Jon Wolleben

Jon Wolleben asked about the disclosure of Phase 2 data for EQUILIBRIUM before Phase 3, patient rollover between phases, and discussions with the FDA regarding a randomized withdrawal design.

Answer

CEO Scott Struthers clarified that Phase 2 patients would be eligible to roll into an open-label extension, and Phase 3 would enroll new patients who would also be eligible for the OLE. He noted that while randomized withdrawal designs have been used, a prospective parallel group, placebo-controlled trial is considered more definitive. He also indicated that Phase 2 results would be communicated at appropriate scientific conferences.

Jon Wolleben asked about the disclosure plans for phase II data from the EQUILIBRIUM ADCS study before phase III, whether the same patients can roll over, and if a randomized withdrawal design was discussed with the FDA.

Answer

Dr. Scott Struthers, Founder and CEO, clarified that phase II patients can roll into an open-label extension, but phase III will enroll new patients. He reiterated that a prospective parallel group, placebo-controlled trial is preferred over randomized withdrawal due to methodological issues. Regarding data disclosure, he stated it's early to be specific but phase II results will be communicated at appropriate scientific conferences to motivate phase III enrollment.

Jon Wolleben inquired about the market opportunity in Japan for Rhythm Pharmaceuticals, specifically asking for insights into the potential adoption trajectory following the announced investments in the region.

Answer

Yann Mazabraud, Executive Vice President and Head of International, estimated the prevalence of acquired HO in Japan to be between 5,000 and 8,000 patients, noting it is a well-documented figure. He detailed the company's progress in building out its Japanese team and affiliate, and projected a launch within 12 months from the March data release, accounting for regulatory, market access, and pricing processes.

Jon Wolleben asked about the opportunity in Japan for Rhythm Pharmaceuticals, specifically regarding the trajectory of potential adoption and the investments being made there.

Answer

Yann Mazabraud, Executive Vice President and Head of International, estimated the prevalence of Acquired Hypothalamic Obesity (HO) in Japan to be between 5,000 and 8,000 patients, noting it is a well-documented figure. He detailed the company's capabilities, including building out a team, establishing an affiliate, and having a field medical team. Mazabraud projected a launch within 12 months following the March data release, accounting for regulatory, market access, and pricing processes.

An analyst on behalf of Jon Wolleben asked about the current reimbursement paid rate, reasons for denials in the U.S., and any early discussions with payers regarding hypothalamic obesity (HO).

Answer

Chief Financial Officer Hunter Smith and Chairman, CEO and President David Meeker clarified that IMCIVREE has high coverage from commercial and Medicaid payers but essentially none from Medicare due to statutory limitations on obesity drugs. They noted that about 20% of scripts transition to free drug and that denials are typically based on payer policy rather than the drug's price. The question about early payer discussions for HO was not directly addressed.

Jon Wolleben inquired about Mirum's interactions with the FDA regarding safety database requirements for volixibat and the implications for the timing of a potential NDA submission.

Answer

CEO Chris Peetz confirmed that pre-IND interactions and subsequent confirmations with the FDA suggest the current VISTAS PSC study will provide a sufficient safety database. He expects an FDA interaction post-top-line data to finalize the submission plan, aiming for submission in the second half of the year.

Jon Wolleben asked if Mirum anticipates Volixibat demonstrating similar disease-modifying effects over time in PSC and PBC as seen with LIVMARLI, the potential timeframe for such effects, and their importance for future adoption.

Answer

CEO Chris Peetz noted that initial readouts would likely be too soon to observe disease-modifying effects, with the immediate focus on the pruritus endpoint for launch. CMO Joanne Quan added that while the primary regulatory discussion for PSC has centered on pruritus as the only approved endpoint, the company will continue to follow patients longer term and engage with agencies on appropriate endpoints, acknowledging that disease-modifying effects may take a considerable time to evolve.

Jon Wolleben of Citizens JMP asked for evidence that pruritus in PSC is driven by excess bile acids and inquired about any sales inflection for the bile acid portfolio (CTX) since gaining the ability to promote it.

Answer

Chief Medical Officer Joanne Quan explained that while bile acids play a role, the core issue in PSC is cholestasis, and serum bile acid levels are likely less important than in other indications. COO & President Peter Radovich stated that for the bile acid portfolio, he expects a "gradual steady build" in sales rather than a sharp inflection due to laborious patient finding.

Jon Wolleben asked about the expected GLP-1 price erosion and how that might affect access and payer decisions for Rezdiffra as Madrigal looks ahead.

Answer

CEO Bill Sibold stated that the expected high 30% gross-to-net range for Rezdiffra in January 2026 already accounts for GLP-1 price erosion. He emphasized that MASH is an expensive disease, and Rezdiffra has been deemed cost-effective by ICER, suggesting payers understand its value despite varying product prices in the category.

Jon Wolleben asked how the expected price erosion of GLP-1s might affect access and payer decisions for Rezdiffra in the future.

Answer

Bill Sibold, Chief Executive Officer, stated that the projected high 30% gross-to-net for 2026 already accounts for the rapidly eroding gross-to-net of GLP-1s. He emphasized that MASH is an expensive disease, and Rezdiffra has been independently validated as cost-effective by ICER. Payers understand the need for multiple medications and mechanisms, with varying prices, to address complex chronic diseases, similar to IBD, RA, and psoriasis.

Jon Wolleben of Citizen JMP questioned how the upcoming CBEYOND data might guide development strategy across the potential maintenance, monotherapy, and combination therapy modalities for Nimazumab.

Answer

President, CEO & Director Punit Dhillon highlighted the significant, underappreciated market for maintenance therapy given high incretin discontinuation rates, alongside clear opportunities in monotherapy and combination therapy. Chief Operating Officer Tu Diep added that KOLs are eager for new, non-incretin modalities that offer better tolerability and different benefits beyond pure weight loss.

Jon Wolleben from Citizens JMP asked for the specific feedback that led to the SOLAR rescue criteria change and inquired about the company's expectation for the cadence of rescues between EYLEA and axpaxly in the SOUL-one trial.

Answer

Pravin Dugel, Executive Chairman, President & CEO, explained the feedback came from investigators who wanted the trial's rescue criteria to reflect their real-world clinical practices, which can be more liberal. Regarding rescue cadence in SOUL-one, he stated that the masked data shows a pattern of rescues consistent with their hypothesis for how the two different agents would perform over time, reinforcing their confidence in the trial's design and potential outcome.

An analyst on for Jon Wolleben asked for an updated number of randomized patients in the SOL-1 trial since the June Investor Day and requested any guidance on the trial's screen failure rate.

Answer

Dr. Pravin Dugel, President and CEO, reiterated the Investor Day update that 151 patients were in various stages of loading and randomization but did not provide a more recent figure. He confirmed that the screen failure rate for SOL-1 remains lower than initially modeled, which is why the company anticipates that most future SOL-R patients will be recruited externally rather than from SOL-1 screen failures. He emphasized that SOL-1 recruitment is now in an 'exponential phase.'

Jon Wolleben of Citizen JMP asked about the typical push-and-pull dynamics for revenue in the second half of the year and whether the positive trends from Q2 were expected to persist.

Answer

President & CCO Charlie Gayer explained that second-half growth is primarily driven by new patient starts, which can slightly lower the overall paid rate temporarily, and lacks the large reauthorization-driven bolus seen in H1. CEO Jon Stonehouse added that Q4 revenue will exclude European sales. Despite these factors, Gayer affirmed confidence in reaching the upper half of the $580M-$600M full-year guidance range after accounting for the divestiture.

Asked how the patient population in the ODYSSEY trial compares to other mid-stage wet AMD studies and inquired about the safety profile of the suprachoroidal administration approach compared to other candidates.

Answer

The executive explained that the ODYSSEY trial made a concerted effort to enroll lightly treatment-experienced patients with documented active fluid, which they believe is a more rigorous approach than some other trials. Regarding safety, he stated that the suprachoroidal injection has a very good safety profile, comparable to intravitreal injections, with no specific safety issues observed in their clinical trials to date.