On September 22, 2021 Endeavor BioMedicines, a clinical-stage precision medicine company targeting the core drivers of multiple terminal diseases including oncology and fibrosis, reported that the company has dosed its first patient in a Phase 2 trial of taladegib (ENV-101) to treat idiopathic pulmonary fibrosis (IPF) (Press release, Endeavor BioMedicines, SEP 22, 2021, View Source [SID1234606753]). Taladegib is a small-molecule inhibitor that uses precision therapy approaches to disrupt the Hedgehog signaling pathway, which has been implicated in chronic wound healing that plays a critical role in IPF disease pathology.
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Endeavor also announced today that Srikanth Pendyala, M.D., has been appointed as the company’s first Chief Medical Officer. Dr. Pendyala is a physician-scientist with over 20 years of experience in clinical research, translational sciences and academic medicine, and will lead the company’s clinical development and global drug development strategy.
"There are currently no approved therapies that stop the progression of fibrosis or treat the underlying causes of the disease," said John Hood, Ph.D., Co-Founder, CEO and Chairman of Endeavor BioMedicines. "This Phase 2 study now underway will help us understand how taladegib may help to stop or even reverse one of the most devastating pulmonary diseases by targeting the Hedgehog pathway. This precision therapy approach targets the underpinnings of the disease rather than solely the symptoms patients face."
Dr. Hood added, "We are also pleased to welcome Srikanth Pendyala as our chief medical officer. With his extensive background in drug development, paired with his expertise in academic medicine, we are confident that his experience will be invaluable as we advance Endeavor’s pipeline of precision medicine treatments."
Dr. Pendyala joins Endeavor from BridgeBio, where he served as vice president of clinical development, and was responsible for spearheading clinical trials at all stages of development across multiple therapeutic areas, as well as leading the strategic development of the company’s rare disease portfolio. Prior to BridgeBio, he focused on immunology-inflammation at Genentech/Roche, Merck and Theravance and led the development of a number of molecules from early/late-stage clinical trials to regulatory approval. Dr. Pendyala was also involved in multiple NDA filings with approvals and in partnered drug development programs. Dr. Pendyala has held numerous positions in academic medicine, most recently serving as assistant professor in pharmacology at the University of Illinois at Chicago. Additionally, he has published over 30 peer reviewed publications. Dr. Pendyala earned his medical degree from The Russian State Medical University. Dr. Pendyala completed his clinical fellowship at Johns Hopkins University, and post graduate coursework at Tufts University School of Medicine.
"I’m excited to be joining Endeavor at this time of growth and evolution for the company. Endeavor’s forward-thinking approach to precision therapies used to treat pulmonary disease and cancer has already exhibited immense potential since the company launched," said Srikanth Pendyala, M.D., Chief Medical Officer, Endeavor BioMedicines. "I look forward to working with the team and helping propel forward Endeavor’s pipeline of medicines for patients with significant unmet medical needs."
The Phase 2 clinical trial is a randomized, placebo controlled, multi-center study, designed to assess the efficacy and safety of taladegib as a monotherapy in subjects with mild to moderate IPF. The Phase 2 trial of taladegib is being conducted in the Asia-Pacific region, and is designed to enroll approximately 60 participants, with 30 patients per arm. It is a single dose level study with adaptive design, starting at 200mg. Patients will be randomized to receive placebo or taladegib as a daily oral dose for 12 consecutive weeks of treatment. Following treatment, patients will be observed for an additional 6 weeks. The primary endpoints of the trial include change from baseline in frequency and severity of adverse events, as well as change in key vital sign measurements. Secondary measures include Forced Vital Capacity (FVC), FEV1 and other measures of lung function. Pending the results of the current monotherapy Phase 2 study, Endeavor anticipates initiating a second Phase 2 study of taladegib in combination with standard of care by 2022. Additional information on the trial can be found at www.clinicaltrials.gov using the identifier NCT04968574.
About Taladegib (ENV-101) for the Treatment of IPF
Taladegib is an orally available small-molecule inhibitor of the Hedgehog signaling pathway, a key modulator for disease progression in IPF. Myofibroblasts – the repair cells activated by the Hedgehog pathway – become dysregulated, relentlessly remodeling lung tissue, forming fibrotic scars and contracting the lung. This tissue remodeling disorder impairs lung function in IPF patients by making the lung inelastic, smaller and with compromised tissue structure. Selectively inhibiting this pathway in lung tissue causes the myofibroblasts responsible for the disorder to become inactivated and undergo apoptosis, thereby eliminating the key cellular driver of IPF and potentially stopping or reversing the disease. Studied in 192 subjects to date, taladegib has been shown to safely and effectively inhibit the Hedgehog pathway, based on prior clinical evidence. Endeavor is also investigating precision therapy approaches for taladegib in multiple types of cancer where the hedgehog pathway is implicated in cancer cell signaling and disease progression.