said Atox fitted with Ar- sheet stages and we’re planning to continue from the FDA and EMA as well as FDA fast ix’s investment strategy “because it offers in a very similar trend of investment in 2018. track designation. a differentiated mechanism in infectious Arix at its IPO in February set a target of “What we’re essentially trying to do is disease.” 12 portfolio assets by end 2017 and of 20 by bring the immune response back into “We had identified infectious diseases the end of 2018. check,” the biotech’s CEO Dan Teleman told as an area of interest to us and previously It will continue to take equity stakes in Scrip. “The reason we’re able to do that with made two investments in that infectious nascent biotechs and is not constrained by a peptide is that it can modulate the im- diseases space and Atox Bio fitted in with therapeutic area, geography or by the de- mune response but not inhibit the immune our strategy and was distinct from what we velopment stage of prospective assets. response.” had already done, as it offers a host mecha- Other areas of interest for Arix besides He said the Phase III study in NSTI would – nism rather than being directly anti-infec- infectious diseases are gene-editing, dif- if successful - be sufficient for making a reg- tive – it was dealing with the pathological ferentiated approaches in oncology such ulatory filing as the FDA has told the com- consequences of infection.” as immuno-oncology and targeted ap- pany it would not require a second Phase III Tobin said infectious diseases had be- proaches, autoimmunity and immunologi- trial for approval. come interesting commercial propositions cal mechanisms in general. “We’re oppor- He said reltecimod’s mechanism of action from Arix’s point of view, in part due to the tunistic and not ruling anything out, given is well suited for infectious diseases. FDA’s Generating Antibiotics Incentives the enormous rate of innovation that we are “An obvious question might be, why don’t Now (GAIN) provisions and increased clar- seeing in general today,” Tobin said. we use an antibody? The short answer is an- ity over clinical trial end-points. “And in this Published online 11 December 2017

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211106_BIO_CEO_18_Ad_210x297mm.indd 1 12/1/17 3:28 PM EXECUTIVE INTERVIEW

Joerg Moeller, Bayer Development Chief, On R&D Consolidation ELEANOR MALONE [email protected]

ollowing the announcement that Bayer AG is to consolidate JM: No, we always look at what our key priorities are. I don’t be- the research and the development organizations of its pharma- lieve in fixed budgets because they don’t give you the flexibility Fceuticals division, Scrip spoke to Joerg Moeller, current head of to shift according to your needs. So while of course we have a development for pharma, who will take the helm for the wider R&D budget plan and we also have an allocation to functions, it is im- group from January 2018. portant that we maintain some flexibility to potentially react to shifting priorities. In fact, one advantage of also having R&D under ELEANOR MALONE: Tell me about the motivation for the con- one roof is that it will also give us even more flexibility to shift solidation of the research and the development activities at Bayer under a larger roof. Pharmaceuticals. JOERG MOELLER: I think we have come to realize that we can EM: Will this consolidation of R&D lead to changes in where peo- improve how seamlessly we work together in research and de- ple are based, or any change in numbers of people working in the velopment. We will have a smoother hand-off between the vari- area? Or is it simply a leadership change? ous functions by having it all under one roof, we can think about JM: I’m officially not in the job, and what I want to do is, together integrated project management, and there are a number of ideas with the research and development leadership team, to carefully that we want to implement in order to further drive efficiency in assess what is our current situation, where we want to take things, the research and development organization. And the good news and following that, to establish the R&D strategic direction, then is that we come from a very good track record: drug discovery un- we can start thinking about what that means for the organization. der Andreas Busch’s leadership has been one of the leading drug But it would premature and even unfair now to start to speculate discovery organizations in industry. We just think we can take it to on any of these. the next level by creating the joint R&D organization. EM: But there is some kind of strategy plan going to come out next EM: How long have you been planning it? year? JM: In my view there’s never an ideal organization. You have an JM: Bayer was a €10bn pharma organization around 2010, and organization that you think addresses what the company needs. we are well on our way to being a €20bn sales pharma company It typically never addresses 100% of what a company needs. If you around 2020. That alone requires a different R&D engine to sup- are good it addresses 90%. As for the remaining 10%, over time port a €20bn business compared to where we were some time you realize there’s a problem we want to address, and you start ago. At the same time we need to build a portfolio that allows thinking ‘ok, maybe now it’s time to get into a different set-up’. us to have growth potential beyond the loss of exclusivity for our current growth drivers [flagged by the company as Xofigo, Adem- EM: Had Andreas Busch already been looking for another role and pas, Stivarga, Xarelto and Eylea – Ed.]. So there are a number of that catalyzed this, or was it that he thought “at this point I need to strategic drivers and all of these influence the way an R&D organi- go somewhere else because it’s all going to be one.”? zation should be set up and what it should be doing. JM: I cannot speculate. EM: Bayer’s pharma pipeline currently has 20 Phase I programs, 14 EM: But it wasn’t him deciding to leave that prompted the change? Phase II programs and 14 Phase III programs. Is that about the right number for now or are you looking to expand that? JM: All I can say is the discovery organization has been very suc- cessful. JM: Well we don’t have a certain number right now. Actually, if Editor’s note: Andreas Busch was announced on Dec. 1 as Shire’s new you look at an R&D portfolio, yes, you have number of projects, R&D head. (Also see “Shire Tempts Busch From Bayer As It Eyes Top Spot but you also have to consider how many of these projects will sur- In Rare Diseases” - Scrip, 1 Dec, 2017.) vive the various stages. And you can have maybe a smaller num- ber, but if you have the ability to really have good quality in these EM: How does the oncology strategic business unit fit under this projects and therefore a higher percentage of them survive, then new umbrella? I’ve seen some speculation that this change brings it also addresses the portfolio needs. So there’s different ways to it back in. play the game. JM: No, no, no. The strategic business unit for oncology is not EM: Is there a target for number of drugs being approved each affected by this. Oncology research has always been part of the year, or new indications? research organization and that will not change, but there is no effect of this reorganization on oncology. JM: No. What we want to have is a portfolio that allows us ideally above-market growth – that is what we strive for and one of the EM: Do you have preserved budgets for each therapeutic area? strategic goals for R&D right now, and I think we have made good

20 | Scrip | 15 December 2017 © Informa UK Ltd 2017 EXECUTIVE INTERVIEW

Bayer’s Development Pipeline progress since I was brought into my current position [in February PHASE I PHASE II PHASE III 2014], but the work isn’t done yet, but we are very confident and (20 PROGRAMS) (14 PROGRAMS) (14 PROGRAMS) optimistic about our ability to build and deliver on that portfolio. Castration-resistant Cancer/rogaratinib EM: Can I ask you about the complexity nowadays of R&D – it’s not Cancer/regorafenib prostate cancer/ (pan-FGFR inhibitor) darolutamide just moving molecules through trials. How have things changed in Bone mets breast Hormone-sensitive terms of building factors like reimbursement, payers, rapidly chang- Cancer/PTEFb cancer/radium-223 prostate cancer/ ing landscape of comparators (especially in oncology) into planning? inhibitor dichloride darolutamide JM: It has fundamentally changed the R&D process. At the very Cancer, various Cancer/MPS1 Adjuvant CRC/ early stages of clinical development we now start thinking about studies/ radium-223 inhibitor regorafenib market access. And what it also means is that the level of innova- dichloride tion that you need to target for has increased. When I started in Comb. Study Cancer/mIDH1 DLBCL/copanlisib CRPC/radium 223 this industry in 1993 you could still have a good economic case inhibitor (PI3K inhibitor) dichloride** when you were number seven or eight in a compound class. Mesothelioma/ Those days are over. So you need to drive your speed, you need NHL/copanlisib Cancer/ATR inhibitor anetumab ravtansine to drive your efficiency, but most importantly, we need to set (PI3K inhibitor) (Mesoth.-ADC) ourselves really ambitious goals and speculate where the stan- Cancer/anetumab Thrombosis/FXI ASO PAD/rivaroxaban dard of care will be maybe 10 years down the road. And I prefer ravtansine (IONIS-FXI antisense) to aim high, because you don’t want to invest all the time and Cancer/lupartumab Thrombosis/anti-FXIa CHF and CAD/ resources and find out that what you bring to the table is not amadotin antibody rivaroxaban (C4.4a-ADC) really perceived as attractive innovation – because innovation is Cancer/anti-CD22- PAD/AR alpha 2c Medically ill/ not defined by us, it’s defined by prescribers, by patients and by thorium conjugate receptor antagonist rivaroxaban payers. And therefore to have something that is really meaningful Renal anemia/ Major Adv. Card. in driving innovation forward is essential. And that has changed Heart failure/ molidustat (HIF-PH- Events Prevention/ compared to where we were maybe 20 years ago. vasopressin-Rec Ant inhibitor) rivaroxaban Chronic kidney Heart failure/ EM: How will it change going forward? Diabetic kidney disease/sGC neladenoson biala- disease/finerenone JM: In general, I believe we probably will see a more collabora- activator 1 nate (p.Ad-A1 Ag) tive process between regulators, payers and also the innovation- Pulmonary hyperten- Heart failure/chy- Chronic HF/vericiguat based pharmaceutical industry. But we probably will need to en- sion/sGC activator 2 mase inhibitor (sGC stimulator) Symptomatic uterine gage and actually we are doing that. We are one of the leaders Endometriosis/ Endometriosis/vila- fibroids/vilaprisan in driving joint interaction between regulators and payers. I be- AKR1C3 inhibitor prisan (S-PRM) (S-PRM) lieve in the European scene we were the first ones to have such a Wet AMD/DME/nes- meeting. We believe that is fundamental and essential and I see Endometriosis/PRLR Lung infections/ vacumab (Ang-2 Ab) antagonist tedizolid that process moving forward and probably also with the advance + Aflibercept* of deep analytics and big data capabilities, also the way we do Diff. syst. Sclerosis/ Gram-negative Endometriosis/P2X3 clinical trials will change: in a more predictive fashion, we will riociguat (sGC pneumonia/amikacin antagonist 1 probably have better ability to simulate outcomes than where we stimulator) inhale*** are today. Really exciting developments, but they all will funda- Endometriosis/P2X3 – – antagonist 2 mentally impact the R&D process. Polycystic ovary syn- – – EM: Are you optimistic about that? Because at the moment there drome/anti-androgen Hemophilia/anti-TFPI is still the confrontational aspect of the patients, politicians, regula- – – antibody tors, payers and the industry – but to really use big data analytics Obstructive sleep you’re going to need to share information: is it going to be easy to apnea/TASK channel – – create a new collaborative spirit? blocker JM: I actually think that there is no other way. I think we need to ARDS/sGC activator 3 – – also engage with society. I was recently reminded that every single RA/IRAK4 inhibitor – – US president since Kennedy, if I’m not mistaken, has signed up for *program discontinued subsequent to compilation of table the fight against cancer. I don’t recall that every single president has (Also see “As Regeneron Worries Rise On Eylea Combo Failure, Eyes Turn To PANORAMA” - Scrip, 27 Nov, 2017.) been signing up for the fight against cardiovascular disease. What I’m saying is, we need to engage into a dialogue with society **trial unblinded following fracture and death imbalance in treatment about standards of care and how can we ensure that we continue to arm (Also see “Bayer Shrugs Off Xofigo Sales Pressure From Study Halt” - Scrip, 1 Dec, 2017.) improve on how patients are being treated with serious medical con- ditions, and I don’t think this can be done in a confrontational manner. ***program missed primary endpoints in November 2017 It can only be done in a collaborative and partnership spirit. Source: Bayer, October 2017 Published online 6 December 2017 scrip.pharmaintelligence.informa.com 15 December 2017 | Scrip | 21 PIPELINE WATCH

Scrip’s weekly Pipeline Watch tabulates the most recently reported late-stage clinical trial and regulatory developments from the more Click here for the entire pipeline than 10,000 drug candidates currently under active research worldwide. with added commentary: http://bit.ly/2mx4jY3

Selected clinical trial developments for the week 1–7 December 2017

LEAD COMPANY/PARTNER COMPOUND INDICATION COMMENTS Phase III Suspended recurrent Cdiffense; Interim analysis indicated unlikely to Sanofi Clostridium difficile vaccine C difficileinfection meet endpoint. Phase III Interim/Top-line Results AbbVie Inc./ risankizumab psoriasis IMMhance; met primary endpoints. Boehringer Ingelheim GMBH chickenpox, shingles ZOE-HSCT; positive in autologous stem GlaxoSmithKline PLC Shingrix vaccine prevention cell transplant. Waldenstrom AbbVie Inc. Imbruvica (ibrutinib) INNOVATE; improved PFS. macroglobulinemia daxibotulinumtoxinA Revance Therapeutics Inc. glabellar lines SAKURA 1, 2; positive results. (RT002) attention deficit Akili Interactive Labs Inc. AKL-T01 STARS-ADHD; A digital medicine. hyperactivity disorder UCB SA Vimpat (lacosamide) focal seizures in children Reduced seizure frequency. advanced non-small CheckMate078; met endpoint of overall survival Bristol-Myers Squibb Co. Opdivo (nivolumab) cell lung cancer (NSCLC), benefit in China. previously treated ARRIVAL; positive results in children aged one to Vertex Pharmaceuticals Inc. Kalydeco (ivacaftor) cystic fibrosis two years. Updated Phase III Results advanced breast cancer, MONALEESA-7; positive in premenopausal Novartis AG Kisqali (ribociclib) HR+, HER2- women. Roche Tecentriq (atezolizumab) advanced NSCLC, first-line IMpower150; clinically meaningful PFS benefit. advanced breast cancer, Pfizer Inc. Ibrance (palbaciclib) PALOMA-2; positive results. HR+, HER2- Xultophy (insulin Novo Nordisk AS diabetes, type 2 DUAL VII; a once-daily option. degludec/liraglutide) Ultragenyx Pharmaceutical Inc./ X-linked hypophos- burosumab (KRN23) Sustained clinical improvement after 48 weeks. Kyowa Hakko Kirin Co. Ltd. phatemia Neurocrine Biosciences Inc. Ingrezza (valbenazine) tardive dyskinesia KINECT 4; improved symptoms long term. Phase III Initiated LJPC-401 (synthetic human La Jolla Pharmaceutical Co. beta thalassemia To reduce cardiac iron levels. hepcidin) Phase III Announced CSL112 CSL Ltd. atherosclerosis AEGIS-II; will take around four years. (apolipoprotein A-I) Renova Therapeutics RT-100 (a gene therapy) congestive heart failure FLOURISH; by intracoronary inj. urinary and reproductive Iterum Therapeutics Ltd. sulopenem etzadroxil An oral penem antibiotic. tract infections Source: Biomedtracker

22 | Scrip | 15 December 2017 © Informa UK Ltd 2017 COMPANIES

Shanghai: J&J’s First Innovation Site Outside N America LUCIE ELLIS [email protected]

n partnership with the Shanghai Munici- opening a JLABS facility in Europe. In No- changing lifestyles, the burden of chronic pal Government, Pudong New Area Gov- vember this year, rumors circulated that the non-communicable diseases is increasing – Iernment and Shanghai Pharma Engine company had pulled out of a deal to open as is the country’s spending on healthcare. Company, Ltd., Johnson & Johnson is set a JLABS site in Cambridge, UK, because of J&J founded its first joint venture in China to launch its first JLABS facility outside of concerns about the withdrawal from the in 1985, known as Xi’an-Janssen Pharma- North America. European Union. However, J&J Innovation ceutical Ltd. The company has continued to The 4,400-square-meter facility, known told Scrip at the time that this story was un- invest in the region and now has 14 wholly as JLABS @ Shanghai, will be located in substantiated. owned and joint-venture companies oper- the city’s Zhangjiang Hi-Tech Park and is Following the announcement of a new ating in China, employing approximately expected to open in the second quarter of JLABS site in China, J&J Innovation’s spokes- 10,000 people across more than 90 loca- 2019. The site will accommodate up to 50 person said it “was not a choice between tions, including Beijing, Shanghai, Guang- life science and healthcare startups, both the UK and Asia.” They added that J&J Inno- zhou, Suzhou and Xi’an. Three of J&J’s sites single entrepreneurs and larger companies, vation was still in discussions with potential in China are R&D facilities, which cover a focused on innovations across the health- partners for a JLABS site in Europe, including broad range of therapeutic areas. care spectrum, including pharmaceuticals, the possibility of a site in the UK. In a Dec. 5 announcement about the new medical devices and consumer products. While the group will be busy setting up JLABS site, Vladimir Makatsaria, Johnson & Johnson & Johnson Innovation, the the new site in Shanghai, J&J Innovation Johnson China group chair, said, “China, and J&J franchise responsible for the JLABS said it is continuing to explore other oppor- Shanghai specifically, have become a global program, already has eight active JLABS tunities. “We’re excited that so many poten- hotspot for healthcare innovation.” facilities across North America, including tial partners around the world are interested JLABS @ Shanghai, following the formula in New York, San Diego, San Francisco and in establishing a JLABS… We will announce used at J&J Innovation’s other JLABS facili- Toronto. But the company has talked of new locations as appropriate,” a spokesper- ties, will provide startups with many of the setting up sites in Asia and Europe over son said. advantages of being part of an established the last year. Home to around 1.41 billion people as of innovation hub, such as access to talent and A spokesperson for J&J Innovation told 2017, China has the world’s largest popula- capital, as well as convergence opportuni- Scrip that the new site in Shanghai does not tion and boasts the second largest econo- ties with other sectors. mean that the company has lost interest in my. Due to a rapidly aging population and Published online 6 December 2017

APPOINTMENTS

Eli Lilly & Co. has announced that Kim- medical affairs, is a board member of sev- Heptagon, a developer of advanced mi- berly Blackwell will join Lilly Oncology as eral growing companies and a member of cro-optics where he was CFO. vice president of early phase development the Science Board to the FDA. and immuno-oncology in March 2018. She Achaogen Inc., a US antibacterials special- is currently professor of medicine and assis- Scotland’s Exscientia Ltd., which spe- ist addressing multi-drug resistant gram- tant professor of radiation oncology at Duke cializes in Artificial Intelligence-driven negative infections, has announced that University Medical Center where she has drug discovery, has appointed Alex Blake Wise, currently its chief operating played a major role in developing therapies Snow as its deputy chairman. A former officer, will succeedKenneth Hillan, as that represent non-chemotherapy based professional rugby union player with CEO. Hillan will take on the newly created approaches for treating breast cancer. Harlequins and England, he previously role of president of R&D as the company founded Oxford Sciences Innovation and makes plans for the potential launch of its The UK’s Cell Medica Ltd. has announced spent 20 years in investment banking first drug, plazomicin. Prior to Achaogen, the appointment of Annalisa Jenkins, and fund management, most recently as Wise spent 13 years at Genentech. as chair of its board of directors, replacing CEO of the hedge fund Lansdowne Part- Thomas Hecht. Prior to joining Cell Medica, ners. He was also the founder and CEO of EMD Serono Inc., Merck KGAA’s biop- she served as CEO of Dimension Therapeu- Evolution Group, a UK investment bank- harma business in the US and Canada, has tics, a gene therapy company acquired by ing and securities firm, sold to Investec appointed John Walsh, as vice president Ultragenyx Pharmaceutical in November Bank for £232m in 2011. of neurology and immunology of its US 2017 and has held a number of high-profile medical affairs team. He joins from Biogen, posts in the industry, notably as head of Desmond Lim is to be the new chief fi- where he served as neurology medical global R&D at Merck Serono. Jenkins, who nancial officer at Tessa Therapeutics, a director lead, and will develop and imple- also had a 14-year career at Bristol-Myers Singapore-based company focusing on ment plans for the multiple sclerosis drug Squibb, attaining the role of head of global cellular immunotherapy. He joins from Rebif (interferon beta-1a).

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