BioAge Labs, a clinical-stage biotechnology company, announced that it’s commenced a phase 2 clinical test of BGE-175, a potent oral inhibitor of prostaglandin D2 (PGD2) DP1 signaling with a security database comprising > 2400 patients, for treating Covid-19 patients aged 60 or older. Top-line results are expected in 2021.
“Covid-19 has devastated elderly populations round the world, largely because the system declines with age, making older people far more susceptible to infection,” said Kristen Fortney, Ph.D., chief military officer of BioAge. “By reversing age-related dysregulation of critical immune mechanisms, BGE-175 could allow older patients to more effectively repel Covid-19. Our strongly encouraging preclinical data show that BGE-175 almost completely protects older mice against lethality from infection with SARS-CoV-2, the virus that causes Covid-19. additionally , BGE-175 dramatically decreases viral load in lung tissue, which is correlated with both disease severity and transmission of the virus.”
“DP1 signaling becomes dysregulated with aging and adversely affects the immune reaction of older animals to SARS-CoV-2 and other viral challenges. we’ve shown that BGE-175 can dramatically improve outcomes in mouse models of Covid-19,” said Dr. Perlman. “Because a number of the rapidly spreading variants of SARS-CoV-2 are vaccine-resistant, it’s critically important to develop Covid-19 treatments, like BGE-175, that are likely to be equally effective against infections with these more contagious and potentially more lethal strains.”
The randomized, placebo-controlled, parallel-group, multicenter, double-blind procedure will recruit patients = 60 years old hospitalized for Covid-19 who aren’t yet in respiratory failure. a complete of 132 participants will receive daily doses of BGE-175 or placebo (66 in each group) for up to 14 days. The study medication are going to be administered orally or, in patients who cannot swallow, via nasogastric tube. The trial is being conducted within the US, Argentina, and Brazil.
The primary endpoint is that the proportion of patients who die or reach respiratory failure within 28 days after receiving the primary dose of BGE-175. Secondary endpoints include viral load, clinical improvement or worsening, incidence and duration of supplementary oxygen or ventilation, time to discharge or rehospitalization, and medical care unit (ICU) admission, everywhere a 57-day period after the primary dose.
The drug’s mechanism might be useful against diseases beyond Covid-19. “By targeting immune aging directly, BGE-175 has the potential to spice up immune cell function while preventing dangerous overreaction,” said Paul Rubin, M.D., chief medic of BioAge. “PGD2 DP1 signaling is related to increased susceptibility to infection and risk of mortality. A correlation between inhibition of PGD2 DP1 and patient response during this trial would offer evidence that BGE-175 has the potential to reverse age-related decline in immune mechanisms that are critical for host defense against major viral challenges like COVID-19, SARS, and pandemic influenza.”
BGE-175 may be a potent, orally administered small-molecule inhibitor of the PGD2 DP1 pathway, which BioAge’s platform identified as a key target for immune aging. DP1 signaling is related to elevated susceptibility to infection and better risk of mortality from communicable disease . Inhibition of DP1 affects immune function in multiple ways, activating dendritic and natural killer (NK) cells while attenuating neutrophil migration. Together, these effects counteract immunosenescence and improve aspects of both adaptive and natural immunity .