Summary of Praxis Precision Medicines Conference Call Company Overview - **Company**: Praxis Precision Medicines (NasdaqGS:PRAX) - **Event**: Guggenheim Emerging Outlook, Biotech Summit 2026 - **Date**: February 11, 2026 - **Key Executives Present**: Marcio Souza (CEO), Tim Kelly (CFO) Core Industry Insights - **Focus Area**: Central Nervous System (CNS) disorders, specifically essential tremor and epilepsy treatments - **Market Potential**: Approximately 2-2.5% of the U.S. population is affected by essential tremor, indicating a significant patient base requiring treatment [9][10] - **Current Treatment Landscape**: There are no effective and safe treatments available for essential tremor, highlighting a substantial unmet medical need [10] Key Points Discussed - **Ulixacaltamide Hydrochloride**: - A potential drug for essential tremor, expected to be a significant advancement in treatment options [9][10] - Positive results from the Essential3 program were highlighted, indicating meaningful benefits for patients [11] - **Patient Population**: - Between 1 and 2 million patients in the U.S. are actively seeking treatment for essential tremor [16] - 80,000 prescriptions are written monthly by neurologists for essential tremor, indicating strong demand [14] - 70% of patients have family members also affected by essential tremor, suggesting a broader market potential [19] - **Commercial Strategy**: - The company plans to deploy a robust sales force to effectively reach physicians across the U.S. [21] - Emphasis on mobilizing patients to participate in clinical studies, achieving recruitment rates 5-7 times faster than larger competitors [24] - The launch strategy will include extensive patient messaging and ensuring coverage from payers [27] - **Pricing Strategy**: - Initial pricing discussions suggest a potential range of $40,000 to $60,000 per year for ulixacaltamide, with considerations for patient copay management [43][44] - The company aims to avoid leaving money on the table to ensure continued innovation [41] Regulatory and Development Updates - **NDA Filing**: - The company is on track to file for ulixacaltamide in mid-February 2026, with confidence in meeting regulatory requirements [47][52] - Two NDAs are being filed simultaneously, indicating a significant operational effort [60] - **Emerald Study**: - The EMERALD study for expanding indications in developmental and epileptic encephalopathies (DEE) is progressing well, with expectations for positive outcomes [64][66] - The study is anticipated to finalize in the second half of the year, potentially qualifying for expedited review under the STAR program [67] Financial Position - **Funding**: - The company has approximately $1.5 billion in cash, providing a strong runway to support drug launches and operations through 2028 [90] - **Priority Vouchers**: - The company is eligible for two priority review vouchers, which could enhance its market positioning for rare disease treatments [90] Additional Considerations - **Market Dynamics**: - The company acknowledges the competitive landscape for epilepsy treatments but believes there is ample opportunity for multiple successful products [78] - **Combination Therapies**: - Future treatments may involve combination therapies, particularly for severe cases, indicating a strategic approach to patient care [86] This summary encapsulates the key insights and strategic directions discussed during the conference call, highlighting Praxis Precision Medicines' focus on addressing significant unmet needs in CNS disorders and its proactive approach to market entry and patient engagement.

Core Insights - The FDA has approved changes to the EMBRAVE3 trial design, converting it to a single-arm, baseline-controlled study for the treatment of SCN2A developmental and epileptic encephalopathy (DEE) with elsunersen [1][2] - Enrollment in the EMBRAVE3 trial is accelerating, with topline results expected in 2026 [1][2] - Elsunersen is an antisense oligonucleotide targeting SCN2A gene expression, showing promise in reducing seizures and improving symptoms in preclinical models [3][5] Group 1: EMBRAVE3 Trial Updates - The EMBRAVE3 study will now enroll 30 patients instead of the previously planned 40, with all patients receiving elsunersen from the start [5] - The primary analysis will focus on the change from baseline in countable motor seizures [5] - The ongoing EMBRAVE study (Part A) has enrolled 9 patients, with topline results expected in the first half of 2026 [1][5] Group 2: Elsunersen Overview - Elsunersen is designed to selectively decrease SCN2A gene expression, addressing the underlying cause of early-onset SCN2A DEE [3] - In vitro studies have shown a reduction in SCN2A gene expression and protein levels, while in vivo studies demonstrated significant reductions in seizures and improved survival in SCN2A mouse models [3] - Elsunersen has received Orphan Drug Designation and Rare Pediatric Disease Designation from the FDA, as well as similar designations from the European Medicines Agency [3] Group 3: Company Background - Praxis Precision Medicines is focused on developing therapies for CNS disorders characterized by neuronal excitation-inhibition imbalance [4] - The company utilizes genetic insights to create therapies for both rare and prevalent neurological disorders through its proprietary platforms [4]

Core Insights - Praxis Precision Medicines is advancing its clinical programs in developmental and epileptic encephalopathies (DEEs), highlighting significant opportunities in this field [2][5] - The company is focusing on two main therapeutic candidates: Relutrigine and Elsunersen, both showing promising results in clinical studies [5][8] Relutrigine - Relutrigine has demonstrated a mean seizure reduction of approximately 90% from baseline after 11 months of patient dosing in the EMBOLD study [5] - The EMBOLD study is expected to provide topline results by the first half of 2026, with a registrational study (EMERALD) planned to start in mid-2025, targeting a US market potential of at least $3 billion [5][7] - Relutrigine is a first-in-class small molecule that selectively inhibits persistent sodium current, showing dose-dependent inhibition of seizures in various DEE mouse models [7] Elsunersen - Elsunersen is an antisense oligonucleotide (ASO) targeting SCN2A gain-of-function mutations, with significant seizure reduction observed in clinical studies [8] - The EMBRAVE3 trial is set to enroll patients aged 2-18, with plans for treatment initiation from birth, reflecting the early onset of SCN2A DEE [5][8] - The global market potential for Elsunersen is estimated at $1 billion, based on a target population of approximately 5,000 patients [5] Pipeline and Future Developments - Praxis plans to nominate a development candidate for its early-stage ASO program PRAX-100, targeting SCN2A loss-of-function mutations, by mid-2025 [11] - The company is also on track to nominate development candidates for PRAX-080 and PRAX-090 by the end of 2025, focusing on PCDH19 and SYNGAP1 mutations respectively [11] - The company is leveraging its proprietary platforms, Cerebrum™ and Solidus™, to develop therapies for CNS disorders [9]