Exavir Therapeutics announces the publication of preclinical data for the ultra-long-acting integrase inhibitor XVIR-110 in Nature Communications, affirming its unique pharmacokinetic profile and potential as a best-in-class yearly antiretroviral

With a single administration, XVIR-110, a nano-formulated prodrug integrase inhibitor, provided year-long plasma drug levels sufficient for HIV treatment and prophylaxis in animal models

Studies demonstrating XVIR-110’s tolerability and ultra-long-acting pharmacokinetic profile were replicated by multiple academic labs and Covance Inc. Additional studies elucidated the novel mechanism of XVIR-110 as predominantly dependent on nanocrystal dissolution

Exavir Therapeutics is preparing IND-enabling studies for XVIR-110 to pursue the clinical development of XVIR-110 as a potential best-in-class ultra-long-acting antiretroviral

NEW YORK and OMAHA, Neb., June 08, 2021 (GLOBE NEWSWIRE) -- Exavir Therapeutics, a company dedicated to transforming the lives of patients living with or at risk for acquiring HIV, announced today the publication of preclinical data for XVIR-110, an investigational agent being developed as an ultra-long-acting antiretroviral for HIV treatment and prophylaxis. The research findings, published in Nature Communications, detailed additional mechanistic, drug product stability, pharmacokinetic, and toxicology studies supporting XVIR-110’s profile as a potential best-in-class once-yearly antiretroviral agent.

“These results demonstrate the two-part mechanism that enables the apparent ultra-long half-life of XVIR-110, as well as the rigor and reproducibility of our broader findings,” said Benson Edagwa, scientific co-founder of Exavir Therapeutics and Associate Professor in the Department of Pharmacology at the University of Nebraska Medical Center. “Our agent is room-temperature stable, has been well tolerated in animal studies, and can provide effective drug concentrations for over a year with a single injection.”

As discussed in the publication, a single injection of XVIR-110, Exavir’s proprietary nanocrystal formulation of NM2CAB, a cabotegravir stearoylate prodrug, provided therapeutic exposures of cabotegravir to mice, rats, and monkeys for over one year. The mechanism of apparent ultra-long half-life was shown to be primarily due to lipophilic nanocrystal dissolution, followed by pH-dependent or esterase catalyzed hydrolysis of XVIR-110 into cabotegravir. Preliminary toxicology studies showed XVIR-110 was well tolerated at all dose levels in all species tested.

Integrase inhibitors, in addition to capsid inhibitors and nucleoside reverse transcriptase inhibitors, are a class of agents under investigation as long-acting antiretroviral therapies. A once monthly long-acting injectable cabotegravir formulation was recently approved by the FDA in the HIV treatment setting in combination with long-acting injectable rilpivirine. Additionally, an investigational once every eight-week long-acting injectable cabotegravir has been shown to be superior to the standard of care in the pre-exposure prophylaxis setting in two Phase 3 trials.

“The current treatment paradigm for HIV treatment and prevention consists of daily oral therapies that create opportunities for viral resistance, as well as undue psychological burden for patients infected with HIV or at risk of acquiring HIV,” said Dr. Howard Gendelman, scientific co-founder of Exavir Therapeutics and Professor of Medicine at the University of Nebraska Medical Center. “There has been a resounding shift towards long-acting antiretrovirals in the HIV community. Although progress has been made in recent years, there continues to be a significant unmet need for injectable antiretrovirals with longer durations, and combination partners for the existing long-acting antiretroviral armamentarium.”

HIV is one of the most deadly viral infections. It is estimated that there are nearly 1.2 million people in the United States living with HIV today, and over $30B is spent annually on antiretroviral HIV therapies worldwide.

About XVIR-110
XVIR-110, also known as NM2CAB, is an aqueous nanocrystalline formulation of a novel cabotegravir prodrug, which can be administered as an intramuscular injection. Preclinical pharmacokinetic and toxicology studies conducted to date support the development of XVIR-110 as a potential once-yearly antiretroviral therapeutic for HIV treatment and prevention.

About Exavir Therapeutics, Inc.
Exavir Therapeutics is a preclinical stage biotechnology company dedicated to eliminating HIV and other viral infections with a broad modality-agnostic approach, beginning with long-acting antiretroviral therapeutics. Exavir’s pipeline includes several ultra-long-acting antiretroviral nanomedicines as well as an earlier stage HIV cure program that utilizes CRISPR nucleases and proprietary LNP formulations to precisely deliver proviral DNA excision to lymphoid tissues that are the target of HIV.

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