Long-term formulation for combination antiviral treatment of HIV

The National Institute of Allergy and Infectious Diseases awarded $306,870 to Collaborations Pharmaceuticals, Inc. on September 1, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop a long-term formulation for combination antiviral treatment of HIV.

Collaborations Pharmaceuticals will conduct in vitro metabolic assessment of a novel anti-HIV compound (12126065) that demonstrates efficacy against wild-type and drug-resistant HIV strains with reduced neurotoxicity. The work includes determining metabolizing enzymes responsible for drug clearance, performing combination antiviral testing with the FDA-approved integrase inhibitor cabotegravir, conducting combination pharmacokinetics studies, and developing a sustained-release formulation. The research aims to generate IND-enabling toxicity study data and GMP manufacturing readiness in preparation for Phase II clinical trial advancement. The compound represents a next-generation non-nucleoside reverse transcriptase inhibitor to address potential drug resistance issues with current antiretroviral therapies.

Work is performed in Raleigh, North Carolina, with a period of performance from September 1, 2026, through August 31, 2027. This is a Project Grant, a competitive assistance type under the NIAID research portfolio supporting novel approaches to infectious disease treatment.

Abstract

Human immunodeficiency virus (HIV) infection, the virus causing acquired immune deficiency syndrome, is one of the most important pathogens affecting mankind with some 31,800 cases reported in the US in 2022 according to the CDC and over 1.2 million living with HIV in the USA. HIV can be managed with a cocktail of antiretroviral drugs that need to be taken regularly as highly active antiretroviral therapy (art) has revolutionized human immunodeficiency virus (HIV) healthcare, turning IT into a chronic disease. New anti-HIV compounds, selected specifically for their ability to overcome the growing list of HIV strains that are resistant to established drugs, are beginning to populate a small pipeline of potential future drugs, but there is certainly a need for more due to the potential to fail in the clinic or earlier in drug discovery. We have identified a new class of anti-HIV compounds and have already amassed a considerable body of preliminary in vitro and in vivo admet and PK preclinical data, including BBB penetration. We identified 12126065 which shows PM efficacy against whole cell HIV and retains activity against mutant HIV strains with no apparent in vitro neurotoxicity and decreased potency against herg and cyps. We now propose further in vitro metabolic assessment, including determining the metabolizing enzymes responsible for clearance, combination antiviral testing with the FDA-approved integrase inhibitor cabotegravir, performing combination pharmacokinetics studies, and developing a sustained release formulation. The proposed study would provide confirmation that our novel chemical series would be worthy of further investment as a HIV treatment, IND enabling toxicity studies and GMP manufacturing in phase II in preparation for a clinical trial. This would also provide a next generation of nnrti to address potential drug resistance issues with current therapies.