Altimmune, Inc.
−Removed: is a clinical stage biopharmaceutical company focused on developing treatments for obesity, metabolic and liver diseases.
−Removed: Our lead product candidate, pemvidutide (formerly known as ALT-801), is a novel, investigational, peptide-based GLP-1/glucagon dual receptor agonist.
−Removed: Pemvidutide is currently in clinical development for obesity and metabolic associated steatohepatitis (“MASH”).
−Removed: We also expect to pursue additional indications for pemvidutide that leverage the differentiated clinical profile of pemvidutide.
+Added: is a late clinical-stage biopharmaceutical company developing novel therapies for serious liver diseases.
+Added: Our lead product candidate, pemvidutide (formerly known as ALT-801), is a balanced 1:1 glucagon/GLP-1 dual receptor agonist in development for the treatment of metabolic dysfunction-associated steatohepatitis (“MASH”), alcohol use disorder (“AUD”) and alcohol-associated liver disease (“ALD”).
+Added: We may also pursue additional indications for pemvidutide that leverage its differentiated clinical profile.
Except where the context indicates otherwise, references to “we,” “us,” “our,” “Altimmune”, or the “Company” refer to the company and its subsidiaries.
−Removed: Pemvidutide is a novel, investigational, peptide-based GLP-1/glucagon dual receptor agonist currently in clinical development for the treatment of obesity and MASH.
−Removed: 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.
−Removed: 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.
+Added: We obtained pemvidutide as part of the acquisition Spitfire Pharma Inc., in July of 2019.
+Added: Pemvidutide was designed as a MASH therapeutic based on the understanding that targeting both metabolic and liver-specific effects could lead to an improved and differentiated candidate.
+Added: Early work provided compelling preclinical efficacy data obtained from a mouse model of MASH.
+Added: Following a first-in-human clinical trial where we observed initial signs of weight loss and pronounced liver effects, we evaluated pemvidutide in participants with fatty liver disease, or metabolic-dysfunction associated liver disease (MASLD), where we observed robust reductions in liver fat content and weight loss.
+Added: These results confirmed the earlier study and paved the way for the biopsy-driven IMPACT Phase 2b trial in MASH.
+Added: To better characterize the quality of the weight loss and cardiometabolic effects of pemvidutide, the MOMENTUM Phase 2 trial in overweight and obese participants was conducted and showed significant weight loss characterized by relative sparing of lean muscle mass and improvements in serum lipids associated with cardiovascular disease.
+Added: In addition to the recently completed IMPACT trial, pemvidutide is currently being evaluated in participants with AUD and, separately, ALD.
+Added: There is evidence that pemvidutide may decrease the craving for alcohol in these individuals, with the added benefit that pemvidutide may reverse the harmful effects that alcohol has on the liver in these patients.
+Added: Pemvidutide is a novel, investigational peptide with balanced 1:1 glucagon/GLP-1 dual receptor agonist activity in clinical development for the treatment of MASH, AUD and ALD.
+Added: We believe pemvidutide is the only glucagon/GLP-1 dual receptor agonist with a balanced 1:1 potency at glucagon and the GLP-1 receptors, in effect placing glucagon activity on an even footing with GLP-1 activity.
+Added: The activation of glucagon receptors results in direct effects on the liver, including reductions in liver fat, inflammation and fibrosis, whereas the activation of GLP-1 receptors mediates suppression of appetite and reduction of cravings as well as metabolic effects such as weight loss.
Pemvidutide mechanism of action
−Removed: Optimized for obesity and MASH
−Removed: Over 500 subjects have received pemvidutide to date in 6 completed clinical trials.
−Removed: In those trials pemvidutide appear safe and demonstrated what we believe to be a favorable safety profile, compelling weight loss, class-leading lean mass preservation, and robust reductions in triglycerides, low density lipoprotein (“LDL”), liver fat content, measures of liver inflammation, and blood pressure.
−Removed: Our clinical development has always focused on the comorbidities of obesity and MASH as these often drive the outcomes of these diseases.
−Removed: Based on the clinical data we have accumulated, we believe pemvidutide may be able to address the most common comorbidities associated with both obesity and MASH as shown below.
−Removed: prevalence of comorbidities in obesity and MASH
−Removed: Obesity is a significant burden to the global healthcare systems and is implicated in two-thirds of the leading causes of death from non-communicable diseases worldwide.
−Removed: Some of the leading risk factors or comorbidities of obesity include elevated LDL cholesterol (“LDL-C”) and other serum lipids, high liver fat content, hypertension, Type 2 diabetes, ischemic heart disease, cerebrovascular events, gallbladder disease, osteoarthritis, sleep apnea and breathing problems, certain cancers and MASH.
−Removed: According to the Center for Disease Control and Prevention, the estimated annual medical cost of obesity in the U.S.
−Removed: was nearly $173.0 billion in 2019 dollars.
−Removed: Globally, the market size for weight loss alone was $2.4 billion in 2022 and it is estimated that it will reach $54.0 billion by 2030.
−Removed: Previous approaches to the treatment of obesity were associated with safety concerns, limiting the success of those approaches;
−Removed: however, the new class of incretin-based therapeutics has demonstrated both substantial weight loss and beneficial cardiovascular effects in clinical outcome studies.
−Removed: MOMENTUM Phase 2 Obesity Trial – 48-Week Analyses
−Removed: On November 30, 2023, we announced topline results from our 48-week MOMENTUM Phase 2 obesity trial of pemvidutide.
−Removed: The trial enrolled 391 subjects with obesity or overweight with at least one co-morbidity and without diabetes.
−Removed: 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.
−Removed: 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.
−Removed: At baseline, subjects had a mean age of approximately 50 years, mean body mass index (“BMI”) of approximately 37 kg/m 2 and mean body weight of approximately 104 kg.
−Removed: Approximately 75% of the subjects were female.
−Removed: At Week 48, subjects receiving pemvidutide achieved mean weight loss of 10.3%, 11.2%, 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.
−Removed: A near-linear trajectory of continued weight loss was observed on the 2.4 mg dose at the end of treatment.
−Removed: 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.
−Removed: 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.
−Removed: Glucose homeostasis was maintained.
−Removed: Below is a summary of the efficacy findings:
−Removed: Weight loss of 15.6% achieved at Week 48 on 2.4 mg pemvidutide
−Removed: On September 10, 2024, we 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.
−Removed: The body composition analyses included 67 subjects, 50 of whom were treated with pemvidutide, and calculated of the lean loss ratio, defined as the change in lean mass compared to the change in total mass, and the percent change in amount of body fat in the subcutaneous and visceral fat compartments.
−Removed: The results demonstrated that treatment with pemvidutide resulted in only 21.9% of the total weight loss was associated with lean mass.
−Removed: These results compare favorably to results obtained with other weight loss agents in the class where up to 40% of weight loss came from lean mass.
−Removed: Lean mass preservation was greater in subjects aged 60 years and older, in whom the lean loss ratio was only 19.9%.
−Removed: In addition to lean mass preservation, there was a preferential reduction of visceral adipose tissue (“VAT”), the fat compartment most clearly associated with cardiovascular risk.
−Removed: At the 2.4mg dose of pemvidutide, VAT was reduced by 28.3% at week 48 compared to a 19.5% loss in subcutaneous adipose tissue.
−Removed: Pemvidutide class leading lean mass preservation
−Removed: One of the most prevalent comorbidities associated with obesity is dyslipidemia, including elevated serum triglycerides, total cholesterol and LDL-C.
−Removed: 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.
−Removed: We believe the reduction in LDL-C is insightful for two reasons;
−Removed: first, high levels of LDL-C are known to increase the risk of cardiovascular disease, and second, the decreases in LDL-C were also observed in subjects already on statins, causing a further decrease in serum LDL-C over that achieved by statin therapy.
−Removed: Greater lipid reductions in subjects with elevated baseline levels
−Removed: Regarding safety and tolerability, more subjects receiving pemvidutide stayed on study compared to those receiving placebo, with 74.1% of pemvidutide subjects completing the trial compared to 61.9% of placebo subjects.
−Removed: and vomiting comprised the majority of the adverse events (“AEs”), which were predominantly mild to moderate in severity with 25.5%, 59.6% and 51.5% of patients reporting nausea at the 1.2 mg, 1.8 mg and 2.4 mg doses, respectively, compared to 11.3% receiving placebo, and 6.2%, 27.3% and 27.8% of subjects reporting vomiting at the 1.2 mg, 1.8 mg and 2.4 mg doses, respectively, compared to 3.1% on placebo, and 8.2%, 10.1% and 18.6% reporting diarrhea at the 1.2 mg, 1.8 mg and 2.4 mg doses, respectively, compared to 5.2% on placebo.
−Removed: Rates of AEs leading to treatment discontinuation were 6.2% in subjects receiving placebo and 5.1%, 19.2%, and 19.6% in subjects receiving 1.2 mg, 1.8 mg and 2.4 mg of pemvidutide, respectively.
−Removed: Study discontinuations related to study drug occurred in 2.1% of placebo subjects and 4.1%, 16.2% and 15.5% in subjects receiving 1.2 mg, 1.8 mg and 2.4 mg of pemvidutide, respectively, with most discontinuations due to AEs in the pemvidutide groups occurring in the first 16 weeks of treatment.
−Removed: It is important to note that unlike other obesity studies with GLP-1 based agents, dose-reduction was not allowed in MOMENTUM.
−Removed: Only one subject experienced a drug-related serious adverse event (“SAE”), a case of vomiting at the 2.4 mg dose.
−Removed: No AEs of special interest or major adverse cardiac events (“MACE”) were observed, and there were low rates of cardiac AEs, including arrhythmias, with no imbalance across pemvidutide or placebo groups.
+Added: As of December 31, 2025, over 700 patients have been exposed to pemvidutide in 8 completed studies and 2 ongoing studies.
+Added: In clinical trials to date, pemvidutide has demonstrated rapid reductions in liver fat, markers of liver inflammation, and early MASH resolution along with improvements in non-invasive tests (“NITs”) such as Enhanced Liver Fibrosis (“ELF”) score and Liver Stiffness Measurement (“LSM”) demonstrating antifibrotic activity.
+Added: In addition, pemvidutide has shown clinically meaningful weight loss while exhibiting class-leading lean mass preservation.
+Added: Pemvidutide has also shown a favorable tolerability and safety profile in clinical trials to date.
+Added: Based on the clinical data we have accumulated, we believe pemvidutide may be able to address several serious liver diseases, and pemvidutide has received Breakthrough Therapy Designation for MASH from the FDA based on data obtained from IMPACT trial at 24 weeks, indicating it has shown early clinical evidence of substantial improvement over existing therapies.
+Added: Pemvidutide is protected by a robust patent portfolio covering its composition, formulation, methods of use and treatment with patent expiration dates extending into the 2040s when the expected patent term extension is included.
MASH is caused by multiple metabolic pathways that lead to an abnormal accumulation of liver fat, toxic lipid metabolites, and inflammation, that leads to liver fibrosis and increased risk of death due to cardiovascular disease and liver failure.
−Removed: Metabolic associated steatotic liver disease (“MASLD”), the precursor to MASH, is characterized by excess liver fat and is present in up to 75% of patients with obesity.
−Removed: Up to 20% of MASLD patients progress to MASH.
−Removed: Accumulating clinical evidence suggests that reduction in liver fat is associated with resolution of liver inflammation and improvement in liver fibrosis, and that the magnitude of liver fat reduction is proportional to the improvement in these indices.
−Removed: As 80-90% of individuals with MASH also have overweight or obesity we believe that combining a reduction in liver fat content with weight loss could be a compelling solution for treating MASH.
−Removed: Food and Drug Administration (“FDA”) has granted Fast Track designation to pemvidutide for the treatment of MASH.
−Removed: Clinical Trial Results –Data from a Phase 1b trial of pemvidutide in MASLD
−Removed: We 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.
−Removed: 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.
−Removed: 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.
−Removed: Both trials were conducted without adjunctive diet and exercise interventions.
−Removed: 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.
−Removed: In December 2022, we announced the topline results from the extension trial where subjects received a total of 24 weeks of treatment with either pemvidutide or placebo.
−Removed: The population of the 12-week extension trial had similar baseline characteristics as the population of the parent, 12-week Phase 1b MASLD trial.
−Removed: At baseline, across all treatment groups in the extension trial, mean BMI was 36.7 kg/m 2 and mean LFC, as measured by MRI-PDFF, was 22.2%.
−Removed: Type 2 diabetes was present in 26.6% of subjects and 73.4% of study subjects were of Hispanic ethnicity.
−Removed: Both the parent and extension trials met the primary endpoint in all pemvidutide treatment groups.
−Removed: For the extension trial, in subjects receiving 1.8 mg and 2.4 mg pemvidutide, mean relative reduction of liver fat content was 75.2% and 76.4%, respectively, compared to 14% in subjects receiving placebo;
−Removed: 92.3% and 100% of subjects at the 1.8 mg and 2.4 mg doses, respectively, achieved a 30% reduction in liver fat, compared to 5.6% on placebo;
−Removed: and 53.8% and 45.5% of subjects, respectively, achieved normalization of liver fat content to below 5%, compared to none of subjects receiving placebo.
−Removed: Reductions in Liver Fat Content
−Removed: Statistically significant declines in mean serum ALT levels were observed in all pemvidutide-treated subjects, and in subjects with baseline serum ALT ≥30 IU/L.
−Removed: Subjects receiving placebo saw a 2.2% decline in ALT that was not significant.
−Removed: In subjects with ALT levels above 30 IU/L at baseline, a statistically significant 17 IU/L or greater reduction in ALT was observed at all pemvidutide dose levels, compared to a 3.1 IU/L reduction in the placebo group that was not significant.
−Removed: In a subset of subjects evaluated for cT1 response, 75.0% and 100% of subjects receiving 1.8 mg or 2.4 mg pemvidutide, respectively, achieved an 80 millisecond (ms) decrease in cT1 relaxation time, compared to none of the subjects receiving placebo.
−Removed: cT1 is an MRI-based quantitative metric for assessing a composite of liver inflammation.
−Removed: Elevated cT1 relaxation times have been associated with increased risk of MACE and major adverse liver outcomes, and an 80 ms reduction in cT1 relaxation time has been associated with a 2-point reduction of NAFLD Activity Score.
−Removed: Pemvidutide was generally well tolerated in this MASLD population.
−Removed: As typical of GLP-1 based agents, AEs occurred primarily in months of dosing and occurred more frequently in the 12-week parent MASLD trial compared to the 12-week extension trial.
−Removed: In the parent trial of 94 randomized subjects, nausea and vomiting comprised 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 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.
−Removed: Dose reduction for intolerability was not allowed in the parent or extension trials.
−Removed: There were no drug-related SAEs, and rates of drug-related AEs leading to treatment discontinuation were 0.0% in subjects receiving placebo and 0.0%, 4.3%, and 4.2% in subjects receiving 1.2 mg, 1.8 mg and 2.4 mg of pemvidutide, respectively.
−Removed: 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;
−Removed: no reported cases of vomiting in any treatment group;
−Removed: 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.
−Removed: 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.
−Removed: Three serious or severe AEs occurred in the extension trial;
−Removed: 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 study drug.
−Removed: No AEs of special interest or MACE were observed, and there were low rates of cardiac AEs, including arrhythmias, with no imbalance across pemvidutide or placebo groups.
−Removed: reductions in systolic blood pressure were observed, and increases in heart rate, typical of the incretin class of agents, were minimal at 0 to 4 beats per minute and independent of dose.
−Removed: Significant Reductions in cT1 Response Rates and ALT
−Removed: Two independent indicators of reduced liver inflammation
+Added: Accumulating clinical evidence suggests that reduction in liver fat and liver inflammation is associated with MASH resolution and improvement in liver fibrosis.
+Added: Furthermore, considering 80-90% of individuals with MASH are also overweight, we believe that combining a direct liver acting mechanism with weight loss could provide a compelling treatment for MASH patients.
+Added: In recognition of pemvidutide’s potential differentiating benefits, the U.S.
+Added: Food and Drug Administration (“FDA”) has granted both Breakthrough Therapy Designation and Fast Track designation to pemvidutide for the treatment of MASH.
+Added: IMPACT Phase 2b MASH Trial – 24 Week Results
+Added: On June 26, 2025, we released 24-week topline efficacy results from the IMPACT Phase 2b trial of pemvidutide in MASH and subsequently published those results in the journal Lancet (Noureddin M., et al., Lancet.
+Added: 2025 Dec 6;406(10520):2644-2655).
+Added: The Phase 2b trial enrolled 212 subjects with biopsy-confirmed MASH and fibrosis stages F2/F3 with and without diabetes randomized 1:2:2 to receive weekly subcutaneous doses of pemvidutide at 1.2 mg, 1.8 mg or placebo.
+Added: In an intent-to-treat (“ITT”) analysis, in which subjects with missing biopsies were considered non-responders, the proportions of subjects achieving MASH resolution without worsening of fibrosis at 24 weeks were 58.2% and 52.1%, for pemvidutide 1.2 mg and 1.8 mg, respectively versus 19.9% for placebo (p< 0.0001 both doses).
+Added: The effects on fibrosis improvement without worsening of MASH in an ITT analysis were 32.6% and 35.7% for pemvidutide 1.2 mg and 1.8 mg, respectively compared with 27.9% for placebo (differences not statistically significant).
+Added: A supplemental AI-based analysis demonstrated statistically significant reductions in fibrosis, including 31% of subjects receiving pemvidutide 1.8 mg achieving a 60% or more reduction in fibrosis compared to 8% receiving placebo (p< 0.001).
+Added: Statistically significant changes in well-established non-invasive tests (“NITs”) of fibrosis, including Enhanced Liver Fibrosis (“ELF”) score and Liver Stiffness Measurement (“LSM”) were also observed compared with placebo at both doses.
+Added: Together, these data suggest strong evidence of MASH resolution and anti-fibrotic activity of pemvidutide in the MASH population after 24 weeks of treatment.
+Added: Pemvidutide Demonstrates Statistically Significant MASH Resolution at 24 Weeks
+Added: **** indicates p<0.0001 vs.
+Added: placebo (Chi-Square Test).
+Added: For ITT Analysis, patients without a biopsy at 24 weeks, or those who did not complete treatment, are treated as non-responders.
+Added: placebo (Chi-Square Test) .
+Added: Pemvidutide also demonstrated a favorable safety and tolerability profile, with low overall treatment discontinuation rates due to adverse events of less than 1% and 1.2% in the pemvidutide 1.2 mg and 1.8 mg groups versus 2.4% in the placebo group, despite that no dose titration was used in the trial.
+Added: There were no serious adverse events related to study medication.
+Added: IMPACT Phase 2b MASH Trial – 48 Week Results
+Added: On December 19, 2025, we announced positive 48-week topline results from the IMPACT Phase 2b trial of pemvidutide in patients with MASH.
+Added: The topline 48-week data from the IMPACT trial, which, by design, did not include histological readout, showed that treatment with pemvidutide achieved statistically significant improvements across treatment arms versus placebo in the key anti-fibrosis NITs of ELF and LSM.
+Added: Importantly, these data exhibited continued reductions from week 24 in multiple tests including ELF and LSM and provide evidence of improvement in antifibrotic activity.
+Added: These are well-established markers of fibrosis and are strongly associated with histological changes and liver related events.
+Added: At 48 weeks, mean weight loss in pemvidutide-treated subjects was observed at the 1.2 mg and 1.8 mg doses, respectively, with no evidence of plateauing in the 1.8mg dose group.
+Added: The 48-week data also maintained the favorable tolerability profile seen at 24 weeks, including a lower discontinuation rate due to adverse events versus placebo.
+Added: A summary of the 48-week topline results is provided below:
+Added: ● Pemvidutide-treated participants achieved statistically significant reductions in non-invasive markers of fibrosis, including ELF and LSM;
+Added: 1.2 mg and 1.8 mg doses achieved a mean reduction from baseline of -0.49 and -0.58 respectively, vs.
+Added: +0.16 in placebo-treated patients (p<0.0001, both doses);
+Added: 1.2 mg and 1.8 mg doses achieved a mean reduction from baseline of -3.04 (p<0.05) and -3.97 (p<0.001), respectively, vs.
+Added: -0.03 in placebo-treated participants;
+Added: o The proportion of participants receiving pemvidutide 1.2 mg and 1.8 mg that achieved both a ≥0.5 reduction in ELF and a 30% reduction in LSM were 27.8% (p<0.001) and 32.4% (p<0.0001) respectively, vs.
+Added: 3.2% in placebo-treated participants.
+Added: ● Pemvidutide-treated participants also achieved statistically significant reductions in key non-invasive measures of liver health and hepatic inflammation, including liver fat content, alanine aminotransferase (“ALT”) and corrected T1 (“cT1”);
+Added: o Liver fat content:
+Added: 1.2 mg and 1.8 mg doses achieved a mean reduction from baseline of 45.2% and 54.7% respectively, compared to 8.2% in participants who received placebo (p<0.0001);
+Added: 1.2 mg and 1.8 mg achieved a mean reduction from baseline of -37.8 IU/L and -37.4 IU/L respectively, vs -10.3 IU/L in placebo-treated participants (p<0.0001, both doses);
+Added: Participants receiving pemvidutide 1.2 mg and 1.8 mg achieved a mean reduction from baseline of -124 and -140 milliseconds (ms) respectively, vs -21 ms in placebo-treated participants (p<0.0001, both doses).
+Added: ● Participants receiving pemvidutide 1.2 mg and 1.8 mg achieved weight loss of 4.5% and 7.5%, respectively, vs.
+Added: 0.2% of placebo-treated participants (p<0.0001, both doses), with no plateauing at 48 weeks with the 1.8 mg dose;
+Added: ● Adverse events (“AEs”) leading to treatment discontinuation occurred in 0% and 1.2% of patients treated with pemvidutide 1.2 mg and 1.8 mg, respectively, vs.
+Added: 3.5% of participants on placebo;
+Added: ● No serious or severe AEs related to treatment were reported.
+Added: In December 2025, we held an End-of-Phase 2 meeting with the FDA to discuss and align on the parameters for a registrational Phase 3 trial of pemvidutide for MASH patients with moderate to advanced fibrosis with biopsy driven endpoints.
+Added: The FDA provided feedback on trial design, endpoints, and agreed to the use of AIM-MASH AI Assist, the first FDA-qualified AI pathology tool for MASH clinical trials, in our Phase 3 trial.
+Added: We received final minutes from the End-of-Phase 2 meeting in January 2026, which we believe describe a clear regulatory path for a Phase 3 trial in MASH.
+Added: We are also in the process of seeking scientific advice from European regulators to further inform the final Phase 3 protocol.
+Added: Based on the clinical data obtained from the IMPACT trial and FDA feedback, we are currently preparing to initiate a pivotal, 52-week, Phase 3 clinical trial in MASH in 2026.
+Added: The registrational program is expected to assess clinical data in support of our key differentiators in MASH including:
+Added: ● Rapid and statistically significant improvements in markers of liver inflammation and fibrosis
+Added: ● Statistically significant responses in both MASH resolution and fibrosis stage
+Added: ● Statistically significant weight loss
+Added: ● Statistically significant improvements in lean mass and/or function compared to placebo
+Added: ● An excellent tolerability profile with low rates of discontinuation from therapy.
Additional Pemvidutide Indications
−Removed: In addition to obesity and MASH, we intend to develop pemvidutide for additional indications which may leverage the clinical profile of pemvidutide in indications where there are few to no effective therapies.
−Removed: Pemvidutide Differentiation and Target Profile
−Removed: We believe the unique molecular structure of pemvidutide is responsible for the diverse and differentiated clinical profile of the compound.
−Removed: With respect to obesity and MASH, pemvidutide has been demonstrated in clinical trials to date to achieve key clinical endpoints that, in the aggregate, may differentiate it from other incretin-based approaches to these diseases.
−Removed: We have shown the important clinical endpoints listed below in our clinical trials to date.
−Removed: Pemvidutide Target Profile
−Removed: Pemvidutide Clinical Development Plan
−Removed: In August 2023 we initiated a 48-week Phase 2b trial, IMPACT, to evaluate the safety and efficacy of pemvidutide in subjects with MASH.
−Removed: 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.
−Removed: 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 to a total of 48 weeks for assessment of safety and additional biomarker responses.
−Removed: Patient enrollment in the IMPACT Phase 2b trial was completed in September 2024.
−Removed: Top-line efficacy data is expected in the second quarter of 2025.
−Removed: In November 2024, we successfully completed our 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.
−Removed: 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.
−Removed: 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.
−Removed: The Phase 3 program is expected to enroll approximately 5,000 subjects across the four trials.
−Removed: 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.
−Removed: 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.
−Removed: ● VELOCITY-1:
−Removed: This trial will assess the effects of pemvidutide on body weight in patients with obesity or overweight without diabetes.
−Removed: Other endpoints will include reductions in waist circumference, serum lipids, and blood pressure.
−Removed: ● VELOCITY-2:
−Removed: 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.
−Removed: The study population will include a subset of subjects with elevated LDL cholesterol levels despite ongoing statin therapy.
−Removed: 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.
−Removed: ● VELOCITY-3:
−Removed: This trial will assess the effects of pemvidutide on body weight in subjects with obesity or overweight and elevated liver fat.
−Removed: Excess liver fat is highly prevalent in patients with obesity and is associated with an increased risk of cardiovascular disease.
−Removed: ● VELOCITY-4:
−Removed: 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.
−Removed: Functional measures and activities of daily living will also be assessed in this patient population.
−Removed: 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.
−Removed: No cardiovascular safety signals were identified, and the FDA did not indicate a requirement for committed cardiovascular safety trial designed to demonstrate the absence of cardiac harm relative to placebo.
−Removed: On March 27, 2024, we announced that the overall response in the Phase 2 trial was deemed to be insufficient to warrant further advancement in clinical trials.
−Removed: As a result, we have stopped any further development related to HepTcell.
+Added: On March 13, 2025, we announced that we are pursuing AUD and ALD as additional indications for our lead product candidate, pemvidutide.
+Added: AUD is a chronic disease characterized by an impaired ability to stop or control alcohol use despite adverse social, occupational, or health consequences.
+Added: In addition to the underlying alcohol misuse by AUD patients, AUD patients have comorbidities that pose significant treatment and management challenges (including liver steatosis, overweight, obesity, hypertension and hyperlipidemia).
+Added: It has been shown that therapies with GLP-1 activity may share neural mechanisms of food and alcohol reward systems and real-world evidence has suggests that the use of GLP-1-containing therapies reduces alcohol consumption.
+Added: We have conducted a preclinical study of a hamster free-choice model in which pemvidutide demonstrated a maximum decrease of 82% in alcohol intake relative to vehicle controls.
+Added: The excess alcohol consumption associated with AUD also often leads to an increase in liver fat, i.e., steatotic liver disease.
+Added: We believe reducing alcohol consumption combined with improving liver health through the effects of glucagon would provide AUD patients with a compelling treatment option.
+Added: On May 19, 2025, we announced the enrollment of the first subject in the RECLAIM Phase 2 trial evaluating the efficacy and safety of pemvidutide in subjects with AUD.
+Added: RECLAIM is a randomized, placebo-controlled trial conducted across approximately 15 sites in the United States, targeting enrollment of approximately 100 subjects.
+Added: Subjects will be randomized 1:1 to receive either 2.4 mg pemvidutide or placebo weekly for 24 weeks.
+Added: The trial’s primary endpoint is a change in alcohol consumption, measured by the change from baseline in the average number of heavy drinking days per week measured at Week 24, with the key secondary endpoints including the proportion of subjects achieving a 2-level reduction in World Health Organization (“WHO”) risk drinking level and the absolute change from baseline in average levels of phosphatidylethanol (“PEth”), a serum biomarker of alcohol intake.
+Added: On August 19, 2025, we announced that the U.S.
+Added: Food and Drug Administration has granted Fast Track designation to pemvidutide for the treatment of AUD.
+Added: Fast Track designation is intended to accelerate the development and review of new drugs that target serious conditions and address unmet medical needs.
+Added: On November 3, 2025, we announced the completion of enrollment in the RECLAIM Phase 2 trial.
+Added: Enrollment completed ahead of schedule, underscoring strong interest from the patient community in a new therapeutic option for AUD.
+Added: We are on track to complete the 24-week treatment period and announce topline results in 2026.
+Added: ALD is a disease characterized by damage to the liver due to excessive and chronic alcohol use.
+Added: ALD progression (like MASH progression) begins with liver steatosis, which may lead to inflammation, fibrosis and, ultimately, to cirrhosis.
+Added: Given the progression of the disease, ALD is one of the leading cause of liver transplants in the US.
+Added: Unfortunately, there are currently no approved treatments for ALD.
+Added: On July 9, 2025, we announced the enrollment of the first patient in the RESTORE Phase 2 trial evaluating the efficacy and safety of pemvidutide in subjects with ALD.
+Added: RESTORE is a randomized, placebo-controlled trial enrolling approximately 100 patients across 34 sites in the United States.
+Added: Subjects will be randomized 1:1 to receive either 2.4mg pemvidutide or placebo weekly for 48 weeks.
+Added: The trial’s primary endpoint is the change from baseline in LSM by vibration-controlled transient elastography (“VCTE”) at Week 24.
+Added: Key secondary endpoints include the change from baseline in LSM by VCTE at Week 48, changes in ELF score at Weeks 24 and 48, and changes in alcohol consumption and body weight at the same time points.
+Added: Our goal is to become a leading biopharmaceutical company offering innovative treatments for serious liver diseases.
Key elements of our strategy include the following:
−Removed: ● Develop pemvidutide for MASH as well as other indications that benefit from the dual activity of GLP-1 and glucagon;
−Removed: ● Pursue partnering of pemvidutide to advance the obesity program and indication;
−Removed: ● Continue to build our experience and capabilities to support the development and commercialization of pemvidutide;
+Added: ● Initiate the registrational Phase 3 development program in MASH that, provided safety and efficacy are established, provides for an accelerated approval based on data obtained after one year of treatment;
+Added: ● Continue development of other liver-related indications such as AUD and ALD that may benefit from the dual activity of glucagon and GLP-1a;
+Added: ● Continue to build and develop our 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;
−Removed: ● Leverage our knowledge in liver and cardiometabolic disease by developing, acquiring, or in-licensing additional investigational candidates.
+Added: ● Assess strategic partnerships and licensing opportunities to help accelerate the development of pemvidutide and achieve our goals.
The biopharmaceutical industry is intensely competitive and is characterized by rapid technological progress.
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We also depend upon our ability to attract and retain qualified personnel, obtain patent protection or otherwise develop proprietary products or processes and secure sufficient capital resources for the often substantial period between technological conception and commercial sale.
−Removed: Large and established companies such as Eli Lilly, Roche,, Novo Nordisk, Pfizer, AstraZeneca, Amgen, Boehringer Ingelheim and Merck, among others, compete in the same market as our product candidates.
+Added: Large and established companies such as Eli Lilly, Roche, Novo Nordisk, Pfizer, AstraZeneca, Amgen, Boehringer Ingelheim and Merck, among others, compete in the same general therapeutic areas as our product programs.
These companies compete with us with their greater experience and resources to support their research and development efforts, conduct testing and clinical trials, obtain regulatory approvals to market products, manufacture such products on a broad scale and market approved products.
2 unchanged sentences
We also face competition from smaller companies who, like us, rely on investors to fund research and development and compete for co-development and licensing opportunities from large and established pharmaceutical companies.
−Removed: We face competition for pemvidutide, our dual GLP-1/glucagon dual agonist for the treatment of obesity and MASH.
−Removed: For obesity, we face 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.
−Removed: Other companies with potentially competitive product candidates include Roche and Viking Therapeutics with GLP-1/GIP dual agonists;
−Removed: Boehringer Ingelheim, AstraZeneca, D&D Pharmatech, and Innovent Biologics/Eli Lilly, with GLP-1/glucagon receptor dual agonists;
−Removed: Hanmi Pharmaceutical and Eli Lilly with GLP-1/glucagon/GIP triple agonists;
−Removed: Amgen with its GLP-1 agonist/GIP antagonist antibody;
−Removed: and Novo Nordisk with Amylin and Amylin-GLP-1 combination candidates.
−Removed: Other companies have been developing oral candidates for the treatment of obesity with GLP-1 monoagonist or GLP-1/GIP dual receptor agonists including Pfizer, Lilly, Structure Therapeutics, AstraZeneca, Viking Therapeutics, and Roche.
−Removed: In addition, Novo Nordisk has an FDA-approved oral GLP-1 therapy, Rybelsus or compound name semaglutide.
−Removed: We face competition in MASH from companies such as Madrigal Pharmaceuticals, Terns, Aligos and Viking Therapeutics, which are developing orally administered, thyroid hormone receptor (“THR”) β-selective agonists;
−Removed: Akero Therapeutics, 89Bio, Novo Nordisk and Boston Pharmaceuticals, which are developing fibroblast growth factor 21 (“FGF-21”) analogs;
+Added: We face competition for pemvidutide, our glucagon/GLP-1 dual agonist for the treatment of MASH from companies such as Madrigal Pharmaceuticals, Aligos and Viking Therapeutics, which are developing orally administered, thyroid hormone receptor (“THR”) β-selective agonists;
+Added: Novo Nordisk, Roche, and GSK, which are developing fibroblast growth factor 21 (“FGF-21”) analogs;
Novo Nordisk, which is developing a GLP-1 agonist;
−Removed: 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;
−Removed: Sagimet which is developing a fatty acid synthetase inhibitor, HEC Pharma which is developing a GLP-1/FGF-21dual agonist;
−Removed: and Pfizer and Eli Lilly, which are developing small molecule GLP-1 agonists.
−Removed: In addition, many other small companies are developing other new technologies directed towards obesity or MASH.
+Added: Merck/Hanmi Pharmaceutical and Boehringer Ingelheim, which are developing GLP-1/glucagon dual agonists;
+Added: Eli Lilly, which is developing a glucose-dependent insulinotropic polypeptide receptor (“GIP”)/GLP-1 dual agonist and a GLP-1 GIP/glucagon triple agonist;
+Added: Roche which is developing a GLP-1/GIP dual agonist;
+Added: AstraZeneca developing a GLP-1/glucagon and amylin combination;
+Added: Inventiva, which is developing a pan-peroxisome proliferator-activated receptor (“PPAR”) agonist;
+Added: Sagimet which is developing a fatty acid synthetase inhibitor, Apollo Therapeutics Group Limited/HEC Pharma which is developing a GLP-1/FGF-21 dual agonist;
+Added: and Pfizer, Roche, Gilead, AstraZeneca, and Eli Lilly, which are developing
+Added: small molecule GLP-1 agonists.
+Added: In addition, many other small companies are developing other new technologies directed towards MASH.
+Added: Similarly, we face competition for pemvidutide in the AUD and ALD markets.
+Added: In ALD, GSK is developing GSK4532990, an RNAi targeting HSD17B13;
+Added: Novo Nordisk is developing NNC0194-0499 (FGF-21), cagrilintide (long acting amylin analogue) and semaglutide (GLP-1).
+Added: In AUD, Alkermes’ vivitrol is an approved product in this market;
+Added: generic products such as naltrexone, acamprosate and disulfiram are also available;
+Added: and Eli Lilly is developing mazdutide, a GLP-1/Glucagon dual agonist and brenipatide, a GLP-1/GIP dual agonist.
+Added: We similarly face competition from smaller entrants in AUD;
+Added: Adial is developing a serotonin-3 receptor antagonist targeting AG+ genotype AD-04, Imbrium is developing sunobinop, a NOP agonist, and Solvonis is developing SVN-001 for AUD in European markets.
Intellectual Property
14 unchanged sentences
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.
−Removed: Patents under Mederis
−Removed: 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.
+Added: Patents under 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.
3 unchanged sentences
Patent Rights Related to our Product Candidates
−Removed: Pemvidutide, Dual GLP-1/Glucagon Dual Agonist for Obesity and MASH
−Removed: We are 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.
+Added: Pemvidutide, Dual GLP-1/Glucagon Dual Agonist for MASH, AUD and ALD
+Added: We are 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 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.
−Removed: 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.
−Removed: 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.
−Removed: 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.
+Added: The claims are directed to GLP-1/glucagon dual agonist peptides conjugated to a surfactant and their use to treat metabolic syndrome and other related diseases.
+Added: 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, with additional patents and patent applications which expire no earlier than 2041 should they be granted, not giving effect to any potential extensions and assuming payment of all associated fees.
+Added: 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 granted patents in the United States, Europe, Japan and Korea 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.
−Removed: 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 us and not subject to the Mederis IP License Agreement.
+Added: Use of pemvidutide in methods with improved tolerability, dosing, dosing formulations 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 us 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.
−Removed: 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 us and not subject to the Mederis IP License Agreement.
−Removed: The claims are directed to the use of pemvidutide in a therapeutic dosing regimen for chronic weight management.
+Added: Use of pemvidutide in methods for inducing weight loss is further covered in a granted patent in the United States and pending applications in the United States, Europe, Japan and Korea, as well as other commercially relevant jurisdictions owned by us and not subject to the Mederis IP License Agreement.
+Added: The claims are directed to the use of pemvidutide for reducing body weight and 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.
−Removed: Use of pemvidutide in methods for reducing body weight in a human with fatty liver disease is further covered in United States patent application and corresponding international (PCT) patent application owned by us and not subject to the Mederis IP License Agreement, and from which we expect to file National Phase patent applications in commercially relevant jurisdictions.
+Added: Use of pemvidutide in methods for reducing body weight in a human with fatty liver disease is further covered in pending patent applications in the United States, Europe, Japan and Korea, as well as other commercially relevant jurisdictions, which are owned by us and not subject to the Mederis IP License Agreement.
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.
−Removed: 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 us and not subject to the Mederis IP License Agreement, and from which we expect to file National Phase patent applications in commercially relevant jurisdictions.
−Removed: The claims are directed to the use of pemvidutide in methods for reducing the risk of cardiovascular
−Removed: (CV) disease in a human with or without also having Type 2 diabetes.
+Added: Use of pemvidutide in methods for reducing the risk of cardiovascular (CV) disease is further covered in pending patent applications in the United States Europe, Japan and Korea, as well as other commercially relevant jurisdictions, which are owned by us and not subject to the Mederis IP License Agreement.
+Added: 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.
+Added: A liquid formulation of pemvidutide for systemic administration and treatment of relevant indications is covered in patent applications owned by us and pending in the United States, Brazil, Canada, China, the European Patent Office, Israel, India, Japan, Korea, and Mexico.
+Added: These patent applications are not subject to the Mederis IP License Agreement.
+Added: If issued, the patent(s) resulting from the pending application(s) have expiration date(s) no earlier than November 2043, not giving effect to any potential extensions and assuming payment of all associated fees.
+Added: Use of pemvidutide in methods for reducing pathological serum lipids is further covered in pending patents in the United States and corresponding international (PCT) patent applications, owned by us and not subject to the Mederis IP License Agreement, and from which we expect to file National Phase patent applications in commercially relevant jurisdictions.
+Added: The claims are directed to the use of pemvidutide in methods for reducing/treating high cholesterol, LDL, triglycerides and/or blood pressure.
+Added: If issued, the patent(s) resulting from the pending application(s) are expected to have expiration date(s) of no earlier than March 2045, not giving effect to any potential extensions and assuming payment of all associated fees.
+Added: Use of pemvidutide in methods for treating AUD is further covered in a pending provisional patent application in the United States, owned by us and not subject to the Mederis IP License Agreement, and from which we expect to file a non-provisional application in the United States and a corresponding international (PCT) patent application.
+Added: The claims are directed to the use of pemvidutide in methods for treating/reducing and/or maintaining reduced alcohol consumption.
+Added: If issued, the patent(s) resulting from the pending application(s) have expiration date(s) of no earlier than March 2047, not giving effect to any potential extensions and assuming payment of all associated fees.
+Added: Use of pemvidutide in methods for treating ALD is further covered in a pending provisional patent application in the United States, owned by us and not subject to the Mederis IP License Agreement, and from which we expect to file a non-provisional application in the United States and a corresponding international (PCT) patent application.
+Added: The claims are directed to the use of pemvidutide in methods for treatment of ALD and methods of reducing liver fibrosis.
+Added: If issued, the patent(s) resulting from the pending application(s) have expiration date(s) of no earlier than March 2047, not giving effect to any potential extensions and assuming payment of all associated fees.
+Added: Use of pemvidutide in methods for treating MASH in a human with noncirrhotic liver fibrosis is further covered in a pending provisional patent application in the United States, owned by us and not subject to the Mederis IP License Agreement, and from which we expect to file a non-provisional application in the United States and a corresponding international (PCT) patent application.
+Added: The claims are directed to the use of pemvidutide in achieving MASH resolution within at least 24 weeks.
+Added: If issued, the patent(s) resulting from the pending application(s) have an expiration date of no earlier than June 2047, not giving effect to any potential extensions and assuming payment of all associated fees.
+Added: The Company, via its wholly-owned subsidiary Spitfire Pharma, LLC, entered into a Collaboration and License Agreement with Adocia S.A.
+Added: on December 24, 2024 under which the Company has exclusive rights to intellectual property pertaining to oral administration of pemvidutide, with patent applications pending, which if issued, would have an expiration date of no later than June 2043, and a US patent issuing in February 2026 that will have an expiration date no later than December 2044.
United States Government Regulation
7 unchanged sentences
The FDA may not grant approval on a timely basis, or at all, and we may encounter difficulties or unanticipated costs in our efforts to secure necessary governmental approvals, which could delay or preclude us from marketing our product candidates.
−Removed: In addition, the FDA may limit the indications for use or place other conditions on any approvals that could restrict the commercial application of the products.
+Added: In addition, the FDA may limit the indications for use or place other conditions on any approvals that could restrict the commercial application
+Added: of the products.
After approval, some types of changes to the approved product, such as adding new indications, manufacturing changes and additional labeling claims, are subject to further testing requirements and FDA review and approval.
3 unchanged sentences
● completion of preclinical laboratory tests and animal studies according to applicable good laboratory practices (“GLP”), applicable requirements for the humane use of laboratory animals, such as the Animal Welfare Act or other applicable regulations;
−Removed: ● submission to the FDA of an application for an IND which must become effective before human clinical trials may begin;
+Added: ● submission to the FDA of an IND application which must become effective before human clinical trials may begin;
● obtaining approval by an independent Institutional Review Board (“IRB”) at each clinical site before a clinical trial may be initiated at that site;
13 unchanged sentences
In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin.
−Removed: Even after the IND has gone into effect and clinical testing has begun, the FDA may impose a partial or complete clinical hold on clinical trials due to safety concerns or non-compliance.
+Added: Even after the IND has gone into effect and clinical testing has begun, the FDA
+Added: may impose a partial or complete clinical hold on clinical trials due to safety concerns or non-compliance.
A partial clinical hold can limit a trial, for example, to certain doses or for a certain length of time or to a certain number of subjects.
21 unchanged sentences
The sponsor must submit an IND safety report within 15 calendar days after the sponsor determines that the information qualifies for reporting.
−Removed: The sponsor also must notify the FDA of any unexpected fatal or life-threatening suspected adverse reaction within 7 calendar days after the sponsor’s initial receipt of the information.
+Added: The sponsor also must notify the FDA of any unexpected fatal or life-threatening suspected adverse reaction within 7
+Added: calendar days after the sponsor’s initial receipt of the information.
Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified period, if at all.
3 unchanged sentences
Under the FDA’s expanded access authority, patients who are not able to participate in a clinical trial may be eligible for accessing investigational products, including through individual compassionate or emergency use in concert with their requesting physician.
+Added: Additionally, a manufacturer of an investigational drug for a serious disease or condition is required to make available, such as by posting on its website, its policy on evaluating and responding to requests for individual patient access to such investigational drug.
+Added: This requirement applies on the earlier of the first initiation of a Phase 2 or Phase 3 trial of the investigational drug or, as applicable, 15 days after the drug receives a designation as a breakthrough therapy, fast track product, or regenerative medicine advanced therapy.
Concurrent with clinical trials, companies usually complete additional animal studies, develop additional information about the physical characteristics of the drug or biological product candidate and finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.
5 unchanged sentences
Each of these programs has its own features and qualifying criteria.
+Added: The Fast Track designation program is intended to expedite or facilitate the process for reviewing new drug candidates that are intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition.
+Added: Fast Track designation applies to the combination of the drug candidate and the specific indication for which it is being studied.
+Added: The sponsor of a Fast Track designated product has opportunities for more frequent interactions with the applicable FDA review team during product development and, once an NDA is submitted, the drug candidate may be eligible for priority review.
+Added: A Fast Track designated drug candidate may also be eligible for rolling review, where the FDA may consider for review sections of the NDA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the NDA, the FDA agrees to accept sections of the NDA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the NDA.
+Added: A drug candidate intended to treat a serious or life-threatening disease or condition may also be eligible for Breakthrough Therapy designation to expedite its development and review.
+Added: A drug candidate can receive Breakthrough Therapy designation if preliminary clinical evidence indicates that the drug candidate, alone or in combination with one or more other drugs or biologics, may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.
+Added: The designation includes all of the Fast Track designation program features, as well as more intensive FDA interaction and guidance beginning as early as Phase 1 and an organizational commitment to expedite the development and review of the drug candidate, including involvement of senior managers.
+Added: In addition, products tested for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may be eligible for accelerated approval and may be approved on the basis of adequate and well-controlled clinical trials establishing that the drug product has an effect on a
+Added: surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, or IMM, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity or prevalence of the disease and the availability or lack of alternative treatments.
+Added: As a condition of approval, the FDA may require a sponsor of a drug or biologic receiving accelerated approval to perform post-marketing studies to verify and describe the predicted effect on IMM or other clinical endpoint, and the drug or biologic may be subject to accelerated withdrawal procedures.
+Added: Further, under the Food and Drug Omnibus Reform Act of 2022 (“FDORA”), the FDA must specify the conditions for any post-approval trials by the date of accelerated approval and the agency has flexibility in setting forth such conditions, which may include enrollment targets, clinical trial protocol and milestones – including the target date of trial completion.
+Added: The FDA may also require, as appropriate, that certain confirmatory trials be underway prior to accelerated approval or within a specified time from the date of approval.
+Added: Accelerated approval sponsors must submit progress reports every six months on required post-approval trials.
+Added: FDORA also gives the FDA increased authority to withdraw approval of a drug or biologic granted accelerated approval on an expedited basis if the sponsor fails to conduct such studies in a timely manner, send the necessary updates to the FDA, or if such post-approval studies fail to verify the drug’s predicted clinical benefit.
+Added: Under FDORA, the FDA is empowered to take action, such as issuing fines, against companies that fail to conduct with due diligence any post-approval confirmatory study or submit timely reports to the agency on their progress.
A sponsor must submit a request for fast track designation, breakthrough therapy designation, or priority review, which may or may not be granted by the FDA.
2 unchanged sentences
Some of these expedited programs could potentially apply to our product candidates, although this cannot be assured, and we do not currently have any products with expedited program designations.
−Removed: The sponsor of a clinical trial or the sponsor’s designated responsible party may be required to register certain information about the trial and disclose certain results on government or independent registry websites, such as ClinicalTrials.gov.
−Removed: Additionally, a manufacturer of an investigational drug for a serious disease or condition is required to make available, such as by posting on its website, its policy on evaluating and responding to requests for individual patient access to such investigational drug.
−Removed: This requirement applies on the earlier of the first initiation of a Phase 2 or Phase 3 trial of the investigational drug or, as applicable, 15 days after the drug receives a designation as a breakthrough therapy, fast track product, or regenerative medicine advanced therapy.
+Added: Even if a product candidate obtains accelerated approval based on surrogate clinical endpoints, the sponsor of such product candidate is still required to complete a more extensive outcomes trial to obtain full regulatory approval.
+Added: Such outcomes trial may not replicate the early positive results that supported the accelerated approval in which case the FDA will remove the accelerated approval.
+Added: The sponsor of a clinical trial or the sponsor’s designated responsible party may be required to register certain information about the trial and disclose certain results on government websites, such as ClinicalTrials.gov.
+Added: Information related to the product, patient population, phase of investigation, trial sites and investigators, and other aspects of the clinical trial is made public as part of the registration.
+Added: Sponsors are also obligated to disclose the results of their clinical trials after completion.
+Added: Disclosure of the results of these trials can be delayed until the new product or new indication being studied has been approved.
+Added: Competitors and patients may use this publicly available information to gain knowledge regarding the progress of development programs.
+Added: Failure to timely register a covered clinical study or to submit study results as provided for in the law could lead to consequences such as public notifications of noncompliance and civil monetary penalties.
Review and Approval Processes
24 unchanged sentences
Before approving an NDA or BLA, the FDA will inspect the facilities at which the product is manufactured.
−Removed: The FDA will not approve the NDA or BLA unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required
−Removed: specifications.
+Added: The FDA will not approve the NDA or BLA unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications.
Additionally, before approving an NDA or BLA, the FDA will typically inspect one or more clinical sites to assure that the clinical trials were conducted in compliance with IND study requirements and GCP requirements.
22 unchanged sentences
Future FDA inspections may identify cGMP compliance issues at manufacturer facilities or at the facilities of third-party suppliers that may disrupt production or distribution or require substantial resources to correct and prevent recurrence of any deficiencies, and could result in fines or penalties by regulatory authorities.
−Removed: In addition, discovery of problems with a product or the failure to comply with applicable requirements may result in restrictions on a product, manufacturer or holder of an approved NDA or BLA, including withdrawal or recall of the product from the market or other voluntary, FDA-initiated or judicial action, including warning letters, fines, injunctions, civil penalties, license revocations, seizure, total or partial suspension of production or criminal penalties, any of which could delay or prohibit
−Removed: further marketing.
+Added: In addition, discovery of problems with a product or the failure to comply with applicable requirements may result in restrictions on a product, manufacturer or holder of an approved NDA or BLA, including withdrawal or recall of the product from the market or other voluntary, FDA-initiated or judicial action, including warning letters, fines, injunctions, civil penalties, license revocations, seizure, total or partial suspension of production or criminal penalties, any of which could delay or prohibit further marketing.
Newly discovered or developed safety or efficacy data may require changes to a product’s approved labeling, including the addition of new warnings and contraindications.
9 unchanged sentences
This three-year exclusivity covers only the conditions of use associated with the new clinical investigations and does not prohibit the FDA from approving ANDAs for drugs containing the active ingredient for other conditions of use.
−Removed: For biological products, the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”) created an abbreviated regulatory approval pathway in the United States for biological products that are found to be “biosimilar” to (and in some instances “interchangeable” with) a biological “reference product” previously licensed under an NDA or BLA.
−Removed: This abbreviated approval pathway is intended to permit a biosimilar to come to market more quickly and less expensively by relying to some extent on the data generated by the reference product’s sponsor and the FDA’s previous review and approval of the reference product.
−Removed: Under the BPCIA, a biosimilar sponsor’s ability to seek or obtain approval through the abbreviated pathway is limited by periods of exclusivity granted by the FDA to the holder of the reference product’s NDA or BLA.
−Removed: In general, no biosimilar application may be accepted by the FDA for review until 4 years after the date the reference product was first licensed by the FDA, and no biosimilar application, once accepted, may receive final approval until 12 years after the reference product was first licensed by the FDA.
−Removed: Although we would expect to be granted this 12-year period of exclusivity for our applicable product candidates, if approved, this period of reference product market exclusivity applies only to the biosimilar pathway and will not, for example, provide protection against any biological product for a similar indication that achieves FDA approval under a traditional NDA or BLA based on the sponsor’s own research data.
−Removed: There is also risk that the 12-year period of biological reference product exclusivity could be shortened due to congressional action, or that the FDA will not consider our product candidates, if they are approved, to be reference products for competing products, potentially creating the opportunity for competition sooner than anticipated.
−Removed: Once approved, biosimilars likely would compete with, and in some circumstances may be deemed under the law to be interchangeable with, the previously approved reference product.
−Removed: The extent to which a biosimilar, once approved, would be substituted for any one of our product candidates, if approved, in a way that is similar to traditional generic substitution for non-biological products is not yet clear, and will depend on a number of marketplace and regulatory factors that are still developing.
−Removed: Given this uncertainty, there is risk that, if approved, a biosimilar competitor to one of our products could have an adverse impact on our business.
−Removed: In particular, a biosimilar could be significantly less costly to bring to market and priced significantly lower than our product, if approved by the FDA.
−Removed: Additionally, products approved under an NDA or BLA may qualify for the restoration of a portion of the patent term lost during product development and FDA review of the application, if approval of the application is the first permitted
−Removed: commercial marketing of a drug containing the active ingredient.
+Added: Additionally, products approved under an NDA or BLA may qualify for the restoration of a portion of the patent term lost during product development and FDA review of the application, if approval of the application is the first permitted commercial marketing of a drug containing the active ingredient.
The patent term restoration period is generally one-half the time between the effective date of the IND or the date of patent grant (whichever is later) and the date of submission of the NDA or BLA, plus the time between the date of submission of the NDA or BLA and the date of FDA approval of the product.
23 unchanged sentences
Moreover, there are no safe harbors for many common practices, such as educational and research grants, charitable donations, product support and patient assistance programs.
−Removed: Violations of the Anti-Kickback Law may be punished by civil and criminal penalties, damages, fines, or exclusion from participation in federal health care programs like Medicare and Medicaid.
+Added: Violations of the Anti-Kickback Law may be punished by civil and criminal penalties, damages, fines, or exclusion from participation in
+Added: federal health care programs like Medicare and Medicaid.
Many states have enacted similar laws, some of which apply regardless of payer.
20 unchanged sentences
The legislative and regulatory landscape for privacy and data protection continues to evolve, and there has been an increasing focus on privacy and data protection issues which may affect our business.
−Removed: Numerous federal and state laws and regulations, including state data breach notification laws, health information and/or genetic privacy laws and federal and state consumer protection laws (including Section 5 of the FTC Act, HIPPA and the California Consumer Privacy Act (“CCPA”)), govern the collection, use, disclosure, and protection of health-related and other personal information.
−Removed: Many of these laws differ from each other in significant ways and may be interpreted and applied in a manner that is inconsistent from one jurisdiction to another, thus complicating compliance
−Removed: Compliance with these laws is difficult, constantly evolving, and time consuming.
−Removed: Federal regulators, state attorneys general, and plaintiffs’ attorneys, including class action attorneys, have been and will likely continue to be active in this space.
−Removed: Any failure or perceived failure by us to comply with such laws may result in governmental enforcement actions, litigation, fines and penalties and/or adverse publicity, and could have an adverse effect on our reputation and business.
−Removed: The CCPA, for example establishes certain requirements for data use and sharing transparency, and provides California residents certain rights concerning their personal data.
−Removed: Other states, including Virginia, Colorado, Utah, Connecticut, Texas, Oregon, Tennessee, Delaware, Iowa, have recently passed or enacted similarly comprehensive privacy and data protection legislation which differ from each other in significant ways.
−Removed: It is not yet fully clear how such laws will be enforced and interpreted.
−Removed: In addition to these comprehensive consumer privacy laws and proposals, a number of other states have passed or proposed more limited privacy laws that focus on specific privacy issues such as biometric data and the privacy of health and medical information, such as Washington state’s My Health My Data Act, which has a private right of action that further increases the relevant compliance risk.
−Removed: Connecticut and Nevada have also passed similar laws regulating consumer health data, and New York’s new health privacy law is awaiting that state’s governor’s signature.
−Removed: The existence of new comprehensive and health privacy laws in different states adds additional complexity, variation in requirements, restrictions and potential legal risk.
−Removed: Such new laws also require additional investment of resources in compliance programs, impact strategies regarding and the availability of personal data, and may result in increased compliance costs and/or changes in business practices and policies.
−Removed: On the federal level, HIPAA imposes requirements relating to the privacy, security and transmission of individually identifiable health information.
−Removed: We may obtain health information from third parties, such as research institutions, that are subject to privacy and security requirements under HIPAA.
−Removed: Although we are not directly subject to HIPAA other than with respect to providing certain employee benefits, we could potentially be subject to criminal penalties if we, our affiliates, or our agents knowingly obtain, use, or disclose individually identifiable health information maintained by a HIPAA-covered entity in a manner that is not authorized or permitted by HIPAA.
−Removed: Outside of the U.S., the legislative and regulatory landscape for privacy and data security continues to become more comprehensive.
−Removed: There has been increased attention to privacy and data security issues that could potentially affect our business, including as a result of the General Data Protection Regulation in the EU and the U.K.
−Removed: and data protection laws in the U.K.
−Removed: The EU GDPR (and the regulation as incorporated in U.K.
−Removed: law) imposes fines of up to EUR 20 million (£17.5 million) or 4% of the annual global revenue of a noncompliant company, for non-compliance.
−Removed: In addition, laws and regulations enacted in the U.S., Europe, Asia and Latin America increases potential enforcement and litigation activity.
−Removed: If we, our agents, or our third-party partners fail to comply or are alleged to have failed to comply with these or other applicable data protection and privacy laws and regulations, or if we were to experience a data breach involving personal information, we could be subject to government enforcement actions or private lawsuits.
−Removed: Any associated claims, inquiries, or investigations or other government actions could lead to unfavorable outcomes that have a material impact on our business including through significant penalties or fines, monetary judgments or settlements including criminal and civil liability for us and our officers and directors, increased compliance costs, delays or impediments in the development of new products, negative publicity, increased operating costs, diversion of management time and attention, or other remedies that harm our business, including orders that we modify or cease existing business practices.
−Removed: Regulators and legislators in the U.S.
−Removed: and other countries are also increasingly scrutinizing and restricting certain personal data transfers and transactions involving foreign countries.
−Removed: For example, Executive Order 14117 of February 28, 2024, on Preventing Access to Americans’ Bulk Sensitive Personal Data and United States Government-Related Data by Countries of Concern as implemented by Department of Justice regulations issued in December 2024, prohibits data brokerage transactions involving certain sensitive personal data categories, including health data, genetic data, and biospecimens, to countries of concern, including China.
−Removed: The regulations also restrict certain investment agreements, employment agreements and vendor agreements involving such data and countries of concern, absent specified cybersecurity controls.
−Removed: Actual or alleged violations of these regulations may be punishable by criminal and/or civil sanctions, and may result in exclusion from participation in federal and state programs.
+Added: Numerous federal and state laws and regulations now govern the collection, use, disclosure, and protection of personal information, including health-related information that we may collect in connection with clinical trials.
+Added: At the state level, the California Consumer Privacy Act (“CCPA”), for example, grants individual privacy rights for California consumers (as defined in the law) and places increased privacy and security obligations on entities handling personal information of consumers and households.
+Added: The CCPA requires covered businesses to provide certain disclosures about its data collection, use and sharing practices, and provide specific notices and opt-out rights to consumers with respect to certain sales and transfers of their personal information.
+Added: As of January 2026, more than a dozen other U.S.
+Added: states have enacted similarly comprehensive privacy legislation.
+Added: Several additional states passed laws specific to consumer health data, such as Washington’s My Health My Data Act, and other state laws, such as the Texas Genomic Privacy Act, focus specifically on genetic information.
+Added: Additionally, HIPAA imposes requirements relating to the privacy, security and transmission of individually identifiable health information.
+Added: While many consumer privacy laws contain exceptions for certain activities involving the processing of health information regulated under HIPAA, and for clinical trials conducted in accordance with federal regulations, this has become an increasingly complex regulatory landscape.
+Added: At the federal level, regulators and legislators are increasingly scrutinizing and restricting certain personal data transfers and transactions involving foreign countries.
+Added: For example, the Department of Justice’s January 8, 2025, rule on “Preventing Access to U.S.
+Added: Sensitive Personal Data and Government-Related Data by Countries of Concern or Covered Persons,” prohibits data brokerage transactions involving certain sensitive personal data categories, including health data, genetic data, and biospecimens, to countries of concern, including China.
+Added: Outside of the U.S., the legislative and regulatory landscape for privacy and data security is just as complex.
+Added: The General Data Protection Regulation in the EU and the U.K.
+Added: and data protection laws in the U.K, for example, impose potentially significant fines, and laws and regulations enacted in Asia and Latin America increase potential enforcement and litigation activity.
+Added: Any associated claims, inquiries, or investigations or other actions under these laws could lead to significant penalties or fines, monetary judgments or settlements including criminal and civil liability.
Health Care Reform Law
16 unchanged sentences
As another example, the Inflation Reduction Act of 2022 (“IRA”) includes several provisions that will impact our business to varying degrees, including provisions that create a $2,000 out-of-pocket cap for Medicare Part D beneficiaries, impose new mandatory discounts from manufacturers under Medicare Part D, allow the U.S.
−Removed: government to negotiate Medicare Part B and Part D pricing for certain high-cost single-source drugs and biologics without generic or biosimilar competition, and require companies to pay rebates to Medicare for drug prices that increase faster than inflation.
−Removed: The IRA provides a five-year temporary increase in Medicare Part B payment for certain qualifying biosimilars, and it
−Removed: also delays the rebate rule that would require pass through of pharmacy benefit manager rebates to beneficiaries.
+Added: government to negotiate Medicare Part B and Part D pricing for certain high-cost single-source drugs and biologics without generic competition, and require companies to pay rebates to Medicare for drug prices that increase faster than inflation.
+Added: The IRA delays the rebate rule that would require pass through of pharmacy benefit manager rebates to beneficiaries.
The effect of IRA on our business and the healthcare industry in general is not yet known.
−Removed: Additional legislative changes, regulatory changes or guidance could be adopted, which may impact the marketing approvals and reimbursement for our product candidates.
+Added: Additional legislative changes, regulatory changes or guidance could be adopted, or executive orders or other actions undertaken, which may impact the marketing approvals and reimbursement for our product candidates.
+Added: The One Big Beautiful Bill Act of 2025 (“OBBBA”), for example, imposed significant reductions in Medicaid funding, additional work requirements for Medicaid recipients, and more frequent reenrollment requirements.
+Added: These changes are expected to place substantial pressure on state Medicaid budgets, reduce enrollment, and limit covered services, which could decrease utilization of, and reimbursement for, our products, if approved.
+Added: The costs of prescription pharmaceuticals have also been the subject of considerable discussion in the United States.
+Added: To date, there have been several recent U.S.
+Added: congressional inquiries, as well as proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the costs of drugs under Medicare and reform government program reimbursement methodologies for drug products.
+Added: The Trump Administration has issued executive orders and supported proposed regulatory initiatives in 2025 that could have a significant impact on the prices that we, or any collaborators, may receive for any approved products.
+Added: On May 12, 2025, President Trump signed an executive order directing the Secretary of HHS to set and communicate most-favored-nation (“MFN”) price targets to manufacturers and propose a rulemaking plan to impose MFN pricing if “significant progress” is not made, and also directing the federal government to support regulatory paths to allow direct-to-patient sales for companies that meet these targets.
+Added: The executive order further states that the Administration will take additional action (for example, examining whether marketing approvals should be modified or rescinded or considering individual drug importation waiver authorities) should manufacturers fail to offer American consumers the MFN lowest price.
+Added: In July 2025, President Trump sent letters to certain pharmaceutical companies demanding that these companies extend MFN pricing to Medicaid and newly launched drugs as well as move to direct-to-consumer models priced at MFN pricing, and soliciting binding commitments by September 29, 2025.
+Added: Since this time, multiple drug manufacturers have announced plans to, for certain of their drugs, lower prices to reflect similar pricing around the world,
+Added: and to sell these reduced-price drugs on a direct-to-consumer purchasing platform developed by the federal government;
+Added: however, it is not known what results will occur to the extent the recipients of these letters do not reduce their U.S.
+Added: On December 19, 2025, CMS released two proposed rules that would incorporate MFN pricing principles into federal reimbursement for prescription drugs.
+Added: The first proposal, the Global Benchmark for Efficient Drug Pricing Model (“GLOBE”) for Medicare Part B, would require manufacturers of specified single source drugs and sole source biologics to pay incremental rebates based on international benchmark prices, with participation triggered for products meeting CMS’s spending and eligibility criteria.
+Added: The second proposal, the Guarding U.S.
+Added: Medicare Against Rising Drug Costs (“GUARD”) model for Medicare Part D, would similarly mandate manufacturer rebates for qualifying sole source drugs where the Medicare net price exceeds an MFN benchmark derived from international reference pricing methodologies.
+Added: As proposed, GLOBE would begin a five year performance period on October 1, 2026 and GUARD would begin its performance period in 2027.
+Added: These proposals will likely be subject to legal challenges that could delay their implementation or modify their impact on manufacturer pricing and revenue.
+Added: Additionally, in November 2025, CMS introduced the GENErating cost Reductions fOr U.S.
+Added: Medicaid (“GENEROUS”) Model, a voluntary MFN framework for manufacturers participating in the Medicaid Drug Rebate Program.
+Added: Although it is voluntary, the GENEROUS Model could also impact the drug pricing landscape for manufacturers.
Further, there has been increasing legislative, regulatory and enforcement interest in the United States with respect to drug pricing practices.
1 unchanged sentence
It is possible that the Health Care Reform Law, as currently enacted or may be amended or otherwise modified in the future, as well as other health care reform measures that may be adopted in the future, may result in additional reductions in Medicare payment and other health care financing, more rigorous coverage criteria, and new payment methodologies and in additional downward pressure on coverage and payment and the price that we receive for any approved product.
−Removed: For example, under the IRA, Congress has enacted a program that allows Medicare to negotiate pricing for certain single-source drugs and biologics under Medicare Parts B and D.
−Removed: The IRA also imposes Medicare Part B and Part D inflation-based rebates, under which manufacturers owe additional rebates if the average sales price of a drug increases faster than the pace of inflation, based on a statutory reference period.
Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payers.
13 unchanged sentences
Adequate coverage and reimbursement from governmental healthcare programs, such as Medicare and Medicaid, and commercial payers is critical to new product acceptance.
−Removed: Our ability to successfully commercialize our product candidates will depend in part on the extent to which coverage and adequate reimbursement for these products and related treatments will be available from government health administration authorities, private health insurers and other organizations.
+Added: Our ability to successfully commercialize our product candidates will depend in part on the extent to which coverage and adequate
+Added: reimbursement for these products and related treatments will be available from government health administration authorities, private health insurers and other organizations.
Government authorities and third-party payers, such as private health insurers and health maintenance organizations, decide which medications they will pay for and establish reimbursement levels.
The availability of coverage and extent of reimbursement by governmental and private payers is essential for most patients to be able to afford treatments such as gene therapy products.
−Removed: Sales of these or other product candidates that we may identify will depend substantially, both domestically and abroad, on the extent to which the costs of our product candidates will be paid by health maintenance, managed care, pharmacy benefit and similar healthcare management organizations, or reimbursed by government health administration authorities, private health coverage
−Removed: insurers and other third-party payers.
+Added: Sales of these or other product candidates that we may identify will depend substantially, both domestically and abroad, on the extent to which the costs of our product candidates will be paid by health maintenance, managed care, pharmacy benefit and similar healthcare management organizations, or reimbursed by government health administration authorities, private health coverage insurers and other third-party payers.
If coverage and adequate reimbursement is not available, or is available only to limited levels, we may not be able to successfully commercialize our product candidates.
22 unchanged sentences
The Clinical Trials Regulation repealed and replaced the Clinical Trials Directive, and introduced a complete overhaul of the existing regulation of clinical trials for medicinal products in the EU, including a new coordinated procedure for authorization of clinical trials that will be conducted in multiple EU Member States, and increased obligations on sponsors to publish clinical trial results.
−Removed: The Regulation is directly applicable in all EU Member States (and so does not require national implementing legislation in each EU Member State) and aims at simplifying and streamlining the approval of clinical studies in the EU.
+Added: The Regulation is directly applicable in all EU Member States (and so does not require national implementing legislation in each EU Member State) and aims at simplifying and streamlining the approval of clinical
+Added: studies in the EU.
The main characteristics of the Regulation include:
3 unchanged sentences
Part I is assessed by a coordinated review by the competent authorities of all EU Member States in which an application for authorization of a clinical trial has been submitted (Member States concerned) of a draft report prepared by a Reference Member State.
−Removed: II is assessed separately by each Member State concerned.
+Added: Part II is assessed separately by each Member State concerned.
Strict deadlines have also been established for the assessment of clinical trial applications.
63 unchanged sentences
There are two types of marketing authorizations:
−Removed: ● The centralized marketing authorization, which is issued by the European Commission through the centralized procedure, based on the opinion of the CHMP and which is valid throughout the entire territory of the EEA.
+Added: ● The centralized marketing authorization, which is issued by the European Commission through the centralized procedure, based on the opinion of the CHMP and which is valid throughout the entire territory
The centralized procedure is mandatory for certain types of drugs, such as medicinal products derived from biotechnology processes (such as genetic engineering), orphan medicinal products, advanced-therapy medicinal products and medicinal products containing new active substances indicated for the treatment of HIV, AIDS, cancer, neurodegenerative disorders, diabetes, auto-immune and other immune dysfunctions and viral diseases.
−Removed: The centralized procedure is optional for products containing a new active substance not yet authorized in the EU, or for products that constitute a significant therapeutic, scientific or
−Removed: technical innovation or which are in the interest of public health in the EU.
+Added: The centralized procedure is optional for products containing a new active substance not yet authorized in the EU, or for products that constitute a significant therapeutic, scientific or technical innovation or which are in the interest of public health in the EU.
To find out whether a product can be evaluated via the centralized procedure, applicants should submit an eligibility request to the EMA, including by a justification of eligibility for evaluation under the centralized procedure.
−Removed: ● National marketing authorizations, which are issued by the competent authorities of the member states of the EEA and only cover their respective territory, are available for drugs not falling within the mandatory scope of the centralized procedure.
+Added: ● National marketing authorizations, which are issued by the competent authorities of the member states of the EEA and only cover their respective territory, are available for medicinal products not falling within the mandatory scope of the centralized procedure.
Where a drug has already been authorized for marketing in a member state of the EEA, this national marketing authorization can be recognized in other member states through the mutual recognition procedure.
If the drug has not received a national marketing authorization in any member state at the time of application, it can be approved by multiple member states in parallel through the decentralized procedure.
−Removed: Under the above described procedures, before granting the marketing authorization, the EMA or the competent authorities of the member states of the EEA make an assessment of the risk-benefit balance of the drug on the basis of scientific criteria concerning its quality, safety and efficacy.
+Added: Under the procedures described above, before granting a marketing authorization, the EMA (through the CHMP) or the competent authorities of the member states of the EEA make an assessment of the risk-benefit balance of the medicinal product on the basis of scientific criteria concerning its quality, safety and efficacy.
The Marketing Authorization Application:
18 unchanged sentences
and (vii) describe the manufacturing facilities and equipment.
−Removed: Other special rules apply certain types of biological medicines.
+Added: Other special rules apply to certain types of biological medicines.
For example, for plasma-derived medicinal products, the applicant must provide an information dossier, the Plasma Master File.
3 unchanged sentences
In the EU, new chemical entities (including both small molecules and biological medicinal products), sometimes referred to as new active substances, qualify for eight years of data exclusivity upon marketing authorization and an additional two years of market exclusivity.
−Removed: This data exclusivity if granted, prevents generic or biosimilar applicants from referencing the innovator’s pre-clinical and clinical trial data contained in the dossier of the reference product when applying for a generic or biosimilar marketing authorization, for a period of eight years from the date on which the reference product was first authorized in the EU.
−Removed: After such eight year period, a generic or biosimilar marketing authorization can be submitted, and the innovator’s data may be referenced, but no generic or biosimilar product can be
−Removed: marketed for a further two years.
+Added: This data exclusivity prevents generic applicants from referencing the innovator’s pre-clinical and clinical trial data contained in the dossier of the reference product when applying for a generic marketing authorization, for a period of eight years from the date on which the reference product was first authorized in the EU.
+Added: After such eight year period, a generic marketing authorization can be submitted, and the innovator’s data may be referenced, but no generic product can be marketed for a further two years.
The overall ten-year period may be extended to a maximum of 11 years if, during the period of data exclusivity, the marketing authorization holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies.
10 unchanged sentences
(ii) the holder of the marketing authorization for the original orphan medicinal product is unable to supply sufficient quantities of the medicinal product;
−Removed: or (iii) the second applicant can establish the its product is safer, more effective or otherwise clinically superior than the authorized orphan product.
+Added: or (iii) the second applicant can establish that its product is safer, more effective or otherwise clinically superior to the authorized orphan product.
A “similar medicinal product” is defined as a medicinal product containing a similar active substance or substances as contained in an authorized orphan medicinal product, and which is intended for the same therapeutic indication.
2 unchanged sentences
The European Commission introduced legislative proposals in April 2023 that, if implemented, will replace the current regulatory framework in the EU for all medicines (including those for rare diseases and for children).
−Removed: The European Commission has provided the legislative proposals to the European Parliament and the European Council for their review and approval, and, in April 2024, the European Parliament proposed amendments to the legislative proposals.
−Removed: Once the European Commission’s legislative proposals are approved (with or without amendment), they will be adopted into EU law.
+Added: In April 2024, the European Parliament adopted its position on the legislative proposals and, in June 2025, the Council of the European Union adopted its position.
+Added: A common position on the text has been agreed upon on December 11, 2025, in the context of subsequent inter-institutional trilogue negotiations.
+Added: The proposed revisions remain to be adopted, and are not expected to become applicable before 2028.
Brexit and the Regulatory Framework in the United Kingdom
−Removed: The UK formally left the EU on January 31, 2020.
−Removed: As a result of the Northern Ireland protocol, following Brexit, the EMA remained responsible for approving novel medicines for supply in Northern Ireland under the EU centralized procedure, and a separate authorization was required to supply the same medicine in Great Britain (England, Wales and Scotland).
−Removed: On February 27, 2023, the UK government and the European Commission announced a political agreement in principle to replace the Northern Ireland Protocol with a new set of arrangements, known as the “Windsor Framework”.
−Removed: The Windsor Framework was approved by the EU-UK Joint Committee on March 24, 2023, and the medicines aspects of the Windsor Framework have applied since January 1, 2025.
−Removed: This new framework fundamentally changes the previous
−Removed: system under the Northern Ireland Protocol, including with respect to the regulation of medicinal products in the UK.
−Removed: In particular, the MHRA is now responsible for approving all medicinal products destined for the UK market (i.e., Great Britain and Northern Ireland), and the EMA no longer has any role in approving medicinal products destined for Northern Ireland under the EU centralized procedure.
−Removed: A single UK-wide marketing authorization will be granted by the MHRA for all novel medicinal products to be sold in the UK, enabling products to be sold in a single pack and under a single authorization throughout the UK.
−Removed: In addition, the new arrangements require all medicines placed on the UK market to be labelled “UK only”, indicating they are not for sale in the EU.
−Removed: However, although a separate authorization is now required to market medicinal products in the UK, under an international recognition procedure which was put in place by the MHRA on January 1, 2024, the MHRA may take into account decisions on the approval of a marketing authorization from the EMA (and certain other regulators) when considering an application for a UK marketing authorization.
+Added: Following the end of the Brexit transition period on January 1, 2021 and the implementation of the Windsor Framework on January 1, 2025, the United Kingdom, or UK, is generally no longer subject to EU laws in respect of medicines.
+Added: EU laws that were transposed into UK law through secondary legislation remain applicable in the UK;
+Added: however, new EU legislation, such as the EU Clinical Trials Regulation, is not applicable in the UK.
+Added: As of January 1, 2021, the Medicines and Healthcare products Regulatory Agency, or MHRA, is the UK's standalone medicines and medical devices regulator.
+Added: As a result of the Northern Ireland Protocol, different rules applied in Northern Ireland than in England, Wales, and Scotland (together, "Great Britain", or GB) for a period following Brexit, with Northern Ireland continuing to follow certain aspects of the EU regulatory regime.
+Added: However, on January 1, 2025, a new arrangement called the "Windsor Framework" came into effect and placed medicinal products supplied to Northern Ireland largely under the regulatory authority of the MHRA.
+Added: The Windsor Framework removes EU licensing processes and certain EU labeling and serialization requirements for medicines supplied to Northern Ireland and introduces a UK-wide licensing process for medicines.
+Added: In particular, the MHRA is responsible for approving medicinal products placed on the UK market, and the EMA no longer has a role in granting UK marketing authorizations.
+Added: A single UK-wide MA will be granted by the MHRA for medicinal products to be sold in the UK, enabling products to be sold in a single pack and under a single authorization throughout the UK.
+Added: In addition, the new arrangements require, for packs placed on the UK market on or after January 1, 2025, a "UK Only" label, indicating they are not for sale in the EU.
+Added: However, although a separate authorization is required to market medicinal products in the UK, since January 1, 2024, the MHRA may rely on the International Recognition Procedure, or IRP, when reviewing certain types of MAAs.
+Added: Pursuant to the IRP, the MHRA may take into account the expertise and decision-making of trusted regulatory partners (e.g., the medicines regulatory authorities in Australia, Canada, Switzerland, Singapore, Japan, the United States and the EMA in the EU), when considering an application for a UK marketing authorization.
Other government regulation in the European Union and United Kingdom
12 unchanged sentences
medical practice.
−Removed: EU Directive 2001/83/EC allows for clinical trials conducted outside the EU to be taken into consideration during the review of a marketing authorization in the EU if such trials have been designed, implemented and reported based on principles equivalent to those of the Clinical Trials Regulation, including with regard to good clinical practice and ethical principles.
+Added: EU Directive 2001/83/EC allows for clinical trials conducted outside the EU to be taken into consideration during the review of a marketing authorization in the EU if such trials have been designed, implemented and reported based on principles equivalent to those of the EU Clinical Trials Regulation, including with regard to good clinical practice and ethical principles.
Moreover, they should comply with the ethical principles outlined in the Declaration of Helsinki.
−Removed: The applicant must submit a statement declaring such compliance as part of the marketing authorization.
+Added: applicant must submit a statement declaring such compliance as part of the marketing authorization.
In April 2012, the EMA published a reflection paper on ethical and GCP aspects of clinical trials of medicinal products conducted outside the EU/EEA and submitted in MAAs to EU regulatory authorities.
4 unchanged sentences
To date, we have obtained materials for clinical trials and non-clinical studies from third-party manufacturers who are suppliers to us.
−Removed: We intend to identify and qualify
−Removed: additional contract manufacturers to provide commercial scale manufacturing prior to submission of an NDA or BLA to the FDA.
+Added: We intend to identify and qualify additional contract manufacturers to provide commercial scale manufacturing prior to submission of an NDA or BLA to the FDA.
Employees and Human Capital Management
1 unchanged sentence
degrees and 23 of whom hold other advanced degrees.
−Removed: Of our total workforce, 39 are engaged primarily in research and development activities and 20 are engaged primarily in executive, finance and accounting, and administrative functions.
−Removed: As of December 31, 2024, 57 employees are located in the United States and 2 employees in the United Kingdom.
−Removed: Of our employees, 49% are female and 51% are male.
+Added: Of our total workforce, the majority are engaged primarily in research and development, and the remainder are engaged primarily in executive, finance and accounting, and administrative functions.
+Added: As of December 31, 2025, 56 employees are located in the United States and 1 employee is located in the United Kingdom.
None of our employees are represented by labor unions or covered by collective bargaining agreements.
Corporate Culture
−Removed: Our values – compliance, collaboration, integrity and high performance – are built on the foundation that the employees we hire and the way we treat one another promote creativity, innovation and productivity, which spur our success.
+Added: Our values – commitment, communicate, collaborate, competence and courage – are built on the foundation that the employees we hire, and the way we treat one another, promote creativity, innovation and productivity, which spur our success.
This culture depends in large part on our ability to attract, retain and develop a diverse population of talents and high-performing employees at all levels of our organization.
5 unchanged sentences
Hybrid Culture
−Removed: In the second quarter of 2020, we made the decision to move to a hybrid workplace model, which means that certain of our employees have the option to be 100% remote, work full-time in our office, or have the flexibility to work between office and remotely.
−Removed: This move provides our employees with continued flexibility to work in person, remotely or in a hybrid model.
+Added: Currently we have a hybrid workplace, which means that we evaluate and determine the optimal work arrangements for our employees on an individual basis including full-time in office, part-time in office or remote depending on our needs and the responsibilities of each employee.
+Added: This approach allows us to maintain flexibility and retain the best talent for the roles that are the most critical to our strategy and success.
Available Information
8 unchanged sentences
Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.