Kambiz Yazdi

Kambiz Yazdi asked for an update on the essential tremor patient database and how it has validated the size of the ET market. He also inquired about Praxis's view on the FDA's default position of one adequate and well-controlled study plus confirmatory evidence for market authorization, specifically for vormatrigine in FOS, and the timing of relutrigine EMERALD top-line data, including the possibility of an interim analysis.

Answer

CEO Marcio Souza stated that the ET patient database continues to be validated and grow, with a larger update planned for the upcoming commercial day. Regarding the FDA's stance on single-study approvals, he applauded the responsible use of such approaches, seeing it as a positive for drug development and potentially for Praxis, though it's too early to guide on its application to their drugs. For EMERALD, he noted that an interim analysis is not currently planned due to the very fast pace of enrollment, which might not allow for it, but did not provide specific top-line timing beyond 'soon enough.'

Kambiz Yazdi requested an update on the essential tremor patient database and its validation of the ET market size. He also asked about Praxis Precision Medicines' view on the FDA's stance on one adequate study for market authorization, particularly for vormatrigine, and the timing and possibility of an interim analysis for the relutrigine EMERALD study.

Answer

President and CEO Marcio Souza stated that the ET patient database continues to be validated and grown, with a larger update planned for the commercial day. He applauded the FDA's position on one adequate study, believing it can be used responsibly for drugs like vormatrigine. For EMERALD, an interim analysis is not currently planned due to the very fast pace of enrollment.

Kambiz Yazdi asked about the measures taken to control for placebo response in the decentralized Essential3 study and inquired about the historical performance of sodium channel blockers in PGTC seizures and what a registrational program for Vormatrigine in generalized epilepsy might entail.

Answer

CEO Marcio Souza explained that to control for placebo in Essential3, they added a formal pre-randomization visit to ensure patient stability at baseline. Regarding Vormatrigine, he noted that historical results for sodium channel blockers are mixed, but Vormatrigine's selectivity is a key advantage. He added that the RADIANT study will inform the design of a future registrational study for generalized epilepsy, an indication with significant physician excitement.

Kambiz Yazdi asked how Praxis will prioritize patient enrollment between the POWER1 and RADIANT studies for PRAX-628, requested more details on the POWER observational study, and inquired about the regulatory feedback received for initiating the elsunersen pivotal study in Brazil.

Answer

Executive Marcio Souza clarified that the POWER1 and RADIANT studies are not competitive for enrollment due to different site footprints and patient characteristics, allowing both to recruit effectively. Regarding elsunersen, he confirmed Praxis received full feedback from Brazil to start the study there. He added that the company is aligning with European regulators for a later 2024 start, with a similar process underway with the FDA for the complex program.

Kambiz Yazdi asked how patient enrollment would be prioritized between the POWER1 and RADIANT studies and requested details on the elsunersen program, including regulatory feedback for its initiation in Brazil and requirements for advancement in the U.S. and Europe.

Answer

CEO Marcio Souza clarified that the POWER1 and RADIANT studies are not competitive for enrollment, as RADIANT is a smaller study that can start more quickly. For elsunersen, he confirmed full feedback was received to start the study in Brazil. He noted that preliminary feedback from Europe is aligned with their plans for a launch later this year, and a similar process is underway with the FDA for the complex program.

Kambiz Yazdi from Jefferies inquired about the target patient characteristics for the upcoming YUTREPIA transition study and requested a status update on the L606 program.

Answer

Chief Medical Officer Dr. Rajeev Saggar responded, stating the transition study will enroll PH-ILD patients currently on TYVASO (nebulized or DPI) to demonstrate a safe transition and potential for improved titration and clinical stability. Regarding L606, he confirmed it is a global study with over 300 patients that is expected to be initiated by the end of the year.

Kambiz Yazdi from Jefferies asked for details on the L606 open-label study, including how many patients achieved a dose over 100-micrograms twice daily and if adverse events were consistent with previous studies. He also inquired about the supply chain robustness for the YUTREPIA DPI inhaler.

Answer

Chief Medical Officer Dr. Rajeev Saggar reported that the 'overwhelming majority' of patients exceeded the 100mcg twice-daily dose, with the median dose surpassing 200mcg, underscoring the drug's tolerability. CEO Dr. Roger Jeffs added that L606 achieves 2-3 times the therapeutic target of nebulized TYVASO. CFO Michael Kaseta confirmed that the company has been manufacturing commercial supply since early 2022 and is 'ultra-prepared' with sufficient inventory for the YUTREPIA launch.

Kambiz Yazdi of Jefferies LLC requested details on the registrational study design for L606 and its start date, and also asked for an update on the number of sites and patients in the ASCENT study.

Answer

Chief Medical Officer Dr. Rajeev Saggar stated that the global, placebo-controlled L606 study in PH-ILD patients is planned to start by the end of the year, with 6-minute walk distance as the primary endpoint. For the ASCENT trial, he reported that the number of sites is close to tripling, with about 15 patients expected by the end of the month, and the company is confident in completing the study by year-end.

Kambiz Yazdi asked for guidance on modeling future R&D expenses and sought perspective on the impact of biosimilars on the wet AMD market, including whether a post-marketing study with a biosimilar load would be considered.

Answer

CFO George Elston advised that while Q1 R&D was higher due to rapid enrollment, full-year models are likely still accurate, with spending just front-loaded. President and CEO Dr. Jay Duker stated the company is agnostic to the loading drug used before DURAVYU and that its differentiated mechanism and 6-month duration will set it apart from biosimilars.

Asked about forward-looking R&D expense modeling and the company's perspective on the impact of biosimilars on the wet AMD market and DURAVYU's positioning.

Answer

Full-year R&D spending models are likely still accurate, but the spending has been front-loaded into Q1 due to rapid enrollment. The company is agnostic to biosimilars, as DURAVYU offers a differentiated MOA and longer duration, and they don't believe the choice of loading anti-VEGF (branded or biosimilar) will impact outcomes.

Kambiz Yazdi of Jefferies asked for guidance on modeling R&D expenses going forward and for perspective on how biosimilars are shaping the wet AMD market, including whether a post-marketing study with a biosimilar could be considered.

Answer

CFO George Elston explained that while Q1 R&D was higher due to rapid enrollment, the full-year model is likely still correct, with some spend shifted earlier. CEO Dr. Jay Duker stated the company is agnostic to which anti-VEGF is used for loading doses, including biosimilars, as they don't expect a difference in outcomes. He emphasized that DURAVYU's different mechanism and 6-month duration differentiate it from the biosimilar market.

Kambiz Yazdi asked about EyePoint's long-term plans for post-marketing studies for DURAVYU and what information from such studies could help further differentiate the product in the wet AMD market.

Answer

President and CEO Dr. Jay Duker explained that a key post-approval study would be a head-to-head trial against a market leader like VABYSMO, with a primary endpoint of supplement-free rate. Chief Medical Officer Ramiro Ribeiro added that they could also explore additional benefits, such as the prevention of atrophy.

Kambiz Yazdi from Jefferies asked about the next steps following the stay in the Padagis patent litigation, the key learnings from ARQ-252 that informed the ARQ-255 formulation, and the potential market white space for a new topical treatment in alopecia areata.

Answer

CEO Frank Watanabe explained the litigation stay is indefinite and was requested by Padagis, suggesting a potential issue with their ANDA filing. He stated Arcutis remains confident in its IP. Patrick Burnett, Chief Medical Officer, clarified that ARQ-255 is a completely new suspension formulation designed to deliver the drug deep into the hair follicle, overcoming the delivery challenges of ARQ-252. He identified the white space for a topical in alopecia areata as treating patients with less than 50% scalp involvement and as a long-term management option for those who have responded to systemic JAK inhibitors.

Kambiz Yazdi from Jefferies asked what proportion of Q4 sales were attributable to the Kowa PCP partnership and inquired about the Q1 OpEx outlook, including how commissions to Kowa would be accounted for.

Answer

Chief Financial Officer David Topper clarified that the contribution from the Kowa partnership in Q4 2024 was not significant, as their efforts began late in the year, but a meaningful contribution is expected in 2025. He confirmed that commissions paid to Kowa will be included in the SG&A line item and will be detailed in future reports once the contribution becomes material.

Kambiz Yazdi of Jefferies asked about the proportion of Q3 sales attributable to the Kowa deal, the terms of the Kowa agreement, the blend of commercial versus government payer contribution to Q3 revenue, and how the company's pricing strategy has aided payer negotiations.

Answer

CFO David Topper stated the Kowa contribution in Q3 was immaterial as the partnership began in mid-September. CEO Frank Watanabe confirmed the Kowa agreement is for five years and positions ZORYVE as a priority product. CCO Todd Edwards noted Q3 revenue was driven primarily by commercial payers. Frank Watanabe explained the pricing strategy was designed to avoid the Medicare specialty tier, which has been validated by rapid commercial and Medicaid coverage wins.