Mineralys Therapeutics, Inc. (MLYS)·Q4 2024 Earnings Summary

Executive Summary

• Q4 2024 was execution-heavy: enrollment completed in pivotal hypertension trials, cash runway reiterated to fund operations through Q1 2026, and multiple readouts guided for H1 2025, setting near-term catalysts .
• Guidance shifted: ADVANCE-HTN topline moved from Q4 2024 (prior) to March 2025; Launch-HTN improved to “mid first half of 2025,” and Explore-CKD to Q2 2025, clarifying the sequencing of data releases .
• Financials reflect scale-up: R&D rose to $44.6M in Q4 (+88% YoY), net loss widened to $48.9M, and cash/equivalents/investments were $198.2M at year-end, consistent with ongoing pivotal program intensity .
• Stock-relevant catalysts: March 2025 ADVANCE-HTN topline (late-breaking ACC abstract accepted), mid-H1 2025 Launch-HTN topline, and Q2 2025 Explore-CKD topline could reset efficacy/safety narratives and payer positioning .

What Went Well and What Went Wrong

What Went Well

• Completed enrollment and tightened timelines for pivotal trials: ADVANCE-HTN (285 subjects) guided to March 2025 and Launch-HTN (1,083 subjects) to mid H1 2025, enhancing near-term visibility .
• Strategic focus on rigorous endpoints and compliance: Use of 24-hour ABPM in ADVANCE and AiCure adherence tech designed to deliver high-quality, guideline-relevant data (“gold standard” measurement) .
• Clear payer narrative on value proposition: Management highlights base-case 8–10 mmHg SBP reduction with potential to “own” resistant hypertension in 4th-line and targeted 3rd-line obese populations (“space we can own”) .

What Went Wrong

• Timeline slippage vs initial plan: ADVANCE-HTN moved from Q4 2024 to March 2025; Explore-CKD shifted to Q2 2025, reflecting complexity in enrollment/execution despite protocol optimizations .
• Elevated cash burn: Q4 R&D expense rose to $44.6M (+88% YoY) and quarterly net loss widened to $48.9M, consistent with broader pivotal program build-out .
• Analyst concerns on extrapolation and ABPM QC: Questions on dose selection (50 mg QD), night-time coverage with half-life, and ABPM compliance/missing data required detailed management reassurances, indicating ongoing scrutiny of trial design/execution .

Financial Results

Income Statement (quarterly)

Notes: The company does not report product revenue (clinical-stage). Non-GAAP adjustments were not disclosed in the press release.

Balance Sheet (selected)

Operational KPIs

Guidance Changes

Earnings Call Themes & Trends

Management Commentary

• “Over the course of the next several months we anticipate delivering topline data from our pivotal program to treat patients with uncontrolled or resistant hypertension.” – CEO Jon Congleton .
• “The trial enrolled 285 subjects…we anticipate announcing the top line data for this trial next month. The second pivotal trial is Launch-HTN with 1,083 subjects enrolled…” – CEO Jon Congleton .
• “We are excited about the potential of lorundrostat to demonstrate a meaningful benefit in patients with uncontrolled or resistant hypertension.” – CMO David Rodman .
• “We have…completed 4 separate payer research projects…a base case of an 8–10 mmHg improvement that’s well tolerated…typically fourth line, we think that’s a space we can own.” – CEO Jon Congleton .

Q&A Highlights

• Dose selection and extrapolation: Management reaffirmed confidence in 50 mg QD dose based on exposure-response across Target-HTN cohorts and 24-hour coverage despite 10–12 hour half-life; morning trough readings supported 24-hour control .
• ABPM adherence and QC: Extensive site/subject training, accepted measurement thresholds, and validated algorithms for missing data (aligned with FDA) to secure high-quality primary endpoint data .
• Safety/hyperkalemia: Physicians accept ≤5% rates; diuretic requirement may reduce K+; benefit-risk emphasized as larger BP response increases tolerance for K+ changes; CKD cohort managed with lower dose and binders if needed .
• Payer positioning and segmentation: Expect to “own” resistant hypertension (4th line) and targeted obese 3rd-line use if 8–10 mmHg profile is replicated; robust KOL/payer research supports access .
• OSA rationale: Mechanistic focus on nocturnal volume shifts and potential inflammatory effects; bedtime dosing strategy to align with hypoxia-driven aldosterone spikes .

Estimates Context

• Wall Street consensus (S&P Global) for Q4 2024 EPS and revenue was unavailable due to system limits at the time of retrieval. As a clinical-stage company, Mineralys does not report product revenue, and estimate coverage may be limited [GetEstimates error: Daily Request Limit Exceeded].
• Where estimates become available, focus should be on EPS trajectory and cash runway; current results are best assessed vs prior quarter and prior year given lack of revenue.

Key Takeaways for Investors

• ADVANCE-HTN topline in March 2025 and Launch-HTN in mid-H1 2025 are the primary stock catalysts; positive, well-controlled ABPM data at ADVANCE could drive guideline relevance and payer access narratives .
• A replicated 8–10 mmHg SBP reduction with manageable K+ profile would be commercially meaningful; obese and rHTN subsets could amplify differentiation and uptake in 3rd/4th-line settings .
• Execution quality remains central: adherence tech (AiCure), rigorous ABPM, and FDA-aligned data handling reduce risk of measurement noise and placebo effects, strengthening readouts .
• Cash runway through Q1 2026 supports pivotal readouts and early launch preparation; monitor quarterly burn as trials approach completion to assess financing needs post-readouts .
• Explore-CKD topline in Q2 2025 broadens cardiorenal footprint; synergy with SGLT2s may improve benefit-risk and positioning in CKD with hypertension .
• ACC late-breaking abstract for ADVANCE elevates clinical visibility; a clean, compelling dataset could accelerate payer and physician engagement .
• Risk: timeline sensitivity and ABPM execution; however, management’s QC/missing-data plans and prior Target-HTN concordance between AOBP and ABPM mitigate concerns .