Rivus Pharmaceuticals, Inc.

As Pfizer talked up the strength of its pipeline Tuesday, it shared details for the first time about its plans in obesity and said it has a multipronged strategy to catch up to rivals in the field. Danuglipron remains the company’s main bet, CEO Albert Bourla said on the company’s earnings call Tuesday, adding that he believes Pfizer can bring the second oral drug to the market. But that’s not Pfizer’s only option. The company disclosed new details about the mechanism of action behind a second candidate, a GIP antagonist that’s in the same category as other promising pipeline drugs developed by rivals. Amgen, for example, is developing a bispecific molecule named MariTide that’s both a GIP antagonist and GLP-1 agonist. Pfizer’s GIP antagonist is set to enter a Phase 2 study before the end of the year. A once-daily oral GLP-1 is also continuing to progress through a Phase 1 study. Outgoing CSO Mikael Dolsten described the first versions of oral GLP-1s being on the lower end of a range of 10% to 20% reduction in body weight. “The upper range is where you can see oral combinations edge towards,” Dolsten said on Tuesday’s call. And Bourla teased that there could be more, saying Pfizer was “exploring several other opportunities right now.” There is no shortage of smaller obesity biotechs looking for drugmakers to work with — or sell to. Zealand Pharma has been on the hunt for a co-development and commercialization partner for its amylin analog drug, petrelintide . And Rivus Pharmaceuticals CEO Jayson Dallas told Endpoints News last month that he thinks the company’s lead asset, in the middle of two Phase 2 trials, will at some point “pique someone’s interest.” Pfizer’s obesity update may be welcome news for investors who felt the company should have been more aggressive, given its strength in primary care. That includes activist shareholder Starboard Value, which outlined in CEO Jeff Smith’s presentation last week how expectations for danuglipron have fallen since early 2023. “Peers have been successful at developing and commercializing GLP-1s whereas Pfizer has not,” the firm wrote in a presentation to investors this month, arguing that Pfizer’s performance needs to improve or the management needs to be held accountable by the board. Bourla remained encouraged Tuesday, underscoring that if danuglipron can get approved, then Pfizer would have a major product. “The market is very, very large,” Bourla said. “And there is a significant need for oral solutions. We know that. So there is no doubt that if successful, we will have our decent market share of oral.” But the product profile looks “suboptimal” as a once-daily pill, Leerink Partners senior analyst David Risinger said in an interview. “I don’t think that danuglipron is going to be their lead obesity drug in five to 10 years,” he said. Editor’s note: This story was updated to correct the second reference to Pfizer’s GIP antagonist.

Boston-area biotechs Upstream Bio and CAMP4 Therapeutics are headed to the Nasdaq on Friday, the latest companies to IPO in what appears to be a recovery for startups trying to raise capital on the public market. Upstream Bio priced at $17 per share, the high end of the $15 to $17 range it set earlier this week . By selling 15 million shares — 2.5 million more than originally planned — it will raise $255 million in new cash. CAMP4, meanwhile, priced its shares $CAMP at $11 apiece, $3 below the low end of the $14 to $16 range it marketed to investors. It sold 6.82 million shares versus an initial plan to offer 5 million and will raise $75 million . The IPO window is “showing signs of recovery,” Oppenheimer bankers wrote in a quarterly analysis this week. GPCR biotech Septerna is also in the IPO queue, and Bain-backed obesity startup Rivus Pharmaceuticals is also considering a listing this fall, Bloomberg reported this week. For Upstream $UPB the offering will add to its coffers as it runs Phase 2 and later-stage trials of its TSLP receptor antagonist verekitug. The experimental treatment, licensed from Astellas, is being studied for severe asthma and chronic rhinosinusitis with nasal polyps . Upstream hopes to enter a similar market as Amgen and AstraZeneca’s Tezspire, as well as Blackstone-backed Uniquity Bio’s solrikitug . CAMP4 is working on regulatory RNA and has a Phase 1 trial of its lead drug, a CPS1-targeting medicine for urea cycle disorders. The IPO comes a few weeks after CAMP4 added BioMarin to its partnership lineup, which already includes Fulcrum Therapeutics and Eli Lilly. Earlier in its startup days, CAMP4 had pacts with Biogen and Alnylam.

HU6 is known as a controlled metabolic accelerator, a new class of therapies that Rivus hopes can “promote sustained body fat loss while preserving muscle mass.” Rivus Pharmaceuticals has unveiled the data behind its phase 2 obesity win in heart failure patients, showing that the candidate can indeed help patients reduce weight while they retain muscle.The asset, dubbed HU6, is designed to boost the breakdown of fat by stopping it from accumulating, rather than by reducing calory intake. The mechanism could help patients lose fat tissue while preserving muscle—the goal of many next-gen obesity drugs.Sparing muscle is particularly important for heart failure patients, who may already be frail and lack skeletal muscle mass. The HuMAIN study specifically recruited patients with obesity-related heart failure with preserved ejection fraction.Rivus already announced in August that the trial hit its key endpoint, but today fleshed out that win with some figures. Specifically, patients who ended on the highest, 450 mg, daily dose of HU6 lost an average of 6.8 pounds after three months, which was 6.3 pounds more than lost among the placebo group.When it came to visceral fat—a term for fat that collects around the internal organs in the abdomen—this was reduced by 1.5% from baseline. What’s more, there was “no significant reduction in lean body mass with HU6 from baseline or compared with placebo,” said the company, keeping alive hopes that the drug can indeed help patients lose the right type of weight.Elsewhere, HU6 was tied to reductions in systolic and diastolic blood pressure from baseline of 8.8 mmHg and 4.1 mmHg, respectively. These reductions weren’t linked to an increase in heart rate, the biotech noted. The 66 patients enrolled in the study were mainly elderly and obese, with multiple comorbidities and taking an average of 15 other medicines. The most common treatment-emergent adverse events were diarrhea, COVID-19 and shortness of breath, with most of these events being mild to moderate in severity. There were no treatment-related serious adverse events.HU6 is known as a controlled metabolic accelerator (CMA), a new class of therapies that Rivus hopes can “promote sustained body fat loss while preserving muscle mass.”“With these new clinical data, which highly correlate to the results from our phase 2 study in [metabolic dysfunction-associated steatotic liver disease], we have now observed in different populations that HU6, a novel CMA, reduced fat mass and preserved lean body mass, which is especially beneficial in patients with HFpEF,” Rivus CEO Jayson Dallas, M.D., said in a statement.“The positive HuMAIN results support the potential differentiating profile of HU6 in HFpEF, which could be the first disease-modifying treatment for this debilitating syndrome,” Dallas added. “The findings also support advancing our HFpEF clinical program with HU6.”Roche is one high-profile entrant in the obesity space that has its own solution to retaining muscle. The Swiss pharma hopes that combining an injectable dual GLP-1/GIP receptor agonist acquired with Carmot alongside its own anti-myostatin antibody could also help patients reduce the muscle loss typically associated with losing weight.