By filing an IND with the FDA to initiate a phase II/III study of EB-05, a monoclonal antibody, Edesa Biotech Inc. joined the handful of companies developing COVID-19 treatments that inhibit Toll-like receptor 4 (TLR4) signaling.
The Toronto-based company’s stock (NASDAQ:EDSA) responded by rocketing 81.38% upward Thursday to close at $9.45, after trading as high as $19.10.
TLR4 signaling is thought to mediate inflammation that is activated by SARS-CoV-1 and influenza viruses, Edesa said. EB-05 is designed to regulate the overactive immune response associated with acute respiratory distress syndrome (ARDS), the leading cause of death of COVID-19 patients, by suppressing pro-inflammatory cytokines often found in patients with severe COVID-19.
Edesa’s IND is for conducting an adaptive, multicenter, randomized, double-blind, placebo-controlled study evaluating EB-05’s efficacy and safety in adult hospitalized patients who either have or who are at risk of developing ARDS. About 450 patients will be enrolled in the phase II study. If the study produces positive results, enrollment continues into a pivotal phase III trial.
"Even excluding COVID-19 patients, there are approximately 3 million cases of ARDS each year globally despite the widespread use of prophylactic vaccines and herd immunity," said Par Nijhawan, Edesa’s CEO.
In June, Edesa received expedited approval from Health Canada to begin a phase II/III trial of EB-05 for treating moderate to severe hospitalized COVID-19 patients. The company said EB-05 is already available and that it’s looking for government grants to accelerate that study’s initiation and rollout, beginning at up to 30 sites with as many as 355 patients in the trial’s first phase. The studies are designed as adaptive, multicenter, randomized, double-blind, placebo-controlled trials. Like the IND study design, if successful, the trial would continue with enrollment into a pivotal phase III.
The two studies have been good for the stock. A year ago, on July 31, 2019, Edesa’s shares went for $4.88 each. The stock got a big bump nearly a year later when, on June 16, shares jumped to $6.62 soon after the company said it had received Health Canada’s expedited approval for the phase II/III study.
In April, Edesa and Light Chain Bioscience, a brand of Geneva-based Novimmune SA, signed a strategic agreement to develop treatments for COVID-19 pneumonia and other disorders. Edesa obtained an exclusive worldwide license to develop and commercialize two phase II-ready biologic drug candidates for all therapeutic and diagnostic applications. The licensed monoclonal antibodies block TLR4 and CXCL10.
Other companies developing COVID-19 treatments with TLR4 include Oragenics Inc., of Tampa, Fla., and Eisai Co. Ltd., of Tokyo.
On July 22, Oragenics said the U.S. NIH-created stabilized pre-fusion spike protein (CoV-2 S-2P) licensed by the company has generated neutralizing antibodies in mice during immunization against SARS-CoV-2, the virus that causes COVID-19. The NIH’s preclinical study showed that the spike protein, adjuvanted with the TLR4-agonist Sigma Adjuvant System (a TLR4 agonist that induces T-cell activation), generates neutralizing antibody titers in both a pseudovirus neutralization assay and a plaque reduction neutralization titer assay. Immunization also produced a balanced Th1/Th2 response.
On July 1, Eisai, of Tokyo, said it would join REMAP-COVID, a substudy of REMAP-CAP (A Randomized, Embedded, Multifactorial, Adaptive Platform trial for Community-Acquired Pneumonia) that tests multiple interventions for treating hospitalized COVID-19 patients. Eritoran, an investigational TLR4 antagonist discovered and developed by Eisai, has been selected as the first investigational immune modulation therapy to be evaluated in the moderate patient group of REMAP-COVID. The trial will be conducted in the University of Pittsburgh Medical Center health system along with other medical centers in the U.S. Eritoran is designed to suppress overproduction and release of various pro-inflammatory mediators to protect against damage in COVID-19 patients’ lungs and other organs.
Other companies entering phase II/III COVID-19 trials with different therapeutic approaches are Evelo Biosciences Inc.’s EDP-1815; Fibrogen Inc.’s pamrevlumab; Neurorx Inc. and Relief Therapeutics Holding SA’s aviptadil (RLF-100), which gained FDA fast track designation in June to treat acute lung injury/ARDS associated with COVID-19; PTC Therapeutics Inc.’s PTC-299; Kiniksa Pharmaceuticals Ltd.’s mavrilimumab; and Algernon Pharmaceuticals Inc.’s NP-120 (ifenprodil).