Trio of tactics to target COVID-19 hyperinflammation
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Three companies announced COVID-19 programs Monday aimed at blocking the excessive inflammatory response seen in severe cases. Alexion unveiled a global program for its C5 inhibitor Ultomiris, while 4D pharma moved its live biotherapeutic therapy closer to the clinic, and Cyclacel partnered with the University of Edinburgh to test its pair of apoptosis regulators.
The programs join the more than 150 therapeutics in the clinic for COVID-19 (see “Daily Chart”).
Alexion Pharmaceuticals Inc. (NASDAQ:ALXN) said it will start a Phase III trial of Ultomiris ravulizumab-cwvz in COVID-19 patients hospitalized with severe pneumonia or acute respiratory distress syndrome (ARDS).
Starting next month, the open-label, randomized study will enroll 270 patients in countries with high numbers of diagnosed cases to receive either the C5 inhibitor or best supportive care. The primary endpoint is survival at day 29.
Alexion said C5 inhibition as a COVID-19 treatment is supported by animal studies that show complement inhibition reduces lung inflammation and viral pneumonia pathology. The company also has preliminary clinical evidence from a compassionate use program suggesting Soliris eculizumab can improve coronaviral-mediated lung injury. Ultomiris is a long-acting formulation of Soliris.
According to BioCentury’s Resource Center, two companies have started clinical testing of C5a inhibitors; however, Ultomiris is approved in the U.S., EU and Japan to treat paroxysmal nocturnal hemoglobinuria, while the other products are not yet approved in any indication.
4D pharma plc (LSE:DDDD) was cleared by the UK Medicines and Healthcare products Regulatory Agency (MHRA) to start a Phase II study of its live biotherapeutic in hospitalized COVID-19 patients.
The randomized, double-blind, placebo-controlled trial of MRx-4DP0004 will enroll 90 patients. The biotherapeutic is a strain of Bifidobacterium breve isolated from the gut microbiome of a healthy human.
MRx-4DP0004 in a Phase I/II study in patients with partly-controlled asthma and has shown the potential to reduce lung inflammation and impact immune cell types and pathways implicated in the hyperinflammatory response to SARS-CoV-2 infection.
4d pharma’s therapies are based on isolated bacterial strains from the gut microbiome. Companies with microbiome products that involve isolating specific cell types believe they will not face the SARS-CoV-2 contamination concerns raised for FMTs (see “Seeking Safe Microbiome Therapies Amid COVID-19 Crisis”).
Cyclacel, Edinburgh’s CDK inhibitors
Cyclacel Pharmaceuticals Inc. (NASDAQ:CYCC) partnered with the University of Edinburgh to study its first- and second-generation CDK2/9 inhibitors Roscovitine seliciclib and fadraciclib (CYC065), respectively, to treat COVID-19.
The partners think CDK inhibition could help resolve COVID-19-related inflammation by promoting inflammatory neutrophil apoptosis and reducing levels of the anti-apoptotic protein Mcl-1 and inhibit transcription of IL-6, which are drivers of overactive, systemic inflammation.
The university will test the inhibitors as part of its STOPCOVID project, which is studying the inflammatory pathways that lead directly to COVID-19 lung injury.
The project has received a £2 million ($2.5 million) grant from LifeArc, a medical research charity; the university is targeting a total raise of £15 from the private sector.
Zydus pursuing long-acting interferon treatment
Zydus Cadila Group (NSE:CADILAHC; BSE:532321) plans to start U.S. and Indian clinical trials of PegiHep, its pegylated IFNA2B HBV and HCV therapy, to treat COVID-19.
The company said that a preprint in bioRxiv from the University of Texas Medical Branch, plus data from patients with moderate COVID-19 in China, Australia and Canada given IFNA2B, suggest that a pegylated version given early in the course of disease can reduce viral load and levels of IL-6, as well as generate a virus-eliminating specific immune response.
Zydus is working with FDA and India’s Department of Biotechnology to start clinical trials.
Separately, the company is also working on a SARS-CoV-2 vaccine.
Edesa licenses pair of mAbs from Novimmune
Edesa Biotech Inc. (NASDAQ:EDSA) gained an exclusive, worldwide license to a pair of Phase II-ready antibodies from the Light Chain Bioscience unit of Novimmune S.A.
The mAbs inhibit TLR4 and CXCL10, respectively; Edesa will develop them to treat ARDS and lung injury resulting from viral respiratory infections, including SARS-CoV-2 infection.
Light Chain will receive $2.5 million in Edesa shares, and be eligible for up to $363.5 million in development and commercial milestones, plus royalties. Edesa has an option to purchase the two antibodies.
Oracle portal offers doctors online reporting system
Oracle said it will provide its Therapeutic Learning System online platform to HHS to collect real-time medical data.
Through the web portal, doctors and clinicians can report how patients respond to COVID-19 treatments.
The system can then analyze what therapies work based on patient experience, and provide data on types of patients, age brackets, underlying health conditions and symptoms.
Further analysis of the coronavirus crisis can be found at https://www.biocentury.com/coronavirus.
C5 - Complement 5
CDK2 - Cyclin dependent kinase 2
CDK9 - Cyclin dependent kinase 9
CXCL10 (IP-10) - Chemokine CXC motif ligand 10
IFNA2B - Interferon alpha 2b isoform
IL-6 - Interleukin-6
Mcl-1 - Myeloid leukemia cell differentiation protein
TLR4 - Toll-like receptor 4