Cocrystal Pharma Selects Two Lead Antiviral Drug Candidates for its COVID-19 Oral Drug Program

Cocrystal Pharma, Inc. has selected two investigational novel antiviral drug candidates for further development as oral treatments for SARS-CoV-2, the virus that causes COVID-19. CDI-988 and CDI-873 target a highly conserved region in the active site of SARS-CoV-2 main (3CL) protease required for viral RNA replication. Cocrystal plans to initiate a first-in-human trial with one selected candidate as soon as possible this year.

Although CDI-988 and CDI-873 are chemically differentiated, both exhibited superior in vitro potency against SARS-CoV-2 with activity maintained against current variants of concern including Omicron. In preclinical studies, both candidates demonstrated a favorable safety profile and pharmacokinetic properties supportive of daily oral dosing. Additionally, CDI-988 and CDI-873 were specifically designed and developed using Cocrystal’s proprietary structure-based drug discovery platform technology.

“We are excited to have discovered two lead COVID-19 oral antiviral candidates that both demonstrate highly encouraging preclinical efficacy and safety data,” said Sam Lee, Cocrystal’s President and interim co-CEO. “We plan to continue evaluating both CDI-988 and CDI-873 for clinical development, while we are also rapidly advancing our inhalation/pulmonary SARS-CoV-2 lead candidate CDI-45205 toward clinical development. The objective of our multipronged strategy is to offer highly potent and safe antiviral therapeutics for hospitalized patients, as well as for those not requiring hospitalization, including for prophylactic use to provide protection to uninfected individuals who may become exposed. We expect one oral candidate in addition to our inhalation/pulmonary candidate to advance into clinical trials this year.”

“Cocrystal is focused on rapidly advancing COVID-19 therapeutic candidates with multiple routes of administration. The newly emerging Omicron variant continues to rapidly spread worldwide with breakthrough infection even in people who are fully vaccinated, demonstrating a critical need for effective antiviral therapy for COVID-19. We are very pleased to have two lead oral candidates, giving us a potential edge in the anticipated large oral delivery therapeutic market. In addition to initiating two COVID-19 trials in 2022, we anticipate completion of our influenza CC-42344 Phase 1 study this year,” said James Martin, Cocrystal’s CFO and interim co-CEO.

Earlier this month Cocrystal received guidance from the US FDA for further development of CDI-45205 in response to the company’s pre-Investigational New Drug (IND) briefing package. The Company believes the FDA’s response clarifies the pathway for a planned Phase 1 study and provides direction for a subsequent Phase 2 study.

CDI-45205 is among a group of protease inhibitors obtained by Cocrystal under an exclusive license agreement with the Kansas State University Research Foundation (KSURF) in 2020. CDI-45205 and several analogs showed potent in vitro activity against the SARS-CoV-2 Delta (India/B.1.617.2), Gamma (Brazil/P.1), Alpha (United Kingdom/B.1.1.7) and Beta (South African/B.1.351) variants, surpassing the activity observed with the original Wuhan strain. CDI-45205 has also shown good bioavailability in mouse and rat pharmacokinetic studies via intraperitoneal injection, and no cytotoxicity against a variety of human cell lines. Preclinical research demonstrated a strong synergistic effect with the FDA-approved COVID-19 medicine remdesivir. Additionally, a proof-of-concept animal study demonstrated that daily injection of CDI-45205 exhibited favorable in vivo efficacy in mice infected with MERS-CoV-2.

CC-42344 is a novel oral PB2 inhibitor that has shown excellent antiviral activity against influenza A strains, including pandemic and seasonal strains, as well as strains resistant to Tamiflu and Xofluza. CC-42344 also has favorable pharmacokinetic and drug-resistance profiles. Cocrystal has completed preclinical IND-enabling studies with CC-42344 and has received clearance from the Australian Human Research Ethics Committees (HREC) to initiate a Phase 1 clinical trial with subject enrollment expected to begin in the first quarter of 2022. The World Health Organization (WHO) estimates there are approximately 1 billion cases of influenza annually worldwide, resulting in 3 million to 5 million cases of severe illness and 290,000 to 650,000 deaths. The Centers for Disease Control and Prevention (CDC) estimates that between October 1, 2019 and April 4, 2020, there were between 39 million and 56 million cases of influenza in the U.S., resulting in 410,000 to 740,000 hospitalizations and 24,000 to 62,000 deaths.

Cocrystal Pharma, Inc. is a clinical-stage biotechnology company discovering and developing novel antiviral therapeutics that target the replication process of influenza viruses, coronaviruses (including SARS-CoV-2), hepatitis C viruses and noroviruses. Cocrystal employs unique structure-based technologies and Nobel Prize-winning expertise to create first- and best-in-class antiviral drugs. For more information, visit www.cocrystalpharma.com.