The FDA has been busy in the past week, first giving accelerated approval to Sarepta Therapeutics Inc.’s injectable Vyondys 53 (golodirsen) for the Duchenne muscular dystrophy (DMD) follow-on therapy after originally turning it down in August. The nod to treat DMD patients with a confirmed dystrophin gene mutation that is amenable to exon 53 skipping will affect about 8% of DMD patients, a group not reached by Sarepta’s first commercial product, Exondys 51 (eteplirsen).  

On Dec. 19, 2019, about three months ahead of its PDUFA date, the FDA granted accelerated approval for Padcev (enfortumab vedotin-ejfv) to treat adults with locally advanced or metastatic urothelial cancer who have previously received a PD-1/L1 inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting. Seattle Genetics Inc. estimates that about 2,000 to 4,000 patients a year will be diagnosed with the cancer Padcev is designed to treat.

The FDA also gave the green light to a label expansion for the already-approved fish oil-based Vascepa (icosapent ethyl) from Amarin Corp. plc for reducing the risk of cardiovascular (CV) events in adults with elevated triglyceride levels. The decision arrived nearly two weeks ahead of an assigned PDUFA date. Vascepa was initially approved in 2012 for adults with severe triglyceride levels.

Horizon Pharma plc also sailed through a meeting of the FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee regarding the BLA for teprotumumab indicated in thyroid eye disease.

Drugs supply

The FDA took concrete steps in mapping out import routes for prescription drugs by issuing a notice of proposed rulemaking and a draft guidance. If finalized, the proposed rule, for the first time, would implement a 20-year-old provision of the Federal Food, Drug and Cosmetics Act that gives the Health and Human Services secretary the authority to authorize the import of certain small-molecule drugs from Canada. However, the proposal is getting pushback from Canada.

Cold shoulder for antibiotics companies

The prospects of companies developing new antibiotics, buoyed by regulatory incentives and grant funding, should on the face of it be an attractive proposition for investors. Unfortunately, the reality is that companies in this space are struggling with investor sentiment hitting an all-time low. As a group, public antibiotics companies have endured a very tough year with the BioWorld Infectious Disease index down over 31% year-to-date.

Deal flow

Roche Holding AG will work with immunometabolism specialist Rheos Medicines Inc. to identify and develop an undisclosed number of new therapies for autoimmune and inflammatory disease. Rheos will receive $42.5 million up front and is eligible to receive nearly $90 million for research, preclinical development and option fees plus what could amount to more than $660 million in additional payments.

Syros Pharmaceuticals Inc. and Global Blood Therapeutics Inc. (GBT) agreed to a discovery, development and commercialization deal to treat sickle cell disease (SCD) and beta-thalassemia. GBT will pay Syros $20 million up front and fund up to $40 million in preclinical research for at least three years, with the goal of identifying targets and discovering drugs to induce fetal hemoglobin.

Takeda Pharmaceutical Co. Ltd. is paying $120 million in up-front, near-term milestones and equity investment and could pay $900 million more in downstream milestones in a strategic alliance with Turnstone Biologics Inc. that is developing a vaccinia-based oncolytic virus platform for cancer immunotherapy.

Catalyst Biosciences Inc. entered a global license and collaboration deal with Biogen Inc. to develop and commercialize pegylated CB-2782 for treating geographic atrophy associated dry age-related macular degeneration. Catalyst receives $15 million up front and could receive up to $340 million in clinical, regulatory, and commercial milestone payments plus future tiered royalties based on net sales.

Ultragenyx Pharmaceutical Inc. sold royalty rights that it's due from Kyowa Kirin Co. Ltd. on the net sales of Crysvita (burosumab) in the EU, U.K. and Switzerland to Royalty Pharma. It will receive $320 million up front and the royalty rights will revert to the company when the aggregate payments are equal to or greater than 1.9 times the purchase price prior to Dec. 31, 2030, or 2.5 times the purchase price if the threshold is not met by the end of 2030.

Zafgen Inc. and Chondrial Therapeutics Inc. are merging with the resulting company named Larimar Therapeutics Inc. that will develop Chondrial’s lead asset, CTI-1601, for the treatment of Friedreich’s ataxia.

Financial transactions

Close to $1 billion was generated this week from follow-on offerings including:

  • Aptose Biosciences Inc.: $64.5 million
  • Assembly Biosciences Inc.: $143.7 million
  • Axsome Therapeutics Inc.: $174 million
  • Constellation Pharmaceuticals Inc.: $257.9 million
  • Forty Seven Inc.: $195.6. million

Pharmakon Advisors LP entered two deals this week providing Global Blood Therapeutics Inc. a $150 million loan and Sarepta Therapeutics Inc. with up to $500 million of borrowing capacity that will be available in two tranches.

It has been a banner year for global private companies raising close to $16 billion so far, a total that will be just shy of the current record of $17.3 billion generated last year. Adding to the total were:

Triplet Therapeutics Inc. launched with $59 million in financing including a $49 million series A round. The company is focused on a transformative approach to developing treatments for repeat expansion disorders, a group of more than 40 known genetic diseases associated with expanded DNA nucleotide repeats. Flagship Pioneering said it made an initial capital commitment of $50 million to Ring Therapeutics, that is developing first-in-class gene therapies using a new viral vector platform based on the human commensal virome. Forma Therapeutics Inc. closed a $100 million series D financing that will support ongoing clinical development of FT-4202, its pyruvate kinase-R activator in clinical development as a potential disease-modifying therapy for sickle cell disease. Freeline Ltd., of Stevenage, U.K., that is developing gene therapies for chronic systemic diseases, said Syncona Ltd. has committed to £61.1 million (US$$80 million) in a series C financing. Epirium Bio Inc. (formerly, Cardero Therapeutics Inc.) raised $85 million in series A financing. Pipeline Therapeutics raised $30 million in a series B financing and will use the proceeds to advance its portfolio of regenerative therapies that promote functional recovery in multiple neurological diseases.

The SEC’s Small Business Capital Formation Advisory Committee is recommending several ways to make crowdfunding a more viable option for small businesses to raise capital. One recommendation is to raise the $1.07 million per year offering cap, which could make the pathway more appealing to small biotechs. Other recommendations include removing limits on accredited investors’ investment amount, changing investment limits to apply on a per investment basis rather than using annual investment limits, allowing eligible investors to invest through special purpose vehicles and allowing greater flexibility in portal compensation.

Word on the Street: BioWorld's favorite quotes of the week

“If the NDA package was not approvable four months ago, it cannot suddenly become approvable without significant new data.”
H.C. Wainwright analyst Debjit Chattopadhyay was startled by the sudden turnaround leading to the approval of Sarepta Therapeutics Inc.’s injectable Vyondys 53 (golodirsen) for the Duchenne muscular dystrophy follow-on therapy after the FDA originally turned it down in August, saying the FDA’s new leadership, perhaps setting a new tone and course, may be the invisible hand guiding the Sarepta reversal

"I think the drive in this field is that we saw the success of Google and Facebook to basically take what seemed like white noise out in the ether and squeeze out this gold; it's like the new gold rush. And in Alzheimer's we've been desperate for success, and it seems like we have this messy, noisy data – it almost feels like static sometimes – and we want a machine learning algorithm to come in and wrangle that up and squeeze gold out of what looks like noise. Unfortunately, I don't think it's going to be that easy."
Newman Knowlton, a statistician at Millcreek, Utah-based statistical consulting firm Pentara Corp. on the potential of machine learning and artificial intelligence to discover treatments for Alzheimer's disease

“We believe that Aprogen will create high value from its existing products and future products using the company’s own drug development platform technology. Also, as the patents of global key original biopharmaceuticals expire, we expect the biosimilar market will be rapidly expanded”
Soon-hak Kwon, General Manager at Lindeman Asia Investment on the corporate valuation of $1.04 billion for the South Korean-based Aprogen Inc. that has become the country’s first biotech “unicorn,” according to U.S. market research firm CB Insights

“Our government will protect our supply of and access to medication that Canadians rely on. We continue to be in communication with the White House and the U.S. Department of Health and Human Services and our message remains firm: we share the goal of ensuring people can get and afford the medication they need – but these measures will not have any significant impact on prices or access for Americans. We remain focused on ensuring Canadians have access to the medication they need.”
Alexander Cohen, press secretary for Canada’s Office of the Minister of Health

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