Biopharma broadens fight vs. COVID-19 as Alnylam, Takeda unveil new programs

The biopharma industry is bringing additional modalities into the fight against COVID-19, with Vir and Alnylam developing an siRNA therapeutic while Takeda adds a plasma-based approach from COVID-19 survivors.

Both programs will broaden and potentially complement existing vaccine, antibody and small molecule initiatives to treat and prevent COVID-19, which currently stand at 48 vaccines and 12 therapeutics (see “Growing List of New Vaccines and Therapies in Development”).

On Wednesday, Alnylam Pharmaceuticals Inc. (NASDAQ:ALNY) and Vir Biotechnology Inc. (NASDAQ:VIR) expanded a 2017 deal to develop RNAi programs for infectious diseases to include siRNA therapeutics for COVID-19.

Alnylam said it has already synthesized more than 350 siRNAs against all available SARS-CoV and SARS-CoV-2 genomes that target highly conserved regions of coronavirus RNAs. Following in vitro potency testing, Vir will be responsible for preclinical testing for antiviral activity and lead selection and will lead clinical development and commercialization. At clinical proof of concept, Alnylam will have an opt-in right for a 50-50 share of profits and losses associated with the program.

While Alnylam’s programs typically target the liver via GalNAC conjugation, the company said it has recently developed a lung delivery technology that will be used in the COVID-19 program. Alnylam spokesperson Christine Lindenboom told BioCentury the company has unpublished data in a mouse model showing intranasal administration of siRNA conjugates achieves “good lung distribution and target knockdown.”

Last June at the International Conference on the Long and the Short of Non-Coding RNAs, Alnylam presented mouse data showing that a high pressure syringe for direct administration of an aerosol formulation of the therapy into the lung had similar potency and duration of activity compared with siRNA delivered subcutaneously into the liver.

As a novel delivery system, the therapy may attract additional regulatory scrutiny prior to being made commercially available.

The deal adds a new modality to industry’s therapeutic programs against COVID-19. Vir is one of at least seven companies or academic organizations developing therapeutic mAbs to treat COVID-19. On Monday Regeneron Pharmaceuticals Inc. (NASDAQ:REGN) said it could have up to 200,000 doses per month for its mAb therapy ready by August (see “Regeneron Could Make 200,000 Doses/Month by August”).

Lindenboom said it was too early to give guidance on when an siRNA therapeutic against COVID-19 might be ready for clinical testing.

Sirnaomics Inc. has also announced RNAi-based programs to treat or prevent COVID-19.

A polyclonal approach

Takeda Pharmaceutical Co. Ltd. (Tokyo:4502; NYSE:TAK) is evaluating use of an old modality via a new approach.

The Japanese pharma said Wednesday it has started development of TAK-888, a plasma-derived anti-SARS-CoV-2 polyclonal hyperimmune globulin (H-Ig) to treat high-risk patients with COVID-19.

As the therapy is derived from COVID-19 patients who have recovered, the company is working with the U.S. and other governments to identify potential donors and the most efficient and safest ways to collect the plasma, according to Takeda spokesperson Katie Joyce.

Takeda has reserved manufacturing capacity at its manufacturing plant in Georgia to begin producing TAK-888, said Joyce, adding that the company believes the therapy could be available to treat high-risk patients in 9-18 months. She did not specify whether the therapy would be available at that point in a clinical trial or emergency authorization setting.

She told BioCentury that TAK-888 could likely progress directly to clinical efficacy studies, bypassing a Phase I safety trial, because IgG immunoglobulin therapies have been shown to be clinically safe.

A polyclonal IgG therapy also could hit multiple epitopes of the spike protein, or other conserved targets on the virus, whereas vaccines and antibody approaches are largely focusing on a single target, the SARS-CoV-2 spike protein. However, a polyclonal approach also raises the question of whether or not such a therapy would be at risk of inducing antibody-dependent enhancement, a concern that’s already been raised around the rapid development of a vaccine against COVID-19 (see “Plotting a Scientific Path to Counter COVID-19”).

It also won’t be the first time convalescent plasma has been used as a possible treatment option for COVID-19. According to ClinicalTrials.gov, at least one trial in China is testing inactivated convalescent plasma to treat COVID-19.

Vir gained $3.93 (10%) to $44.90 on Wednesday, while Alnylam added $5.82 to $117.24 on a day that had big gains in the broader markets and biotech indexes.

Further analysis of the coronavirus crisis can be found at https://www.biocentury.com/coronavirus. The COVID-19 content found on this page, which details policy developments, scientific advances, and progress on countermeasures, is free to all who visit the site.

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