Praxis Precision Medicines, Inc. (PRAX) Earnings

Management highlights

### Regulatory Updates for Lead Pipeline Candidates - **ulexacultamide (for essential tremor, ETC):** FDA completed mid-cycle communications with no efficacy-related significant issues and confirmed it will not request an advisory committee meeting. The full FDA bioresearch monitoring (BiOMO) inspection of Praxis as a sponsor concluded with no findings and no Form 483 issued. All core commercial launch capabilities are in place, and the company is prepared to launch ahead of the PDUFA action date. - **relutrigine (for SCN2A/SCN8A developmental epileptic encephalopathies (DEEs)):** A submitted major amendment to the NDA extended the review period, with a new PDUFA target date of December 27 of the current year. The FDA also confirmed it will not hold an advisory committee meeting for this application. The BiOMO inspection also covered this application with no findings. Launch preparations are complete, with full commercial/medical teams hired, supply chain established, and a patient support program built. If approved, relutrigine would be the first approved therapy for this indication and eligible for a pediatric review voucher. - **Emerald trial (relutrigine for broad DEEs):** Enrollment exceeded its target of approximately 200 patients, spanning more than 50 distinct genetically defined etiologies. Top-line results are expected next year, and if positive alongside initial relutrigine approval, the study will serve as the basis for a supplemental NDA submission targeting approval in 2027. - **vermatrogen (for focal onset seizures):** The Phase 1 Power One study missed its primary endpoint of monthly focal seizure frequency reduction but met the key secondary endpoint of a significantly higher proportion of patients achieving at least 50% seizure reduction. Management concluded the miss was due to fixable issues with dose, trial duration, and entry criteria, not the drug's activity. Plans to amend the Power 2 and Power 3 studies are being finalized, with both studies expected to launch in Q4 of the current year. - **Alzheimer's program:** The FDA granted Breakthrough Therapy Designation (BTD) for relutrigine in seizures associated with SCN2A-DE caused by gain-of-function variants, marking the company's third BTD across three assets in 12 months. Embrave 3 trial enrollment is on track, with top-line results expected next year. - **New collaboration:** The company announced a new collaboration with Reimagine to extend the reach of ulexacultamide and expand value for patients beyond the initial launch year. ### Commercial Preparation Highlights - Leadership is in place for both upcoming launches, and teams are fully staffed. The field force buildout for ulexacultamide is on track, with an expected 300-person field team targeting 13,000 to 15,000 neurologists for the launch. - Patient support and hub infrastructure, inventory buildout, and disease awareness campaigns are all progressing as planned.

Guidance

- The company confirmed its current cash position of $1.4 billion is sufficient to support operating activities into 2028, covering planned launches and ongoing pipeline development. - Management reaffirmed its conservative peak sales estimate floor for ulexacultamide of ~$10 billion, noting this estimate is increasingly likely to prove conservative as the launch approaches. - Initial pricing for ulexacultamide is expected to fall in the $50,000 to $100,000 per year range, and management continues to have confidence in this range based on payer discussions. - The amended Power 2 and Power 3 trials for vermatrogen are expected to be operational by Q4 of the current year, with full design details to be released once finalized in the near future.

Segment performance

Praxis is a clinical-stage biotech company with no product revenue yet, so no product segment financial performance is reported. For the second quarter, total operating expenses were $96.9 million: $69.4 million allocated to research and development (R&D), and $27.5 million allocated to general and administrative (G&A). Operating cash burn for the quarter was $78 million, up from $55 million in Q2 2025, reflecting increased spending across both R&D and G&A. The company ended Q2 with $1.4 billion in cash, cash equivalents, and marketable securities.

Risks & headwinds

- Final FDA approval of both ulexacultamide and relutrigine remains pending, with no further updates planned before the respective PDUFA action dates, so final labeling and approval outcomes are still uncertain. - The vermatrogen program carries ongoing uncertainty: while management attributes the Power One primary endpoint miss to fixable trial design issues, the revised trials have not yet launched, and success is not guaranteed. - Relutrigine's broader efficacy across a heterogeneous population of genetically distinct DEEs in the Emerald trial has not yet been confirmed, and response rates may vary across different etiologies. - Pricing and reimbursement access for both launch candidates has not been finalized, and even with positive early payer feedback, unexpected restrictions could impact patient access and launch uptake.

Analyst Q&A

• Q: What is the size and composition of the sales force for the upcoming launches, and how far along is hiring? /

  A: For relutrigine, the entire commercial team is already hired and trained, with time remaining before launch to complete account profiling to ensure launch readiness. For ulexacultamide, the 300-person field force buildout targeting 13,000 to 15,000 neurologists is well underway and on track for launch. The company has been able to recruit high-caliber talent with prior rare neurology launch experience due to the significant unmet need for both indications. (338 characters)

• Q: Were there any surprises in the ulexacultamide mid-cycle FDA meeting, and what progress has been made on discussions of alternate titration regimens to improve tolerability? /

  A: There were no major unexpected issues, which management called a positive outcome. Most of the discussion focused on proper clinical use of the drug and labeling, which was earlier in the process than expected, indicating strong FDA alignment. The topic of titration to manage initial tolerability issues (which are not safety issues and resolve over time for most patients) was discussed, and there was strong alignment on the value of titration to improve patient persistence on therapy. (397 characters)

• Q: What key learnings from the failed Power One trial for vermatrogen are guiding the redesigned Power Two and Power Three trials, and why is management confident the program can succeed after the miss? /

  A: Management confirmed that suboptimal dose and trial duration were the core issues behind the primary endpoint miss, along with overly broad entry criteria allowing too many patients with extensive prior treatment failure. All of these issues are easy to adjust and fix in the trial design. Final design changes will be shared publicly in the near future once finalized with advisors, and management expects effect sizes in the revised trials to be meaningfully higher than observed in Power One. (369 characters)

• Q: Is the company prepared for a potential early approval of ulexacultamide ahead of the PDUFA date, and what key steps remain in the regulatory process? /

  A: Late-stage regulatory discussions and labeling negotiations are already complete. The company has prioritized being ready for launch well ahead of the PDUFA date as a responsible approach given the large unmet need among untreated patients, so it is already fully prepared to launch immediately if approval is granted earlier than expected. (272 characters)

• Q: What has the company heard from payers about ulexacultamide, and how is the company planning for potential step-therapy requirements? /

  A: Payer discussions have been more positive than expected, with payers recognizing the large unmet need and looking to be ready for access at launch. The company's planning assumption includes a potential step edit through propranolol, but this is not what the company is hearing across the board from payers. Roughly half of the addressable patient population cannot take propranolol due to contraindications, creating a large immediate patient pool at launch. (312 characters)