Post by icemandios on Nov 13, 2023 14:26:36 GMT
Cocrystal Pharma Reports Third Quarter 2023 Financial Results and Provides Updates on its Antiviral Drug Development Programs
Enrollment underway in Phase 1 trial with novel protease inhibitor CDI-988, the first potential dual coronavirus-norovirus oral antiviral
Dosing expected to begin later this year in Phase 2a human challenge trial with oral CC-42344 for the treatment of pandemic and seasonal influenza A
Phase 1 trial with inhaled CC-42344 expected to begin in the first half of 2024
“We are making excellent progress in the clinical development of potent antivirals that address some of the world’s leading viral diseases,” said Sam Lee, Ph.D., President and co-CEO of Cocrystal. “With our novel oral PB2 inhibitor CC-42344 for the treatment of pandemic and seasonal influenza A, we expect to dose the first subjects in a Phase 2a human challenge study before year-end. We also are on track to begin a Phase 1 healthy volunteer trial in the first half of 2024 with inhaled CC-42344 as a potential therapeutic and prophylactic treatment for influenza A.
“Enrollment is underway in a Phase 1 trial with our first-in-class pan-coronavirus and pan-norovirus protease inhibitor CDI-988 ,” added Dr. Lee. “This oral potent antiviral candidate could reduce severity and death from pandemic outbreaks of highly contagious viral infections. CDI-988 has shown activity against multiple coronavirus and norovirus strains, including the genogroup II, genotype 4 (GII.4) norovirus strain, which is responsible for major norovirus outbreaks . With no approved treatments or vaccines, norovirus represents a significant unmet medical need.”
“With three clinical-stage antiviral programs in high-value unmet medical indications, the coming year promises to be active and potentially transformational for Cocrystal,” said James Martin, CFO and co-CEO. “I’m pleased to report that under our cost-efficient business model, we believe our current cash position is sufficient to fund planned operations beyond the next 12 months.”
Antiviral Product Pipeline Overview
We are developing therapeutics that inhibit the viral replication function of RNA viruses that cause acute and chronic diseases. Our drug-discovery process focuses on the highly conserved regions of the viral enzymes and inhibitor-enzyme interactions at the atomic level. By designing and selecting antiviral drug candidates that interrupt the viral replication process and have specific binding characteristics, we seek to develop drugs that are effective against the virus and mutants of the virus, and also have reduced off-target interactions that may cause undesirable side effects. Our drug discovery process differs from traditional, empirical medicinal chemistry approaches that often require iterative high-throughput compound screening and lengthy hit-to-lead processes.
Influenza Programs
Influenza is a severe respiratory illness caused by the influenza A or B virus that results in disease outbreaks mainly during the winter months. Influenza is a major global health threat that may become more challenging to treat in the future due to the emergence of highly pathogenic avian influenza viruses and resistance to approved influenza antivirals.
Each year there are approximately 1 billion cases of seasonal influenza worldwide, 3-5 million severe illnesses and up to 650,000 deaths, according to the World Health Organization. On average about 8% of the U.S. population contracts influenza each season . In addition to the health risk, influenza is responsible for approximately $10.4 billion in direct costs for hospitalizations and outpatient visits for adults in the U.S. annually .
Pandemic and Seasonal Influenza A
Our novel oral PB2 inhibitor CC-42344 has shown excellent in vitro antiviral activity against influenza A strains including pandemic and seasonal strains, as well as strains that are resistant to Tamiflu ® and Xofluza ® .
In March 2022 we initiated enrollment in a randomized, double-controlled, dose-escalating Phase 1 trial to evaluate the safety, tolerability and pharmacokinetics (PK) of orally administered CC-42344 in healthy adults.
In July 2022 we reported PK results from the single-ascending dose portion of the trial that support once-daily dosing.
In December 2022 we reported favorable safety and tolerability results from the CC-42344 Phase 1 trial.
In October 2023 we announced authorization from the United Kingdom Medicines and Healthcare Products Regulatory Agency to conduct a Phase 2a human challenge trial and we expect to begin treating influenza-infected subjects in this trial during the fourth quarter of 2023.
Pandemic and Seasonal Influenza A/B Program
In January 2019 we entered into an Exclusive License and Research Collaboration Agreement with Merck Sharp & Dohme Corp. (Merck) to discover and develop certain proprietary influenza antiviral agents that are effective against influenza A and B strains. This agreement includes milestone payments of up to $156 million plus royalties on sales of products discovered under the agreement.
In January 2021 we announced completion of all research obligations under the agreement, making Merck solely responsible for further preclinical and clinical development of these compounds.
In early 2023 Merck notified us of its intent to continue development of the compounds discovered under this agreement and of their filing on behalf of both companies of multiple U.S. and international patent applications associated with these compounds. Merck continues to be responsible for managing the patents.
By targeting viral replication enzymes and protease, we believe it is possible to develop effective treatments for all diseases caused by coronaviruses including COVID-19, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Our main SARS-CoV-2 protease inhibitors showed potent in vitro pan-viral activity against common human coronaviruses, rhinoviruses and respiratory enteroviruses that cause the common cold, as well as against noroviruses that can cause symptoms of acute gastroenteritis. Driven by the anticipated emergence of new COVID-19 variants, the global COVID-19 therapeutics market is estimated to exceed $16 billion by the end of 2031 .
Oral Protease Inhibitor CDI-988
In October 2022 we announced the selection of CDI-988 as our lead candidate for development as a potential oral treatment for SARS-CoV-2. Designed and developed using our proprietary structure-based drug discovery platform technology, CDI-988 targets a highly conserved region in the active site of SARS-CoV-2 3CL (main) protease required for viral RNA replication.
CDI-988 exhibited superior in vitro potency against SARS-CoV-2 with activity maintained against variants of concern, and demonstrated a safety profile and PK properties that support once-daily dosing.
In May 2023 we announced approval of our application to the Australian regulatory agency for a planned randomized, double-blind, placebo-controlled Phase 1 trial to evaluate the safety, tolerability and PK of oral CDI-988 in healthy volunteers.
Intranasal/Pulmonary Protease Inhibitor CDI-45205
CDI-45205 is our novel SARS-CoV-2 3CL (main) protease inhibitor and was among the broad-spectrum viral protease inhibitors we obtained from Kansas State University Research Foundation (KSURF) under an exclusive license agreement announced in April 2020. We believe the protease inhibitors obtained from KSURF have the ability to convert the inactive SARS-CoV-2 polymerase replication enzymes into an active form.
CDI-45205 and several analogs showed potent in vitro activity against the main SARS-CoV-2 variants, surpassing the activity observed with the original Wuhan strain of the virus.
CDI-45205 delivered via intraperitoneal injection demonstrated good bioavailability in mouse and rat PK studies, and no cytotoxicity against a variety of human cell lines. CDI-45205 also demonstrated a strong synergistic effect with the FDA-approved COVID-19 medicine remdesivir.
In January 2022 we received guidance from the FDA regarding further preclinical and clinical development of CDI-45205 .
Norovirus is a highly contagious infection and is the most common cause of acute gastroenteritis, accounting for nearly one in five cases . According to the Centers for Disease Control and Prevention (CDC), an estimated 685 million cases and an estimated 200,000 deaths are attributed to norovirus each year worldwide, with an estimated societal cost of $60 billion.
In August 2023 we announced our selection of the novel broad-spectrum 3CL protease inhibitor CDI-988 as our lead potential oral treatment for norovirus.
CDI-988 is being evaluated in a first-in-human trial in healthy volunteers in Australia. The CDI-988 trial is expected to serve as a Phase 1 trial for both our norovirus and our coronavirus programs.
In September 2023 we dosed the first subject in our dual norovirus-coronavirus oral CDI-988 Phase 1 trial.
Research and development (R&D) expenses for the third quarter of 2023 were $4.2 million, compared with $3.9 million for the third quarter of 2022. The increase was primarily due to the influenza CC-42344 product candidate moving into a Phase 2a clinical trial and the ongoing Phase 1 clinical trial of CDI-988 for norovirus-coronavirus. General and administrative (G&A) expenses for the third quarters of 2023 and 2022 were relatively stable at $1.8 million.
During the third quarter of 2023, the Company received a $1.6 million refund from the registry of the court reflecting the recovery of funds following a successful appeal in the Company’s litigation with an insurer, which created a positive impact by reducing operating expenses by that amount.
Total other income, net for the third quarter of 2023 was $0.3 million, which was primarily related to interest earned on cash in bank accounts. This compared with minimal other expense, net for the third quarter of 2022.
The net loss for the third quarter of 2023 was $4.2 million, or $0.41 per share, compared with the net loss for the third quarter of 2022 of $5.7 million, or $0.70 per share.
Nine Month Financial Results
R&D expenses for the nine months ended September 30, 2023 were $10.9 million, compared with $9.1 million for the nine months ended September 30, 2022, with the increase primarily due to clinical advancement of our Influenza A and norovirus-coronavirus programs. G&A expenses for the first nine months of 2023 were $4.6 million, compared with $4.5 million for the first nine months of 2022.
During the first nine months of 2023, the Company received a $1.6 million refund from the registry of the court, as noted above. The Company obtained a summary judgment during the second quarter of 2022 and accounted for a potential $1.6 million adverse award by expensing the same amount during the first nine months of 2022.
During the first nine months of 2022, the Company recorded a $19.1 million non-cash goodwill impairment. There was no comparable impairment charge during the first nine months of 2023.
Total other income, net for the first nine months of 2023 was $0.4 million, compared with minimal other expense, net for the first nine months of 2022.
The net loss for the nine months ended September 30, 2023 was $13.5 million, or $1.43 per share. The net loss for the nine months ended September 30, 2022 was $34.3 million, or $4.23 per share, and reflected the litigation expense and non-cash impairment charge described above.
Cocrystal reported unrestricted cash as of September 30, 2023 of $29.7 million, compared with $37.1 million as of December 31, 2022. Net cash used in operating activities for the first nine months of 2023 was $11.3 million, compared to $16.5 million for the first nine months of 2022. The Company had working capital of $30.3 million and 10.2 million common shares outstanding as of September 30, 2023.
About Cocrystal Pharma, Inc.
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), noroviruses and hepatitis C viruses. Cocrystal employs unique structure-based technologies and Nobel Prize-winning expertise to create first- and best-in-class antiviral drugs. For further information about Cocrystal, please visit www.cocrystalpharma.com .
