Apelin

Dive Brief:BioAge Labs said it is terminating a mid-stage study of its obesity drug candidate azelaprag in combination with Eli Lillys tirzepatide due to safety concerns, causing its share price to slide by three-quarters in after-hours trading Friday.Eleven people who received azelaprag in STRIDES, BioAges Phase 2 study, showed elevated levels of liver enzymes that can warn of potential organ damage. As a result, the company is discontinuing dosing and halting further enrollment.The San Francisco Bay Area company raised $170 million in February and banked a $198 million initial public offering in September to fund its ambitious foray into metabolic drugs, not long after it pivoted from making treatments for age-related diseases.Dive Insight:Study researchers spotted the spike in liver enzymes, or liver transaminitis, among people who received BioAges drug either as monotherapy or in combination with tirzepatide, which Lilly sells as Zepbound. No participants who were treated only with Zepbound experienced liver transaminitis.The increase in enzyme counts was not associated with any clinically significant symptoms, BioAge said. The company plans to share an update in early 2025 on its plans for azelaprags development.We made the difficult decision to discontinue the STRIDES Phase 2 study of azelaprag because it became clear that the emerging safety profile of the current doses tested is not consistent with our goal of a best-in-class oral obesity therapy, Kristen Fortney, BioAges CEO, said in a statement.Azelaprag is designed to mimic a peptide called apelin, which is excreted in response to physical exercise. Preclinical data from BioAge seemed to show that combining azelaprag with incretin drugs could boost the effects of the latter, helping patients shed weight but preserve muscle.The company launched the study, which was set to enroll 220 people with obesity ages 55 and older, in July. At the time, Fortney said the drug could be a powerful pharmacological parallel to the exercise and diet interventions that form the foundation of obesity management.BioAge had originally planned to launch a Phase 2 clinical trial with semaglutide, or Novo Nordisks Wegovy, in the first half of 2025.With azelaprag, BioAge was targeting a niche that venture investors and pharmaceutical companies alike have been trying to fill as Wegovy and Zepbound have gained popularity: preserving lean muscle mass while still shedding weight. The company licensed azelaprag from Amgen in 2021 with plans to develop it to combat muscle aging.Over the past two years, several companies have shared plans to make experimental weight loss drugs designed to do the same thing, including Scholar Rock, Biohaven Pharmaceutical and Regeneron. Venture investors have also bought in, backing early startups such as SixPeaks Bio.Shares in BioAge, which closed Friday at just over $20 apiece, plunged by two-thirds in post-market trading Friday.The company plans to file an application to advance another program it's developing for central nervous system targets in the second half of 2025. '

Trial to evaluate weight loss efficacy of azelaprag, an oral small molecule apelin receptor agonist that mimics key biological effects of exercise STRIDES is being conducted in collaboration with Lilly’s Chorus clinical development organization Primary endpoint is weight loss at 24 weeks, with exploratory endpoints including body composition and physical activity RICHMOND, CA, USA I July 29, 2024 I BioAge Labs, Inc., (“BioAge”), a clinical-stage biopharmaceutical company developing therapeutic product candidates for metabolic diseases by targeting the biology of human aging, today announced that the first patient has been dosed in the STRIDES Phase 2 clinical trial evaluating BioAge’s lead product candidate azelaprag in combination with tirzepatide for the treatment of obesity in adults aged 55 and older. Azelaprag is an orally available small molecule agonist of the apelin receptor APJ. Apelin is an exercise-induced signaling molecule (exerkine) that acts on APJ to mediate many of the metabolic benefits of physical activity. In a Phase 1b clinical trial in healthy older volunteers on 10 days of bed rest, azelaprag was observed to improve muscle metabolism, decrease muscle atrophy, and preserve measures of resting energy expenditure and cardiorespiratory fitness ( link ). Azelaprag has been well tolerated in more than 240 subjects across seven Phase 1 clinical trials to date. In mouse models of obesity, the addition of azelaprag approximately doubled the weight loss achieved with incretin drugs (GLP-1 receptor agonists) while restoring healthy body composition and physical function ( link ). “We believe combining azelaprag, an exercise mimetic, with tirzepatide, a GLP-1/GIP receptor agonist that decreases food intake, could provide a powerful pharmacological parallel to the exercise and diet interventions that form the foundation of obesity management,” said Kristen Fortney, PhD, CEO and co-founder of BioAge. “The STRIDES trial aims to demonstrate that activating apelin signaling with azelaprag is a potent complementary mechanism that can deliver increased weight loss efficacy in patients on incretins. In addition, this trial will provide a direct read-through to azelaprag’s potential as an orally available small molecule to achieve efficacy on par with injectable weight loss drugs when combined with incretins in an all-oral regimen.” STRIDES is a randomized, double-blind, placebo-controlled Phase 2 clinical trial of azelaprag in combination with tirzepatide that will enroll approximately 220 obese individuals aged 55 years and older. The trial will evaluate the efficacy, safety, and tolerability of two oral doses of azelaprag (300 mg once or twice daily) in combination with tirzepatide (5 mg subcutaneous injection once weekly). The primary endpoint is mean percent change in body weight at 24 weeks. Additional exploratory endpoints include body composition, glycemic control, obesity-related biomarkers, and patient-reported outcomes related to health and quality of life. Top-line results are anticipated in the fourth quarter of 2025. STRIDES is being conducted in collaboration with Eli Lilly and Company’s (Lilly) Chorus clinical development organization. Lilly is providing tirzepatide for the trial ( link ). A second planned Phase 2 clinical trial will assess azelaprag in combination with semaglutide (Wegovy ® ) with initiation expected in the first half of 2025. Together, the trials will seek to support BioAge’s therapeutic goal of developing an all-oral combination product for obesity. About BioAge Labs BioAge is a clinical-stage biopharmaceutical company developing therapeutic product candidates for metabolic diseases, such as obesity, by targeting the biology of human aging. BioAge’s lead product candidate, azelaprag, is an orally available small molecule agonist of APJ that was observed to promote metabolism and prevent muscle atrophy on bed rest in a Phase 1b clinical trial. In mid-2024, BioAge initiated a Phase 2 trial of azelaprag in combination with tirzepatide for the treatment of obesity in older adults. Azelaprag has potential as an oral regimen to amplify weight loss and improve body composition in patients on obesity therapy with incretin drugs. BioAge is also developing orally available small molecule brain penetrant NLRP3 inhibitors for the treatment of diseases driven by neuroinflammation. BioAge’s preclinical programs, based on novel insights from the company’s discovery platform built on human longevity data, also address key pathways in metabolic aging. SOURCE: BioAge Labs