Altimmune’s Pemvidutide Can’t Be Denied (NASDAQ:ALT)

Altimmune, Inc. (NASDAQ: ALT) is a biopharmaceutical firm growing peptide therapeutics resembling pemvidutide, a twin GLP-1 and glucagon receptor agonist. The drug has already produced spectacular Section 2 knowledge in weight problems and is about to be produced Information from a part 2 trial in metabolic dysfunction-associated steatohepatitis (MASH) is potential. This text examines the present state of the corporate.

Pemvidutide: Scientific Growth Highlights

The primary human examine

ALT’s 10-Ok, filed in March 2024, notes medical growth for pemvidutide, which started in late 2020 with a first-in-human trial. The outcomes of this trial, reported in September 2021, famous a weight reduction amongst chubby or overweight individuals of 10.3% when handled with 1.8 mg of pemvidutide for 12 weeks (subcutaneous injection as soon as weekly). This compares favorably with just one.6% within the placebo group. As well as, the examine didn’t instruct about altering their food regimen or conduct, in order that the load the loss figures are much more encouraging.

Notably, there was no dose titration within the examine, which can improve the incidence of unwanted side effects in comparison with regularly titrating sufferers to the complete dose. Due to this fact, the remark that there have been no discontinuations attributable to unwanted side effects within the examine is actually optimistic. Nonetheless, a 3- to 5-fold improve in alanine aminotransferase was noticed in a single affected person receiving 1.8 mg of pemvidutide. Elevation of this enzyme alone isn’t sufficient to say that the drug might trigger liver injury, however it’s one thing to look at for.

Along with the load loss knowledge, there have been additionally considerably larger reductions in LDL ldl cholesterol and triglycerides from baseline to week 12 with 1.8 mg and a couple of.4 mg pemvidutide. The 1.2 mg pemvidutide dose was not utterly superior to placebo by way of reducing LDL from baseline, however the outcomes tended to favor even the decrease dose in comparison with placebo. ALT additionally famous {that a} discount in liver fats was famous, which means the drug undoubtedly had potential in MASH.

Section 1b MASLD examine

In a subsequent 12-week examine in 94 sufferers with metabolic-related steatotic liver illness (MASLD), pemvidutide 1.8 mg resulted in a 68.5% discount in liver fats by MRI, in contrast with solely 4 .4% within the placebo group. .

There was additionally a lower in alanine aminotransferase, which is used right here as one other marker of liver irritation, which means that though the drug precipitated a rise in ALT in a single affected person in a earlier weight problems examine, the MASLD examine, the web impact of the drug was truly reducing alanine aminotransferase ranges. Moreover, on this bigger examine (94 sufferers vs. 34 sufferers within the earlier examine), there have been no clinically important will increase in ALT. With that in thoughts, the possibly troubling aspect impact seen earlier did not rear its head. As well as, no critical or extreme unwanted side effects had been noticed within the examine in any respect, and solely two discontinuations attributable to unwanted side effects (1/23 sufferers within the 1.8 mg group and 1/24 sufferers within the 2.4 mg group).

Section 2 of the MOMENTUM examine

MOMENTUM is a 48-week, randomized, placebo-controlled part 2 examine of pemvidutide in 391 sufferers in chubby or overweight people with a minimum of one comorbidity (however not diabetes). Not like the primary human examine, the drug was administered together with food regimen and train, and a 4-week titration was used for the two.4 mg dose. The headline numbers, which included a 15.6% discount in physique weight with 2.4 mg of pemvidutide, actually rival Novo Nordisk A/S ( NVO )’s semaglutide.

For instance, within the STEP 5 examine, chubby or overweight individuals with a minimum of one comorbidity (however not diabetes) acquired 2.4 mg of semaglutide or placebo plus a behavioral intervention (food regimen and train) for 104 weeks. The imply change in physique weight from baseline was 15.2% with semaglutide 2.4 mg at Week 104, which was much like the change at Weeks 44-52 (corresponding time level for comparability with the MOMENTUM examine from ALT).

Buyers who wish to see the same graph of weight reduction over time and the proportion of sufferers who achieved 5% weight reduction within the MOMENTUM examine ought to view slides 11 and 12 of ALT’s company presentation. In any case, semaglutide 2.4 mg seems related, albeit in a crossover trial comparability, to pemvidutide 2.4 mg by way of weight reduction efficacy a minimum of via 44 weeks. Nonetheless, there may be potential for additional weight discount with 2.4 mg pemvidutide with longer remedy durations. ALT famous sustained weight reduction with 2.4 mg pemvidutide over time, suggesting no plateau in efficacy. Certainly, an extended examine might even permit the two.4 mg dose of pemvidutide to compete with the likes of Eli Lilly and Firm’s ( LLY ) Mounjaro (tirzepatide). It is usually potential that longer titration might scale back discontinuation.

Along with the load loss profit within the MOMENTUM examine, pemvidutide additionally outperformed placebo in lowering triglycerides and whole ldl cholesterol from baseline to week 48. Nonetheless, on this case, the discount in LDL ldl cholesterol was not important in comparison with placebo. Nonetheless, general, the development towards decrease LDL ldl cholesterol, decrease triglycerides, and decrease blood stress, in my view, bodes nicely for any future outcomes of the pemvidutide examine.

The bigger and longer MOMENTUM trial actually had a greater probability of detecting opposed occasions and discontinuations than earlier shorter trials. On this case, there was one critical aspect impact of vomiting with 2.4 mg of pemvidutide, albeit in 97 sufferers. Though there have been cardiac opposed occasions, together with arrhythmias, they occurred on the identical frequency within the placebo group.

Virtually 20% withdrawal, even on the 1.8 mg dose, isn’t preferrred, however titration of those doses was not used. As well as, a 1.2 mg dose of pemvidutide supplied a ten.3% discount in weight reduction with solely 5% of opposed occasions resulting in discontinuation. Given the efficacy and security knowledge thus far, I feel ALT has a compelling proposition with pemvidutide.

Preserving muscle mass?

When ALT reported the outcomes of the MOMENTUM examine in November 2023, the inventory fell. It ought to be famous, nevertheless, that on March 27, ALT supplied extra evaluation of the MOMENTUM examine with This fall 2023 earnings, which weren’t met with a rally.

ALT famous that solely 25.5% of the load loss within the MOMENTUM examine got here from muscle mass, with 74.5% of the load loss coming from adipose tissue. I wish to see a head-to-head comparability with semaglutide on this endpoint, as preserving muscle mass might assist preserve the load loss impact and scale back weak point. ALT will report additional on physique composition knowledge, amongst different knowledge, at scientific conferences in 2024. Maybe the corporate will be capable of present extra clearly how these numbers are higher than competing medication.

Monetary evaluation

ALT reported Q1 2024 earnings on Might 9, noting that money, money equivalents and short-term investments totaled $182.1 million as of March 31, 2024. In Q1 2024, ALT had analysis and growth bills of $21.5 million, normal and customary bills of $5.3 million, and a web lack of $24.4 million. ALT’s web money utilized in working actions was $16.4 million within the first quarter of 2024, which signifies that on the present fee of spending, ALT can have 11 quarters of money, offering a runway via the top of 2026. the truth is, if ALT goes to enter a big part 3 program for pemvidutide, it could want to boost extra funds within the close to future.

As of Might 3, 2024, 70,902,191 shares of ALT frequent inventory had been excellent, giving ALT a market capitalization of $519.7 million ($7.33 per share).

Conclusions, score and dangers

ALT is now getting ready to fulfill with the FDA on the completion of Section 2, anticipated on the finish of Q3 2024, which might set the corporate up for a big Section 3 anti-obesity program. There may be additionally faucet knowledge within the first quarter of ’25 from the corporate’s IMPACT examine in MASH, which is able to embrace biopsy knowledge, which can be thought of simpler than simply measuring liver fats primarily based on MRI.

I truly assume that the ALT drug affords a really compelling profit, though muscle loss mixtures with different GLP-1 agonists and associated medication are potential, utilizing one drug avoids introducing a second set of unwanted side effects. The issue is that the market has already assigned a small premium to the inventory given the corporate’s money steadiness. In my opinion, there isn’t a very short-term catalyst to maneuver the inventory out of its present vary until ALT publicizes a partnership or buyout. I suppose any acquirer or accomplice may first wish to see what the FDA has to say in regards to the Section 3 anti-obesity program. That will not occur till the top of Q3 when the FDA assembly takes place, and the suggestions from that will not trigger a lot development (or a minimum of I can not foresee it taking place).

Additionally, the catalyst for MASH with IMPACT is not that shut proper now. I actually assume that identify ought to be revisited, maybe within the subsequent quarter or so, to have a look at it within the context of any developments within the compound and developments within the GLP-1 house. As such, I fee ALT as a maintain, however might contemplate elevating it to a purchase later this 12 months as there’s a potential upside in Q1 2025 knowledge.

The dangers of holding ALT have a number of elements, a few of which I’ll focus on. First, if suggestions from the FDA assembly comes with information that ALT has to launch a larger-than-expected program, the inventory might fall. Additionally, if ALT sees delays in enrollment within the IMPACT examine, the inventory might dump because the Q1’25 catalyst might transfer additional into the long run. Lastly, if ALT publicizes important dilution to assist Section 3, the inventory might additionally fall.