Amy Li

Amy Li asked about the extent to which the FDA is allowing Ironwood to reference or bridge existing clinical data for a future NDA submission for STARS-2. She also questioned the rationale behind the STARS-2 enrollment size of 124 patients, which is higher than some competitors, and whether a higher dose arm might be added to maximize efficacy differentiation.

Answer

Michael Shetzline, Chief Medical Officer, confirmed that Ironwood anticipates using the original STARS data in the NDA submission, leveraging PK bridging. He explained that the 124-patient sample size for STARS-2 was chosen to ensure adequate and robust power for primary and secondary endpoints, providing high confidence in the trial's outcome. While a higher dose arm is continually evaluated, the current focus is on achieving the fastest time to market with the existing robust efficacy and tolerability profile.

Amy Li from Jefferies Financial Group asked about the extent to which the FDA will allow Ironwood to reference or bridge existing clinical data from the original STARS trial for the STARS-2 NDA submission. She also questioned if the STARS-2 enrollment size of 124 patients was an FDA request or a conservative decision, especially compared to competitors enrolling fewer patients. Finally, she inquired about the potential to add a higher dose arm to maximize efficacy differentiation, given competitive pressures and potential generic scenarios in the short bowel syndrome market.

Answer

Michael Shetzline, Chief Medical Officer, stated that Ironwood anticipates using the original STARS data for the NDA submission, leveraging PK bridging given the similar dose in STARS-2. He confirmed that the 124-patient sample size for STARS-2 was aligned with the FDA and chosen to ensure robust power for primary and secondary endpoints, providing confidence in the trial's outcome. Regarding higher doses, Dr. Shetzline mentioned that while considered, the current focus is on achieving the fastest market entry with the established 3.5 mg dose, which has demonstrated robust efficacy and excellent tolerability, though opportunities for broader response are continuously evaluated.

Amy Li inquired about the potential for LINZESS's commercial margin to continue expanding and offset pricing headwinds, and also asked for the latest outlook on the impact of the 2025 Medicare Part D redesign on the drug.

Answer

Sravan Emany, COO and CFO, acknowledged an expected pricing headwind for LINZESS in 2025 but deferred specific guidance until early next year. He expressed satisfaction with the current quarter's commercial margins, stating they are a good predictor for the full year and that the company will continue managing expenses to maximize profits.

Amy Li inquired if the apraglutide launch is still anticipated in 2025 following the revised Q1 2025 submission timeline, and requested more details on the optimization of the commercial use kit.

Answer

COO & CFO Sravan Emany responded that a potential approval could occur in 2025 or early 2026, contingent on receiving priority or standard review. Regarding the vial kit, he noted that based on human factor trials, enhancements are being made to the commercial presentation to make it easier for patients to self-administer, which is a common practice to optimize for commercial use versus clinical trial use.

Amy Li inquired about the expected durability of apraglutide treatment and whether upcoming DDW data would show differentiation. She also asked for an update on the addressable market size following the implementation of new ICD-10 codes and the reach of Ironwood's current sales force into this patient population.

Answer

CMO Michael Shetzline addressed durability, stating that the once-weekly dosing is well-supported and that patients with short bowel syndrome typically require continued therapy to maintain intestinal growth. CFO Sravan Emany noted that the new ICD-10 codes are reinforcing the company's market size estimates, with about 7,000 patients identified so far. He expressed high confidence in their sales force's ability to penetrate this market and achieve blockbuster potential for apraglutide.

Amy Li asked about the bar for success in the myositis trial across its three subsets and how the company plans to integrate the new steroid tapering protocol while mitigating placebo risk.

Answer

Tim Van Hauwermeiren, Chief Executive Officer, stated that the primary goal is statistically significant separation from placebo, with a Total Improvement Score (TIS) of 20 generally considered clinically meaningful. He referenced Phase 2 data showing increasing VYVGART effects at TIS 40 and 60, framing these as indicators of success.

Amy Li from Jefferies asked about argenx's bar for success in the myositis trial across its three subsets and how the company plans to integrate the new steroid tapering protocol while mitigating placebo risk.

Answer

Tim Van Hauwermeiren, Chief Executive Officer, stated that the primary bar for success in the myositis basket trial is statistically significant separation from placebo, with a Total Improvement Score (TIS) of 20 generally considered clinically meaningful. He referenced Phase II data showing increasing VYVGART effects at TIS 20, 40, and 60.

Amy Li, on for Akash Tewari, asked if argenx's fill-finish process is considered 'substantially transformative' for MFN purposes, how quickly manufacturing could be moved to the U.S., and what mitigation measures, like differential pricing, could be employed.

Answer

Chief Executive Officer Tim Van Hauwermeiren advised using the drug substance manufacturing, which occurs on U.S. territory, as the guide for substantial transformation. He reiterated that argenx is in a strong position regarding MFN due to its disciplined global pricing strategy within a narrow band and stated the company has strong cards to navigate future policy developments without speculating on specifics.

Amy Li, on for Akash Tewari, asked about potential changes to the myositis trial design, the probability of success across its subsets, and the company's thoughts on the read-across from obinutuzumab data to their lupus nephritis trial.

Answer

CEO Tim Van Hauwermeiren confirmed there are no changes to the myositis trial protocol and the company has equal belief in all three subsets. Regarding lupus nephritis, he emphasized the significant unmet need allows for multiple mechanisms and that argenx is focused on generating its own data to test its specific mechanism of action.

Amy Li, on for Akash Tewari at Jefferies, asked about expectations for the control arm performance in the HERIZON-GEA trial and the company's confidence that the control arm won't outperform historical benchmarks.

Answer

Rob Iannone, Head of R&D, expressed confidence, noting that the control arm of trastuzumab plus chemotherapy has shown consistent performance across three prior large Phase III trials, with a median PFS between 6.9 and 8.1 months. He stated that the trial was planned accordingly and highlighted promising Phase II data for zanidatamab in the same setting.

Speaking on behalf of Akash Tewari, Amy Li from Jefferies asked about Jazz's pricing strategy for zanidatamab in GEA, questioning if it would differ based on the success of the doublet versus the triplet arm in the HERIZON-GEA trial and how either outcome would affect peak sales estimates.

Answer

Renée Galá, President and COO, explained that the current Ziihera price for BTC was established with the future GEA launch in mind. She noted differences in dosing and cycle length for GEA but did not provide specific pricing guidance based on the trial arm outcomes. She reiterated confidence in the significant opportunity in GEA and breast cancer, which form the basis of the peak sales potential.

Amy Li, on behalf of Akash Tewari at Jefferies, inquired about the pricing strategy for zanidatamab (Ziihera) based on the potential outcomes of the doublet versus triplet arms in the HERIZON-GEA trial.

Answer

President & COO Renée Galá stated that the current BTC WAC price of approximately $35,550 per 28-day cycle was set with the future GEA launch in mind. She noted GEA has a different cycle length (21 days) and dosing but did not provide specific pricing guidance based on the trial arm outcomes, emphasizing the focus is on the meaningful opportunity in GEA and breast cancer.

Amy Li, on behalf of Akash Tewari at Jefferies, asked for Madrigal's perspective on competitor FGF21 data in cirrhotic NASH, the potential net sales impact from Medicare Part D redesign, and whether the company would consider additional discounts ahead of a potential semaglutide launch.

Answer

CEO William Sibold declined to comment on competitor data but stressed confidence in Rezdiffra's profile and their disciplined gross-to-net strategy. CFO Mardi Dier clarified that the 2025 impact from Part D redesign is incremental, not a significant step-up, as they were already paying Medicare rebates in 2024, and this is factored into their expectations.