Altimmune’s Pemvidutide Is Not To Be Dismissed (NASDAQ:ALT)

Altimmune, Inc. (NASDAQ:ALT) is a biopharmaceutical company developing peptide therapeutics like pemvidutide, a dual agonist of GLP-1 and glucagon receptors. The drug has already produced impressive phase 2 data in obesity and is set to produce data from a phase 2 trial in metabolic dysfunction-associated steatohepatitis (MASH) in the future. This article takes a look at where the company stands now.

Pemvidutide: Clinical Development Highlights

First-in-human study

ALT’s 10-K, filed in March 2024, notes the clinical development of pemvidutide, which started in late 2020 with the first-in-human trial. Results from that trial, reported in September 2021, noted weight loss among overweight or obese participants of 10.3% when treated with 1.8 mg pemvidutide for 12 weeks (administered subcutaneously, once weekly). That compared favorably to just 1.6% in the placebo group. Further, the study didn’t instruct on modifying their diet or behavior, so the weight loss data is even more encouraging.

Notably, there was no dose titration in the study, which could increase the rate of adverse events compared to titrating patients up to their full dose gradually. As such the observation that there were no discontinuations due to adverse events in the study is certainly a positive. There was however a 3-5 fold alanine aminotransferase elevation in one patient treated with 1.8 mg pemvidutide. An elevation in this enzyme alone is not enough to say a drug would cause liver injury but is something worth keeping an eye on.

Beyond the weight loss data, there were also significantly greater reductions from baseline to week 12 in LDL cholesterol and triglycerides with 1.8 mg and 2.4 mg pemvidutide. The 1.2 mg dose of pemvidutide did not quite beat the placebo in terms of LDL reduction from baseline, but the results did trend in favor of even that lower dosage vs. placebo. ALT also noted that reductions in liver fat content were marked, meaning the drug certainly had potential in MASH.

Phase 1b MASLD study

In a subsequent 12-week study in 94 patients with metabolic dysfunction-associated steatotic liver disease (MASLD), pemvidutide at 1.8 mg yielded a 68.5% reduction in liver fat content, as assessed by MRI, compared to just 4.4% in the placebo group.

There were also reductions in alanine aminotransferase, here used as another marker of liver inflammation, meaning even if the drug caused an increased ALT in one patient in the prior obesity study, in a MASLD trial, the net effect of the drug is actually to reduce alanine aminotransferase levels. Further, in this larger study (94 patients vs. 34 patients for the prior study) there were no clinically significant increases in ALT seen. Given that, the potentially worrying side effect seen previously had not reared its head. Beyond that, there were no serious or severe adverse events seen in the study at all, and only two discontinuations due to adverse events (1/23 patients in the 1.8 mg group, and 1/24 patients in the 2.4 mg group).

Phase 2 MOMENTUM study

MOMENTUM was a 48-week, 391-patient, randomized, placebo-controlled phase 2 study of pemvidutide in overweight or obese individuals with at least one comorbidity (but not diabetes). Unlike the first-in-human study, the drug was administered in combination with diet and exercise, and a 4-week titration was used for the 2.4 mg dose. The headline numbers, which included a 15.6% reduction in body weight seen with 2.4 mg pemvidutide, are certainly competitive with the likes of Novo Nordisk A/S’s (NVO) semaglutide.

For example, in the STEP 5 study, overweight or obese participants with at least one comorbidity (but not diabetes) were treated with 2.4 mg semaglutide, or placebo, plus behavioral intervention (diet and exercise) for 104 weeks. The mean change in body weight from baseline was 15.2% with 2.4 mg semaglutide at 104 weeks, which was similar to the change at 44-52 weeks (a relevant time point for comparison to ALT’s MOMENTUM study).

Investors looking to see a similar plot of weight loss over time and proportions of patients achieving 5% weight loss in the MOMENTUM study should see slides 11 and 12 of ALT’s corporate presentation. In any case, 2.4 mg semaglutide appears similar, albeit via cross-trial comparison, to 2.4 mg pemvidutide in terms of weight loss efficacy, at least at 44 weeks. However, there is the possibility of further weight loss with 2.4 mg pemvidutide, given longer treatment durations. ALT noted that there was a continuing reduction in weight with 2.4 mg pemvidutide across time, suggesting an absence of a plateauing of efficacy. Indeed, a longer study might even allow the 2.4 mg pemvidutide dose to compete more closely with the likes of Eli Lilly and Company’s (LLY) Mounjaro (tirzepatide). It’s also possible a longer titration could reduce discontinuations.

Beyond the benefit of weight loss in the MOMENTUM study, pemvidutide also beat placebo in terms of reductions in triglycerides, and total cholesterol from baseline to week 48. However, in this case, the reductions in LDL cholesterol were not significant compared to placebo. Overall though, a trend to reduction in LDL cholesterol, a reduction in triglycerides, and a reduction in blood pressure bode well for any future outcomes study of pemvidutide, in my opinion.

The larger and longer MOMENTUM study, of course, had a better chance of picking up adverse events and discontinuations than the prior shorter studies. There was in this case one serious adverse event of vomiting with 2.4 mg pemvidutide, albeit in 97 patients. While there were cardiac adverse events including arrhythmias, these were seen at a similar rate in the placebo group.

A near 20% rate of discontinuation, even at the 1.8 mg dose isn’t ideal, but no titration was used at these doses. Further, the 1.2 mg dose of pemvidutide provided a 10.3% weight loss reduction with just a 5% rate of adverse events leading to discontinuation. Considering the efficacy and safety data seen thus far, I think ALT has a compelling offering with pemvidutide.

Preserving muscle mass?

When ALT reported the results from the MOMENTUM study in November 2023, the stock went on a run. It is worth noting, however, that ALT provided further analysis of the MOMENTUM study with Q4’23 earnings, on March 27, that weren’t met with a rally.

ALT noted that only 25.5% of weight loss in the MOMENTUM study came from lean mass, with 74.5% of weight loss coming from adipose tissue. I’d like to see a head-to-head comparison with semaglutide on this endpoint as preserving muscle mass could aid the maintenance of weight loss effect and reduce frailty. ALT will report further on the body composition data, among other data, at scientific meetings in 2024. Perhaps the company can lay out more clearly how much better those numbers are or aren’t than competing drugs.

Financial Overview

ALT reported Q1’24 earnings on May 9, noting cash, cash equivalents, and short-term investments of $182.1M as of March 31, 2024. In Q1’24, ALT’s R&D expenses were $21.5M, G&A expenses were $5.3M, and net loss was $24.4M. ALT’s net cash used in operating activities was $16.4M in Q1’24, meaning at the current rate of burn ALT would have 11 quarters of cash, providing runway until the end of 2026. In reality, if ALT is going to enter a large phase 3 program for pemvidutide, then it could find itself needing to raise additional funds in the not-too-distant future.

There were 70,902,191 shares of ALT’s common stock outstanding as of May 3, 2024, giving ALT a market cap of $519.7M ($7.33 per share).

Conclusions, rating, and risks

ALT is now preparing for an end-of-phase 2 meeting with the FDA, expected in late Q3’24, which could set the company up to run a large phase 3 program in obesity. There is also data on tap in Q1’25 from the company’s IMPACT study in MASH, which will include biopsy data, which could be considered higher impact than MRI-based measures of liver fat alone.

I actually think ALT’s drug offers a very compelling benefit, even if combinations to reduce muscle mass are possible with other GLP-1 agonists and related drugs, doing it with one drug saves introducing a second set of side effects. The problem is, that the market has already assigned a bit of a premium to the stock considering the company’s cash balance. A very near-term catalyst to move the stock beyond the current range isn’t there, in my opinion, unless ALT happens to announce a partnership or a buyout. I would imagine any acquirer or partner might first like to see what the FDA has to say about a phase 3 program in obesity. It won’t be until late Q3 when the FDA meeting occurs, and the feedback from that might not trigger much of a rally (or at least I can’t predict that it will).

Further, the catalyst to MASH with the IMPACT isn’t that close right now. I do think the name could be worth revisiting, maybe in another quarter or so, to consider in the context of any developments in the stock and developments in the GLP-1 space. As such, I rate ALT a hold, but could consider upgrading it to a buy later in the year, as a potential run-up into Q1’25 data could occur.

The risks of holding ALT are several folds, a few of which I’ll discuss. Firstly, if the feedback from the FDA meeting comes with news that ALT needs to run a larger program than expected, the stock could fall. Further, if ALT sees delays in enrolling the IMPACT study, the stock could sell off as the Q1’25 catalyst could move further into the future. Lastly, if ALT announces a hefty dilution to support the phase 3 work, the stock could also tumble.