Executive Summary

Q4 2024 showed a sharp step-up in collaboration revenue ($7.5M) and continued investment behind late-stage programs, but the ulixacaltamide interim outcome was a material negative surprise; the IDMC recommended stopping Study 1 for futility, though Praxis will complete both Essential3 studies with topline now expected in Q3 2025 .
Net loss widened to $58.7M (vs. $51.9M in Q3 and $26.9M in Q4 2023) on higher R&D as epilepsy and ET programs advanced; cash, cash equivalents and marketable securities ended 2024 at $469.5M, extending runway into 2028 .
Vormatrigine (PRAX-628) remains the key 2025 catalyst suite: RADIANT topline by mid-2025 and POWER1 topline in 2H 2025; EMPOWER consents exceeded 3,000, supporting enrollment funnel .
Relutrigine momentum continues: strong Cohort 1 data (46% placebo-adjusted motor seizure reduction; ~33% seizure-free) underpins registrational Cohort 2 (topline 1H 2026) and EMERALD all-DEE initiation by mid-2025; FDA granted RPDD in Dravet in Dec-2024 .

What Went Well and What Went Wrong

What Went Well

Robust financing and extended runway: year-end 2024 cash, cash equivalents and marketable securities of $469.5M support operations into 2028, improving from prior “into 2027” messaging .
Epilepsy portfolio execution: EMPOWER consents >3,000; RADIANT topline expected by mid-2025; POWER1 on track for 2H 2025, sustaining a readout-rich 2025 trajectory .
Relutrigine clinical momentum and regulatory designations: Cohort 1 delivered 46% placebo-adjusted seizure reduction with ~33% seizure-free; FDA awarded RPDD for Dravet; Cohort 2 registrational study enrolling, EMERALD to initiate by mid-2025 .
- “We are…focused on delivering…RADIANT and POWER1…with vormatrigine, and the initiation of our EMERALD registrational study of relutrigine…by mid-year 2025” — CEO Marcio Souza .

What Went Wrong

Ulixacaltamide interim: IDMC recommended stopping Essential3 Study 1 for futility; company will complete Study 1 and Study 2 with topline in Q3 2025, and will assess NDA viability after final analyses—pushing out timing and increasing uncertainty .
Operating losses widened: Q4 R&D rose to $56.3M (vs. $41.9M in Q3 and $18.4M in Q4 2023), primarily from Cerebrum platform costs and personnel, driving a larger quarterly net loss .
POWER2 schedule slipped: earlier plans to begin enrollment in 1H 2025 were updated to 2H 2025, modestly moderating the 2025 cadence for vormatrigine registrational work .

Financial Results

Metric	Q4 2023	Q2 2024	Q3 2024	Q4 2024
Collaboration Revenue ($USD Millions)	$0.515	$0.357	$0.302	$7.463
Research & Development Expense ($USD Millions)	$18.388	$27.260	$41.881	$56.288
General & Administrative Expense ($USD Millions)	$9.933	$10.585	$15.256	$15.131
Total Operating Expenses ($USD Millions)	$28.321	$37.845	$57.137	$71.419
Loss from Operations ($USD Millions)	$(27.806)	$(37.488)	$(56.835)	$(63.956)
Other Income, net ($USD Millions)	$0.928	$4.811	$4.925	$5.277
Net Loss ($USD Millions)	$(26.878)	$(32.677)	$(51.910)	$(58.679)
Net Loss per Share (Basic & Diluted) ($)	$(2.97)	$(1.74)	$(2.75)	$(2.94)
Weighted Avg Shares (Millions)	9.061	18.824	18.885	19.980
Cash, Cash Equivalents & Marketable Securities (Period End) ($USD Millions)	$81.3 (cash only)	$433.8	$411.2	$469.5

Notes: Collaboration revenue drives “Revenue” for PRAX; there is no product revenue. FY disclosure confirms the quarterly figures above .

Segment breakdown: Not applicable (no commercial segments reported) .

KPIs and Balance Sheet Highlights:

Cash runway: “into 2028” (improved from “into 2027”) .
Shares outstanding at 12/31/24: 19.4M .
Collaboration economics: UCB exercised option on KCNT1; up to ~$100M in future milestones plus tiered royalties, though revenue recognition timing depends on development progress .

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
Ulixacaltamide Essential3 Study 1 – Interim	Q1 2025	Interim planned; timing update to follow interim	IDMC recommended stop for futility; PRAX to complete both studies; topline Q3 2025	Lowered/extended
Ulixacaltamide – NDA Filing	2025	NDA filing expected in 2025	Decision on NDA after final Study 1 & 2 results in Q3 2025	Lowered/uncertain vs 2025
Vormatrigine (RADIANT) topline	1H 2025	1H 2025	Mid-2025	Maintained
Vormatrigine (POWER1) topline	2H 2025	2H 2025	2H 2025	Maintained
Vormatrigine (POWER2) begin enrollment	2025	1H 2025 begin	2H 2025 begin	Lowered/slipped
Relutrigine (EMBOLD Cohort 2) topline	1H 2026	1H 2026	1H 2026	Maintained
Relutrigine (EMERALD) initiation	2025	1H 2025 planned	By mid-2025	Maintained
Elsunersen (EMBRAVE3) start	2025	Global registrational planning/harmonization	EMBRAVE3 24-week sham-controlled study to start enrolling by mid-2025	Clarified/added timing
Cash runway	Multi-year	Into 2027	Into 2028	Raised

Earnings Call Themes & Trends

Topic	Previous Mentions (Q2 2024)	Previous Mentions (Q3 2024)	Current Period (Q4 2024)	Trend
Ulixacaltamide Essential3	Interim built into design; aiming for 2025 NDA	Interim shifted to Q1 2025; caution on placebo/variability; sample size re-estimation optionality	IDMC futility recommendation; continue Study 1/2; topline Q3 2025; NDA decision after final data	Negative
Vormatrigine (PRAX-628) ENERGY	Launching EMPOWER; RADIANT/POWER plans set	RADIANT/POWER1 on track; EMPOWER >1,000 enrolled	EMPOWER >3,000 consents; RADIANT mid-2025; POWER1 2H 2025; POWER2 2H 2025 start	Improving
Relutrigine (PRAX-562)	EMBOLD topline expected Q3 2024	Positive EMBOLD Cohort 1: 46% reduction; ~33% seizure-free; OLE benefit	Cohort 2 registrational enrolling; EMERALD mid-2025 start; RPDD for Dravet	Positive
Elsunersen (PRAX-222)	Global registration first arm in Brazil	Protocol harmonization; global expansion plans	EMBRAVE3 design finalized; start by mid-2025	Progressing
Funding runway	$433.8M; runway into 2027	$411.2M; runway into 2027	$469.5M; runway into 2028	Improving
BD/Partnerships	—	—	UCB exercised KCNT1 option; up to ~$100M milestones + royalties	Positive

Management Commentary

“We are disappointed with and surprised by the outcome of the interim analysis for Study 1. Following the advice of the committee, we will explore different analysis methods for the final dataset…We remain focused on delivering…RADIANT and POWER1…with vormatrigine, and the initiation of our EMERALD registrational study of relutrigine…by mid-year 2025.” — Marcio Souza, President & CEO .
“Cash and investments ~ $470 million at the end of 2024 support runway into 2028.” — Company release highlighting 2025 strategy .
CFO (Q3 call): “We ended Q3 with $411.2 million in cash, cash equivalents and marketable securities…runway into 2027.” .

Q&A Highlights

Note: A Q4 2024 earnings call transcript was not available in our document set; highlights below reflect Q3 2024 Q&A.

Ulixacaltamide interim timing and disclosure: Management explained the move to Q1 2025, the desire to avoid influencing Study 2, and potential interim outcomes including futility/effect boundaries and sample size re-estimation .
Essential3 design and placebo control: Added screening/variability controls versus Phase 2; discussed responder-only randomization for the withdrawal study and maintaining study integrity .
Vormatrigine strategy: RADIANT dose plan (30mg), POWER1/2 dose schema (20→30mg), inclusion of generalized epilepsy, and potential expansion into pain indications .
Relutrigine expansion: Registrational Cohort 2 design, gene-inclusive all-DEE (EMERALD) rationale, and expectations for broader DEE applicability beyond SCN2A/SCN8A .

Estimates Context

S&P Global consensus estimates for Q4 2024 EPS and revenue were unavailable at query time; we therefore cannot present a versus-consensus comparison for this quarter. We will update when S&P Global data becomes available.

Metric	Actual Q4 2024	S&P Global Consensus	Delta
Revenue ($USD Millions)	$7.463	N/A	N/A
EPS (Basic & Diluted) ($)	$(2.94)	N/A	N/A

Key Takeaways for Investors

The ulixacaltamide interim futility recommendation is a meaningful setback; near-term stock overhang likely persists until Q3 2025 topline when both Essential3 studies read out and an NDA path can be reassessed .
2025 catalysts pivot to epilepsy: vormatrigine RADIANT mid-2025 and POWER1 2H 2025, plus EMERALD initiation for relutrigine by mid-2025—these can re-anchor value if data are supportive .
Relutrigine’s Cohort 1 data (46% seizure reduction; ~33% seizure-free) de-risks the registrational pathway in SCN2A/SCN8A and supports broader DEE expansion; RPDD in Dravet adds optionality .
Balance sheet strength (year-end $469.5M; runway into 2028) allows continued investment through multiple readouts without near-term financing pressure—an important differentiator among clinical-stage peers .
Watch for study timing updates: POWER2 slipped to 2H 2025 start, but overall epilepsy cadence is intact; Essential3 topline consolidated to Q3 2025 following interim guidance .
Collaboration optionality: UCB’s KCNT1 option exercise validates BD appetite and provides potential non-dilutive economics (up to ~$100M milestones plus royalties) .
Trading setup: Negative ET headline risk offsets, but epilepsy milestones (RADIANT/POWER1) create asymmetric upside catalysts in 2025; maintain focus on clinical execution and safety/efficacy signals across programs .

Appendix: Additional Q4 2024 Disclosures

Q4 2024 collaboration revenue: $7.5M; FY 2024: $8.6M (UCB option/license accounting) .
Q4 2024 operating expenses: R&D $56.3M; G&A $15.1M; FY R&D rise driven by Cerebrum platform (+$61.9M) and personnel costs (+$14.5M) .
Shares outstanding at year-end 2024: 19.4M .

Sources: PRAX Q4 2024 8-K/press release and financials (Feb 28, 2025) ; PRAX corporate/strategy update 8-K (Jan 29, 2025) -; Q3 2024 press release and 8-K (Nov 6, 2024) - -; Q3 2024 earnings call transcript (Nov 6, 2024) -; Q2 2024 press release and call transcript (Aug 13, 2024) - -; RPDD press release (Dec 18, 2024) -.

Praxis Precision Medicines, Inc. (PRAX)·Q4 2024 Earnings Summary