From the start of the pandemic, antibodies have been the focus of attempts to understand the immune response to SARS-CoV-2 and ascertain what it will take for vaccines to be protective. Now, the focus is widening to harder-to-measure T cells, with reports beginning to accumulate that people who test positive for the virus show a T-cell adaptive immune response. That is giving cause for hope that it is possible to induce a protective response, given the evidence to date that antibody responses to SARS-CoV-2 are extremely variable and in many cases, ephemeral.

There were also encouraging results from trials of three COVID-19 vaccines, with Astrazeneca plc, Biontech SE/Pfizer Inc. and Cansino Biologics Inc. all reporting T-cell responses in ongoing phase I/II studies of their respective products. The trial of the Astrazeneca adenoviral vector vaccine, AZD-1222, run by Oxford University, showed it was well-tolerated and generated robust immune responses against the SARS-CoV-2 virus in all 1,077 healthy adult participants, ages 18 to 55. The results published in The Lancet confirmed a single dose of AZD-1222 resulted in a fourfold increase in antibodies to the SARS-CoV-2 virus spike protein in 95% of participants one month after injection.

Other COVID-19 developments

Bangalore-based Biocon Ltd. has received the Indian drug regulator's approval for restricted emergency use of its psoriasis biologic, itolizumab, to treat patients with severe cases of COVID-19 in need of ventilator support.

Covaxx, a unit of United Biomedical Inc., said it is developing a multitope peptide-based vaccine against SARS-CoV-2 and will enter human trials next month.

Glaxosmithkline plc is putting £130 million (US$164.3 million) into one of the leading COVID-19 vaccines developers, Curevac AG, acquiring a 10% stake, and will also invest £104 million cash up front to fund research and development of the company’s mRNA vaccines. In addition, GSK will make a one-off payment of £26 million to reserve capacity at Curevac’s commercial-scale mRNA vaccines manufacturing facility, which currently is under construction. The agreement explicitly excludes Curevac’s COVID-19 vaccine and a phase I rabies vaccine. Rather it includes five unspecified mRNA vaccines and monoclonal antibodies targeting infectious diseases. However, the deal involves the two companies pooling their mRNA expertise, and with GSK owning 10% of the equity, gives the London-based pharma a stake in one of the most advanced COVID-19 vaccines.

Pfizer Inc. and Biontech SE agreed with the U.K. to supply 30 million doses of the BNT-162 mRNA-based vaccine candidate against SARS-CoV-2, which is in development, subject to clinical success and regulatory approval. Financial details were not disclosed.

Synairgen plc has detected what appear to be promising efficacy signals in a phase II trial of its inhaled formulation of interferon-beta 1a, SNG-001, in hospitalized COVID-19 patients. Those data remain preliminary at this stage, pending a peer-reviewed publication, which will provide a more detailed picture, but the key finding from the placebo-controlled study in 101 patients was that the odds of those in the drug treatment arm developing severe disease – defined as requiring ventilation or death during the treatment period (day one to day 16) – were reduced by 79% as compared with the odds of those in the placebo group having the same outcome.

Deal transactions

According to BioWorld, a total of 1,116 deals so far in 2020 are valued at $101.04 billion, with June logging 209 worth $27.97 billion. The next highest for a month this year was the 188 deals in January worth $20.39 billion. The value in June is 265% higher than the $7.66 billion recorded for May, and the number of deals is a climb of 31% over the prior month. Compared to recent years, the first six months of 2020 is in the lead in terms of both value and volume.

Product development

The number of clinical trials initiated annually has continued to grow every year over the last decade, sans a slight decrease in 2013, according to data presented in a webcast facilitated by Applied Clinical Trials. Near the halfway point of the year, 2020 is already on pace to overtake the 2019 total.

The FDA approved Kite Pharma Inc.’s Tecartus (brexucabtagene autoleucel, KTE-X19), the first cell-based gene therapy for adults with mantle cell lymphoma (MCL) who have not responded to or who have relapsed following other kinds of treatment. The CAR T-cell therapy’s July 24 approval came more than two weeks ahead of its Aug. 10 PDUFA date.

The FDA has approved Xywav (calcium, magnesium, potassium and sodium oxybates; JZP-258), an oxybate product for treating both cataplexy and excessive daytime sleepiness in narcolepsy patients ages 7 and older, from Jazz Pharmaceuticals plc. It is the first approved new treatment option for the indications in more than 15 years, and the company plans Xywav’s launch by year-end. In the meantime, Jazz will implement a risk evaluation and mitigation strategy for the treatment.

Deals of the week

Abcellera Biologics Inc. signed a deal with Alloy Therapeutics LLC to use the ATX-Gx humanized mice platform to enable in vivo human antibody discovery. Contrafect Corp. said that nonprofit Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) gave the company up to $18.9 million in additional nondilutive capital to progress its second product candidate, CF-370, an engineered lysin targeting Pseudomonas aeruginosa, into IND-enabling activities toward future phase I trials. Initial funding is $4.9 million, and Contrafect could receive more if certain project milestones are met. Cytocom Inc. said it acquired Imquest Life Sciences Inc., which focuses on cancer, inflammation and infectious disease treatments, in an all-stock transaction. Gilead Sciences Inc. will invest $300 million to acquire a 49.9% equity interest in Tizona Therapeutics Inc., which is developing cancer immunotherapies. Inozyme Pharma Inc. has acquired Alexion Pharmaceuticals Inc.’s intellectual property and assets focusing on ENPP1 gene deficiencies. The acquisition complements ongoing development of Inozyme’s lead product candidate, INZ-701, which Inozyme is investigating for treating ENPP1 and ABCC6 deficiencies, rare diseases of abnormal mineralization. Fulcrum Therapeutics Inc. and Myokardia Inc. agreed to discover, develop and commercialize therapies for treating genetic cardiomyopathies. Roche Holding AG has joined Jnana Therapeutics Inc. in its quest to drug the human repertoire of solute carrier (SLC) metabolite transporters as a means of tackling a swath of immune-mediated and neurological diseases. The Basel, Switzerland-based pharma is paying Boston-based Jnana $40 million up front and could pay more than $1 billion more in research funding, preclinical, development and commercial milestones, as well as sales royalties, in a multitarget deal.

Neurological Diseases

With an increasing number of neurological manifestations being reported in patients suffering from COVID-19 infection, the need for therapies to treat those conditions as well as other major CNS disorders has, once again, been highlighted. That may be one of the reasons why investors have turned their attention to the space once again, with several members of the BioWorld Neurological Diseases index enjoying an uptick in their share valuations. Those performances have helped push the index into positive territory for the first time this year.

Government funding

Research and health emerged as the biggest losers following a marathon four days of negotiations by EU leaders on the bloc’s €1.1 trillion (US$1.3 trillion) 2021 - 2027 budget and the formation of a €750 billion (US$872 billion) pandemic recovery fund. Rather than €94.4 billion over the next seven years as proposed, the R&D program Horizon Europe will get €80.9 billion. In current prices, that is less than the current program, Horizon 2020, which draws to a close at the end of the year. From 2014 – 2020, research got 7.1% of the overall EU budget; for 2021 – 2027, research is in line for just 4.5%.

Financial transactions

Public offerings: CASI Pharmaceuticals Inc. priced a public offering of 20 million shares at $1.90 per share for gross proceeds of about $38 million. Cytokinetics Inc. closed its underwritten public offering for gross proceeds of approximately $201.3 million. Kiniksa Pharmaceuticals Ltd. priced its public offering that generated approximately $155 million.

IPOs: Alx Oncology Holdings Inc., which is developing therapies that block the CD47 checkpoint pathway, closed its IPO for gross proceeds of approximately $185.7 million. Annexon Inc. offered 14.75 million of its shares at $17 each, raising $250.8 million. Freeline Therapeutics Ltd. filed a registration statement to conduct a proposed U.S IPO of its American depositary shares (ADSs), each representing one ordinary share. The company has applied to list its ADSs on Nasdaq under the ticker symbol FRLN. Inhibikase Therapeutics Inc. filed to raise up to $18 million in an IPO. Inozyme Pharma Inc. is raising $112 million with its offering of 7 million shares at $16 each. Iteos Therapeutics Inc. raised $210 million with its offering of about 10.6 million shares priced at $19 each. Nurix Therapeutics Inc. priced 11 million shares at $19 raising $209 million. Processa Pharmaceuticals Inc., focused on necrotic skin disease, plans to raise $20 million in an IPO by offering 2.5 million shares at a price range of $7 to $9. Relay Therapeutics Inc. closed its IPO for gross proceeds of $460 million. Sunshine Guojian Pharmaceutical (Shanghai) Co. Ltd. launched an IPO that raised ¥1.7 billion (US$240 million) on Shanghai’s STAR market.

Venture funding: Antengene Corp. has closed a $97 million series C financing round, with proceeds mainly directed toward funding the continuing clinical development of its pipeline of hematology and oncology therapies. Encoded Therapeutics Inc.’s raised $135 million from an oversubscribed series D financing. Forge Biologics, a viral vector gene therapy manufacturing and development company, said it closed a $40 million series A financing. Olema Oncology Inc. closed an oversubscribed $54 million series B financing. T3 Pharma AG has raised CHF25 million (US$26.7 million) in a series C round, to fund a 100-patient phase I/II study of its live bacteria cancer immunotherapy. Tubulis GmbH raised €10.7 million (US$12.3 million) in a series A round. Vesigen Therapeutics Inc. said Leaps by Bayer and Morningside Ventures led its series A financing that raised $28.5 million.

Regulatory news

The FDA has published the proposed rule, Annual Summary Reporting Requirements Under the Right to Try Act, that when finalized, will implement a statutory requirement for sponsors and manufacturers to provide an annual summary to the agency for any eligible investigational drug they provide to eligible patients under the Right to Try Act, which provides a pathway for patients who have been diagnosed with life-threatening diseases or conditions who have tried all approved treatment options and who are unable to participate in a clinical trial, to access certain unapproved treatments.

A decision by the U.S. Patent Trial and Appeal Board rejected a request by Moderna Inc. to invalidate U.S. Patent 8,058,069 held by Arbutus Biopharma Inc. relating to lipid formulations for nucleic acid delivery. In their decision, the judges determined Moderna has not “shown by a preponderance of the evidence” that claims relating to the patent are unpatentable. Calling the decision “a disappointing turn” for Moderna investors, SVB Leerink analysts wrote in a research note last week that the move “opens the door to a fascinating (and likely protracted) period of investor controversy and debate around the implications of any potential infringement of claims” by Arbutus regarding Moderna’s use of the lipid nanoparticle delivery technology.

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

“All the hardcore negotiations occurred via Zoom and by telephone. We were not in a single room together, which speaks a little to the world we’re moving into. The prior behavior of flying to a hotel in New York or San Francisco and locking ourselves up until we hammer something out are fading.”
Robert Gould, CEO, Fulcrum Therapeutics Inc., which entered a deal with Myokardia Inc. to discover, develop and commercialize therapies for treating genetic cardiomyopathies

“The value of any future COVID-19 vaccine lies in the willingness of the American people to get vaccinated and their ability to get access and to afford it.”
Rep. Diana DeGette (D-Colo.), chair of the Energy and Commerce Subcommittee on Oversight and Investigations

"When we look at the data for 2020 alone, COVID-19 is actually the top condition being studied by a landslide. So, there's as many as eight times as many trials for COVID-19 in 2020 as there is for pain, which is the next leading condition. You can see how quickly the trial landscape can change when something this large has an impact on the world happening."
Samantha Chesney, clinical product manager at Clarivate, speaking on a webcast facilitated by Applied Clinical Trials