Kostas Biliouris

Kostas Biliouris referenced a recent Avidity publication on DM1 showing inconsistent splicing correction despite muscle concentration, asking if Sarepta anticipates similar outcomes and how such a scenario would be interpreted if muscle concentration is achieved but biomarkers are inconsistent.

Answer

Louise Rodino-Klapac, Executive VP, Chief Scientific Officer, and Head of Research and Development, stated that Sarepta's preclinical data shows a clear correlation between muscle concentration and correction, suggesting Avidity's results might be due to dose limitations. Doug Ingram, President and Chief Executive Officer, added that for an siRNA, a direct correlation between muscle concentration, knockdown, and downstream splice correction is expected, based on Sarepta's preclinical models.

Kostas Biliouris referenced a recent Avidity publication on DM1 showing muscle concentration but inconsistent splicing correction, asking if this could occur with Sarepta's program and how to interpret such an outcome.

Answer

President and Chief Executive Officer Doug Ingram and Executive VP, Chief Scientific Officer, and Head of Research and Development Louise Rodino-Klapac stated that based on Sarepta's preclinical data, they observe a correlation between muscle concentration and correction. They suggested Avidity's limitations in dosing might have played a role and expect a clear, direct correlation for Sarepta's siRNA.

Representing Kostas Biliouris, Dale asked how Sarepta is leveraging the FDA's platform designation to accelerate its LGMD pipeline and about the impact of the time function test data in the ELEVIDYS label on payer negotiations.

Answer

Head of R&D Dr. Louise Rodino-Klapac confirmed they are leveraging the ELEVIDYS experience and Fast Track designation to accelerate the LGMD platform. CCO Dallan Murray added that the new time function test data in the label is a primary focus of payer conversations and has been met with high engagement and interest, supporting the case for broad access.

Kostas Biliouris asked for Legend's perspective on a competitor's recently presented 18-month PFS data and how the company is thinking about CARVYKTI's competitive positioning.

Answer

Interim CFO Jessie Yeung positioned CARVYKTI as the best-in-class BCMA CAR-T, citing its demonstrated overall survival benefit and unprecedented long-term data. She argued the competitor's study involved a fundamentally different, less heavily pretreated patient population and that its data is immature with insufficient follow-up, making direct comparisons difficult.

Kostas Biliouris asked about the competitive dynamics with a potential new CAR-T product entering the market and whether Legend's focus is on protecting late-line share or gaining share across all lines.

Answer

CEO Ying Huang challenged the competitor's near-term timeline, citing lengthy regulatory requirements. SVP of Commercial Development, Steven Gavel, stated the promotional focus will remain on earlier lines where CARVYKTI is differentiated, adding that payers typically don't cover a second CAR-T therapy. Ying Huang also cited outpatient administration and established hospital formularies as key commercial advantages.

Kostas Biliouris from BMO Capital Markets sought clarification on the BMN 333 data, asking if the 3x AUC difference was seen across all doses and how its Cmax compares to TransCon CNP, and if Cmax is relevant for safety or efficacy.

Answer

Gregory Friberg, EVP and Chief R&D Officer, clarified that two of the five completed dose cohorts have already met the greater-than-3x AUC criterion. He explained that while BMN 333's Cmax is predicted to be higher than the competitor's, it remains well below levels known to cause blood pressure effects with VOXZOGO and has not been problematic. The safety and efficacy profile will be further evaluated in the upcoming dose-ranging study in patients.

Kostas Biliouris of BMO Capital Markets sought clarification on the BMN-333 data, asking if the 3x AUC difference was observed across all doses and how its Cmax compares to TransCon CNP and its relevance for safety.

Answer

Gregory Friberg, EVP and Chief R&D Officer, clarified that two of the five completed dose escalation cohorts have already met the >3x AUC criteria compared to the published data for the other agent. He explained that while Cmax increases with AUC, they remain well below levels known to cause blood pressure drops. The upcoming dose-ranging study in patients will further test the safety and efficacy at different levels.

Kostas Biliouris of BMO Capital Markets inquired about the prevalence of payer policies that require prior use of a stabilizer before Amvuttra and the percentage of patients affected by these requirements.

Answer

CEO Yvonne Greenstreet and CCO Tolga Tanguler both emphasized that access is not a barrier. Tanguler specified that such step-edit policies are 'incredibly minimal,' affecting a single-digit percentage of commercial lives, and are manageable. The minimal use of the company's Quick Start program was cited as evidence of seamless access.

Kostas Biliouris noted that a competitor reported an impact from the AMVUTTRA launch, particularly from switch patients, and asked if the majority of Alnylam's early uptake was from switches or new patients.

Answer

Chief Commercial Officer Tolga Tanguler described the early uptake as "broad," encompassing both first-line patients and switch patients. He noted that physicians who are switching patients are also initiating new patients on AMVUTTRA, indicating a positive early trend. He concluded by praising his commercial team's "world-class" execution.

An analyst on behalf of Kostas Biliouris asked for Intellia's thoughts on the potential competition from Alnylam's AMVUTTRA in ATTR-CM, given its dosing schedule and TTR knockdown.

Answer

CEO John Leonard emphasized that the key differentiator is achieving the lowest possible absolute TTR levels, stating nex-Z achieves levels approximately one-third of those reported for AMVUTTRA. He highlighted that a 'one-and-done' therapy offers significant advantages for patients, physicians, and payers regarding access and long-term management.

Asked about how the new Zerlasiran data informs Phase III design, for more detail on the 'promising' Divesiran (PV) data, and about the potential for partnering the PV program.

Answer

The technology has been very consistent across all studies. For the PV program, the 'promising' data refers to relevant clinical outcomes like the number of phlebotomies and maintenance of hematocrit. Regarding partnering for PV, the company is open to it and is evaluating options, noting they could also pursue it themselves, but there is interest from other parties.