COVID-19 roundup: Amgen taps Adaptive as its antibody therapeutic partner; plus Alnylam-Vir’s siRNA targets, Ansun’s data and more

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Amgen entered the race to develop an antibody-based COVID-19 therapy Thursday, partnering with Adaptive Biotechnologies to screen for neutralizing mAbs. The day also saw Alnylam and Vir name the first targets from their siRNA partnership and data for a recombinant sialidase therapy.

Neutralizing mAbs against SARS-CoV-2 have arisen as a leading approach among companies designing preclinical therapies for COVID-19. At least 20 groups have disclosed mAb programs (see “COVID-19 Therapies and Vaccines: Preclinical”).

Adaptive Biotechnologies Corp. (NASDAQ:ADPT) will use its high-throughput immune medicine platform to screen B cell receptors (BCRs) from recovered COVID-19 patients to identify tens of thousands of antibodies, from which it can select those that neutralize SARS-CoV-2.

Amgen Inc. (NASDAQ:AMGN) will then use its antibody engineering platform to select, develop and manufacture mAbs.

“The scale, efficiency and accuracy with which Adaptive can sequence immune receptors sets us apart,” Adaptive co-founder and CSO Harlan Robins told BioCentury. “It enables us to explore more BCRs, more thoroughly and more rapidly, than any other company.”

Internally, Adaptive applies its technology to detect T cell receptors. By measuring the proliferation of T cell clones that target disease-specific antigens, rather than a direct signal from the diseased tissue itself, the company’s ImmunoSEQ Dx test aims to catch diseases before tissue changes rise to detectable levels (see “Adaptive is Surfing a Wave of Enthusiasm in Disease Detection”).

Alnylam, Vir unveil COVID-19 targets

Vir Biotechnology Inc. (NASDAQ:VIR) and Alnylam Pharmaceuticals Inc. (NASDAQ:ALNY) announced Thursday the targets of the first two programs in their collaboration to develop three siRNA therapies to treat COVID-19.

The first, ACE2, is the host protein mediating viral cell invasion and an emerging target for COVID-19 therapeutics. TMPRSS2, the second target, is believed to cleave the SARS-CoV-2 spike protein to facilitate cellular attachment. The siRNAs will be administered using lung delivery technology from Alnylam.

Vir is employing its functional genomics technology to identify a third host factor pertinent to coronaviral infection and targetable by siRNA, mAbs or small molecules.

Vir told BioCentury that it is “too early to have timelines in place” for the three programs.

The COVID-19 collaboration, which the pair announced last month, expands on a 2017 deal to develop RNAi programs for infectious diseases (see “Biopharma Broadens Fight vs. COVID-19”).

Apeiron Biologics AG, which is also developing an ACE2-based COVID-19 therapy, said Thursday that it has been cleared to begin a Phase II trial of its antiviral APN01 in 200 patients in Austria, Germany and Denmark.

APN01 is a soluble recombinant form of ACE2. Rather than binding ACE2 on the cell surface, Apeiron said SARS-CoV-2 instead binds APN01, which prevents the virus from infecting the cells. APN01 also reduces inflammatory reactions in the lungs and protects against acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), the company said.

In human blood vessel and kidney organoids, APN01 reduced viral replication of SARS-CoV-2 by over 1,000-fold. The study, from the Karolinska Institutet and the University of British Columbia, was published Thursday in Cell.

Aperion said APN01 has been shown to be safe in patients with pulmonary arterial hypertension and ALI/ARDS.

Data for Ansun’s recombinant sialidase

Ansun BioPharma Inc. reported preliminary data from a Chinese trial of DAS191 to treat COVID-19, and concurrently announced the start of a U.S. trial for the therapy.

The study, conducted with the Renmin Hospital of Wuhan University, evaluated a 10-day treatment regimen of nebulized DAS181 in four patients with severe bilateral viral pneumonia and hypoxemia.

After two weeks, two of the patients no longer required supplemental oxygen and showed stabilized vital signs, increased oxygen saturation and resolution of infiltrates on chest CT scans. The third patient, who had been a SARS-CoV-2 carrier for more than 33 days, was virus-free and met all discharge criteria. The fourth patient is still being treated and shows positive trends, according to the company.

DAS181 consists of a recombinant sialidase domain that removes sialic acid, fused with an amphiregulin sequence that binds glycosaminoglycans on airway epithelial cells. Because viruses use sialic acid as a receptor for infecting epithelial cells, Ansun thinks DAS181 can block SARS-CoV-2 entry and prevent infection and spread.

Ansun’s U.S. trial will enroll 20 patients with severe COVID-19 pneumonia.

The company raised an $80 million series B in October to support a Phase III trial of DAS181 to treat lower respiratory tract parainfluenza virus infections in immunodeficient patients (see “China-Heavy Syndicate Backs Series B for Antiviral Play Ansun”).

Phage-derived COVID-19 therapy

A drug design strategy behind a nanoparticle flu therapy, described Monday in Nature Nanotechnology, could be applied to produce a COVID-19 treatment. The flu treatment is a virus-like particle derived from a bacteriophage’s capsid, or protein shell, that had been engineered to display the ligand for influenza virus hemagglutinin (HA), which mediates cell entry. The capsid used had the ideal physical geometry to enable the nanoparticles to occupy all the HA sites and prevent the virus from interacting with host cells.

Dependent on physical geometry, capsids from the phage or from other viruses -- including those that infect humans -- could be engineered as decoys that occupy the SARS-CoV-2 spike to neutralize the COVID-19 virus.

Novartis, Incyte to test Jakavi for COVID-19

Novartis AG (NYSE:NVS; SIX:NOVN) and partner Incyte Corp. (NASDAQ:INCY) plan to start a Phase III trial of Jakavi ruxolitinib to treat COVID-19.

Data for the JAK-1/2 inhibitor in diseases such as graft-versus-host disease support its potential to mitigate cytokine storms in patients with severe COVID-19 pneumonia, Novartis said.

USPTO grants extension

Utilizing a provision in the $2 trillion coronavirus stimulus package, the U.S. Patent and Trademark Office said it will provide a 30-day extension to file certain patent-related documents or fees. The extension is available if someone is unable to meet a deadline on or between March 27 and April 30 due to the COVID-19 pandemic.

The extension applies to certain Patent Trial and Appeal Board filings: requests for a rehearing, petitions and preliminary responses.

President Donald Trump signed the Coronavirus Aid, Relief, and Economic Security (CARES) Act into law last week, (see “Revamped Stimulus Bill”).

Further analysis of the coronavirus crisis can be found at https://www.biocentury.com/coronavirus.

Targets

ACE2 - Angiotensin-converting enzyme 2

JAK-1 - Janus kinase-1

JAK-2 - Janus kinase-2

TMPRSS2 - Transmembrane protease serine 2

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