Altimmune Presents Data at EASL International Liver Congress™ 2024 Supporting the Disease Modifying Potential and Differentiated Therapeutic Profile of Pemvidutide in Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Rhea-AI Summary

Altimmune presented new data at the EASL International Liver Congress 2024 highlighting the potential of pemvidutide in treating Metabolic Dysfunction-Associated Steatohepatitis (MASH). The data from Phase 1 trials indicate significant improvements in non-invasive tests, suggesting potential histologic benefits by Q1 2025. The trials show that pemvidutide's dual GLP-1/glucagon agonism could outperform GLP-1 alone in resolving MASH and reducing fibrosis. Additionally, lipidomic profiling supports its potential in addressing MASH-related co-morbidities like cardiovascular disease. Pemvidutide is currently being evaluated in a Phase 2b trial.

Positive

• 60% of subjects achieved a reduction in both MRI-PDFF (≥ 30%) and ALT (≥ 17 IU/L) at Week 24 with pemvidutide.
• 75% of subjects at high risk of MASH progression had their risk reduced to low at Week 24 with pemvidutide.
• The QSP computational model predicts complete resolution of MASH and a 1-point median improvement in fibrosis by Week 24 with pemvidutide.
• Lipidomic profiling shows significant decreases in serum lipids linked to MASH and cardiovascular diseases, supporting pemvidutide's disease-modifying potential.
• Pemvidutide demonstrated strong anti-inflammatory and anti-fibrotic properties in Phase 1 trials.

Negative

• No significant improvements in MRI-PDFF and ALT were observed with placebo treatment.
• GLP-1 receptor monotherapy showed no effect on fibrosis within the 24-week timeframe in the QSP model.
• The reported data are from ongoing trials, and the final outcomes are still uncertain.
• The current evaluation of pemvidutide is to Phase 1 and 2b trials; further phases are needed for conclusive results.
• Potential risks associated with dual GLP-1/glucagon agonism have not been fully explored.

Medical Research Analyst

The presentation of new data on pemvidutide at the EASL International Liver Congress underscores its potential in treating Metabolic Dysfunction-Associated Steatohepatitis (MASH). This could be game-changing, as MASH currently lacks efficient treatments. The data from Phase 1 trials indicate that pemvidutide can significantly reduce the risk of MASH progression, demonstrated by improved FibroScan®-AST (FAST) scores and reductions in MRI-PDFF and ALT scores. This suggests substantial liver health improvements.

Moreover, the quantitative systems pharmacology (QSP) model predictions highlight the additive benefits of dual receptor agonism (GLP-1 and glucagon) over GLP-1 monotherapy, which could translate into better long-term outcomes for patients. These aspects, combined with the lipidomic profiling results, reinforce pemvidutide's potential not only for liver health but also for addressing cardiovascular comorbidities associated with MASH.

From a retail investor's perspective, these findings suggest promising developments in Altimmune’s pipeline, potentially increasing the company's market valuation if subsequent trials maintain these outcomes.

Financial Analyst

Altimmune's recent data presentation provides a strong indication of pemvidutide's potential market impact. If Phase 2b and subsequent trials confirm these results, pemvidutide could be a significant revenue driver given the high prevalence of MASH and MASLD. The projected histologic improvements and added benefits over existing treatments suggest a unique market position for Altimmune.

The announcement’s timing aligns strategically with Q1 2025 biopsy readouts, setting the stage for potential news-driven stock movements. Investors should monitor further clinical updates and FDA interactions closely, as positive results could lead to substantial stock appreciation.

Importantly, one should consider the competitive landscape. While Altimmune's dual agonism approach is promising, other players are also advancing in the MASH space. Thus, execution risk remains, but the data presented here tilt favorably towards Altimmune's growth prospects.

Follow-on analyses of non-invasive tests from Phase 1 trials in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) suggest the potential for meaningful histologic improvements with MASH biopsy readouts in Q1 2025

Based on a quantitative systems pharmacology (QSP) computational model, pemvidutide’s GLP-1/glucagon dual agonism could have additive effects on MASH resolution and fibrosis improvement compared with GLP-1 alone 

Lipidomic profiling reinforces the disease modifying potential of pemvidutide on MASH and MASH-associated co-morbidities, including cardiovascular disease

Pemvidutide is currently being evaluated in the ongoing Phase 2b IMPACT trial in subjects with MASH

GAITHERSBURG, Md., June 05, 2024 (GLOBE NEWSWIRE) -- Altimmune, Inc. (Nasdaq: ALT), a clinical-stage biopharmaceutical company, today presented new data on the potential anti-inflammatory and anti-fibrotic properties of pemvidutide in Metabolic Dysfunction-Associated Steatohepatitis (MASH) at the EASL International Liver Congress™ 2024 in Milan, Italy.

“These data, coupled with MOMENTUM Phase 2 obesity trial results that showed class-leading lean mass preservation in body composition, further reinforce the opportunity for pemvidutide to distinguish itself broadly from approved therapies and other clinical candidates targeting MASH and obesity,” said Vipin K. Garg, Ph.D., President and Chief Executive Officer of Altimmune. “The balanced GLP-1 and glucagon dual agonism of pemvidutide represents a potentially differentiated approach to achieving clinically meaningful reductions in body weight, liver fat, and lipids to ameliorate MASH and address the many MASH-associated co-morbidities.”

The data presented are summarized below:

WED-212 (Abstract #3002): Pemvidutide treatment is associated with improvement in non-invasive tests indicating greater likelihood of histologic response in subjects with metabolic dysfunction-associated steatotic liver disease: a 24-week, randomized, double-blind, placebo-controlled trial

• 64 subjects who participated in the Phase 1 study of pemvidutide in MASLD were evaluated for changes in FibroScan^®-AST (FAST) over 24 weeks of treatment. A subset of subjects with baseline ALT ≥ 30 IU/L were also evaluated for changes in MRI-PDFF and ALT scores.
• Up to 75% of subjects with intermediate-to-high risk of MASH progression (FAST ≥ 0.35) at baseline who received pemvidutide had their risk reduced to low (FAST < 0.35) at Week 24 vs 25% in subjects receiving placebo.
• Up to 60% of subjects achieved a reduction of both MRI-PDFF (≥ 30%) and ALT (≥ 17 IU/L) at Week 24 compared with 0% in subjects receiving placebo. Simultaneous reductions in MRI-PDFF and ALT have been shown in other MASH clinical trials to be associated with a significantly greater likelihood of achieving MASH resolution.
  

WED-219 (Abstract #2881): Pemvidutide, a glucagon-like peptide 1/glucagon dual receptor agonist, improves metabolic dysfunction-associated steatohepatitis activity and fibrosis in a clinical quantitative systems pharmacology model

• A quantitative systems pharmacology (QSP) computational model was used to predict the effects of pemvidutide and the relative contributions of GLP-1 and glucagon receptor agonism on MASH outcomes. Data from a completed clinical trial of pemvidutide in metabolic dysfunction-associated steatotic liver disease (MASLD) subjects were used to calibrate the quantitative effects of pemvidutide 1.8 mg once weekly dosing over 24 weeks.
• A strong correlation was observed between clinically reported and QSP predicted effects of pemvidutide on weight loss and liver fat content.
• The QSP model predicted pemvidutide 1.8 mg would result in complete resolution of MASH and a 1-point median improvement in fibrosis by Week 24.
• Adding glucagon receptor agonism to GLP-1 receptor agonism was also predicted to result in additional reductions in liver fat content and median NAFLD activity score (NAS) compared to GLP-1 receptor agonism alone. GLP-1 receptor monotherapy was predicted to have no effect on fibrosis within the 24-week timeframe.
• Taken together, these results suggest that glucagon receptor agonism could have potent effects on MASH fibrosis, over and above GLP-1 monotherapy.
  

WED-251 (Abstract #2985): Plasma lipidomic profiling of subjects with overweight or obesity following treatment with the glucagon-like peptide 1/glucagon dual receptor agonist pemvidutide: an investigation of lipid signatures associated with metabolic dysfunction-associated steatohepatitis

• Plasma lipidomic profiling was performed on samples collected during Phase 1 studies of pemvidutide in subjects with overweight or obesity, with or without MASLD.
• Subjects treated with pemvidutide had significantly decreased serum lipids from baseline, including glycophospholipids, sphingolipids and other inflammatory lipid subspecies associated with MASH and cardiovascular disease.
• Pemvidutide treatment was also associated with reduced bile acid dysregulation. Obesity and insulin resistance, two key risk factors for MASH and MASLD, contribute to bile acid dysregulation. Evidence has shown that bile acid dysregulation worsens as MASLD progresses.
• These findings support the disease modifying potential of pemvidutide on MASH and MASH-associated co-morbidities, including cardiovascular disease.

The posters presented at the EASL International Liver Congress™ 2024 are accessible on the Events section of the Altimmune website.

About Pemvidutide
Pemvidutide is a novel, investigational, peptide-based GLP-1/glucagon dual receptor agonist in development for the treatment of obesity and MASH. Activation of the GLP-1 and glucagon receptors is believed to mimic the complementary effects of diet and exercise on weight loss, with GLP-1 suppressing appetite and glucagon increasing energy expenditure. Glucagon is also recognized as having direct effects on hepatic fat metabolism, which is believed to lead to rapid reductions in levels of liver fat and serum lipids. In clinical trials to date, once-weekly pemvidutide has demonstrated compelling weight loss, robust reductions in triglycerides, LDL cholesterol, liver fat content and blood pressure. The U.S. FDA has granted Fast Track designation to pemvidutide for the treatment of MASH. Pemvidutide recently completed the MOMENTUM Phase 2 obesity trial and is being studied in the ongoing IMPACT Phase 2b MASH trial.

About Altimmune
Altimmune is a clinical-stage biopharmaceutical company focused on developing innovative next-generation peptide-based therapeutics. The Company is developing pemvidutide, a GLP-1/glucagon dual receptor agonist for the treatment of obesity and MASH. For more information, please visit www.altimmune.com.

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Company Contact:
Richard Eisenstadt
Chief Financial Officer
Phone: 240-654-1450
ir@altimmune.com

Investor Contacts:
Lee Roth
Burns McClellan
Phone: 646-382-3403
lroth@burnsmc.com

Julia Weilman
Burns McClellan
Phone: 646-732-4443
jweilman@burnsmc.com

Media Contact:
Danielle Cantey
Inizio Evoke, Biotech
Phone: 619-826-4657
Danielle.cantey@inizioevoke.com

FAQ

What data did Altimmune present at the EASL International Liver Congress 2024?

Altimmune presented data on pemvidutide showing potential histologic improvements in MASH from non-invasive tests in Phase 1 trials and its potential to outperform GLP-1 monotherapy.

What is the potential of pemvidutide in treating MASH?

Pemvidutide's dual GLP-1/glucagon agonism may lead to significant reductions in liver fat, fibrosis, and MASH-associated co-morbidities, as indicated in Phase 1 trial data.

When can we expect histologic readouts for pemvidutide in MASH?

Histologic readouts for pemvidutide in MASH are expected in Q1 2025.

How did subjects respond to pemvidutide in non-invasive tests?

Up to 60% of subjects achieved reductions in MRI-PDFF and ALT, and 75% reduced their MASH progression risk from intermediate-to-high to low.

What are the findings from the lipidomic profiling of pemvidutide?

Lipidomic profiling showed significant decreases in serum lipids and reduced bile acid dysregulation, suggesting a potential to treat MASH and cardiovascular diseases.