AZ targeting cytokine storms as ranks of repurposed agents for COVID-19 grow

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AstraZeneca joins the growing list of companies targeting cytokine storms caused by COVID-19 with plans to start a trial of its Btk inhibitor to treat patients with severe disease. The announcement came Tuesday amid another flurry of updates from companies around the globe developing countermeasures to battle the outbreak.

Only about one quarter of the repurposed agents in clinical testing for COVID-19 got their start in infectious disease; almost as many were initially developed for cancer like Calquence acalabrutinib from AstraZeneca plc (LSE:AZN; NYSE:AZN) as for infections (see Daily Chart).

AZ’s CALAVI trial will evaluate Calquence in patients hospitalized with severe COVID-19. The first part of the randomized, open-label trial will enroll patients in the U.S. and Europe in the coming days to receive either Calquence plus best supportive care or best supportive care alone; the second part of the study will evaluate Calquence in patients in intensive care. The study’s primary endpoint will be the reduction of mortality or the use of assisted ventilation.

Because Btk inhibition reduces the production of several cytokines including TNFα, IL-6, IL-10 and MCP-1, AZ believes Calquence could reduce respiratory complications of COVID-19 (see “Matching Therapeutic Mechanism to Disease Stage”).

The pharma said that in mouse models of influenza, Btk inhibition can decrease inflammatory mediators and rescue the animals from lethal acute lung injury. Calquence is approved to treat chronic lymphocytic leukemia and mantle cell lymphoma.

At least 256 therapies and vaccines are in development for COVID-19, according to BioCentury’s COVID-19 Resource Center.

Sosei searching for protease inhibitors

Sosei Group Corp. (Tokyo:4565) said its Heptares unit will use its structure-based drug design StaR technology to discover inhibitors of 3CLpro, a SARS-CoV-2 protease.

The company said it is interested in partnering with a biopharma to support the program and pursue additional COVID-19 R&D. All findings from the 3CLpro program will be made freely available to the global research community.

Other groups are exploring 3CLpro as a COVID-19 target.

A University of Luebeck team described the X-ray crystal structure of 3CLpro in a March Science paper. The researchers also developed an inhibitor tailored to the protease’s structure (see “Coronavirus Protease Structure Guides Optimization of Inhibitor”).

Lopinavir/ritonavir from AbbVie Inc. (NYSE:ABBV) is another inhibitor of 3CLpro.

BillionToOne prepares to roll out Sanger test

BillionToOne Inc. said its COVID-19 test, which will be available in two weeks, could add testing capacity of one million tests per day. The test, which is pending Emergency Use Authorization from FDA, uses Sanger sequencing and machine learning and has throughput capacity that is 30-times higher than PCR tests, BillionToOne said. According to the company, 1,536 samples can be processed at a time, compared with 48 samples via PCR testing, and its test can be adopted at labs with Sanger sequencers to perform 3,840 tests per day.

INTELLiStem, Sinovac prepare vaccines for the clinic

INTELLiSTEM Technologies Inc. said it expects to start a Phase I trial of IPT-001, its COVID-19 vaccine, in September. The biotech is in the process of submitting an IND for the peptide vaccine, which targets both the SARS-CoV-2 spike and nucleocapsid proteins.

Separately, Sinovac Biotech Ltd. (NASDAQ:SVA) said it has been cleared to start clinical testing of its vaccine. The company said an animal challenge study showed the candidate protects from the virus without antibody-dependent enhancement.

Further analysis of the coronavirus crisis can be found at


3CLpro (Coronavirus NSP5; Mpro) - Coronavirus 3C-like proteinase

Btk - Bruton’s tyrosine kinase

IL-6 - Interleukin-6

IL-10 - Interleukin-10

MCP-1 (CCL2) - Monocyte chemoattractant protein-1

TNFα - Tumor necrosis factor alpha

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