Altimmune Details Pemvidutide Phase III MASH Plans, Breakthrough Status at Citizens Conference

Key Points

• Altimmune received Breakthrough Therapy designation for pemvidutide and plans a phase III MASH study with biopsy-based primary endpoints at 52 weeks in a cohort of just under 1,000 patients, testing two doses (1.8 mg anchor and 2.4 mg) with titration and FDA-aligned use of the AIM-MASH AI Assist for consensus reads.
• Phase II showed a strong impact on MASH resolution at 24 weeks with good tolerability, and 48-week topline data reported continued weight loss and improved non-invasive anti-fibrotic signals (FibroScan, ELF), though the 24-week fibrosis biopsy endpoint was not met amid placebo response and biopsy variability.
• Management says cash runway extends into 2028 after raising roughly $300 million last year, and the company expects topline phase II data in alcohol use disorder in Q3 plus full enrollment of an alcohol-associated liver disease trial this year.

Altimmune NASDAQ: ALT executives used a presentation at the Citizens Life Sciences Conference to outline recent clinical results and development plans for pemvidutide, the company’s lead drug candidate being developed primarily for metabolic dysfunction–associated steatohepatitis (MASH). Chief Executive Officer Jerry Durso, Chief Commercial Officer Linda Richardson, and Chief Financial Officer Greg Weaver discussed phase II learnings, the planned phase III trial design, additional liver-related programs, and the company’s balance sheet.

Pemvidutide’s phase II MASH readouts and what changed at 48 weeks

Durso said Altimmune remains encouraged by pemvidutide’s potential across multiple liver indications, with MASH as the lead program. He highlighted that the phase II MASH trial was designed to read out biopsy endpoints at 24 weeks, which he characterized as potentially “a little early” for the mechanism. Even so, he said the company saw a strong impact on the MASH resolution endpoint with good tolerability and continued weight loss at 24 weeks. The trial showed positive trends on fibrosis, but did not meet the fibrosis endpoint, which Durso attributed in part to a high placebo response rate and biopsy variability.

Altimmune later reported 48-week topline results (without biopsies at that time point). Durso said the company observed improvement from 24 to 48 weeks on non-invasive tests associated with anti-fibrotic activity, specifically liver stiffness measurement by FibroScan and the Enhanced Liver Fibrosis (ELF) test. He also noted that weight loss on the 1.8 mg dose continued and did not plateau over the period discussed, and that tolerability remained favorable.

Phase III plans: 52-week biopsies, two doses, and an AI-assisted read

Durso said Altimmune held an end-of-phase II meeting with the FDA late last year and received minutes in early January confirming alignment on key elements of the phase III design. He said pemvidutide also received Breakthrough Therapy designation.

According to Durso, the FDA indicated it is still premature to move away from biopsy-based endpoints in MASH. As a result, the phase III study is expected to include biopsies and assess the two common endpoints—fibrosis improvement and MASH resolution—at 52 weeks. The company plans a cohort of “a little under 1,000” patients for the primary 52-week efficacy readout.

Altimmune intends to evaluate two active doses: 1.8 mg, which Durso described as the anchor dose from phase II, and 2.4 mg, a higher dose previously studied in the company’s obesity program. Durso said the trial will be powered around the 1.8 mg dose, while the 2.4 mg arm is being included as a potential upside option based on weight-loss experience in obesity.

Durso also said the FDA aligned on the use of the AIM-MASH AI Assist tool in conjunction with pathologists as part of a consensus read process, with the goal of reducing variability associated with biopsies.

For dosing, Durso said the phase III program will include a titration scheme. Patients targeting 1.8 mg will start at 1.2 mg and move to 1.8 mg after four weeks. Patients targeting 2.4 mg will start at 1.2 mg, then step to 1.8 mg, and then to 2.4 mg. Durso contrasted this with the phase II program, where patients started directly at the target dose without titration. He said gastrointestinal events occurred primarily in the first four to six weeks and suggested a simpler titration could further improve tolerability.

Mechanism and positioning: one-to-one glucagon/GLP-1 ratio

Durso and Richardson emphasized what they view as differentiation from pemvidutide’s one-to-one glucagon to GLP-1 activity. Durso said glucagon acts directly on the liver, driving a rapid reduction in liver fat and downstream effects on inflammation and fibrotic activity, while GLP-1 contributes metabolic benefits including weight loss. He said the company is not aware of other glucagon/GLP-1 combinations that use a one-to-one ratio, and argued that other programs tend to be weighted more heavily toward GLP-1, which he said can be associated with greater tolerability challenges and higher drop-off rates.

Richardson said recent market research conducted by the company found that tolerability and “falloffs” on GLP-1 therapy—both due to tolerability and perceived failure of efficacy—are increasingly concerning to physicians. She said Altimmune believes this creates an opportunity for a therapy that patients can stay on, with a simpler titration schedule.

She also pointed to lean muscle mass preservation as an attribute that is resonating with endocrinologists, describing muscle loss and sarcopenia risk as an important consideration in MASLD/MASH and alcohol-related disease populations. Richardson said the company expects to further evaluate this in MASH patients, noting that Altimmune observed the signal in obesity data.

Market context and competitive landscape

During the discussion, management referenced the growing MASH treatment market and early launch dynamics of existing therapies. Durso said he is not surprised to see physicians valuing the first entrants, and added that payers appear to recognize the use of non-invasive tests to identify appropriate patients. He also said he expects identification of patients to increase as more therapies enter the market.

Richardson said the lack of weight loss is a concern for certain approaches, and argued that pemvidutide could be competitive by combining anti-fibrotic signals on non-invasive tests with weight loss and tolerability. Durso added that he expects the MASH market to evolve like other chronic categories, with multiple mechanisms used across different patient segments.

Additional programs: alcohol use disorder and alcohol-related liver disease

Altimmune is also running two phase II studies beyond MASH. Durso said the company expects topline phase II data in alcohol use disorder (AUD) in the third quarter of this year, with reduction in drinking as the primary endpoint, alongside exploratory assessment of liver impact. He also said the company anticipates the phase II trial in alcohol-associated liver disease (ALD) will be fully enrolled this year.

Balance sheet and runway

Weaver said Altimmune’s end-of-February cash position provides runway “into 2028,” while noting there is “more work to do.” He said the company raised “approaching $300 million” over the last year through a combination of a registered direct offering and at-the-market activity, and added that Altimmune remains open to strategic funding options. Management also said it remains open to discussions regarding partnering, including ex-U.S., while focusing on being positioned to initiate phase III.

About Altimmune NASDAQ: ALT

Altimmune, Inc is a clinical-stage biopharmaceutical company headquartered in Gaithersburg, Maryland, dedicated to the development of vaccines and immunotherapeutics. The company leverages proprietary technology platforms to create intranasal vaccine candidates and novel therapies targeting liver diseases and metabolic disorders. Altimmune's approach emphasizes the stimulation of both systemic and mucosal immune responses to address unmet medical needs in infectious and chronic conditions.

Among its lead programs, NasoVAX is an investigational intranasal influenza vaccine designed to provide broad, long-lasting protection through a single, non-invasive dose.

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