Following revelations that a randomized, placebo-controlled study of the Gilead Sciences Inc.’s antiviral, remdesivir, reduced time to recovery for hospitalized patients with "advanced" COVID-19, along with additional data from an open-label phase III trial from its maker, the FDA is "working with Gilead to figure out a mechanism to make this easily available to people who need it," Anthony Fauci, director of the NIH’s National Institute for Allergy and Infectious Diseases (NIAID), said last week.

Describing an adaptive trial sponsored by the NIAID that met its primary endpoint of time to recovery, Fauci said that "remdesivir has a clear-cut significant positive effect in diminishing the time to recovery," calling the outcome "quite important." In addition, "the mortality rate trended towards being better, in the sense of less deaths in the remdesivir group: 8% vs. 11% in the placebo group." He added that "all of the other trials that are taking place now have a new standard of care."

The U.K. has started a fast track national trial of experimental drugs in COVID-19 patients, with Bergenbio ASA’s phase II cancer immunotherapy, bemcentinib, the first of six products that are due to join the study. The drugs to be tested in the government-funded Accord (Accelerated COVID-19 research and development) program were chosen by the COVID-19 Therapeutics Taskforce of experts from the Medical Research Council and the National Institute of Health Research. Any that show positive effects in phase II will be fed into the national phase III Recovery trial.

In other COVID-19 developments

Leading genome sequencing groups are launching the first meta-analysis in the hunt for genetic factors that explain why some people have worse COVID-19 symptoms than others, after agreeing to share patient sequence data from around the world. The COVID-19 Host Genetics Initiative, set up by scientists at the Institute for Molecular Medicine Finland, now includes 151 registered studies that are searching for genetic variation associated with severity and outcomes. The findings will be a potential source of drug targets, both for de novo discovery and repurposing, and could form the basis of prognostics for identifying people at unusually high risk. The aim of the initiative is to make it possible to work cooperatively, for example, by agreeing to standard protocols; to increase the statistical power of the various studies by organizing analyses across datasets; and to provide a platform to share research.

Preliminary data from the first part of a phase II/III trial testing the interleukin-6 (IL-6) receptor antibody Kevzara (sarilumab, Regeneron Pharmaceuticals Inc. and Sanofi SA) in patients with severe or critical respiratory illness caused by COVID-19 found that, relative to a placebo, the medicine "had no notable benefit on clinical outcomes" among that combined group. In some cases, in the phase II part of the trial, patients treated with Kevzara did even worse than those on placebo on some exploratory measures. Following a review of the study by its independent data monitoring committee of all available phase II and phase III data, the trial will be immediately amended so that only critical patients continue to be enrolled to receive Kevzara 400 mg or placebo.

Astrazeneca plc and the University of Oxford have entered an agreement for the global development and distribution of the university’s potential recombinant adenovirus vaccine aimed at preventing COVID-19 infection from SARS-CoV-2. It aims to advance the ChAdOx1 nCoV-19 vaccine, being developed by the Jenner Institute and Oxford Vaccine Group at the University of Oxford. Atreca Inc., Beigene Ltd. and IGM Biosciences Inc. said they plan to collaborate to help address the COVID-19 pandemic. The companies will leverage their combined technology and expertise to discover, develop and manufacture IgM and IgA antibodies targeting SARS-CoV-2. All six critically ill COVID-19 patients survived after being treated as compassionate care cases with Capricor Therapeutics Inc.’s lead candidate, an off-the-shelf cardiac cell therapy. The success prompted the FDA to review the data and approve the company’s expanded access protocol for treating as many as 20 more COVID-19 patients. Faron Pharmaceuticals Oy will donate supplies of its investigational intravenous interferon beta-1a for 2,000 patients in the World Health Organization's Solidarity trial investigating potential COVID-19 treatments. The global Solidarity trial is comparing four treatment options against standard of care to assess their relative effectiveness against COVID-19 – remdesivir; lopinavir/ritonavir; lopinavir/ritonavir with IFN beta-1a; and chloroquine or hydroxychloroquine. Fujifilm Diosynth Biotechnologies said it will reserve manufacturing capacity for a future COVID-19 therapy for the COVID-19 Therapeutics Accelerator, an initiative launched by the Bill & Melinda Gates Foundation, Wellcome Trust and Mastercard to speed up the response to the global pandemic. Kamada Ltd. and Kedrion Biopharma Inc. said they will collaborate to develop, manufacture and distribute a human plasma-derived anti-SARS-CoV-2 polyclonal immunoglobulin to treat coronavirus patients. Marinomed Biotech AG said it received funding from the Austrian Research Promotion Agency to develop a SARS-CoV-2 therapy based on its Carragelose inhalation platform, designed to target viral infections of the respiratory tract. Merck & Co. Inc. and the Seattle-based Institute for Systems Biology announced a new research collaboration to investigate and define the molecular mechanisms of SARS-CoV-2 infection and COVID-19 and identify targets for medicines and vaccines. Moderna Inc. and Lonza Ltd. entered a 10-year strategic collaboration agreement to enable larger-scale manufacture of Moderna’s mRNA vaccine, mRNA-1273, against SARS-CoV-2 and additional Moderna products in the future. Redhill Biopharma Ltd. is looking to extend access to its investigational drug, opaganib (Yeliva, ABC-294640), following the drug’s initial success from a compassionate-use study treating six patients in Israel hospitalized with moderate to severe COVID-19 symptoms. Santhera Pharmaceuticals Holding AG plans to collaborate with Cold Spring Harbor Laboratory to investigate the potential of lonodelestat (POL-6014), an inhibitor of human neutrophil elastase (hNE), as a therapeutic intervention for COVID-19-related acute respiratory distress syndrome. Sarepta Therapeutics Inc. said it inked a Cooperative Research and Development Agreement with the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) involving use of its phosphorodiamidate morpholino oligomer platform in a collaboration to identify antisense oligonucleotides with activity against SARS-CoV-2 for the potential treatment of COVID-19. Secarna Pharmaceuticals GmbH & Co. KG has inked a cooperative agreement with First Affiliated Hospital at Guangzhou Sun Yat-sen University to develop a treatment or prophylactic for SARS-CoV-2 viral infections using Secarna’s locked nucleic acid (LNAplus) platform to develop antisense oligonucleotides that suppress the expression of a certain host factor essential for the viral infection cycle. Shionogi & Co. Ltd. said it is working with public institutions, academic researchers and partner companies to accelerate development of vaccine and therapeutic candidates against COVID-19. The company initiated a collaborative research effort with the Hokkaido University Research Center for Zoonosis Control to identify drugs active against COVID-19 and identified multiple potential lead compounds from internal in vitro studies.

New product approvals…

A once-daily add-on therapy for Parkinson's disease (PD) used in Europe for years has now gained clearance in the U.S. with FDA approval of Ongentys (opicapone). The drug, an improvement upon generics in its class, will be sold by Neurocrine Biosciences Inc. The medicine, a catechol-O-methyltransferase (COMT) inhibitor first approved by the EMA in 2016, extends the half-life of levodopa, increasing doses of which are required to achieve motor control as PD progresses. Portugal-based Bial-Portela & Ca SA, from which Neurocrine licensed North American rights to the drug, will receive a $20 million award from its partner.

and trial misses

The phase III failure of Blueprint Medicines Corp.’s avapritinib to meet its primary endpoint of improving progression-free survival (PFS) in patients with locally advanced unresectable or metastatic gastrointestinal stromal tumors (GIST) pummeled the company stock but boosted shares and hopes at Deciphera Pharmaceuticals Inc. and its NDA for ripretinib in treating advanced GIST in patients who have received prior treatment with imatinib, sunitinib and regorafenib.

Deals of the week

Affinia Therapeutics Inc. is collaborating with Vertex Pharmaceuticals Inc. in a deal potentially worth more than $1.6 billion. The companies plan to engineer AAV capsids to deliver genetic therapies for treating Duchenne muscular dystrophy, myotonic dystrophy type 1 and cystic fibrosis. Affinia is responsible for the discovery of capsids and will receive $80 million in up-front payments, with research milestones to be paid during the research term. It is also eligible to earn tiered royalties on future net global sales on any products resulting from the collaboration. Bioage Labs Inc. has entered an exclusive worldwide license agreement with Taisho Pharmaceutical Co. Ltd. to develop and commercialize its clinical-stage hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitor, BGE-117 (named TS-143 by Taisho), to ameliorate multiple diseases of aging. Denovo Biopharma LLC said it is acquiring Tocagen Inc.’s entire retroviral replicating vector platform, including Toca 511 and Toca FC (now known as DB-107), and several early stage development programs targeting PD-L1 and other immune-oncology targets. Photocure ASA reached an agreement with Ipsen Pharma SAS on key terms for the return of sales, marketing and distribution rights in Europe and other markets controlled by Ipsen for the product known in Europe as Hexvix (hexaminolevulinate hydrochloride). In 2011, Photocure inked a global commercialization agreement with Ipsen for the sales, marketing and distribution of the 5-aminolevulinic acid ester optical molecular imaging agent outside the Nordic region and the U.S. Shares in Valneva SE rose by as much as 32% last week on news that Pfizer Inc. is paying $130 million up front to in-license its Lyme disease candidate vaccine, VLA-15. Valneva could also receive a further $35 million in development milestones and $143 million in early commercial milestones, as well as tiered sales royalties starting at 19%.

Financial transactions

Public offerings: Actinium Pharmaceuticals Inc. closed its underwritten public offering of 210.83 million shares at 15 cents each for gross proceeds of approximately $31.6 million. ADC Therapeutics SA said it filed a registration statement with the SEC to conduct a proposed IPO of its common shares. Aeglea Biotherapeutics Inc. closed its public offering for gross proceeds of approximately $138 million. Avadel Pharmaceuticals plc priced an underwritten public offering for expected gross proceeds of approximately $125 million. Cyclacel Pharmaceuticals Inc. said it closed its public offering of 4 million shares and common warrants to purchase up to 4 million shares at $5 per share and accompanying common warrant. Fennec Pharmaceuticals Inc. priced a public offering for gross proceeds of $30 million. Immunomedics Inc. priced an underwritten public offering for expected gross proceeds of about $420 million. Lyra Therapeutics Inc. priced its IPO of 3.5 million shares at $16 per share, grossing the company $56 million. Neubase Therapeutics Inc. closed its public offering of about 6 million shares of common stock, including 787,500 shares sold as part of the underwriters' option, for $6 per share, netting the company approximately $33.3 million. Syndax Pharmaceuticals Inc. priced a public offering for gross proceeds of about $100 million. VBI Vaccines Inc. closed its underwritten public offering for gross proceeds of approximately $57.5 million.

Other public offerings: Acer Therapeutics Inc. entered a purchase agreement with Lincoln Park Capital Fund LLC to sell up to $15 million in common stock. ADC Therapeutics SA gained a $115 million convertible credit facility with funds affiliated with Deerfield Management Co. LP. Biogen Inc. priced two series of senior unsecured notes for a total of $3 billion.

Venture funding: Actym Therapeutics Inc. said it completed a $34 million series A financing. Avalyn Pharma Inc. said it completed a $35.5 million series B financing round. Compass Pathways Ltd. raised $80 million in a series B round to continue its development of the psychedelic drug psilocybin in treatment-resistant depression. Erasca Inc. raised $200 million from a series B financing round co-led by Arch Venture Partners and Cormorant Asset Management. Genespire Srl closed a €16 million (US$17.4 million) series A financing from Sofinnova Partners. Kurma Partners closed its third biotech fund, Kurma Biofund III, at €160 million (US$174 million), €10 million ahead of its initial target. The Paris-based fund will allocate the bulk of the capital to therapeutics firms, but it is also open to opportunistic investments in med tech, particularly in digital health applications and in biotech-med tech convergence. Lifesprout Inc. said it closed a $28.5 million series A financing. Rome Therapeutics Inc. raised $50 million from a series A round. Taysha Gene Therapies Inc. has launched with a $30 million seed financing intended to advance a pipeline of 15 new AAV-based candidates.

Regulatory news

With the current pipeline of antibiotics in development insufficient to meet the growing threat of bacterial resistance, the U.S. Government Accountability Office (GAO) found that one of the biggest impediments to expanding the pipeline is a poor return on investment for drug companies due to the low prices of older generic antibiotics and a limited patient population. While Health and Human Services and the Department of Defense have provided financial premarket incentives to support antibiotic R&D, more postmarket incentives are needed, the GAO said in a report on antibiotic resistance. Unless HHS develops a strategy to further incentivize the developments of new treatments for drug-resistant infections and gets the authority and funding to implement them, “more drug companies may exit the antibiotic development sector, and the pipeline of new treatments may continue to decrease,” the GAO warned.

Word on the Street: Industry responses to the issues of the week

"Emerging evidence with Kevzara and other repurposed drugs in the COVID-19 crisis highlight the challenges of making decisions about existing medicines for new viral threats using small, uncontrolled studies. We await results of the ongoing phase III trial to learn more about COVID-19, and better understand whether some patients may benefit from Kevzara treatment."
Regeneron Pharmaceuticals Inc.’s president and chief scientific officer, George Yancopoulos, commenting on the lack of clinical benefit from the first part of a phase II/III trial testing the interleukin-6 receptor antibody Kevzara

“When the crisis first unfolded there was a sense that it would be abrupt but that we would bounce back quickly, and now as the weeks rolled on there was this dawning realization that this could have a very long impact. Long-term planning is almost close to impossible these days.”
Lorraine Chiroiu, CEO, Ausbiotech, noting that, from a recent Ausbiotech survey, about 40% of Australia’s biotech companies are seeking capital as they feel the pinch from international travel bans that seriously hamper capital raising

"Cell therapies are among the most promising new modalities in medicine, yet they are limited by challenges of cell viability, delivery and therapeutic dosing. By encouraging cell survival and natural tissue integration, the Regenerative Matrix may enhance traditional cell therapy approaches."
Sashank Reddy, co-founder and CEO, Lifesprout Inc., a Johns Hopkins University startup, that closed a $28.5 million series A financing to support clinical development of therapeutic products from its Regenerative Matrix platform

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