Rohan Mathur

Rohan Mathur from Oppenheimer inquired about any pre-specified decision rules, such as futility analysis or sample size re-estimation, for the Phase 2b PLATEAU study's interim analysis, and sought clarification on the required degree of weight loss if functional benefit is pursued as a primary endpoint with less than 5% incremental weight loss.

Answer

Dr. Gary Barnette, Chief Scientific Officer of Veru, confirmed there are no futility analyses or sample size re-estimations for the interim analysis. Dr. Mitchell Steiner, Chairman, CEO, and President, added that the interim analysis focuses on lean and fat mass to confirm the study's direction without incurring a statistical penalty, as the primary endpoint is total weight loss. Dr. Steiner further clarified that an incremental weight loss of less than 5%, even if similar to GLP-1 alone, could still lead to approval if a statistically significant and clinically meaningful physical function benefit is demonstrated.

Rohan Mathur (Oppenheimer & Co. Inc.) asked about pre-specified decision rules, such as futility or sample size re-estimation, for the interim analysis in the Phase II-B PLATEAU study, and the required degree of weight loss if functional benefit becomes the primary approval pathway.

Answer

Dr. Gary Barnette (Chief Scientific Officer, Veru) clarified that there are no futility analyses or sample size re-estimations planned for the interim analysis. Dr. Mitchell Steiner (Chairman, CEO, and President, Veru) added that the interim analysis focuses on lean and fat mass changes to confirm direction without incurring a statistical penalty. Regarding the functional benefit pathway, Dr. Steiner reiterated that a clinically significant benefit in physical function could support approval even with less than 5% incremental weight loss, or similar weight loss to GLP-1 alone.

Rohan Mathur asked about the potential flexibility in regulatory discussions following the Plateau study, specifically concerning the balance between achieving a certain degree of weight loss and demonstrating improvements in muscle function.

Answer

Dr. Mitchell Steiner, Chairman, CEO, and President of Veru Inc., reiterated that a 5% or greater placebo-corrected incremental weight loss is a key benchmark for regulatory approval. He emphasized that if this target is met, all clinically meaningful secondary physical function data will be included. Dr. Steiner also highlighted the multiple physical function measures being explored in the Plateau study, including stair climb tests, clinical outcomes questionnaires, and mobility disability assessments, to build a robust case for regulatory discussions on the best way to measure and present physical function improvements.

Rohan Mathur with Oppenheimer asked about the potential flexibility in future regulatory discussions concerning the balance between weight loss and muscle function outcomes from the PLATEAU study, particularly regarding the degree of weight loss required for approval.

Answer

Dr. Mitchell Steiner, Chairman, CEO, and President, reiterated that a 5% or greater placebo-corrected incremental weight loss is a clear benchmark. He emphasized that the PLATEAU study includes various physical function assessments (stair climb, clinical outcomes questionnaires, mobility disability assessment) to build a strong case for clinically meaningful benefits in older patients, offering multiple pathways for regulatory presentation.

An analyst on behalf of Rohan Mata from Oppenheimer & Co. Inc. asked how Crinetics plans to manage the progression toward NDA submission and labeling discussions for adamelin, given the different timelines for the adult and pediatric CAH trials.

Answer

Chief Medical & Development Officer Dana Pizzuti stated that the company views the adult and pediatric programs as distinct submissions. She explained that they will not hold one for the other; the adult Phase III trial is expected to finish first and will be submitted. Following a successful outcome, the company would then submit a supplement or amendment to add the pediatric data and indication.

Rohan Mathur asked about the commercial synergies for paltusotine between the acromegaly and carcinoid syndrome indications, given potential overlapping call points.

Answer

CEO R. Struthers identified several areas of synergy. He noted the geographic overlap of pituitary and oncology centers of excellence, the confidence that safety data in acromegaly will provide for the carcinoid indication, and the significant prescriber overlap between the two conditions in many European countries, which creates direct efficiencies.

Rohan Mathur of Oppenheimer asked which aspects of AGAMREE's clinical profile, as evaluated in the SUMMIT study, are expected to most resonate with prescribers. He also followed up by asking how these benefits would be quantified in the study.

Answer

Chief Medical Officer Gary Ingenito responded, highlighting that the key differentiating findings from the SUMMIT study are expected to be related to bone health and cardiac effects. He specified that the study will quantify these benefits by measuring fracture rates, bone age, bone density, and the prevention of cardiomyopathy.

Rohan Mathur from Oppenheimer asked how the ongoing launch of a competitor's cardiac myosin inhibitor might help catalyze market awareness and payer coverage, benefiting aficamten's potential launch.

Answer

Andrew Callos, EVP and CCO, explained that as a second-to-market agent, aficamten benefits from the incumbent's efforts in building broad disease awareness through HCP and patient campaigns. This allows Cytokinetics to focus its resources more on educating physicians about aficamten's specific profile and points of differentiation, which should aid uptake in an already primed market.