Praxis Precision Medicines, Inc. Q4 FY2021 earnings call

• Discussed the Aria study for major depressive disorder (MDD), including patient eligibility criteria, higher-than-expected screen fail rates indicating effective eligibility review, and standard deviation of HAMD-17 changes around 7 points for study powering.
• Outlined compliance measures in the Aria study, such as using customized AiCure tools to monitor patient engagement and ensure good compliance with drug administration procedures.
• Addressed the Essential Tremor studies, including the design of the Essential1 trial to select doses for potential Phase III studies, focusing on safety, tolerability, and efficacy measures like activities of daily living and tremor assessment.
• Mentioned reallocation of resources towards therapeutic areas with clearer market support and regulatory frameworks, such as narrowing focus to certain epilepsy and depression indications based on data and market needs.

No detailed financial performance by product segment with revenue contribution percentages was discussed in the transcript.

• Anticipates maintenance of effect and potential statistical significance at Day 29 in the Aria study for MDD, with plans to report results in June and potentially start Phase III studies later in the year for Essential Tremor.
• Expectations of dose-dependent efficacy in the Essential Tremor trials, with the intention to narrow focus of doses based on trial data and regulatory discussions.
• Focus on using data from studies like Essential1 to inform subsequent Phase III or Phase 3 trials for Essential Tremor, depending on regulatory feedback.

• Higher-than-expected screen failure rates in the Aria study, which could impact the homogeneity of the patient population.
• Uncertainty in dose response and efficacy outcomes in the Essential Tremor trials, as dose-dependent effects are not yet fully understood.
• Regulatory risks in determining appropriate responder definitions and dose selections for trials, particularly in therapeutic areas like Essential Tremor.

Q: Yasmeen Rahimi asked about the homogeneity of the patient population in the Aria study and standard deviation of HAMD-17 baseline.

A: Bernard Ravina responded that eligibility was HAMD-17 of 23 or higher, with a higher-than-expected screen fail rate indicating effective eligibility review, and standard deviation for powering was around 7 points.

Q: Laura Chico asked about patient compliance in the Aria study and potential impacts on anxiety.

A: Marcio Souza and Bernard Ravina discussed compliance measures using customized AiCure tools and expected anxiety impacts in the MDD population, with expectations of around 50% improvement in anxiety measures.

Q: Ritu Baral asked about expectations for the Aria study results and sedation in MDD.

A: Marcio Souza and Bernard Ravina talked about maintenance of effect, potential statistical significance at Day 29, and sedation expectations, noting the drug's safety profile and expected behavior.

Q: Tazeen Ahmad asked about the Essential1 study for Essential Tremor, dose-dependent efficacy, and narrowing focus of doses.

A: Marcio Souza and Bernard Ravina discussed the design of Essential1 to select doses for Phase III, expectations of dose-dependent efficacy, and potential narrowing of doses based on trial results.

Q: Myles Minter asked about mitigators in the Aria study and placebo response.

A: Marcio Souza and Bernard Ravina talked about patient population selection and site eligibility as key mitigators, emphasizing the importance of proper patient screening.

Q: Douglas Tsao asked about screening failures in the Aria study and timing of the PPD study.

A: Marcio Souza discussed screen failures driven by HAMD-17 confirmation and noted plans to restart the PPD study shortly after the Aria results.

Q: Ritu Baral asked about the strategy behind the second dose in Acapella.

A: Marcio Souza and Bernard Ravina discussed dose ranges, dose proportional side effects, and commercial considerations, noting the focus on lower doses with clean safety profiles.

Q: Myles Minter asked about the randomized withdrawal portion of the 944-2A Study and pediatric epilepsy focus.

A: Bernard Ravina and Marcio Souza talked about randomized withdrawal details and reallocation of resources for epilepsy programs based on market and regulatory needs.