A U.S. biotech company called Equillium, Inc. recently received a Study May Proceed letter from the U.S. Food and Drug Administration (FDA) to commence a Phase 3 clinical trial, referred to as EQUINOX. The company will now investigate itolizumab, a monoclonal antibody developed by the Cuban Center for Molecular Immunology (CIM) and BICON, one of India’s largest biotech companies in hospitalized COVID-19 patients suffering from acute respiratory distress syndrome (ARDS). The study will start enrolling patients during the fourth quarter of 2020 with initial clinical data expected by mid 2021. The FDA has informed the company that if the trial data meets primary and key secondary endpoints that the investigational product may be eligible for a Biological License Application (BLA). Equillium, a startup biotech formed in 2017 is staking its future on this potentially promising, but not well known investigational product. TrialSite’s InvestorWatch takes a look.
TrialSite provides a breakdown of this novel investigational product targeting COVID-19 patients combatting what is often a deadly condition.
What is itolizumab?
A clinical-stage, first-in-class monoclonal antibody that selectively targets the CD6-ALCAM pathway, which apparently plays a central role in modulating the activity and trafficking of T cells that drive a plethora of immuno-inflammatory diseases. The drug, derived from a Cuban and Indian partnership, surfaced as early as 2013.
Currently under investigation for multiple clinical trials in patients with severe diseases, including acute-draft-versus-host disease (aGVHD), lupus nephritis and uncontrolled asthma, several years ago itolizumab also successfully met the pre-specified primary endpoint of significant improvement in PASI-75 (Psoriasis Area and Severity Index) score after 12 weeks of treatment in patients with moderate to severe psoriasis compared to placebo.
Was the drug approved in India for moderate to severe chronic plaque psoriasis?
Yes, in 2013. BIOCON gave the drug the name ALZUMAb.™
Why was the drug repurposed to target COVID-19?
Yes. First Cuban researchers suggested that based on a unique mechanism of action in reducing cytokine release syndrome (CRS) and hence, approved a single-arm clinical trial couple with expanded use. Thereafter once Indian regulatory authorities gave the green light, researchers in India initiated a Phase 2, open-label, randomized controlled trial investing the therapy in 30 COVID-19 patients in that country.
Are Cubans using it to target COVID-19?
Yes. According to some reports, apparently in Cuba at least some hospitals have embraced this drug since April with excellent results reported.
Did India’s regulatory, Drugs Controller General of India (DCGI) authorize a ‘restricted emergency use’ for COVID-19?
Yes. As discussed by researchers in a recent paper from All India institute of Medical Sciences Bhopal, based on the results of that 30 patient trial, the DCGI approved itolizumab back in July 2020 for ‘restricted emergency use’ for the treatment of CRS in moderate to severe acute ARDS as a result of COVID-19. The drug is again referred to there as ALZUMAb.
Why has some in the scientific community critiqued this decision?
Critics have certainly surfaced including a recent paper titled Scientists criticize use of unproven COVID drugs in India. Essentially some scientists believe that the data sets used as a basis for the decisions are too small, based on a relatively small Phase 2 trial, without conduct of a conventional Phase 3 trial and the lack of any “real-world evidence in the public sphere.
Are there examples of EUAs without Phase 3 clinical trials?
Absolutely consider the FDA’s EUA authorization for convalescent plasma targeting COVID-19.
Did Biocon Limited initiate a Phase 4 study?
Yes. In October 2020, the Indian biotech commenced a 300-patient Phase 4 trial testing ALZUMAb to treat COVID-19 patients in India to produce a larger body of scientific evidence to support the safety, efficacy and usefulness of itolizumab to treat COVID-19 patients.
How did U.S. biotech Equillium enter the picture?
Equillium Inc., a San Diego-based biotech venture involved with the development of immunobiology-based products, first entered into a licensing deal with Biocon securing exclusive intellectual property rights of itolizumab to the U.S. and Canada markets in May 2017. By December 2019, the San Diego-based venture expanded the collaboration with Biocon to include Australia and New Zealand.
When did Equillium file for an IND?
On Sept. 15, the company announced a successful completion of the FDA Pre-IND meeting enabling advancement of itolizumab into a potential registration study for treating COVID-19. They targeted IND submission of IND and commencement of Phase 3 clinical trial in Q4 2020—they met these targets.
What are the formal details of the Phase 3 trial investigating the use of itolizumab in the United States and abroad?
Called the EQUINOX trial (NCT04605926), the sponsor will randomize up to 800 patients at trial sites in the Untied States and abroad, including Mexico and Brazil according to a report in Emergency Live. The study team will administer intravenously either itolizumab or placebo on Day 1 and Day 8 of the study, with follow-up to Day 90. Two interim analyses of futility are planned. In the first one, the sponsor will evaluate once 20% of the subjects have been evaluated for the primary endpoint; the second includes the point when approximately 50% of the subjects have been evaluated for the primary endpoint.
With an estimated start date of November, 2020, the study runs till the estimated primary completion date of April 2021 with an estimated final study completion date of June 2021. Key study contacts include Study Director Maple Fung, VP Clinical Development.
Founded in 2017, Equillium Inc. is a clinical-stage biotech venture leveraging deep understanding of immunobiology to pioneer new products with a mission to dramatically improve the lives of patients with severe autoimmune and inflammatory disease who suffer with high unmet medical needs. The company’s primary product candidate is the itolizumab based product called EQ001.
Based in San Diego, California, the company closed its initial public offering IPO) just in August 2018. Raising a total of $35 million at $7 per share, Jefferies, SVB Leerink and Stifel acted as the joint book-running managers for the offering, while Equillium leveraged H.C. Wainwright as a financial advisor during the process.
Again, they licensed the intellectual property developed by Biocon Ltd. in collaboration with the Cuban Center for Molecular Immunology back in 2017.
Bruce Steel is Co-founder & CEO—who is he?
Bruce Steel is a financial professional with nearly 20 years’ experience in biotech operations and investment activity.
Who is Biocon Ltd.?
Biocon is an Indian biopharmaceutical company based in Bangalore. Founded by Kiran Mazumdar-Shaw, the company produces generic active pharmaceutical ingredients sold in over 120 countries worldwide. The company is approaching $1 billion in sales and employs over 3,000.