Altimmune, Inc., a clinical stage biopharmaceutical company, focuses on developing treatments for obesity, metabolic and liver diseases.
The company’s lead product candidate, pemvidutide, is a novel, investigational, peptide-based GLP-1/glucagon dual receptor agonist. Pemvidutide is currently in clinical development for obesity and metabolic associated steatohepatitis (‘MASH’). The company also expects to pursue additional indications for pemvidutide that leverage its differentiated clinical pr...
Altimmune, Inc., a clinical stage biopharmaceutical company, focuses on developing treatments for obesity, metabolic and liver diseases.
The company’s lead product candidate, pemvidutide, is a novel, investigational, peptide-based GLP-1/glucagon dual receptor agonist. Pemvidutide is currently in clinical development for obesity and metabolic associated steatohepatitis (‘MASH’). The company also expects to pursue additional indications for pemvidutide that leverage its differentiated clinical profile.
Pemvidutide
Pemvidutide is a novel, investigational, peptide-based GLP-1/glucagon dual receptor agonist currently in clinical development for the treatment of obesity and MASH. Activation of the GLP-1 and glucagon receptors is intended 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.
The company’s clinical development has always focused on the comorbidities of obesity and MASH, as these often drive the outcomes of these diseases.
MOMENTUM Phase 2 Obesity Trial – 48-Week Analyses
On November 30, 2023, the company announced topline results from its 48-week MOMENTUM Phase 2 obesity trial of pemvidutide. The trial enrolled 391 subjects with obesity or overweight, with at least one co-morbidity and without diabetes. Subjects were randomized 1:1:1:1 to 1.2 mg, 1.8 mg, 2.4 mg pemvidutide, or placebo administered weekly for 48 weeks in conjunction with diet and exercise. The 1.2 mg and 1.8 mg doses were administered without dose titration, while a short 4-week titration period was employed for the 2.4 mg dose. At baseline, subjects had a mean age of approximately 50 years, a mean body mass index (‘BMI’) of approximately 37 kg/m2, and a mean body weight of approximately 104 kg. Approximately 75% of the subjects were female.
At Week 48, subjects receiving pemvidutide achieved mean weight loss of 10.3%, 11.2%, and 15.6% at the 1.2 mg, 1.8 mg, and 2.4 mg doses, respectively, compared to weight loss of 2.2% for placebo. A near-linear trajectory of continued weight loss was observed on the 2.4 mg dose at the end of treatment. Over 50% of subjects achieved at least 15% weight loss, and over 30% of subjects achieved at least 20% weight loss on the 2.4 mg dose. As in prior clinical trials, pemvidutide resulted in robust reductions in serum lipids and improvements in blood pressure, without imbalances in cardiac events, arrhythmias, or clinically meaningful increases in heart rate. Glucose homeostasis was maintained.
On September 10, 2024, the company presented additional results of an MRI-based body composition sub-study from the 48-week MOMENTUM Phase 2 obesity trial of pemvidutide in subjects with overweight and obesity. The body composition analyses included 67 subjects, 50 of whom were treated with pemvidutide, and calculated the lean loss ratio, defined as the change in lean mass compared to the change in total mass, and the percent change in the amount of body fat in the subcutaneous and visceral fat compartments.
One of the most prevalent comorbidities associated with obesity is dyslipidemia, including elevated serum triglycerides, total cholesterol, and LDL-C. In the MOMENTUM obesity trial, patients with mildly elevated serum lipids at baseline, pemvidutide treatment realized significant reductions in each of these lipid classes at 48 weeks.
Clinical Trial Results – Data from a Phase 1b trial of pemvidutide in MASLD
The company studied the effects of pemvidutide in subjects with MASLD in two clinical trials, an initial 12-week trial followed by a 12-week extension trial in the majority of the same subjects. In the parent trial, 94 subjects were randomized 1:1:1:1 to 1.2 mg, 1.8 mg, 2.4 mg pemvidutide, or placebo administered weekly for 12 weeks. In the extension trial, 64 subjects who completed the parent trial and consented to the extension trial were enrolled and remained in their original treatment group, and the trial remained double-blinded. Both trials were conducted without adjunctive diet and exercise interventions. Identical endpoints were evaluated in the 12-week parent trial and the 12-week extension trial, with the primary efficacy endpoint as percent (%) reduction in relative liver fat content, and key secondary endpoints including liver inflammation, as measured by serum alanine aminotransferase (‘ALT’) levels and corrected T1 (‘cT1’), and percent weight loss.
In December 2022, the company announced the topline results from the extension trial where subjects received a total of 24 weeks of treatment with either pemvidutide or placebo.
The population of the 12-week extension trial had similar baseline characteristics as the population of the parent, 12-week Phase 1b MASLD trial. At baseline, across all treatment groups in the extension trial, the mean BMI was 36.7 kg/m2, and the mean LFC, as measured by MRI-PDFF, was 22.2%. Type 2 diabetes was present in 26.6% of subjects, and 73.4% of study subjects were of Hispanic ethnicity.
Pemvidutide was generally well tolerated in this MASLD population. As typical of GLP-1-based agents, AEs occurred primarily in the months of dosing and occurred more frequently in the 12-week parent MASLD trial compared to the 12-week extension trial. In the parent trial of 94 randomized subjects, nausea and vomiting constituted the majority of AEs, which were predominantly mild to moderate in severity, with 17.4%, 52.2%, and 37.5% of patients reporting nausea at the 1.2 mg, 1.8 mg, and 2.4 mg doses, respectively, compared to 12.5% receiving placebo, and 13.0%, 8.7%, and 8.3% of subjects reporting vomiting at the 1.2 mg, 1.8 mg, and 2.4 mg doses, respectively, compared to no subjects on placebo, and 13.0%, 21.7%, and 4.2% reporting diarrhea at the 1.2 mg, 1.8 mg, and 2.4 mg doses, respectively, compared to 16.7% on placebo.
The incidence of AEs was markedly reduced in the 12-week extension trial of 64 subjects, with 0.0%, 20.0%, and 7.1% of patients reporting nausea at the 1.2 mg, 1.8 mg, and 2.4 mg doses, respectively, compared to 0.0% receiving placebo; no reported cases of vomiting in any treatment group; and 6.3%, 6.7%, and 0.0% reporting diarrhea at the 1.2 mg, 1.8 mg, and 2.4 mg doses, respectively, compared to 5.3% on placebo. Study discontinuations related to AEs occurred in 0.0% of placebo subjects and 12.5%, 6.7%, and 0.0% in subjects receiving 1.2 mg, 1.8 mg, and 2.4 mg of pemvidutide, respectively. Three serious or severe AEs occurred in the extension trial; and were the same events, one (5.3%) occurred in the placebo group for chest pain following elective coronary stent placement, one (6.3%) at 1.2 mg pemvidutide for Salmonella infection, and one (6.7%) at 1.8 mg pemvidutide for hypotension occurring greater than 3 weeks post-pemvidutide dosing, all unrelated to the study drug.
Pemvidutide Clinical Development Plan
In August 2023, the company initiated a 48-week Phase 2b trial, IMPACT, to evaluate the safety and efficacy of pemvidutide in subjects with MASH. The biopsy-driven trial enrolled 212 subjects with and without diabetes randomized 1:2:2 to receive 1.2 mg, 1.8 mg pemvidutide, or placebo weekly for 48 weeks. The key efficacy endpoints are MASH resolution and fibrosis improvement after 24 weeks of treatment, with subjects to be followed for an additional 24 weeks, for a total of 48 weeks, for assessment of safety and additional biomarker responses. Patient enrollment in the IMPACT Phase 2b trial was completed in September 2024. Top-line efficacy data is expected in the second quarter of 2025.
In November 2024, the company successfully completed its End-of-Phase 2 Meeting with the FDA and agreed on the design of a Phase 3 registrational program for pemvidutide in the treatment of obesity.
The interaction with the FDA included an extensive review of the preclinical and clinical data generated to date, including data from six completed clinical trials of pemvidutide. The planned registrational program will include four Phase 3, randomized, double-blind, placebo-controlled, parallel-group trials, each evaluating treatment with pemvidutide over a 60-week period. The Phase 3 program is expected to enroll approximately 5,000 subjects across the four trials. The safety and efficacy of pemvidutide doses of 1.2 mg, 1.8 mg, and 2.4 mg will be evaluated with the intention of seeking approval for all three doses.
The Phase 3 program is designed to leverage the key attributes of pemvidutide, including the effects of balanced GLP-1/glucagon dual agonism in subjects with overweight and obesity.
VELOCITY-1: This trial will assess the effects of pemvidutide on body weight in patients with obesity or overweight without diabetes. Other endpoints will include reductions in waist circumference, serum lipids, and blood pressure.
VELOCITY-2: This trial will assess the effects of pemvidutide on body weight and serum lipids in subjects with obesity or overweight and elevated LDL cholesterol levels. The study population will include a subset of subjects with elevated LDL cholesterol levels despite ongoing statin therapy. A large proportion of patients taking statins fail to achieve target LDL levels, and in a previous Phase 2 clinical trial in subjects with overweight or obesity, pemvidutide appeared to enhance LDL-lowering effects in subjects receiving concomitant statin therapy.
VELOCITY-3: This trial will assess the effects of pemvidutide on body weight in subjects with obesity or overweight and elevated liver fat. Excess liver fat is highly prevalent in patients with obesity and is associated with an increased risk of cardiovascular disease.
VELOCITY-4: This trial will assess the effects of pemvidutide on body weight and body composition, including in an elderly population, with emphasis on individuals entering the study with sarcopenia at baseline. Functional measures and activities of daily living will also be assessed in this patient population.
The FDA agreed that a committed study of subjects with Type 2 diabetes was not required and agreed that the number of these subjects in the VELOCITY-2, VELOCITY-3, and VELOCITY-4 trials was sufficient to assess the safety of pemvidutide in this population.
HepTcell
On March 27, 2024, the company announced that the overall response in the Phase 2 trial was deemed to be insufficient to warrant further advancement in clinical trials.
Strategy
Key elements of the company’s strategy are to develop pemvidutide for MASH, as well as other indications that benefit from the dual activity of GLP-1 and glucagon; pursue partnering of pemvidutide to advance the obesity program and indication; continue to build its experience and capabilities to support the development and commercialization of pemvidutide; research and develop alternative formulations, doses, and presentations of pemvidutide for the benefit of patients; and leverage its knowledge in liver and cardiometabolic disease by developing, acquiring, or in-licensing additional investigational candidates.
Competition
For obesity, the company faces competition from companies, such as Novo Nordisk, whose GLP-1 agonist, brand named Wegovy, or compound name semaglutide, was approved for weight loss in June 2021, and Eli Lilly, whose GLP-1/glucose-dependent insulinotropic polypeptide receptor (‘GIP’) dual agonist, brand named Zepbound, or compound name tirzepatide, was approved for obesity in November 2023.
The company faces competition in MASH from companies, such as Madrigal Pharmaceuticals, Terns, Aligos, and Viking Therapeutics, which are developing orally administered, thyroid hormone receptor (‘THR’) ß-selective agonists; Akero Therapeutics, 89Bio, Novo Nordisk, and Boston Pharmaceuticals, which are developing fibroblast growth factor 21 (‘FGF-21’) analogs; Novo Nordisk, which is developing a GLP-1 agonist; Merck/Hanmi Pharmaceutical and Boehringer Ingelheim, which are developing GLP-1/glucagon dual agonists; Eli Lilly, which is developing a GLP-1/GIP dual agonist; Inventiva, which is developing a pan-peroxisome proliferator-activated receptor (‘PPAR’) agonist; Sagimet, which is developing a fatty acid synthetase inhibitor; HEC Pharma, which is developing a GLP-1/FGF-21 dual agonist; and Pfizer and Eli Lilly, which are developing small molecule GLP-1 agonists.
Intellectual Property
Patent Rights Related to EuPort Technology
EuPort Technology — In-Licensed from Mederis Diabetes, LLC
Pursuant to a license agreement between the company and Mederis Diabetes, LLC (‘Mederis’) (the ‘Mederis IP License Agreement’), the company is the exclusive licensee of patent rights owned by Mederis to develop and commercialize surfactant functionalized (‘EuPort domain’) incretin-based peptide therapeutics, including (GLP-1-glucagon)/oxyntomodulin, and variants thereof, including pemvidutide, for any indication, and Mederis has certain patent rights granted back to it for the use of the EuPort technology outside of the company’s exclusive field of incretin-based peptide therapeutics. The EuPort domain comprises a hydrophobic domain (e.g., substituted or unsubstituted alkyl chain) and a hydrophilic group (e.g., saccharide) conjugated to a non-terminal amino acid of the peptide. Patents under the Mederis IP License Agreement have been granted in the United States, Japan, and Korea, and applications are pending in the United States, Japan, as well as other commercially relevant jurisdictions. The claims are directed to peptides (at least four amino acids in length), including peptides that bind receptors for glucagon and/or GLP-1, conjugated to an alkyl saccharide surfactant, including an alkyl glycoside surfactant. The patents and, if issued, the patent(s) resulting from the pending application(s) have an expiration date of no earlier than May 2032, not giving effect to any potential extensions and assuming payment of all associated fees. Patents subject to the Mederis IP License Agreement have also been granted in the United States, Canada, Europe, Korea, Australia, Israel, and Japan, and applications are pending in the United States, Europe, Japan, China, and other commercially relevant jurisdictions, wherein the claims are directed to specific GLP-1 and/or glucagon peptides conjugated to the EuPort domain. The patents and, if issued, the patent(s) resulting from the pending application(s) have an expiration date of no earlier than May 2035.
Patent Rights Related to the Company’s Product Candidates
Pemvidutide, Dual GLP-1/Glucagon Dual Agonist for Obesity and MASH
The company is the exclusive licensee of patent rights owned by Mederis to develop and commercialize surfactant functionalized (GLP-1-glucagon)/oxyntomodulin-based peptide therapeutics, and variants thereof, including pemvidutide, for any use, including the treatment of obesity, metabolic syndrome, insulin resistance, diabetes, and cardiovascular disease. Patents under the Mederis IP License Agreement have been granted in the United States, Europe, Japan, Australia, and Mexico, with pending applications in the United States, Europe, Japan, and Korea, as well as other commercially relevant jurisdictions. The claims are directed to GLP-1/glucagon dual agonist peptides conjugated to a surfactant and their use to treat metabolic syndrome, obesity, and other related diseases. The patents and, if issued, the patent(s) resulting from the pending application(s) have an expiration date of no earlier than May 2032 and extending to May 2035, not giving effect to any potential extensions and assuming payment of all associated fees. Use of pemvidutide for treating MASH or MASLD (referred to as NASH or NAFLD in the patent and patent applications) is further covered by, and subject to the Mederis IP License Agreement, with a granted patent in the United States, and pending applications in the United States, Europe, Japan, and other commercially relevant jurisdictions. The patents and, if issued, the patent(s) resulting from the pending patent applications, are expected to have an expiration date of no earlier than January 2039, not giving effect to any potential extensions and assuming payment of all associated fees.
Use of pemvidutide in methods with improved tolerability, dosing, and therapeutic regimens is further covered in pending applications in the United States, Europe, Japan, and Korea, as well as other commercially relevant jurisdictions, which are owned by the company and not subject to the Mederis IP License Agreement. The claims are directed to liquid formulations and the use of pemvidutide in a therapeutic dosing regimen with improved tolerability. If issued, the patent(s) resulting from the pending application(s) have an expiration date of no earlier than February 2041, not giving effect to any potential extensions and assuming payment of all associated fees.
Use of pemvidutide in methods for inducing weight loss is further covered in pending applications in the United States, Europe, Japan, and Korea, as well as other commercially relevant jurisdictions owned by the company and not subject to the Mederis IP License Agreement. The claims are directed to the use of pemvidutide in a therapeutic dosing regimen for chronic weight management. If issued, the patent(s) resulting from the pending application(s) have an expiration date of no earlier than December 2041, not giving effect to any potential extensions and assuming payment of all associated fees.
Use of pemvidutide in methods for reducing body weight in a human with fatty liver disease is further covered in the United States patent application and corresponding international (PCT) patent application owned by the company and not subject to the Mederis IP License Agreement, and from which the company expects to file National Phase patent applications in commercially relevant jurisdictions. The claims are directed to the use of pemvidutide in methods for reducing body weight in a human with MASH or MASLD (referred to as NASH or NAFLD in the patent and patent applications), with or without also having type II diabetes. If issued, the patent(s) resulting from the pending application(s) have an expiration date of no earlier than September 2043, not giving effect to any potential extensions and assuming payment of all associated fees.
Use of pemvidutide in methods for reducing the risk of cardiovascular (CV) disease is further covered in a United States patent application and corresponding international (PCT) patent application owned by the company and not subject to the Mederis IP License Agreement, and from which the company expects to file National Phase patent applications in commercially relevant jurisdictions. The claims are directed to the use of pemvidutide in methods for reducing the risk of cardiovascular (CV) disease in a human with or without also having Type 2 diabetes. If issued, the patent(s) resulting from the pending application(s) have an expiration date of no earlier than November 2043, not giving effect to any potential extensions and assuming payment of all associated fees.
Government Regulation
There has been increased attention to privacy and data security issues that could potentially affect the company’s business, including as a result of the General Data Protection Regulation in the EU and the U.K., and data protection laws in the U.K.
The company is also subject to regulation under the Occupational Safety and Health Act, the Environmental Protection Act, the Toxic Substances Control Act, the Resource Conservation and Recovery Act, and other present and potential federal, state, or local regulations. Additionally, for formulations containing controlled substances, the company is subject to Drug Enforcement Act regulations.
Manufacturing and Source of Supply
The company intends to identify and qualify additional contract manufacturers to provide commercial scale manufacturing prior to submission of a new drug application (‘NDA’) or biologics license application (‘BLA’) to the U.S. Food and Drug Administration (‘FDA’).
Trademarks
‘Altimmune,’ the company’s logo, and other trademarks, trade names, or service marks of the company, including NasoVAX, EuPort, and RespirVec, are the property of the company.
History
The company was founded in 1997. The company was formerly known as Vaxin Inc. and changed its name to Altimmune, Inc. in 2015.
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