Altimmune (ALT) H.C. Wainwright 3rd Annual BioConnect Investor Conference 2025 summary

Pipeline overview and scientific rationale

• Pemvidutide is a dual GLP-1/glucagon agonist targeting both metabolic and liver diseases, aiming to address MASH and obesity simultaneously by combining weight loss and direct liver effects in a single molecule.

• Approximately 80%-90% of MASH patients are obese, making weight loss a critical therapeutic component; pemvidutide's dual mechanism is positioned as a significant advantage over single-mechanism drugs.

• The glucagon component enables direct, rapid reduction of liver fat and serum lipoproteins, distinguishing it from GLP-1s and GIPs, which act indirectly and require longer treatment durations.

• The molecule is designed for a 1:1 GLP-1 to glucagon ratio, optimizing glycemic control and maximizing glucagon's liver effects, with demonstrated consistent blood sugar control in studies.

• Among dual agonists in development, pemvidutide is noted for having the most potent glucagon effect due to its balanced ratio.

Clinical development and trial design

• The IMPACT phase IIb trial in MASH features a unique 24-week biopsy-based primary endpoint, enabled by the drug's rapid direct liver effects.

• To minimize placebo response bias, all biopsies are de-identified and read simultaneously, aiming for more reliable statistical significance.

• The trial does not require dose titration for the 1.2 mg and 1.8 mg doses, simplifying administration and improving tolerability compared to other incretins.

• The 2.4 mg dose, planned for phase III, will have only a short titration period, further differentiating the regimen.

• Data readout for the IMPACT trial is expected by the end of the current quarter, with an End of Phase II meeting planned soon after and phase III initiation targeted for early 2026.

Efficacy, safety, and differentiation

• Pemvidutide has shown weight loss comparable to semaglutide at 48 weeks, with potential for greater loss beyond that period, and class-leading preservation of lean mass.

• The drug demonstrates potent reductions in serum lipids, including statin-like LDL lowering, even in patients already on statins.

• Preservation of lean and bone mass is superior to other incretins, addressing concerns about increased fracture risk seen with competitors.

• Recruitment for trials has been rapid due to the appeal of weight loss, suggesting strong future compliance and commercial potential.

• The molecule's slow bloodstream entry avoids peak effects and heart rate increases, enhancing safety and tolerability.