Oct. 4 at 6:43 PM
$ALT I bought myself a Plaud AI pin not long ago. I used it to record the September 30th fireside chat at the Stifel 2025 Virtual Cardiometabolic Forum. It drafted a transcript for me and this summary below.
OVERVIEW: PEMVIDUTIDE FOR MASH
Pemvidutide: Overview and Mechanism:
• Drug Class: GLP-1/glucagon dual agonist.
• Mechanism of Action: Combines the direct liver-acting effects of glucagon with the metabolic benefits of GLP-1.
• Therapeutic Approach: A multi-faceted strategy targeting the liver and the broader metabolic profile, including improvements in serum lipids and blood pressure, aiming to deliver a comprehensive treatment for MASH.
Phase 2 Trial (24-Week) Key Results:
• MASH Resolution: Achieved a class-leading MASH resolution rate at 24 weeks.
• Fibrosis Improvement:
o Although the traditional histological endpoint was not met at 24 weeks, strong anti-fibrotic activity was observed.
o Non-invasive tests (NITs) and AI-powered biopsy analysis both showed significant fibrosis improvement.
o The company is confident a positive result on the traditional biopsy endpoint would have been achieved if the trial had extended to 48 weeks.
• Weight Loss: Demonstrated robust ~6% weight loss at 24 weeks, with the trend continuing without plateau.
• Tolerability:
o Exhibited an excellent tolerability profile.
o Achieved the lowest adverse event–related discontinuation rate among all drugs in MASH development.
o High tolerability was achieved without dose titration.
• Biomarkers: Improved anti-inflammatory markers and other cardiovascular biomarkers.
Regulatory Strategy and AI-Based Biopsy Analysis:
• AI-Based Biopsy Reading (PathAI):
o AI-based biopsy reading methods are already approved in Europe.
o PathAI has submitted a proposal to the FDA for US approval.
o The FDA is expected to act in Q4 this year; a positive decision could retroactively validate the Phase 2 fibrosis results by FDA standards.
o AI analysis is considered more accurate than human assessment and viewed as the future of biopsy readouts.
• FDA Engagement:
o The MASH resolution endpoint is sufficient for US approval.
o The Phase 3 base case is a traditional biopsy-based endpoint.
o The primary goal is a flexible Phase 3 protocol that can pivot to AI-based or NIT-based endpoints if and when the FDA approves these methods.
Tolerability, Dosing, and Adherence:
• Dosing Flexibility: Excellent tolerability without titration provides significant optionality for Phase 3. The decision to use a fixed dose or introduce titration will follow FDA discussions.
• Speed of Effect: Rapid onset is a key differentiator.
o Statistically significant ALT improvements by week 4.
o Liver fat reductions at week 12 comparable to week 24.
• Patient Adherence: High tolerability supports persistence on therapy. Payers note many patients on other therapies discontinue after three months, limiting benefits. Pemvidutide’s profile may help overcome this.
Future Development and Phase 3 Trial Design:
• Upcoming Data: 12-month (48-week) data from the current study will be released in Q4, expected to show continued NIT improvements and further weight loss.
• Phase 3 Trial Design:
o Expected 52-week duration to meet FDA expectations for endpoint assessment and safety.
o Flexible design to accommodate potential shifts away from mandatory biopsies.
o Earlier NIT data can demonstrate rapid onset even with a 52-week primary endpoint.
Market Positioning and Competitive Landscape:
• Value Proposition: Delivers the benefits of a combination therapy (liver-directed agent + metabolic agent) in one molecule, avoiding complexities of combining separate drugs (tolerability, titration, PK).
• vs. Semaglutide: Semaglutide’s effect takes ~72 weeks. Pemvidutide’s rapid action is advantageous, especially for F3 patients at ~10% annual risk of progressing to cirrhosis.
• Target Market: Dual mechanism enables treatment across MASH fibrosis stages F1–F4, simplifying prescribing when staging is uncertain.
• Strategic Interest: Roche’s acquisition of 89Bio signals renewed big pharma interest in MASH, particularly combination mechanisms. Altimmune is engaged in strategic discussions.
Other Pipeline Indications:
• Alcohol Use Disorder (AUD):
o Holds the only FDA Fast Track status for a drug in this indication.
o Trial is ongoing and enrolling well.
o Data readout anticipated in H2 2026.
• Alcohol-associated Liver Disease (ALD):
o Study recently initiated.
o Utilizes the same VCTE endpoint that achieved statistical significance in the MASH trial.
Corporate Strategy:
• Obesity Indication: Not pursuing obesity as a primary indication; focusing on higher-value, complex diseases where weight loss is part of a broader therapeutic effect, avoiding the crowded obesity market.
• Financial Position: Actively strengthening the balance sheet and exploring all options to fully fund the upcoming Phase 3 trial.
Next Arrangements:
[ ] Hold an end-of-Phase 2 FDA meeting in Q4 to discuss Phase 3 design.
[ ] Finalize Phase 3 dosing strategy (fixed dose vs. titration) in consultation with the FDA.
[ ] Release 12-month (48-week) Phase 2 MASH data in Q4.
[ ] Monitor the FDA’s Q4 decision on PathAI’s AI-based biopsy analysis proposal.
[ ] Design a flexible Phase 3 protocol that can pivot to AI- or NIT-based endpoints as regulations evolve.
[ ] Continue exploring strategic and financing options to fully fund the Phase 3 program.
[ ] Prepare for the AUD trial data readout, expected in H2 2026.
