WEEK OF SEPTEMBER 25, 2017

1 COMPANY NEWS 5 CLINICAL NEWS 16 FINANCIAL NEWS Deals, Sales & Marketing, Other Regulatory, Clinical Results, Completed Offerings, Other News Clinical Status Financial News

COMPANY NEWS line data are expected in mid-2018 from Phase III trials to treat myelodysplastic syndromes (MDS) and beta-thalassemia (see DEALS BioCentury, Aug. 8, 2011). Luspatercept is a modifiedACVR2B fusion protein that inhibits Acceleron Pharma Inc. (NASDAQ:XLRN), Cambridge, Mass. several ligands in the transforming growth factor (TGF) beta (NASDAQ:CELG), Summit, N.J. Celgene Corp. superfamily. Business: Cancer, Hematology, Cardiovascular Acceleron Pharma Inc. (NASDAQ:XLRN) gained worldwide Arcus Biosciences, Hayward, Calif. rights to develop and commercialize sotatercept to treat pulmonary Taiho Pharmaceutical Co. Ltd., Tokyo, Japan hypertension, amending a deal with partner Celgene Corp. Business: Cancer (NASDAQ:CELG). Acceleron expects to begin a Phase II trial of Cancer company Arcus Biosciences (Hayward, Calif.) granted Taiho sotatercept to treat pulmonary arterial hypertension (PAH) in 1H18. Pharmaceutical Co. Ltd. (Tokyo, Japan) an option to develop and In 2008, Acceleron and Celgene partnered to co-develop and commercialize compounds in Japan and other Asian territories commercialize Acceleron's sotatercept for all indications, with an excluding China. Arcus said the deal includes anything listed on its initial focus on cancer, including breast and ovarian cancers, and pipeline chart. cancer-related bone loss. At the time, Acceleron received $50 million Arcus will receive $35 million over the first three years of the five- up front, including a $5 million equity investment by Celgene, and year agreement and is eligible to receive up to $275 million in was eligible for up to $510 million in milestones, plus tiered royalties milestones for each molecule, plus high-single to mid-double-digit (see BioCentury, Feb. 25, 2008). royalties. Arcus declined to disclose additional financial terms. Under the amended deal, Celgene is now eligible for low-twenty According to its website, Arcus expects to begin Phase I trials of percent royalties for pulmonary hypertension indications. Acceleron AB928 next quarter and AB154 in 2Q18. AB928 is a dual adenosine spokesperson Brad Miles told BioCentury that Celgene and other A2A receptor (ADORA2A) and ADORA2B antagonist, and AB154 investigators are evaluating sotatercept in multiple myeloma (MM) is a mAb that inhibits T cell immunoreceptor with Ig and ITIM and Diamond-Blackfan syndrome. According to ClinicalTrials.gov, domains (TIGIT). sotatercept completed a Phase II trial in MM and is in Phase I/II testing for Diamond-Blackfan syndrome. CritiTech Inc., Lawrence, Kan. Sotatercept is a soluble fusion protein consisting of the extracellular DFB Pharmaceuticals LLC, Fort Worth, Texas domain of activin receptor type 2A (ACVR2A) linked to the Fc NanOlogy LLC, Fort Worth, Texas protein of human IgGI. U.S. Biotest Inc., San Luis Obispo, Calif. Acceleron and Celgene are also partnered under a 2011 deal to Business: Cancer, Drug delivery co-develop and commercialize luspatercept (ACE-536). Top- COMPANY CLINICAL FINANCIAL NEWS NEWS NEWS WEEK IN REVIEW POWERED BY BCIQ

DFB Pharmaceuticals LLC (Fort Worth, Texas), CritiTech Inc. Dimension's most advanced gene therapy product, DTX301, is (Lawrence, Kan.) and U.S. Biotest Inc. (San Luis Obispo, Calif.) in Phase I/II testing to treat ornithine transcarbamylase (OTC; formed NanOlogy LLC (Fort Worth, Texas) to develop nanoparticle OTCD) deficiency. DTX301 is an adeno-associated virus 8 (AAV8) drug-delivery technology to treat cancer. vector that delivers the OTC gene to liver cells. Dimension plans to The newco's pipeline includes NanoPac, a nanoparticle form of submit an IND early next year for its next lead candidate DTX401, paclitaxel, in Phase II testing to treat ovarian, prostate and pancreatic an AAV vector that delivers glucose-6-phosphatase catalytic subunit- cancer as well as mucinous cystic pancreatic neoplasms. Data from related protein (G6PC; G6Pase), to treat glycogen storage disease the prostate and two pancreatic trials are expected next year. Data type Ia (GSDIa). Both products have Orphan Drug designation in are also expected early next year from a Phase II trial of SOR007, a the U.S. and EU. topical ointment of uncoated nanoparticle paclitaxel, to treat actinic Dimension developed all of its candidates using RegenxBio's NAV keratosis lesions. A Phase II study of SOR007 to treat cutaneous technology, to which Dimension has a license. metastases from non-melanoma cancer is expected to begin next Ultragenyx's recombinant human glucuronidase beta (rhGUS) is quarter. DFB's affiliate DFB Soria LLC granted NanOlogy rights to under FDA and EMA review to treat mucopolysaccharidosis VII SOR007 for cancer indications. (MPS VII; Sly syndrome). The BLA's PDUFA date is Nov. 16. In NanOlogy's pipeline is being developed under section 505(b)(2) August, the company submitted a BLA to FDA for burosumab of the Food, Drug and Cosmetic Act, which allows sponsors to (KRN23, UX023) to treat X-linked hypophosphatemia (XLH). reference data on safety and efficacy from the scientific literature or An MAA for burosumab to treat XLH is under EMA review from previously approved products. with a CHMP opinion expected around year end Burosumab is a recombinant human IgG1 mAb against fibroblast growth factor 23 Dimension Therapeutics Inc. (NASDAQ:DMTX), Cambridge, Mass. (FGF23). Ultragenyx Pharmaceutical Inc. (NASDAQ:RARE), Novato, Calif. RegenxBio Inc. (NASDAQ:RGNX), Rockville, Md. Fred Hutchinson Cancer Research Center, Seattle, Wash. Business: Gene/cell therapy, Endocrine/Metabolic Fortress Biotech Inc. (NASDAQ:FBIO), New York, N.Y. On Sept. 18, Ultragenyx Pharmaceutical Inc. (NASDAQ:RARE) Business: Gene/Cell therapy, Cancer, Hematology offered to acquire gene therapy play Dimension Therapeutics Inc. Fred Hutchinson Cancer Research Center (Seattle, Wash.) granted (NASDAQ:DMTX) for $5.50 per share in cash, or about $138 the Mustang Bio Inc. (NASDAQ:MBIO) subsidiary of Fortress million. In August, RegenxBio Inc. (NASDAQ:RGNX) agreed to Biotech Inc. (NASDAQ:FBIO) exclusive, worldwide rights to a acquire Dimension in a stock deal with an implied value of $3.41 per third-generation CD20-specific chimeric antigen receptor (CAR) Dimension share. T therapy that incorporates tumor necrosis factor (TNF) receptor Dimension said its board will review and consider Ultragenyx's superfamily member 9 (4-1BB; TNFRSF9; CD137) and CD28 co- unsolicited offer, which is a 358% premium to Dimension's close of stimulatory domains. Mustang will partially fund a Phase I/II trial to $1.20 on Aug. 24, the day before it announced the RegenxBio deal. evaluate the candidate in patients with relapsed or refractory B cell On Sept. 19, Dimension said Ultragenyx's offer could reasonably be non-Hodgkin’s lymphoma (NHL). The trial is expected to begin at expected to lead to a "Superior Proposal" as defined in Dimension’s the center next quarter. merger agreement with RegenxBio, which would legally allow The center and Mustang declined to provide further details. Dimension to sit down at the table with Ultragenyx. Immunocore Ltd., Abingdon, U.K. Ultragenyx is developing biologics and small molecules to treat Bill & Melinda Gates Foundation, Seattle, Wash. rare genetic diseases. The company believes it can offer its "clinical and regulatory expertise" and "growing rare metabolic disease Business: Infectious commercial infrastructure to advance Dimension’s rare disease T cell receptor (TCR) company Immunocore Ltd. (Abingdon, U.K.) focused gene therapies through the clinic and to maximize their received a $40 million equity investment from the Bill & Melinda reach with patients." Ultragenyx said it would maintain a gene Gates Foundation (Seattle, Wash.) as part of a collaboration to therapy development unit at Dimension's Massachusetts facilities. develop new therapies to treat infectious diseases. Under the terms of RegenxBio's deal, Dimension would become Immunocore said the new capital will be used to accelerate the a RegenxBio subsidiary and Dimension shareholders would own development of the biotech's two infectious disease platforms: about 10.9% of the combined company. In August, the companies immune mobilizing monoclonal TCRs against virus (ImmTAV) and said they expect the deal to close by year end. Dimension would have immune mobilizing monoclonal TCRs against bacteria (ImmTAB). to pay RegenxBio a $2.9 million fee to terminate the deal, according The ImmTAV and ImmTAB technologies are similar in design and to an SEC filing. RegenxBio declined to comment. function to Immunocore's ImmTAC platform for cancer. Each is a bispecific biologic that combines an affinity-enhanced T cell

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receptor with an anti-CD3 single chain variable fragment (scFv) In 1H18, Provention plans to begin a Phase IIa proof-of-concept effector function to activate a T cell response against the target cell. study of PRV-6527 to treat Crohn's disease and a Phase I/II study of Under the collaboration, Immunocore's first infectious disease PRV-300 to treat ulcerative colitis. programs will target tuberculosis and HIV. J&J spokesperson Brian Kenney said Janssen out-licensed PRV- Most of Immunocore's pipeline is focused on cancer, with the lead 6527 and PRV-300 to Provention after "considering the depth of program, IMCgp100, in a pivotal Phase II trial to treat advanced our portfolio" and said Provention has the "translational and clinical uveal melanoma. expertise" needed to progress the assets. In 2015, Immunocore raised $320 million in a series A round, which Provention also has exclusive, worldwide rights to a preclinical at the time was the largest ever venture round for a European biotech enterovirus vaccine against coxsackievirus B (CVB) infection from (see BioCentury, July 20, 2015). Vactech Oy (Tampere, Finland), which it is developing to prevent or delay the onset of Type I diabetes. Inovalon Holdings Inc. (NASDAQ:INOV), Bowie, Md. The terms of the deals with Janssen and Vactech are undisclosed. Daiichi Sankyo Co. Ltd. (Tokyo:4568), Tokyo, Japan Provention launched in June with all three assets and a $28.4 million Business: Neurology, Bioinformatics series A round from the J&J's Johnson & Johnson Innovation-JJDC Daiichi Sankyo Co. Ltd. (Tokyo:4568) partnered with Inovalon Inc. arm, the JDRF T1D fund and undisclosed private investors (see Holdings Inc. (NASDAQ:INOV) to use Inovalon’s MORE2 BioCentury, July 6). Registry and Inovalon ONE platform to identify outcomes for abuse-deterrent opioids that would be valuable to health plans and Synpromics Ltd., Edinburgh, U.K. then design outcomes-based contracts based on their findings. Solid Biosciences LLC, Cambridge, Mass. Inovalon declined to provide financial terms. Business: Musculoskeletal, Gene/Cell therapy The Medical Outcomes Research for Effectiveness and Economics Synpromics Ltd. (Edinburgh, U.K.) will provide Solid Biosciences (MORE2) Registry houses longitudinal demographic and medical LLC (Cambridge, Mass.) access to muscle-selective synthetic DNA data from 230 million patients. The Inovalon ONE cloud- transcription promoter candidates based on Synpromics' PromPT based platform combines more than 70 data tool sets including platform which will be used to develop therapies for Duchenne technologies for data integrity analysis, predictive analysis, clinical muscular dystrophy (DMD). data optical character recognition, natural language processing, The companies said the promoters will be evaluated in vivo and that decision support and large-scale transactional computation. Dan they will “enhance” Solid’s adeno-associated virus (AAV) program. Mendelson, President of Inovalon’s Avalere Health LLC subsidiary, The companies declined to provide terms of the deal, but Solid told BioCentury that the company’s analysis will seek to determine spokesperson Courtney Heath told BioCentury that "Synpromics' the outcomes which would be the “most compelling” to health plan technology has the potential to help enhance specificity, expression providers. Daiichi did not respond to inquiries. and gene delivery for new gene therapy candidates as the company In the U.S., Daiichi markets MorphaBond ER, an extended-release continues to build its portfolio." morphine formulation, and RoxyBond, an immediate-release oral By year end, Solid plans to begin a Phase I/II trial of its preclinical oxycodone, to treat pain. The company has rights to the products AAV vector candidate, SGT-001, to treat DMD. The gene therapy from Inspirion Delivery Sciences LLC (Morristown, N.J.), on whose delivered via an AAV vector is designed to stabilize the dystrophin SentryBond abuse-deterrent technologies the products are based. glycoprotein complex by delivering microdystrophin, a shortened but functional copy of dystrophin. Heath added that promoter Johnson & Johnson (NYSE:JNJ), New Brunswick, N.J. candidates identified under the deal will not be applied to Solid's Provention Bio Inc., Lebanon, N.J. existing candidates, including SGT-001. Business: Autoimmune, Inflammation Provention Bio Inc. (Lebanon, N.J.), a newco pursuing autoimmune COMPANY NEWS and inflammatory disease therapies, disclosed details regarding two in-licensed programs from the Janssen unit of Johnson & Johnson SALES & MARKETING (NYSE:JNJ). Bristol-Myers Squibb Co. (NYSE:BMY), New York, N.Y. Provention holds exclusive, worldwide rights to PRV-6527 (JNJ- Business: Cancer 40346527), an oral colony-stimulating factor 1 receptor (CSF1R; C-FMS; CD115) inhibitor, to treat inflammatory bowel disease The U.K.'s NICE issued a final appraisal determination (FAD) (IBD) and to PRV-300 (JNJ-42915925), a toll-like receptor 3 recommending the use of Opdivo nivolumab from Bristol-Myers (TLR3) mAb, for all indications. Squibb Co. (NYSE:BMY) to treat squamous and non-squamous non-small cell lung cancer (NSCLC). The committee recommended

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the PD-1 inhibitor after BMS presented additional data and agreed package is about a 19% discount to Remicade's WAC of $1,167.82 to an arrangement through the country's Cancer Drugs Fund. per package. Approximately 950 squamous and 350 non-squamous patients will The complaint also argues that by "inappropriately excluding be treated within the CDF agreement. biosimilar competitors," J&J also undermines the principal goals of In 2016, NICE issued draft guidance recommending against the the Biologics Price Competition and Innovation Act (BPCIA). use of Opdivo for the indication, but asked BMS to make a case for In a statement to BioCentury, Scott White, president of J&J's the inclusion of Opdivo in the CDF. At the time, NICE said BMS's Janssen Biotech Inc. unit, said the lawsuit has no merit. "We are CDF proposal should describe its plans for collecting data to address effectively competing on value and price and to date, Pfizer has clinical uncertainties, including Opdivo's effectiveness in patients failed to demonstrate sufficient value to patients, providers, payers with high PD-L1 expression, and "demonstrate a plausible potential and employers," he added. for cost effectiveness" (see BioCentury,Oct. 17, 2016). Inflectra posted $172 million in 1H17 sales, while Remicade Under the CDF arrangement, five-year follow-up data will become generated 1H17 revenues of $3.2 billion. available in June 2019 from the the Phase III CheckMate -017 trial to treat squamous NSCLC and the Phase III CheckMate -057 trial Pfizer launched Inflectra in the U.S. last November. to treat non-squamous NSCLC. Both trials are evaluating Opdivo In August 2016, a federal judge invalidated a patent covering vs. docetaxel. Remicade, removing an obstacle to biosimilar competition. J&J filed The committee said the most plausible incremental cost- the suit in 2015 seeking to prevent Pfizer from marketing Inflectra effectiveness ratio (ICER) would be £50,014 ($67,779) and £49,160 (see BioCentury, Aug. 22, 2016). ($66,622) per quality-adjusted life year (QALY) gained for squamous Pfizer has U.S. rights to Inflectra fromCelltrion Inc. and non-squamous NSCLC, respectively. The list price of Opdivo is (KOSDAQ:068270). The companies both market the biosimilar in £5,268 ($7,140) per month for a 73 kg patient. the EU, where they share co-exclusive rights. Celltrion markets it as In the EU, Opdivo is approved to treat NSCLC, renal cell carcinoma Remsima. (RCC), classical Hodgkin's lymphoma, squamous cell carcinoma of Remicade is a humanized mAb against TNF alpha. the head and neck (SCCHN) and urothelial carcinoma. In April, FDA approved a second Remicade biosimilar, Renflexis infliximab-abda, from Merck & Co. Inc. (NYSE:MRK) and Samsung COMPANY NEWS Bioepis, a JV between Biogen Inc. (NASDAQ:BIIB) and Samsung OTHER NEWS BioLogics Co. Ltd. (KOSDAQ:20740) (see BioCentury, July 28).

Pfizer Inc. (NYSE:PFE), New York, N.Y. Johnson & Johnson (NYSE:JNJ), New Brunswick, N.J. Business: Autoimmune, Biosimilars Pfizer Inc. (NYSE:PFE) filed a lawsuit alleging that Johnson & Johnson (NYSE:JNJ) violated antitrust laws by engaging in anticompetitive practices aiming at blocking sales of Pfizer’s biosimilar version of autoimmune drug Remicade infliximab. Pfizer's antitrust action takes a different approach than other biosimilar lawsuits, which typically allege patent infringement. In its complaint, filed in the U.S. District Court for the Eastern District of Pennsylvania, Pfizer says J&J threatened to withhold significant rebates unless insurers agreed to “biosimilar-exclusion” contracts that effectively block coverage for Pfizer’s Inflectra infliximab-dyyb and other infliximab biosimilars. Pfizer also alleged that J&J offered providers anticompetitive contracts that gave discounts on Remicade in exchange for not purchasing biosimilars to Remicade. Pfizer claims that those exclusionary contracts have caused insurers to deny coverage for Inflectra, even though the biosimilar has a lower cost. Inflectra's wholesale acquisition cost (WAC) of $946.28 per

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CLINICAL NEWS Business: Neurology Braeburn Pharmaceuticals Inc. (Princeton, N.J.) said FDA accepted REGULATORY and granted Priority Review to an NDA for weekly and monthly buprenorphine injection depot (CAM2038) to treat opioid use AB Science S.A. (Euronext:AB), Paris, France disorder. Its PDUFA date is Jan. 19, 2018. Product: Masipro masitinib (Masiviera, Masican, AB1010) Business: Dermatology Braeburn has exclusive, North American rights as well as option rights in Japan, Korea, Taiwan and China to CAM2038 under an EMA's CHMP for the second time recommended against approval expanded 2014 deal with Camurus (see BioCentury, Dec. 8, 2014 & of a resubmitted MAA from AB Science S.A. (Euronext:AB) for Oct. 31, 2016). Masipro masitinib (Masiviera, Masican, AB1010) to treat systemic mastocytosis in adults. CHMP's concerns echoed those of a May CAM2038 is a ready-to-use prefilled syringe containing a lipid negative opinion for the application, citing GCP failings, changes to solution of buprenorphine with Camurus' FluidCrystal injection the study design while the study was ongoing and limited safety data depot technology. (see BioCentury, May 19). The committee was also concerned about Bristol-Myers Squibb Co. (NYSE:BMY), New York, N.Y. side effects, including neutropenia and harmful effects on the skin Ono Pharmaceutical Co. Ltd. (Tokyo:4528), Osaka, Japan and liver. AB Science said it plans to initiate a confirmatory study in response. Product: Opdivo nivolumab (BMS-936558, MDX-1106, ONO- 4538) Masitinib is a stem cell factor (SCF) receptor tyrosine kinase (c-Kit; Business: Cancer KIT; CD117) inhibitor. EMA's CHMP announced that in July Bristol-Myers Squibb Co. Biogen Inc. (NASDAQ:BIIB), Cambridge, Mass. (NYSE:BMY) withdrew an MAA seeking to expand label for Opdivo Samsung BioLogics Co. Ltd. (KOSDAQ:207940), Seoul, South Korea nivolumab (BMS-936558, MDX-1106, ONO-4538) to include Product: Ontruzant biosimilar trastuzumab (SB3) treatment of hepatocellular carcinoma in adults previously treated Business: Cancer with Nexavar sorafenib. The committee said that at the time of the withdrawal, it was of the provisional opinion that the data BMS EMA’s CHMP backed approval of Ontruzant (SB3) from Samsung provided were insufficient to support approval because the study did Bioepis Co. Ltd. The product is a biosimilar of Herceptin not compare Opdivo directly with other treatments. CHMP also trastuzumab from Roche (SIX:ROG; OTCQX:RHHBY) and its said there was insufficient information about the patients enrolled Genentech Inc. unit. The biosimilar is recommended to treat HER2- in the study. positive metastatic breast cancer, HER2-positive early breast cancer and HER2-positive metastatic gastric cancer. Ontruzant is the first The human IgG4 mAb against PD-1 is approved in the EU to treat trastuzumab biosimilar recommended for approval by CHMP. NSCLC, renal cell carcinoma (RCC), classical Hodgkin's lymphoma, squamous cell carcinoma of the head and neck (SCCHN) and Herceptin is a humanized mAb against HER2. Samsung Bioepis, a JV urothelial carcinoma. between Biogen Inc. (NASDAQ:BIIB) and Samsung BioLogics Co. Ltd. (KOSDAQ:207940), launched in 2012 to develop biosimilars. BMS has worldwide rights to Opdivo from Ono Pharmaceutical Co. Ltd. (Tokyo:4528), except in Japan, South Korea and Taiwan, where Boehringer Ingelheim GmbH, Ingelheim, Germany Ono and BMS are partnered for the product (see BioCentury, July Product: Cyltezo adalimumab (BI 695501) 28, 2014). Business: Autoimmune CSL Ltd. (ASX:CSL), Melbourne, Australia EMA’s CHMP recommended approval of Cyltezo adalimumab (BI Product: Privigen 695501) from Boehringer Ingelheim GmbH (Ingelheim, Germany). Business: Neurology The product is a biosimilar of Humira adalimumab from AbbVie Inc. (NYSE:ABBV). The biosimilar is recommended to treat rheumatoid CSL Ltd. (ASX:CSL) said FDA approved Privigen to treat chronic arthritis (RA), juvenile idiopathic arthritis, axial spondyloarthritis, inflammatory demyelinating polyneuropathy (CIDP). The 10% psoriatic arthritis, psoriasis, pediatric plaque psoriasis, hidradenitis formulation of IV immunoglobulin is approved in the U.S. to treat suppurativa (HS), Crohn’s disease (CD), ulcerative colitis (UC) and primary immunodeficiency (PI) and immune thrombocytopenic uveitis. FDA approved Cyltezo in August. Humira is a mAb against purpura (ITP). tumor necrosis factor (TNF) alpha (see BioCentury, Sept. 1). GlaxoSmithKline plc (LSE:GSK; NYSE:GSK), London, U.K. Braeburn Pharmaceuticals Inc., Princeton, N.J. Innoviva Inc. (NASDAQ:INVA), South San Francisco, Calif. Camurus AB (SSE:CAMX), Lund, Sweden Product: Trelegy Ellipta fluticasone furoate/umeclidinium/vilanterol Product: CAM2038 Business: Pulmonary

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FDA approved an NDA from GlaxoSmithKline plc (LSE:GSK; determine a patient’s baseline liver function prior to starting NYSE:GSK) for Trelegy Ellipta fluticasone furoate/umeclidinium/ Ocaliva, monitor patients frequently for disease progression, and vilanterol for maintenance treatment of chronic obstructive reduce dosing frequency for patients who progress to moderate or pulmonary disease. GSK said Trelegy Ellipta is the first once-daily severe liver impairment. single inhaler triple therapy approved for COPD in the U.S. Through the FDA Adverse Event Reporting System (FAERS), the Trelegy Ellipta is specifically indicated for COPD patients already agency said it received reports of 19 deaths and 11 cases of serious receiving fixed-dose Breo Ellipta fluticasone furoate/vilanterol with liver injury associated with Ocaliva in the 13 months since the drug or without Incruse Ellipta umeclidinium. was approved in May 2016. Of the 8 cases that provided information On Sept. 19, GSK spokesperson Juan Carlos Molina told BioCentury about the patient's cause of death, the cause was reported to be that GSK will launch Trelegy Ellipta in the U.S. "shortly" at a worsening of PBC in 7 cases and cardiovascular disease in the other wholesale acquisition cost (WAC) of $530 for a 30-day supply. The case. Seven deaths and 6 cases of serious liver injury described pharma will pay tiered royalties of 6.5-10% on annual net sales of the patients with moderate to severe decreases in liver function who product to Innoviva Inc. (NASDAQ:INVA) under a deal to develop were dosed more frequently with Ocaliva than the drug's FDA label inhaled long-acting adrenergic receptor beta 2 agonist (LABA) recommends. products. Spokesperson Christopher Frates told BioCentury it is reviewing FDA partly based the approval on data from the Phase III 200109 FDA's warning and will provide a company statement "as soon as and 200110 trials, which showed that adding umeclidinium to possible." fluticasone furoate/vilanterol significantly improved lung function Ocaliva is also in Phase III testing for non-alcoholic steatohepatitis in COPD patients. (NASH) and Phase II testing for primary sclerosing cholangitis Trelegy Ellipta is a fixed-dose combination of 100 µg fluticasone (PSC) and biliary atresia. furoate, an inhaled corticosteroid; 62.5 µg umeclidinium bromide, Sumitomo Dainippon Pharma Co. Ltd. (Tokyo:4506) has a long-acting muscarinic antagonist (LAMA); and 25 µg vilanterol, a exclusive rights in Japan and China from Intercept to develop and LABA, delivered with GSK's Ellipta dry powder inhaler. commercialize the product for chronic liver disease (see BioCentury, On Sept. 15, EMA's CHMP recommended approval of Trelegy April 4, 2011). Ellipta for maintenance treatment of COPD. Ipsen Group (Euronext:IPN; Pink:IPSEY), Boulogne-Billancourt, France Intercept Pharmaceuticals Inc. (NASDAQ:ICPT), New York, N.Y. Teijin Pharma Ltd., Tokyo, Japan Sumitomo Dainippon Pharma Co. Ltd. (Tokyo:4506), Osaka, Japan Product: Somatuline Autogel (Somatuline Depot) lanreotide acetate Product: Ocaliva obeticholic acid (DSP-1747) (ITM-014) Business: Hepatic Business: Cancer On Sept. 21, FDA issued a drug safety communication warning of Ipsen Group (Euronext:IPN; Pink:IPSEY) said FDA approved serious liver injury in some patients incorrectly dosed with Ocaliva Somatuline Depot lanreotide acetate (ITM-014) to treat carcinoid obeticholic acid (DSP-1747) from Intercept Pharmaceuticals Inc. syndrome. (NASDAQ:ICPT). The extended-release formulation of somatostatin analog Ocaliva is an oral farnesoid X receptor (FXR; NR1H4) agonist that lanreotide is already approved in the U.S. to treat acromegaly and has accelerated approval in the U.S. to treat primary biliary cholangitis gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The (PBC) in combination with ursodeoxycholic acid (UDCA) in adults product is approved to treat acromegaly and neuroendocrine tumors with inadequate response to UDCA, or as monotherapy in patients in 70 countries, and is marketed outside the U.S. as Somatuline unable to tolerate UDCA. The drug also has conditional approval in Autogel. the EU for the indication. Teijin Pharma Ltd. (Tokyo, Japan) and Ipsen have a joint development Earlier this month, Intercept issued a "Dear Health Care Provider" and marketing deal for the compound in Japan. letter warning that liver injury, liver decompensation, liver failure Merck KGaA (Xetra:MRK), Darmstadt, Germany and death have been reported in PBC patients with moderate to severe hepatic impairment when Ocaliva was dosed more frequently Pfizer Inc. (NYSE:PFE), New York, N.Y. than recommended on its label (see BioCentury, Sept. 15). Product: Bavencio avelumab (MSB0010718C, PF-06834635) Business: Cancer In its announcement, FDA warned that Ocaliva is being incorrectly dosed in some patients with moderate to severe decreases in liver The European Commission approved Bavencio avelumab function, leading to an increased risk of serious liver injury and (MSB0010718C, PF-06834635) from Merck KGaA (Xetra:MRK) death. The agency recommended that healthcare professionals and Pfizer Inc. (NYSE:PFE) to treat metastatic Merkel cell

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carcinoma. The companies expect to initially launch the human IgG1 The small molecule that inhibits multiple tyrosine kinases is also mAb against PD-L1 in Germany and the U.K. as early as October. approved in the U.S. to treat gastrointestinal stromal tumors (GIST) Bavencio has accelerated approval in the U.S. to treat metastatic and advanced pancreatic neuroendocrine tumors. The company Merkel cell carcinoma and locally advanced or metastatic urothelial reported 2016 Sutent sales of $1.1 billion, representing 24% of its carcinoma. Merck and Pfizer share Bavencio's rights under a 2014 oncology revenue and 2% of its total revenue that year. deal (see BioCentury, Nov. 24, 2014). Santhera Pharmaceuticals Holding AG (SIX:SANN), Liestal, Switzerland MorphoSys AG (Xetra:MOR; Pink:MPSYY), Martinsried, Germany Johnson & Johnson (NYSE:JNJ), New Brunswick, N.J. Product: Raxone idebenone (SNT-MC17) Business: Musculoskeletal Product: Tremfya guselkumab (CNTO 1959) Business: Autoimmune EMA's CHMP recommended against approving an MAA for Raxone idebenone (SNT-MC17) from Santhera Pharmaceuticals EMA’s CHMP recommended approval of Tremfya guselkumab Holding AG (SIX:SANN) to slow down the worsening of breathing (CNTO 1959) from Johnson & Johnson (NYSE:JNJ) to treat function in Duchenne muscular dystrophy (DMD) patients who are moderate to severe plaque psoriasis in patients who are candidates not taking corticosteroids. CHMP said the data Santhera provided for systemic therapy. The human HuCAL mAb targeting the p19 were insufficient because while Raxone did improve peak expiratory subunit of IL-23 was approved by FDA in July (see BioCentury, July flow compared to placebo, the data showed "no clear improvement in 14). other indicators of breathing function or in muscle strength, motor Under a 2000 deal, MorphoSys AG (Xetra:MOR; Pink:MPSYY) function or quality of life." The committee also said it had concerns used its HuCAL human combinatorial antibody library to generate about the way the study was conducted and analyzed, but did not antibodies, including guselkumab, for J&J. The discovery portion of provide details. Santhera said it plans to appeal the recommendation. the deal expired in 2007 and MorphoSys is eligible for milestones Raxone, a short-chain benzoquinone, is approved in Europe to treat and royalties (see BioCentury, Jan. 8, 2001). visual impairment in adolescents and adults with Leber’s hereditary Pfizer Inc. (NYSE:PFE), New York, N.Y. optic neuropathy (LHON). Product: Sutent sunitinib Tesaro Inc. (NASDAQ:TSRO), Waltham, Mass. Business: Cancer Merck & Co. Inc. (NYSE:MRK), Kenilworth, N.J. FDA’s Oncologic Drugs Advisory Committee voted 6-6 on Sept. Product: Zejula niraparib (MK-4827, ZL-2306) 19 that the benefit-risk profile of Sutent sunitinib from Pfizer Inc. Business: Cancer (NYSE:PFE) is acceptable for the adjuvant treatment of patients at high risk of recurrent renal cell carcinoma following nephrectomy. EMA’S CHMP recommended approval of Zejula niraparib The drug, which is already approved in the U.S. to treat advanced (MK-4827, ZL-2306) from Tesaro Inc. (NASDAQ:TSRO) as RCC, has a January PDUFA date for the indication. monotherapy for the maintenance treatment of adult patients with platinum-sensitive, relapsed, high-grade serous epithelial ovarian, In briefing documents released ahead of the meeting, FDA asked fallopian tube or primary peritoneal cancer who are in response to the panel to discuss whether Sutent showed an improvement on the platinum-based chemotherapy. primary endpoint of disease-free survival (DFS) in the Phase III S-TRAC trial and whether DFS as defined in S-TRAC is a clinically FDA approved the oral PARP inhibitor in March (see BioCentury, relevant endpoint. The briefing documents noted that there is no March 30). In 2012, Merck & Co. Inc. (NYSE:MRK) granted Tesaro widely agreed upon definition of DFS in RCC as there is in breast exclusive, worldwide rights to Zejula (see BioCentury, June 11, 2012). cancer. ViiV Healthcare Ltd., Brentford, U.K. S-TRAC enrolled 615 treatment-naïve patients at high risk of Product: Triumeq dolutegravir/abacavir/lamivudine (Triumec, 572- recurrent RCC following surgery and showed that adjuvant treatment Trii, S-349572/S-265744/S-247303) with Sutent led to a median DFS as determined by an independent Business: Infectious radiology committee of 6.8 years vs. 5.6 years for placebo (HR=0.76, 95% CI: 0.59, 0.98, p=0.03). The 5-year DFS rate was 59% for Sutent China FDA approved Triumeq dolutegravir/abacavir/lamivudine vs. 51% for placebo (see BioCentury, Oct. 17, 2016). (Triumec, 572-Trii, S-349572/S-265744/S-247303) from ViiV Healthcare Ltd. (Brentford, U.K.) to treat HIV/AIDS. According to Pfizer, about 15% of patients with primary resected RCC are at high risk for recurrence and about 60% of these high- Triumeq is a once-daily tablet that comprises Tivicay dolutegravir, risk patients will have recurrence and develop metastatic disease an HIV integrase inhibitor, plus the nucleoside reverse transcriptase within 5 years. inhibitors (NRTIs) abacavir and lamivudine. It is approved in >70 countries, including the U.S. and EU, to treat HIV-1 infection.

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GlaxoSmithKline plc (LSE:GSK; NYSE:GSK), Pfizer Inc. Neuropathy (Norfolk QOL-DN) score vs. placebo (p<0.00001), (NYSE:PFE) and Shionogi & Co. Ltd. (Tokyo:4507) own ViiV. as well as the 5 other secondary endpoints of improving motor strength on the NIS-Weakness subdomain of the mNIS+7, disability XBiotech Inc. (NASDAQ:XBIT), Austin, Texas on the Rasch-built Overall Disability Scale (R-ODS), gait speed as Product: Hutruo (Xilonix, CV-18C3, T2-18C3, RA-18C3, MABp1, measured by the 10-meter walk test, nutritional status as measured CA-18C3) by modified BMI, and autonomic symptoms as measured by the Business: Cancer COMPASS-31 questionnaire vs. placebo (p<0.001 for all). EMA's CHMP reiterated its May negative opinion regarding an The frequency of adverse events (96.6% vs. 97.4%) and deaths MAA from XBiotech Inc. (NASDAQ:XBIT) for Hutruo (Xilonix, (4.7% vs. 7.8%) was similar between the patisiran and placebo arms. CV-18C3, T2-18C3, RA-18C3, MABp1, CA-18C3) to treat Additionally, there were fewer discontinuations from treatment symptoms of advanced colorectal cancer, including cachexia, saying (7.4% vs. 37.7%) and fewer discontinuations from treatment due to the data provided did not show clear improvements in either lean adverse events (4.7% vs. 14.3%) in the patisiran arm compared to the body mass or quality of life (see BioCentury, April 28). The product placebo arm. Peripheral edema occurred in 29.7% of patients in the is a human IgG1k mAb against IL-1 alpha. patisiran arm compared to 22.1% of patients in the placebo arm. Full data from the double-blind, international trial will be presented CLINICAL NEWS at the European ATTR Amyloidosis Meeting for Patients and CLINICAL RESULTS Doctors in Paris on Nov. 2. Sanofi Genzyme is also preparing regulatory applications for Alnylam Pharmaceuticals Inc. (NASDAQ:ALNY), Cambridge, Mass. patisiran in Japan, Brazil and other countries, with submissions Sanofi (Euronext:SAN; NYSE:SNY), Paris, France slated to begin in 1H18. Product: Patisiran (ALN-TTR02, GENZ438027, GZ438027, Sanofi Genzyme has exclusive rights to patisiran from Alnylam SAR438027) outside of the U.S., Canada and Western Europe under a 2014 Business: Endocrine/Metabolic expansion of a 2012 RNAi deal (see BioCentury, Oct. 29, 2012 & Jan. Molecular target: Transthyretin (TTR) 20, 2014). Patisiran uses second-generation lipid nanoparticle (LNP) Description: IV RNAi therapeutic targeting the TTR gene using technology from Arbutus Biopharma Corp. (NASDAQ:ABUS), second-generation lipid nanoparticle (LNP) technology which is eligible for milestones and royalties from Alnylam (see Indication: Treat familial amyloidotic polyneuropathy (FAP) BioCentury, Nov. 19, 2012). Endpoint: Change from baseline in modified Neuropathy Impairment Score+7 (mNIS+7) at 18 months; Norfolk Quality of Life Amunix Operating Inc., Mountain View, Calif. Questionnaire-Diabetic Neuropathy (Norfolk QOL-DN) score, Versartis Inc. (NASDAQ:VSAR), Redwood City, Calif. NIS-Weakness subdomain of the mNIS+7, Rasch-built Overall Teijin Pharma Ltd., Tokyo, Japan Disability Scale (R-ODS), 10-meter walk test, modified BMI, and Product: Somavaratan (VRS-317) COMPASS-31 questionnaire Business: Endocrine/Metabolic Status: Phase III data Molecular target: NA Milestone: Additional Phase III data (11/2/2017); submit NDA (year Description: Long-acting recombinant human growth hormone end 2017); submit MAA (early 2018) (rhGH) Alnylam Pharmaceuticals Inc. (NASDAQ:ALNY) and the Sanofi Indication: Treat pediatric growth hormone deficiency (GHD) Genzyme unit of Sanofi (Euronext:SAN; NYSE:SNY) reported Endpoint: Annual height velocity at 12 months; safety and top-line data showing that patisiran (ALN-TTR02) met the primary pharmacokinetics and all secondary endpoints in the Phase III APOLLO trial in 225 Status: Phase III data patients with familial amyloidotic polyneuropathy (FAP), a form of Milestone: NA transthyretin (TTR) amyloidosis (ATTR). Late this year, Alnylam Versartis Inc. (NASDAQ:VSAR) said somavaratan (VRS-317) plans to submit an NDA to FDA for the IV RNAi therapeutic missed the primary endpoint of non-inferiority to Genotropin targeting the TTR gene, with an MAA submission to EMA expected somatropin in the Phase III VELOCITY trial to treat pediatric early next year. growth hormone deficiency (GHD). On the primary endpoint, 0.3 mg/kg IV patisiran every 3 weeks In the intent-to-treat (ITT) population, twice-monthly significantly improved mean modified Neuropathy Impairment subcutaneous somavaratan failed to show non-inferiority to once- Score+7 (mNIS+7) from baseline to 18 months vs. placebo daily Genotropin in annual height velocity at 12 months (9.44 vs. 10.7 (p<0.00001). Patisiran also met the key secondary endpoint of cm). Non-inferiority was defined as a lower bound of the 2-sided 95% improving the Norfolk Quality of Life Questionnaire-Diabetic CI for the difference in height velocity between treatment groups

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of greater than or equal to -2.0 cm/year. In the ITT population, the negative advanced breast cancer in women who had disease lower bound of the 2-sided 95% CI was -2.3 cm/year. progression following endocrine therapy (see BioCentury, July 12). Versartis said somavaratan did show non-inferiority to Genotropin Abemaciclib is a selective dual inhibitor of cyclin dependent kinase on the primary endpoint in the per protocol (PP) population (9.71 vs. 4 (CDK4) and CDK6. It has breakthrough therapy designation 10.63 cm). Secondary endpoints in the open-label, international trial in the U.S. for refractory, hormone receptor-positive advanced or included safety and pharmacokinetics. metastatic breast cancer. The company said it will continue to evaluate the data and provide an GeNeuro S.A. (Euronext:GNRO), Geneva, Switzerland update on the program later this year. Versartis has rights to the long- acting recombinant human growth hormone (rhGH) from Amunix Product: GNbAC1 Operating Inc. (Mountain View, Calif.). Teijin Pharma Ltd. (Tokyo, Business: Autoimmune Japan) has exclusive, Japanese rights to develop and commercialize Molecular target: Endogenous retrovirus group W member 1 somavaratan from Versartis (see BioCentury, Aug. 15, 2016). (HERVW; ERVW-1) Description: Humanized IgG4 mAb targeting the envelope protein Eli Lilly and Co. (NYSE:LLY), Indianapolis, Ind. of human HERVW Product: Abemaciclib (LY2835219) Indication: Treat relapsing-remitting multiple sclerosis (RRMS) Business: Cancer Endpoint: Cumulative number of gadolinium-enhancing T1 lesions Molecular target: Cyclin dependent kinase 4 (CDK4); CDK6 on brain MRI at 6 months; MRI measures of neurodegeneration, Description: Selective dual inhibitor of CDK4 and CDK6 clinical parameters at 6 and 12 months and biomarkers Indication: Treat hormone receptor-positive, HER2-negative Status: Phase IIb data advanced breast cancer Milestone: Final Phase IIb data (1Q18) Endpoint: Progression-free survival (PFS); objective response rate GeNeuro S.A. (Euronext:GNRO) and Servier (Neuilly-sur-Seine, (ORR), overall survival (OS), duration of response, disease control France) reported data from the 12-month Phase IIb CHANGE- rate and pharmacokinetics MS trial in 270 patients with relapsing-remitting multiple sclerosis Status: Additional Phase III data (RRMS) showing that once-monthly IV GNbAC1 missed the Milestone: PDUFA date (1Q18) primary endpoint of reducing the cumulative number of gadolinium- Eli Lilly and Co. (NYSE:LLY) reported additional data from the enhancing T1 lesions on brain MRI at 6 months vs. placebo. The Phase III MONARCH 3 trial in 493 postmenopausal women companies also said there was no significant difference between with hormone receptor-positive, HER2-negative, locoregionally treatment groups on other MRI measures of neuroinflammation. recurrent or metastatic breast cancer showing that median GNbAC1 was well tolerated. Final 12-month data from the double- progression-free survival, the primary endpoint, was not reached in blind, European trial are expected in 1Q18. GeNeuro said the study patients receiving twice-daily 150 mg oral abemaciclib (LY2835219) will continue as planned to explore "potential benefits" of the plus anastrozole or letrozole vs. 14.7 months for anastrozole or compound on MRI and clinical measures, including remyelination letrozole alone (HR=0.54, 95% CI: 0.41, 0.72, p=0.000021). properties. Abemaciclib plus anastrozole or letrozole led to an ORR, a GNbAC1 is a humanized IgG4 mAb targeting the envelope protein secondary endpoint, of 59% vs. 44% for anastrozole or letrozole of human endogenous retrovirus group W member 1 (HERVW; alone (p=0.04). Data were presented at the European Society for ERVW-1). Data from a Phase IIa trial of GNbAC1 to treat Type I Medical Oncology meeting in Madrid. diabetes are expected in 3Q18. Lilly previously reported that abemaciclib plus anastrozole or Servier has an option to license exclusive rights to develop and letrozole met the PFS and ORR endpoints (see BioCentury, April commercialize GNbAC1 worldwide, excluding the U.S. and Japan, 27). Additional secondary endpoints in the double-blind, placebo- after CHANGE-MS is completed (see BioCentury, Dec. 8, 2014 & controlled, international trial include overall survival (OS), duration Jan. 11, 2016). of response, disease control rate (DCR), clinical benefit rate and GlaxoSmithKline plc (LSE:GSK; NYSE:GSK), London, U.K. pharmacokinetics. Product: Nucala mepolizumab (SB-240563) In July, FDA accepted and granted Priority Review to an NDA for Business: Pulmonary abemaciclib to treat advanced breast cancer, with a PDUFA date Molecular target: IL-5 in 1Q18. Specifically, abemaciclib is under review as monotherapy Description: Humanized IgG mAb against IL-5 to treat hormone receptor-positive, HER2-negative advanced Indication: Treat chronic obstructive pulmonary disease (COPD) breast cancer in patients who had prior endocrine therapy and chemotherapy for metastatic disease; and in combination with Faslodex fulvestrant to treat hormone receptor-positive, HER2-

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Endpoint: Annual rate of moderate or severe exacerbations; time to Innoviva Inc. (NASDAQ:INVA), South San Francisco, Calif. first moderate or severe exacerbation, annual rate of exacerbations GlaxoSmithKline plc (LSE:GSK; NYSE:GSK), London, U.K. requiring hospitalization, St. George’s Respiratory Questionnaire Product: Trelegy Ellipta fluticasone furoate/umeclidinium/vilanterol (SGRQ) score and COPD assessment score (FF/UMEC/VI) Status: Phase III data Business: Pulmonary Milestone: Submit regulatory application (2H17) Molecular target: Muscarinic receptor; Adrenergic receptor beta 2 GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) plans to submit (ADRB2) regulatory applications this half for Nucala mepolizumab (SB- Description: Fixed-dose combination of fluticasone furoate, an 240563) to treat chronic obstructive pulmonary disease (COPD) inhaled corticosteroid; umeclidinium bromide, a long-acting with an eosinophilic phenotype after reporting mixed data muscarinic receptor antagonist (LAMA); and vilanterol, a long- from the double-blind, international Phase III METREX and acting ADRB2 agonist (LABA) METREO trials. The trials enrolled COPD patients at high risk Indication: Treat chronic obstructive pulmonary disease (COPD) of exacerbations despite the use of optimal standard of care (SOC) Endpoint: Annual rate of on-treatment moderate and severe background therapy consisting of an inhaled corticosteroid (ICS), exacerbations; change from baseline in trough forced expiratory long-acting adrenergic receptor beta 2 agonist (LABA) and long- volume in 1 second (FEV1), St. George's Respiratory Questionnaire acting muscarinic receptor antagonist (LAMA). (SGRQ) score and time to first on-treatment moderate or severe In the 836-patient METREX (Study 117106) trial, 100 mg exacerbation subcutaneous mepolizumab every 4 weeks met the primary endpoint Status: Phase III data of reducing the mean annual rate of moderate or severe exacerbations Milestone: NA in patients with a blood eosinophil count of >150 cells/µL at study GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) and Innoviva Inc. entry or >300 cells/µL within the past year (n=462) vs. placebo (1.4 (NASDAQ:INVA) reported data from the Phase III IMPACT vs. 1.71 exacerbations per year, p=0.036). Mepolizumab also met the trial in 10,355 chronic obstructive pulmonary disease (COPD) secondary endpoint of increasing the time to first moderate and patients showing that once-daily Trelegy Ellipta fluticasone furoate/ severe exacerbation vs. placebo (192 vs. 141 days, p=0.04), but missed umeclidinium/vilanterol (FF/UMEC/VI) met the primary endpoint the secondary endpoints of reducing the annual rate of exacerbations of reducing the annual rate of on-treatment moderate and severe requiring hospitalization, St. George’s Respiratory Questionnaire exacerbations compared to both fluticasone furoate/vilanterol (0.91 (SGRQ) score and COPD assessment score vs. placebo. vs. 1.07 exacerbations per year, p<0.001) and umeclidinium bromide/ In the 674-patient METREO (Study 117113) trial, 100 and 300 vilanterol (0.91 vs. 1.21 exacerbations per year, p<0.001). The mg doses of mepolizumab every 4 weeks each missed the primary double-blind, international trial enrolled patients with moderate to endpoint of reducing the mean annual rate of moderate or severe very severe symptomatic COPD and a history of exacerbation in the exacerbations in patients with a blood eosinophil count of >150 previous 12 months. cells/µL at study entry or >300 cells/µL within the past year (n=674) Trelegy Ellipta also met the secondary endpoints of improving vs. placebo (1.19 and 1.27 exacerbations per year, respectively, vs. trough forced expiratory volume in 1 second (FEV1) from baseline 1.49 exacerbations per year, p=0.068 and p=0.14). Both doses of to week 52, St. George’s Respiratory Questionnaire (SGRQ) score mepolizumab also missed all secondary endpoints vs. placebo. and time to first on-treatment moderate or severe exacerbation GSK said a prespecified meta-analysis of patients with an compared to both fluticasone furoate/vilanterol and umeclidinium eosinophilic phenotype treated with mepolizumab in both trials bromide/vilanterol (p<0.001 for all). showed that the rate of exacerbation reduction increased as baseline On Sept. 18, FDA approved an NDA for Trelegy Ellipta for blood eosinophil counts increased, suggesting that blood eosinophil maintenance treatment of COPD. GSK said Trelegy Ellipta is the levels could be used as a biomarker to identify COPD patients most first once-daily single inhaler triple therapy approved for COPD likely to respond to mepolizumab. in the U.S. Trelegy Ellipta is specifically indicated for COPD Data were presented at the European Respiratory Society meeting patients already receiving fixed-doseBreo Ellipta fluticasone furoate/vilanterol with or without Incruse Ellipta umeclidinium. in Milan and published in the New England Journal of Medicine. GSK reported preliminary data from METREX and METREO in May. EMA's CHMP has recommended approval of Trelegy Ellipta for maintenance treatment of COPD. GSK markets the humanized IgG mAb against IL-5 as Nucala as an add-on maintenance therapy to treat severe asthma in patients In 2Q18, GSK plans to begin submission of global regulatory ages ≥12 with an eosinophilic phenotype in the U.S., and for severe applications for Trelegy Ellipta based on the IMPACT data. eosinophilic asthma in the EU and Japan. An sBLA for Nucala Trelegy Ellipta is a fixed-dose combination of 100 µg fluticasone is under FDA review to treat eosinophilic granulomatosis with furoate, an inhaled corticosteroid; 62.5 µg umeclidinium bromide, polyangiitis. a long-acting muscarinic receptor antagonist (LAMA); and 25 µg

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vilanterol, a long-acting adrenergic receptor beta 2 agonist (LABA), Merck has previously reported data from open-label, crossover, delivered with GSK's Ellipta dry powder inhaler. international KEYNOTE-021 trial (see BioCentury, May 25, 2015; GSK and are partnered under a deal to develop inhaled LABA May 23, 2016 & Oct. 17, 2016). products. Based on data from KEYNOTE-021, FDA granted accelerated GSK's fluticasone furoate/vilanterol is approved for COPD and approval in May to Keytruda in combination with carboplatin and asthma as Breo Ellipta in the U.S. and as Relvar Ellipta in Europe. Alimta as a first-line treatment of NSCLC, regardless of PD-L1 The pharma's umeclidinium bromide/vilanterol is approved as expression. Keytruda already had approval as a monotherapy for first- Anoro Ellipta in the U.S. and EU for COPD. line treatment of NSCLC in patients with high PD-L1 expression with no EGFR or ALK genomic tumor aberrations, and for NSCLC Merck & Co. Inc. (NYSE:MRK), Kenilworth, N.J. patients whose tumors express PD-L1 with disease progression on Product: Keytruda pembrolizumab (MK-3475) or after platinum-containing chemotherapy (see BioCentury, May Business: Cancer 12). Molecular target: PD-1 The humanized IgG4 mAb against PD-1 also has full or accelerated Description: Humanized IgG4 mAb against PD-1 approval to treat microsatellite instability-high (MSI-H) or Indication: Treat unresectable or metastatic non-small cell lung mismatch repair deficient (dMMR) cancer regardless of tissue of cancer (NSCLC) origin, melanoma, squamous cell carcinoma of the head and neck Endpoint: Recommended Phase II dose (Phase I) and objective (SCCHN), classical Hodgkin's lymphoma and urothelial carcinoma. response rate (ORR) (Phase II); overall survival (OS), progression- free survival (PFS) and duration of response Mirati Therapeutics Inc. (NASDAQ:MRTX), San Diego, Calif. Status: Updated Phase I/II data Product: Sitravatinib (MGCD516) (formerly MG516) Milestone: N/A Business: Cancer Merck & Co. Inc. (NYSE:MRK) reported updated data from 123 Molecular target: Ret proto-oncogene (RET); TYRO3 protein chemotherapy-naive patients with metastatic, non-squamous tyrosine kinase (TYRO3; SKY) EGFR- and anaplastic lymphoma kinase (ALK)-negative non-small Description: Spectrum-selective kinase inhibitor that inhibits cell lung cancer (NSCLC) in cohort G of the Phase II portion of the multiple receptor tyrosine kinases (RTKs) including RET, TYRO3, Phase I/II KEYNOTE-021 trial showing that first-line treatment AXL receptor tyrosine kinase (AXL; UFO), c-Mer proto-oncogene with 200 mg IV Keytruda pembrolizumab (MK-3475) every 3 weeks tyrosine kinase (MERTK), VEGF receptor 2 (VEGFR-2; KDR/Flk- plus Alimta pemetrexed and carboplatin continued to improve 1) and stem cell factor (SCF) receptor tyrosine kinase (c-Kit; KIT; progression-free survival (PFS) and overall response rate (ORR) with CD117) an additional 5 months of follow-up. Indication: Treat advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) In cohort G, Keytruda plus Alimta and carboplatin led to a median Endpoint: Number of patients with tumor size reduction; safety and PFS of 19 months vs. 8.9 months for Alimta and carboplatin alone pharmacokinetics (HR=0.54, 95% CI: 0.33, 0.88, p=0.0067). Keytruda plus Alimta and Status: Phase II data carboplatin also improved the PFS rate at 12 (57% vs. 37%) and 18 Milestone: NA (52% vs. 29%) months vs. Alimta and carboplatin alone. Keytruda plus Alimta and carboplatin led to an ORR of 56.7% vs. 31.7% for Mirati Therapeutics Inc. (NASDAQ:MRTX) reported preliminary Alimta and carboplatin alone (p=0.0029). At a median follow-up of data from a Phase II trial showing that sitravatinib (MGCD516) in 18.7 months, median duration of response has not been reached in combination with PD-1 mAb Opdivo nivolumab led to 3 confirmed either arm. partial responses in 11 evaluable patients with non-squamous non- small cell lung cancer (NSCLC) who progressed on or after treatment Median overall survival (OS) has not yet been reached in the with checkpoint inhibitor therapy. The company said the predefined Keytruda arm compared to 20.9 months for Alimta and carboplatin criteria for expansion from stage 1 to stage 2 of the open-label, U.S. alone. Despite the trial's crossover design, Merck also said there trial, which will enroll a combined total of 34 patients, have been was a trend toward improvement in OS for the Keytruda arm met. Data were presented at the International Association for the compared to Alimta and carboplatin alone (HR=0.59, 95% CI: 0.34, Study of Lung Cancer (IASLC) Multidisciplinary Symposium in 1.05, p=0.03). In the 63 patients randomized to receive Alimta and Thoracic Oncology in Chicago. carboplatin alone, 40 went on to receive subsequent anti-PD-1 or PD-L1 therapy, including 25 who received Keytruda as part of the Mirati also presented a case study from a heavily pretreated NSCLC study crossover. Data were presented at the European Society for patient harboring an inactivating Cbl proto-oncogene (CBL) Medical Oncology meeting in Madrid. mutation in a Phase Ib trial evaluating sitravatinib as monotherapy. The company said the patient achieved a confirmed partial response with a maximum reduction in target lesions of 77%.

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Sitravatinib is a spectrum-selective kinase inhibitor that inhibits (85.1% vs. 6.9%, p<0.001) response rates at week 16 vs. placebo (see multiple receptor tyrosine kinases (RTKs) including Ret proto- BioCentury, Oct. 10, 2016). oncogene (RET), TYRO3 protein tyrosine kinase (TYRO3; SKY), FDA approved Tremfya in July to treat moderate to severe plaque AXL receptor tyrosine kinase (AXL; UFO), c-Mer proto-oncogene psoriasis in adults who are candidates for systemic therapy or tyrosine kinase (MERTK), VEGF receptor 2 (VEGFR-2; KDR/Flk- phototherapy. An MAA for Tremfya is under EMA review with a 1) and stem cell factor (SCF) receptor tyrosine kinase (c-Kit; KIT; decision expected by year end (see BioCentury, July 14). CD117). Under a 2000 deal, MorphoSys used its HuCAL human combinatorial MorphoSys AG (Xetra:MOR; Pink:MPSYF), Martinsried, Germany antibody library to generate antibodies, including Tremfya, for J&J. Johnson & Johnson (NYSE:JNJ), New Brunswick, N.J. The discovery portion of the deal expired in 2007 and MorphoSys is eligible for milestones and royalties (see BioCentury, Jan. 8, 2001). Product: Tremfya guselkumab (CNTO 1959) Business: Autoimmune Nabriva Therapeutics plc (NASDAQ:NBRV), Dublin, Ireland Molecular target: IL-23 Product: Lefamulin (BC-3781) Description: Human HuCAL mAb targeting the p19 subunit of IL- Business: Infectious 23 Molecular target: Ribosomal 50S subunit Indication: Treat moderate to severe plaque psoriasis Description: Semi-synthetic derivative of the antibiotic Endpoint: Proportion of patients with an Investigator’s Global pleuromutilin that binds the peptidyl transferase center on the Assessment (IGA) score of 0 or 1 point and who achieve a Psoriasis ribosome Area and Severity Index (PASI) 90 response at week 16 compared to Indication: Treat moderate to severe community-acquired bacterial placebo; proportion of patients with an IGA score of 0 or 1 point and pneumonia (CABP) PASI 90 response rates at week 16, 24 and 48 compared to Humira Endpoint: Early clinical response at 72-120 hours after the start of adalimumab and Dermatology Life Quality Index (DLQI) score treatment; Investigator’s Assessment of Clinical Response at the Status: Additional Phase III data test-of-cure (TOC) visit 5-10 days after the end of treatment in Milestone: NA the modified intent-to-treat (mITT) and clinically evaluable (CE) The Janssen Research & Development LLC unit of Johnson & populations Johnson (NYSE:JNJ) reported 2-year data from the open-label Status: Phase III data extension of the double-blind, international Phase III VOYAGE 1 Milestone: Phase III data (2Q17); submit NDA (2H18) trial of Tremfya guselkumab (CNTO 1959) showing that the drug Nabriva Therapeutics plc (NASDAQ:NBRV) reported that IV-to- maintained long-term efficacy in patients with moderate to severe oral lefamulin (BC-3781) met the FDA- and EMA-defined primary plaque psoriasis. endpoints in the double-blind, international Phase III LEAP 1 In the 837-patient trial, 82.1% of patients who received subcutaneous trial to treat moderate to severe community-acquired bacterial Tremfya at weeks 0 and 4 and then every 8 weeks for 100 weeks had pneumonia (CABP). Top-line data from the Phase III LEAP 2 trial 90% skin clearance as measured by the Psoriasis Area and Severity evaluating oral lefamulin to treat CABP are expected next spring, Index (PASI 90). Additionally, 82.4% of patients achieved an with an NDA submission to FDA to follow in 2H18. The company Investigator’s Global Assessment (IGA) score of cleared or minimal plans to submit an MAA to EMA “within a few months” after its disease at week 100. NDA submission. Among patients initially randomized to receive Humira adalimumab In LEAP 1's 551-patient intent-to-treat (ITT) population, 150 mg from AbbVie Inc. (NYSE:ABBV) and then transitioned at week lefamulin every 12 hours was non-inferior to moxifloxacin with or 52 to receive Tremfya every 8 weeks, the proportion of patients without adjunctive Zyvox linezolid on the FDA-defined primary achieving PASI 90 increased from 50.5% at week 52 to 81.1% endpoint of early clinical response at 72-120 hours after the start at week 100. Among this group, the proportion of patients who of treatment (87.3% vs. 90.2%). The non-inferiority margin was achieved an IGA score of cleared or minimal disease increased from 12.5%. Early clinical response was defined as improvement in ≥2 60.4% at week 52 to 84% at week 100. Janssen also said that patients of the 4 cardinal symptoms of CABP -- difficulty breathing, cough, initially randomized to receive placebo and crossed over to Tremfya production of purulent sputum and chest pain -- with no worsening at weeks 16 and 20 showed "consistent levels" of skin clearance at in any of those symptoms or use of a concomitant antibiotic (other weeks 52 and 100. Data were presented at the European Academy of than linezolid). Investigators could switch patients to 600 mg oral Dermatology and Venereology meeting in Geneva. lefamulin every 12 hours after 3 days of IV treatment. Last year, Janssen reported that the human HuCAL mAb targeting Lefamulin was also non-inferior to moxifloxacin with or without the p19 subunit of IL-23 met VOYAGE 1's co-primary endpoints adjunctive linezolid on the EMA-defined primary endpoints of of improving PASI 90 (73.3% vs. 2.9%, p<0.001) and IGA success Investigator’s Assessment of Clinical Response at the test-of-cure (TOC) visit 5-10 days after the end of treatment in the modified

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ITT (mITT) (81.7% vs. 84.2%) and clinically evaluable (CE) (86.9% Description: Donor-sourced mobilized peripheral blood modulated vs. 89.4%) populations. The non-inferiority margin for both EMA ex vivo with dexamethasone (FT4145) and 16,16-dimethyl endpoints was 10%. prostaglandin E2 (PGE2) (FT1050) Lefamulin is a semi-synthetic derivative of the antibiotic Indication: Prevent graft-versus-host disease (GvHD) pleuromutilin that binds the peptidyl transferase center on the Endpoint: Safety and incidence of grade B-D acute GvHD by Day ribosome. The product has Qualified Infectious Disease Product 100 post-HCT; For CMV-positive patients, incidence of patients (QIDP) and Fast Track designations in the U.S. to treat CABP and with CMV viremia or who initiate anti-viral therapy for CMV by acute bacterial skin and skin structure infections (ABSSSIs). Day 100 post-HCT Status: Phase II started Vanda Pharmaceuticals Inc. (NASDAQ:VNDA), Washington, D.C. Milestone: Phase I data (12/2017) Eli Lilly and Co. (NYSE:LLY), Indianapolis, Ind. Fate Therapeutics Inc. (NASDAQ:FATE) began enrollment in Product: Tradipitant (formerly LY686017, VLY-686) the double-blind Phase II portion of the U.S and European Phase Business: Dermatology I/II PROTECT trial of ProTmune to prevent acute graft-versus- Molecular target: Tachykinin receptor (TACR1; NK1R) host disease (GvHD) in patients with hematologic malignancies Description: TACR1 antagonist undergoing allogeneic hematopoietic cell transplantation (HCT) in Indication: Treat chronic pruritus associated with atopic dermatitis accordance with a recommendation by an independent DMC. Endpoint: Chronic pruritus as measured by itch visual analog scale Fate said the DMC's review showed all 7 patients who received (VAS) score; worst itch VAS, total Scoring Atopic Dermatitis Index ProTmune in the open-label Phase I portion met the day 28 safety (SCORAD), Clinical Global Impression of Change (CGI-C) and objectives of neutrophil engraftment and survival with no graft quality of life (QOL) failure events or treatment-related serious adverse events. The Status: Phase II data company said the median time to neutrophil engraftment was 18 Milestone: NA days. The Phase II portion of the trial will enroll 60 patients to Vanda Pharmaceuticals Inc. (NASDAQ:VNDA) reported data receive ProTmune or non-programmed mobilized peripheral blood from the double-blind, U.S. Phase II Study 2102 in 168 chronic cells (MPBC). pruritus patients with mild to severe atopic dermatitis showing that The trial's primary endpoints are safety and incidence of Grade B-D twice-daily 85 mg oral tradipitant for 8 weeks missed the primary acute GvHD by Day 100 post-HCT. The secondary endpoint is endpoint of improving mean itch visual analog scale (VAS) score vs. incidence of cytomegalovirus (CMV) viremia or initiation of CMV placebo (reductions of 41.5 vs. 35.8 points, p=0.306). Tradipitant did antiviral therapy in CMV-positive patients. meet the secondary endpoints of improving worst itch VAS score Fate expects to present data from the trial's Phase I portion at the (reductions of 44.2 vs. 30.6 points, p=0.019), total Scoring Atopic American Society of Hematology meeting in December. Dermatitis Index (SCORAD) scale score (reductions of 21.3 vs. 13.6 points, p=0.008), Clinical Global Impression of Change (CGI-C) ProTmune comprises donor-sourced mobilized peripheral blood (2.6 vs. 3.3 points, p=0.007) and quality of life (QOL) as measured by modulated ex vivo with dexamethasone (FT4145) and 16,16-dimethyl the Patient Benefit Index (PBI) (p=0.038) vs. placebo. prostaglandin E2 (PGE2) (FT1050). It has Orphan Drug designation in the U.S. and EU and Fast Track designation in the U.S. Vanda said it plans to meet with FDA "in the near future to further define and confirm the clinical development path towards Madrigal Pharmaceuticals Inc. (NASDAQ:MDGL), West registration" of tradipitant for atopic dermatitis. Conshohocken, Pa. In 2012, Eli Lilly and Co. (NYSE:LLY) granted Vanda exclusive, Roche (SIX:ROG; OTCQX:RHHBY), Basel, Switzerland worldwide rights to develop and commercialize the tachykinin Product: MGL-3196, VIA-3196 receptor (TACR1; NK1R) antagonist (see BioCentury, April 23, Business: Endocrine/Metabolic 2012). Molecular target: Thyroid hormone receptor beta Description: Selective agonist of thyroid hormone receptor beta CLINICAL NEWS Indication: Treat heterozygous familial hypercholesterolemia (HeFH) CLINICAL STATUS Endpoint: Mean percent change from baseline in LDL-C; mean percent change from baseline in non-HDL-C, triglycerides, Fate Therapeutics Inc. (NASDAQ:FATE), San Diego, Calif. lipoprotein(a) (LPA), apolipoprotein B (APOB), total cholesterol/ Product: ProTmune HDL-C ratio, apolipoprotein A-1 (APOA1; apo(a))/APOB ratio and Business: Transplant lipoprotein particle assessment and safety Molecular Target: NA Status: Completed Phase II enrollment Milestone: Phase II data (early 2018)

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Madrigal Pharmaceuticals Inc. (NASDAQ:MDGL) said it has at 14 and 42 post-dose, PCR-uncorrected ACPR at 28 days post- enrolled 113 patients in a Phase II trial of MGL-3196 (VIA-3196) dose, incidence of recrudescence and reinfection at 14, 28 and 42 to treat heterozygous familial hypercholesterolemia (HeFH), days post-dose, parasite and fever clearance times, proportion of exceeding its target enrollment of 105. The company said it would patients with parasitemia 12, 24 and 48 hours after treatment and continue enrollment "for the next several days." pharmacokinetics. The double-blind, placebo-controlled, European trial is evaluating KAF156 is an imidazolopiperazine derivative. Coartem is a fixed- MGL-3196 for 12 weeks in combination with patients' current dose artemisinin-based combination treatment. drug regimens, including high-dose statins and/or the cholesterol absorption inhibitor Zetia ezetimibe from Merck & Co. Inc. Oncolytics Biotech Inc. (TSX:ONC; OTCQX:ONCYF), Calgary, Alberta (NYSE:MRK). The primary endpoint is the mean percent change Product: Reolysin pelareorep from baseline in LDL-C. Secondary endpoints include mean percent Business: Cancer change from baseline in non-HDL-C, triglycerides, lipoprotein(a) Molecular target: NA (LPA), apolipoprotein B (APOB), total cholesterol/HDL-C ratio, Description: Formulation of human reovirus type 3, an oncolytic apolipoprotein A-1 (APOA1; apo(a))/APOB ratio and lipoprotein virus particle assessment and safety. Indication: Treat relapsed or refractory multiple myeloma (MM) Madrigal also said an independent DSMB recommended the trial, Endpoint: Dose-limiting toxicities (DLTs) and maximum tolerated as well as another Phase II trial of MGL-3196 in non-alcoholic dose (MTD); safety, response rate, maximum response rate within steatohepatitis (NASH), continue without modification based on 6 cycles of therapy, time to maximum response, progression-free its second review. survival (PFS) and overall survival (OS) Madrigal has exclusive, worldwide rights to MGL-3196 from Roche Status: Phase Ib started under a 2008 deal. The company expects top-line data from the Milestone: Preliminary Phase Ib data (1Q18) HeFH trial in early 2018. Oncolytics Biotech Inc. (TSX:ONC; OTCQX:ONCYF) said the first patient has been dosed in the Phase Ib MUK eleven trial of Novartis AG (NYSE:NVS; SIX:NOVN), Basel, Switzerland Reolysin pelareorep in combination with Revlimid lenalidomide or Medicines for Malaria Venture, Geneva, Switzerland Imnovid pomalidomide from Celgene Corp. (NASDAQ:CELG) as a Product: KAF156 rescue treatment in relapsing or refractory multiple myeloma (MM) Business: Infectious patients who are progressing despite treatment with 1 of those Molecular target: NA immunomodulatory agents (IMiDs). Description: Imidazolopiperazine derivative The open-label, dose-escalation, U.K. trial is evaluating IV Reolysin Indication: Treat malaria on days 1, 8, 15 and 22 of each 28-day cycle at a starting dose of Endpoint: PCR-corrected adequate clinical and parasitological 3x1010 50% tissue culture infective dose (TCID50) in about 44 patients. The primary response (ACPR) at 28 days post-dose; safety, PCR-uncorrected and- endpoints are dose-limiting toxicities (DLTs) and maximum corrected ACPR at 14 and 42 post-dose, PCR-uncorrected ACPR tolerated dose (MTD). Secondary endpoints include safety, response at 28 days post-dose, incidence of recrudescence and reinfection rate, maximum response rate within 6 cycles of therapy, time to at 14, 28 and 42 days post-dose, parasite and fever clearance times, maximum response, progression-free survival (PFS) and overall proportion of patients with parasitemia 12, 24 and 48 hours after survival (OS). treatment and pharmacokinetics Reolysin is a formulation of human reovirus type 3, an oncolytic Status: Phase IIb started virus. Milestone: NA Preliminary data from the trial are expected in 1Q18. Novartis AG (NYSE:NVS; SIX:NOVN) and Medicines for Malaria Venture (Geneva, Switzerland) began a Phase IIb trial of KAF156 In March, Myeloma UK partnered with Oncolytics and Celgene to plus a "new, improved formulation" of the antimalarial lumefantrine conduct the trial (see BioCentury, March 24). to treat malaria. ViroMed Co. Ltd. (KOSDAQ:084990), Seoul, South Korea The single-blind, African and Asian trial will enroll about 512 Product: VM202 adults, adolescents and children to receive Novartis' Coartem Business: Dermatology artemether/lumefantrine or lumefantrine in combination with Molecular target: NA a single dose of 200, 400 or 800 mg KAF156; 400 mg KAF156 Description: Plasmid DNA carrying the hepatocyte growth factor once daily for 2 days; or 200 or 400 mg KAF156 once daily for 3 (HGF) gene days. The primary endpoint is PCR-corrected adequate clinical and Indication: Treat non-healing diabetic foot ulcers and concomitant parasitological response (ACPR) at 28 days post-dose. Secondary peripheral artery disease (PAD) endpoints include safety, PCR-uncorrected and -corrected ACPR

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Endpoint: Proportion of patients with confirmed target wound closure by the 4-month follow-up; changes in ankle-brachial index and toe-brachial index, time to complete wound closure, proportion of patients with confirmed target wound closure at ≤7 months, percent change in wound volume, area and depth and proportion of patients with new ulcer formation on the target foot at 2, 3, 4 and 7 months, time to major and minor amputations and change in each Cardiff Wound Impact Questionnaire (CWIQ) domain score from baseline to months 4 and 7 Status: Phase III started Milestone: NA VM BioPharma, the U.S. division of ViroMed Co. Ltd. (KOSDAQ:084990), began a Phase III trial of VM202 to treat non-healing diabetic foot ulcers and concomitant peripheral artery disease (PAD). The double-blind, placebo-controlled, U.S. study will enroll 300 patients. The primary endpoint is the proportion of patients with confirmed target wound closure by the 4-month follow- up. Secondary endpoints include changes in ankle-brachial index and toe-brachial index; time to complete wound closure; proportion of patients with confirmed target wound closure at ≤7 months; percent change in wound volume, area and depth and proportion of patients with new ulcer formation on the target foot at 2, 3, 4 and 7 months; time to major and minor amputations and change in each Cardiff Wound Impact Questionnaire (CWIQ) domain score from baseline to months 4 and 7. The candidate is a plasmid DNA carrying the hepatocyte growth factor (HGF) gene.

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FINANCIAL NEWS Array BioPharma Inc. (NASDAQ:ARRY), Boulder, Colo. Marinus Pharmaceuticals Inc. (NASDAQ:MRNS), Radnor, Pa. COMPLETED OFFERINGS T2 Biosystems Inc. (NASDAQ:TTOO), Lexington, Mass.

AbClon Inc. (KOSDAQ:174900), Seoul, South Korea Cancer company Array BioPharma Inc. (NASDAQ:ARRY), neurology company Marinus Pharmaceuticals Inc. On Sept. 18, AbClon Inc. (KOSDAQ:174900) raised W6.8 billion (NASDAQ:MRNS), and diagnostics play T2 Biosystems Inc. ($6.1 million) through the sale of 680,741 shares at W10,000 in an (NASDAQ:TTOO) each priced follow-on offerings, raising more IPO. than $270 million. Director Kyu-Tae Kim told BioCentury that AbClon's lead Array raised $258.8 million through the sale of 24.1 million shares candidate is AC101, a mAb targeting epidermal growth factor (EGF) at $10.75 in a bumped-up follow-on underwritten by JPMorgan, that is in preclinical testing to treat gastric and breast cancer. In Cowen, Piper Jaffray, Stifel, Wells Fargo and SunTrust Robinson 2016, AbClon granted Shanghai Henlius Biotech Inc. (Shanghai, Humphrey. The price is a 2% increase to Array's close of $10.53 China), a JV between Shanghai Fosun Pharmaceutical Group Co. on Sept. 13 when it proposed the offering after trading hours. The Ltd. (Shanghai:600196; HKSE:2196) and Henlius Biotech Co. Ltd. figures include the sale of a 3.1 million share overallotment on Sept. (Shanghai, China), exclusive, Chinese rights to AC101. 19. Acceleron Pharma Inc. (NASDAQ:XLRN), Cambridge, Mass. On Sept. 12, FDA accepted for review NDAs for binimetinib and encorafenib in combination to treat BRAF-mutant advanced, On Sept. 20, Acceleron Pharma Inc. (NASDAQ:XLRN) raised unresectable or metastatic melanoma. Binimetinib is a small $200 million through the sale of 5.4 million shares at $37 in a molecule selective MAP kinase kinase 1 (MAP2K1; MEK1) and bumped-up follow-on underwritten by JPMorgan, Citigroup and MEK2 inhibitor, and encorafenib is a small molecule BRAF Leerink Partners. The price is a 5% discount to Acceleron's close inhibitor. of $38.97 on Sept. 19, when it proposed after trading hours to raise $150 million. Marinus raised $40.3 million through the sale of 10.7 million shares at $3.75 in a follow-on underwritten by JMP Securities. The price is a Acceleron expects top-line data in mid-2018 from Phase III studies 6% discount to Marinus' close of $4.01 on Sept. 14 when it proposed of lead candidate luspatercept (ACE-536) to treat myelodysplastic the offering after trading hours. The figures include the sale of a 1.4 syndromes (MDS) and beta-thalassemia. Celgene Corp. million share overallotment on Sept. 19. (NASDAQ:CELG) shares rights to luspatercept, a modifiedactivin receptor type 2B (ACVR2B) fusion protein that inhibits several On Sept. 11, Marinus reported top-line data from the intent-to-treat ligands in the TGF beta superfamily. population of a Phase II study in children with cyclin dependent kinase like 5 (CDKL5) epilepsy showing that oral ganaxolone (CCD- On Sept. 18, Acceleron gained worldwide rights to develop and 1042) reduced median 28-day seizure frequency by 43% from commercialize sotatercept to treat pulmonary hypertension, baseline, the trial's primary endpoint. Ganaxolone is a synthetic amending a deal with Celgene that originally granted Acceleron co- analog of the endogenous neurosteroid allopregnanolone, a GABA development rights. Acceleron expects to begin a Phase II trial of A receptor neuromodulator. the candidate to treat pulmonary arterial hypertension (PAH) in 1H18. Sotatercept is a soluble ACVR2A fusion protein linked to the T2 raised $17.5 million on Sept. 15 through the sale of 4.4 million Fc protein of human IgGI. shares at $4 in a follow-on underwritten by Canaccord Genuity, Cantor Fitzgerald, Janney Montgomery Scott, JonesTrading Services Aldeyra Therapeutics Inc. (NASDAQ:ALDX), Lexington, Mass. and WBB Securities. The price is a 34% discount to T2's close of Aldeyra Therapeutics Inc. (NASDAQ:ALDX), which focuses on $6.08 on Sept. 14 when it proposed the offering after trading hours. diseases related to aldehydes, raised $28.8 million through the sale The company received CE Mark approval in July for its T2Bacteria of 4 million shares at $7.25 in a follow-on underwritten by Cantor panel, which identifies six sepsis-causing bacteria from a blood Fitzgerald and Laidlaw. The price is a 20% discount to Aldeyra’s sample. close of $9.10 on Sept. 18 when it proposed the offering after market BiondVax Pharmaceuticals Ltd. (Tel Aviv:BVXV; NASDAQ:BVXV), hours. The figures include the sale of a 517,500 overallotment on Ness Ziona, Israel Sept. 21. Flu vaccine company BiondVax Pharmaceuticals Ltd. (Tel Earlier this month, the company reported data from a Phase IIa trial Aviv:BVXV; NASDAQ:BVXV) raised $10 million through the sale showing that ADX-102 ophthalmic solution significantly improved of 1.7 million American Depositary Shares (ADS) at $6 in a follow-on multiple signs and symptoms of dry eye disease. The product is underwritten by Joseph Gunnar. Each ADS represents 40 ordinary a topical eye drop formulation of a small molecule that covalently shares. The figures include the sale of a 166,667 share overallotment binds and traps free aldehydes (see BioCentury, Sept. 14). on Sept. 18.

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Celcuity Inc. (NASDAQ:CELC), Minneapolis, Minn. DNA Script raised €2.5 million ($2.7 million) in 2016 in a seed On Sept. 20, cancer diagnostic company Celcuity Inc. funding round led by Sofinnova Partners. (NASDAQ:CELC) raised $22.8 million through the sale of 2.4 million shares at $9.50 in an IPO underwritten by Craig-Hallum Ennovabio, Shanghai, China Capital. Oncology company Ennovabio (Shanghai, China) said it closed a pre-series A round, led by HighLight Capital with participation Cofactor Genomics Inc., San Francisco, Calif. from Shanghai Zhangjiang Leading Venture Capital Co. Ltd. On Sept. 18, precision medicine company Cofactor Genomics Ennovabio's founder Lei Jiang declined to disclose financial details, Inc. (San Francisco, Calif.) raised $18 million in an oversubscribed but said the company expects to raise a series A in mid- to late-2018. series A round led by Menlo Ventures. Data Collective, Ascension Ventures, iSelect, Y Combinator, Wilson Sonsini Goodrich & Gilead Sciences Inc. (NASDAQ:GILD), Foster City, Calif. Rosati, and Stanford also participated. On Sept. 14, Gilead Sciences Inc. (NASDAQ:GILD) raised $3 billion Cofactor Genomics' CLIA-validated Pinnacle assay measures the in an offering of senior unsecured notes underwritten by Merrill expression of nearly 600 RNA biomarkers known to be associated Lynch, Pierce, Fenner & Smith and Wells Fargo. The biotech will use with response to targeted therapeutics. The company's Paragon the funds for its acquisition of Kite Pharma Inc. (NASDAQ:KITE). test is an RNA-based immunophenotyping assay that profiles the In August, Gilead agreed to acquire Kite at $180 per share in cash, cellular components of the tumor microenvironment. which the companies say values Kite at about $11.9 billion. Gilead Menlo's Mark Siegel, Data Collective's Matt Ocko and Ascension said it would finance the deal with a combination of cash, bank debt Venture's John Kuelper joined Cofactor Genomics' board. and senior unsecured notes. The deal, which has been approved by both companies' boards, is expected to close next quarter (see Disarm Therapeutics Inc., Cambridge, Mass. BioCentury, Sept. 1). On Sept. 19, Disarm Therapeutics Inc. (Cambridge, Mass.) raised The offering comprises $1 billion in notes that bear interest at 1.85%; $30 million in a series A round led by existing investor Atlas Venture. the remainder have floating rates. New investors Lightstone Ventures and AbbVie Ventures also Kite's lead chimeric antigen receptor T cell (CAR T) therapy participated. axicabtagene ciloleucel (KTE-C19) is under FDA Priority Review to Disarm is developing small molecule inhibitors of sterile alpha and treat refractory aggressive non-Hodgkin's lymphoma (NHL), with a TIR motif containing 1 (SARM1) to prevent axonal degeneration PDUFA date of Nov. 29. The therapy comprises autologous T cells in a range of neurological disorders, including multiple sclerosis genetically modified to express a CAR targetingCD19 . (MS), amyotrophic lateral sclerosis (ALS), glaucoma and peripheral neuropathies. Iovance Biotherapeutics Inc. (NASDAQ:IOVA), San Carlos, Calif. Chairman and acting CEO Jason Rhodes said the series A will enable On Sept. 20, Iovance Biotherapeutics Inc. (NASDAQ:IOVA) raised Disarm to bring at least one SARM1 inhibitor to the clinic "in a few $50 million through the sale of 7.7 million shares at $6.50 in a follow-on years." underwritten by Jefferies, Wells Fargo, Oppenheimer, H.C. Wainwright Rhodes, who is also a partner at Atlas, co-founded Disarm in 2016 and Chardan. The price is a 24% discount to Iovance's close of $8.55 on with CSO Rajesh Devraj and Washington University in St. Louis Sept. 19, when it proposed the offering after market hours. professors Jeffrey Milbrandt and Aaron DiAntonio. The company The biotech's lead compound, LN-144, is an autologous T cell exclusively licensed IP covering its SARM1 inhibitors from therapy that utilizes tumor infiltrating lymphocytes (TILs) derived Washington University for undisclosed terms. from the patient's tumor. The candidate is in Phase II testing to treat metastatic melanoma. DNA Script, Paris, France On Sept. 12, synthetic DNA manufacturer DNA Script (Paris, Kaleido Biosciences Inc., Bedford, Mass. France) said it raised €11 million ($13 million) in a series A round led On Sept. 18, Flagship Pioneering announced Kaleido Biosciences by Illumina Ventures. Merck Ventures BV participated along with Inc. (Bedford, Mass.), a biopharmaceuticals company that uses its existing investors Sofinnova Partners, Kurma Partners and Idinvest chemistry platform to discover and develop products that modulate Partners. the metabolic profile of the microbiome in order to treat and prevent DNA Script spokesperson Justin Jackson told BioCentury the severe diseases. Kaleido has been operating in stealth since it was company will use the funding, which it expects to cover the next two founded by the life science venture firm in 2015. years, to develop its lab-based enzymatic technology and nucleotide Geoffrey von Maltzahn, partner at Flagship Pioneering, said Kaleido chemistry platform for industrial scale-up. has raised an undisclosed funding round. Kaleido also named Mike Bonney CEO and chairman. He was CEO of Cubist Pharmaceuticals Inc., which Merck & Co. Inc. (NYSE:MRK) acquired.

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Maltzahn and Bonney declined to disclose financial details, but Pool Capital, Merck & Co. Inc. (NYSE:MRK) and Alexandria said the latest round brings Kaleido's total amount raised to $65 Venture Investments also participated. million. Flagship led the latest round with participation from several The company's drug discovery platform combines genomics undisclosed investors, including Bonney. Maltzahn and Bonney with artificial intelligence and synthetic biology to identify small said the latest funds will be used to advance Kaleido's pipeline into molecules from fungi. LifeMine told BioCentury the company plans additional human studies. to use the funds to build out its drug discovery engine and identify They added that Kaleido is planning an additional round of funding the first targets, with plans to enter the clinic within the next four "soon." years. The company added that its goal is to focus on oncology "for The company's pipeline includes clinical-stage compounds for the foreseeable future." rare genetic disorders, metabolic disease, oncology and infectious In conjunction with the series A, WuXi's Edward Hu, Foresite's disease, with preclinical efficacy demonstrated in five other James Tananbaum, GV's Krishna Yeshwant and Boyu's Yanling Cao indications. It has three lead products in first-in-human studies. joined LifeMine's board. Richard Klausner, who is founder and director of Juno Therapeutics Inc. (NASDAQ:JUNO) and Grail Inc. Krystal Biotech Inc. (NASDAQ:KRYS), Pittsburgh, Pa. (Menlo Park, Calif.), also joined the company's board and will serve Krystal Biotech Inc. (NASDAQ:KRYS) raised $39.6 million after as its chairman. market close Sept. 19 through the sale of 4 million shares at $10 in an IPO underwritten by Ladenburg Thalmann. Shares began trading MediWound Ltd. (NASDAQ:MDWD), Yavne, Israel on Sept. 20. On Sept. 19, dermatology company MediWound Ltd. The company's lead product, KB103, is in preclinical testing to treat (NASDAQ:MDWD) raised $22 million through the sale of 4.4 dystrophic epidermolysis bullosa. In 1Q18, Krystal plans to submit million shares at $5 in a follow-on underwritten by Cowen, Wells an IND to FDA for KB103, which is a replication-defective, non- Fargo, Oppenheimer, SunTrust Robinson Humphrey and Aegis integrating viral vector that delivers functional human collagen type Capital. VII (COL7A1) genes directly to the patients' dividing and non- dividing skin cells. Nabriva Therapeutics plc (NASDAQ:NBRV), Dublin, Ireland

Landos Biopharma Inc., Blacksburg, Va. Nabriva Therapeutics plc (NASDAQ:NBRV) raised $80 million on Sept. 19 through the sale of 9.4 million shares at $8.50 in a follow- On Sept. 21, Landos Biopharma Inc. (Blacksburg, Va.) spun out of life on underwritten by Morgan Stanley, BofA Merrill Lynch, SunTrust sciences accelerator Xontogeny LLC (Boston, Mass) with the first Robinson Humphrey, Needham and Wedbush. The price is a 4% $5 million tranche of a $10 million series A round from Perceptive discount to Nabriva's close of $8.87 on Sept. 18 when it proposed Advisors. the offering after market hours. CEO Josep Bassaganya-Riera said the final $5 million tranche will On Sept. 18, Nabriva gained 29% after reporting that IV-to-oral be triggered after the company files an IND for lead candidateBT-11 lefamulin (BC-3781) met the primary endpoints in the Phase III next year. LEAP 1 trial to treat moderate to severe community-acquired BT-11 is an oral LanC like 2 (LANCL2) inhibitor in preclinical bacterial pneumonia (CABP). Top-line data from the Phase development to treat Crohn's disease and ulcerative colitis. III LEAP 2 trial evaluating oral lefamulin to treat CABP are Bassaganya-Riera said the A round will enable Landos to complete expected next spring, with an NDA submission to FDA to follow Phase I testing of BT-11 for Crohn's disease by early 2019. in 2H18. Lefamulin is a semi-synthetic derivative of the antibiotic pleuromutilin that binds the peptidyl transferase center on the Landos is the first newco tospin out of Xontogeny, which closed a ribosome. $15 million tranche of a $25 million series A from Perceptive in May (see BioCentury, May 19). Xontogeny's other portfolio companies are pursuing preclinical (LSE:RLM), Malvern, Pa. candidates in oncology, inflammation, infectious disease and Realm Therapeutics plc cardiovascular disease. CEO Christopher Garabedian declined to On Sept. 21, dermatology and ophthalmology company Realm disclose the number of companies in the accelerator. Garabedian Therapeutics plc (LSE:RLM) raised £19.3 million ($26.2 million) joined Landos’ board. through the sale of 66.4 million units at 29p in a private placement to new and existing investors. New investors included OrbiMed, LifeMine Therapeutics Inc., Cambridge, Mass. BVF Partners, RA Capital Management, Abingworth and Polar On Sept. 18, LifeMine Therapeutics Inc. (Cambridge, Mass.) raised Capital. CEO Alex Martin and Charles Spicer, who is non-executive $55 million in a series A round led by WuXi Healthcare Ventures. chairman of Realm, also participated in the placement. Each unit Foresite Capital, GV, Arch Ventures Partners, Boyu Capital, Blue

18 week of September 25, 2017 COMPANY CLINICAL FINANCIAL NEWS NEWS NEWS WEEK IN REVIEW POWERED BY BCIQ

comprises a share and a two-and-a-half year warrant to purchase 0.4 The company said at least one of its programs will enter the clinic shares, with each whole warrant exercisable at 58p. next year. By year end, Realm plans to start a pair of Phase II trials evaluating In March, the University of Pittsburgh granted XW Labs an PR022 to treat atopic dermatitis and PR013 to treat allergic exclusive license to a class of novel mitochondria targeted bis- conjunctivitis, respectively. Top-line data from both trials are nitroxide compounds, with potential opportunities in CNS diseases expected in mid-2018. PR022 and PR013 are topical gel and topical and cancer indications. XW is also developing existing drugs for new ophthalmic solution formulations, respectively, containing a high indications using technologies which "improve the pharmacokinetics concentration of hypochlorous acid. and safety profiles of existing drugs" (see BioCentury,March 24).

Rodin Therapeutics Inc., Cambridge, Mass. Zai Lab Ltd. (NASDAQ:ZLAB), Shanghai, China On Sept. 18, Rodin Therapeutics Inc. (Cambridge, Mass.) raised On Sept. 20, Zai Lab Ltd. (NASDAQ:ZLAB) raised $150 million $27 million in a tranched series B round from existing investor through the sale of 8.3 million American Depository Shares (ADSs) Atlas Venture and new investors GV, Hatteras Venture Partners, at $18 per share in an upsized IPO on NASDAQ underwritten by Remeditex Ventures and Third Point Ventures. Details regarding the JPMorgan, Citigroup and Leerink Partners. The price values the tranches are not disclosed. Shanghai cancer, autoimmune and infectious disease company Rodin is developing selective HDAC2 inhibitors to treat neurological at $888.9 million. Zai had previously proposed to sell 5.9 million disorders. The company plans to select a lead candidate this year shares at $16-$18 per share, and subsequently increased the number and bring it into the clinic in 2018 to treat cognitive impairment in of shares to 8 million. Alzheimer's disease (AD). Zai launched in 2014 to in-license therapeutics that target diseases In late 2016, Rodin and Biogen Inc. (NASDAQ:BIIB) mutually prevalent in China and greater Asia. The company has a pipeline of five terminated a collaboration and option agreement. Under a deal in clinical candidates in-licensed from Western biopharma companies, January of that year, Rodin and Biogen had partnered exclusively to the most advanced of which is niraparib. This year, the PARP inhibitor research neuronal epigenetics and develop HDAC2 inhibitors for is expected to start a Chinese Phase III trial to treat ovarian cancer. neurology indications, and Biogen held an option to acquire Rodin Zai has exclusive Chinese rights to the molecule from Tesaro Inc. for up to $485 million in upfront and milestone payments. (NASDAQ:TSRO), which markets the drug as Zejula in the U.S. President and CEO Adam Rosenberg said Rodin did not receive any Zai has increasingly focused on internal discovery and development upfront or milestone payments from Biogen before the deal was of biologics for oncology and autoimmune disease. In 2015, Zai terminated. opened an R&D center in Shanghai and announced a discovery and development partnership with Tsinghua University Immunology "We think Biogen could certainly be a natural partner for this going Institute. forward, but at this point, we want to take on the translational work ourselves," Rosenberg told BioCentury. Last year, Zai expanded its business model further when it decided to use some of its VC-raised cash to invest in other life science He said it made sense for both companies to end the deal, but companies (see BioCentury, Dec. 14, 2016). declined to elaborate. Prior to going public, Zai raised $164.5 million in three venture Rodin raised $17.3 million in a series A extension round from Atlas rounds, including $30 million in a series C round in June led by Venture and Biogen last year, and $12.9 million in a series A round existing investor OrbiMed Advisors. The crossover round included from Atlas and Johnson & Johnson Development Corp. (JJDC) in participation from new investors Vivo Capital, Cormorant Asset 2014. Management and Rock Springs Capital. In conjunction with the series B, Hatteras' Clay Thorp, Remeditex's Zai is led by Chairman and CEO Samantha Du, who was managing John Creecy and Third Point's Jason Hong joined Rodin's board. director for Sequoia Capital China, where she was responsible for XW Laboratories Inc., Wuhan, China the firm’s healthcare investments in China. Before that, she was founder and CEO of Hutchison MediPharma Ltd., one of China’s On Sept. 20, XW Laboratories Inc. (Wuhan, China) said it raised first innovator biotechs and a subsidiary ofHutchison China $17.5 million in a series B round led by Elements Capital and WI MediTech Ltd. (LSE:HCM; NASDAQ:HCM). Harper. New Korean investor KTB Network and all existing investors comprised of Kleiner Perkins Caufield & Byers China, FINANCIAL NEWS Johnson & Johnson Innovation - JJDC Inc., and WuXi Venture participated. OTHER FINANCIAL NEWS XW Labs said it has raised a total of $23 million between the series B and a 2014 series A led by KPCB China. Flagship Pioneering, Cambridge, Mass. Life science venture firm Flagship Pioneering set a $500 million

19 week of September 25, 2017 COMPANY CLINICAL FINANCIAL NEWS NEWS NEWS WEEK IN REVIEW POWERED BY BCIQ

target for its Flagship Pioneering Fund VI, according to an SEC filing on Sept. 14. The firm declined to disclose details. Flagship closed its fifth fund at $537 million in 2015. The firm's portfolio includes gene editing playEditas Medicine Inc. (NASDAQ:EDIT), mRNA therapeutics company Moderna Therapeutics Inc. (Cambridge, Mass.) and microbiome companies Seres Therapeutics Inc. (NASDAQ:MCRB) and Kaleido Biosciences Inc. (Bedford, Mass.).

Lightstone Ventures, Menlo Park, Calif. On Sept. 20, Lightstone Ventures (Menlo Park, Calif.) closed Lightstone Ventures II at $250 million. Lightstone said the fund will invest $15-$20 million in each of about 15 early stage biotech and medical device companies. The fund has invested in one undisclosed company and participated in a $30 million series A round for Disarm Therapeutics Inc. (Cambridge, Mass.). In 2014, Lightstone closed its first fund at $172 million with investments including rare disease and lipid disorders company Catabasis Pharmaceuticals Inc. (NASDAQ:CATB), neurological diseases company Flex Pharma Inc. (NASDAQ:FLKS) and peptide therapeutics company Ra Pharmaceuticals Inc. (NASDAQ:RARX). Last year, the firm closed Lightstone Singapore, a $50 million fund to invest in and create Singapore-based life sciences companies (see BioCentury, May 5, 2014 & Feb. 22, 2016).

20 week of September 25, 2017 COMPANY CLINICAL FINANCIAL NEWS NEWS NEWS WEEK IN REVIEW POWERED BY BCIQ

BIOCENTURY WEEK IN REVIEW

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