Monday, June 1, 2026
Biohaven looks to obesity to bounce back from run of clinical and regulatory failures
After trial flops in spinal muscular atrophy, depression and bipolar disorder—and a costly rare disease drug rejection—Biohaven is undergoing a reset, recasting its former SMA candidate for obesity.
Biohaven’s taldefgrobep alfa may have missed the mark for spinal muscular atrophy, failing a Phase 3 trial in November 2024, but the biologic did help patients lose weight while preserving lean muscle and bone density—a holy grail of obesity treatments. Now the company is hoping the drug will help pivot its pipeline toward the lucrative weight loss market.
“We’re a small biopharma company, and when we have good assets, we do a full vetting of that asset, and we’ll play where that asset can bring real value to patients and to the company,” Peter Ackerman, senior vice president of clinical development, told BioSpace ahead of the American Diabetes Association (ADA) annual conference this week in New Orleans.
In an interview with BioSpace in January, CEO Vlad Coric discussed his company’s plans to repurpose taldefgrobep alfa, which Biohaven acquired from Bristol Myers Squibb in 2022. Ackerman and several of his Biohaven colleagues are BMS alumni.
“We’ve been talking about obesity as an indication for taldefgrobep for many years,” Ackerman said.
Currently in a Phase 2 study for obesity, taldefgrobep is a myostatin and activin receptor blocker, according to Ackerman. Activin [ActRII] receptors reside primarily on skeletal muscle and adipose tissue, he explained. “Blocking myostatin signaling optimizes skeletal muscle growth.”
The preservation of lean muscle mass is a major challenge with GLP-1 medicines, Ackerman continued. On these drugs, 30% to 45% or more of the total weight loss is being driven by loss of lean muscle mass. “We won’t have that,” he said. “We believe that we can bring higher quality of weight loss.”
Companies like Roche and Scholar Rock have targeted the latent form of myostatin, Ackerman said, which “has no interaction with the ActRII receptor.” Taldefgrobep’s binding of this receptor is key, Ackerman said, “because it competitively inhibits other key growth factors, including . . . activin A, B, C and E,” which are important to fat storage.
“If you can shut down both the myostatin and activin signaling pathway, we believe that you can optimize lean mass growth and optimize the reduction in fat mass,” he said.
Biohaven completed enrollment in the Phase 2 proof-of-concept study—which is evaluating taldefgrobep as a once-weekly and once-monthly monotherapy—in March. The trial’s primary endpoint is change in body weight at 24 weeks, with change in total body fat, change in total body lean mass and safety as key secondary endpoints. Topline data are expected in the second half of this year.
And when it comes to taldefgrobep, Biohaven isn’t planning to stop with obesity.
“Obesity is a good first indication, because of the hardcore outcome measures, but muscle mass is very important to longevity and keeping quality of life as we all age,” Coric told BioSpace last week, adding that each decade after age 30, people lose almost 8% of their muscle mass. Therefore, he said, future indications could include healthy aging and preventing age-related muscle loss.
The regulatory pathway for obesity therapies is still very much focused on weight loss, however. Biohaven recognized this during the company’s R&D Day, held May 27.
“While Biohaven is aiming to differentiate taldefgrobep alfa as a lean-mass sparing agent for obesity, at the R&D day it acknowledged that the regulatory path forward for endpoints other than percent weight loss is unclear,” William Blair said in a note the following day.
However, the analysts added, “[m]anagement expressed confidence that taldefgrobep alfa monotherapy can demonstrate weight loss that will meet regulatory standards for approval, and that an alternative regulatory path will not be required.”
Can Biohaven bounce back?
After a challenging couple of years, Biohaven has a lot riding on these early signals of efficacy in obesity. Since before taldefgrobep’s Phase 3 fail, when the company’s share price had topped $50, the stock has fallen some 80%, selling for just over $10 apiece at the time of publication.
Indeed, taldefgrobep is not Biohaven’s only experimental asset to fail a key trial recently. In January, the company recorded a flop for its potassium channel agonist BHV-7000, or opakalim, in a Phase 2 proof-of-concept trial for major depressive disorder (MDD). BHV-7000 previously failed a Phase II/III bipolar mania trial, and the company said it would move on from the drug candidate in psychiatric disorders.
This followed an FDA rejection in November 2025 for Biohaven’s glutamate modulator troriluzole in spinocerebellar ataxia (SCA).
William Blair analysts at the time called the rejection “disappointing” and said it raises “potential liquidity ramifications.” Indeed, the FDA’s decision caused Biohaven to miss out on a $150-million tranche of funding from Oberland Capital Management, part of a larger private investment worth up to $600 million. The biotech also cut R&D spending by 60%.
Over the past year, Coric said Biohaven has “spent considerable time advocating” for troriluzole in SCA. “We stand by the data and believe this is an approvable package, and we are continuing to interact with the FDA, and we will not stop advocating for patients that this should be approved,” he added.
Overall, however, these events have sent Biohaven back to the drawing board in many respects.
“Biohaven is in a period of pipeline reprioritization and R&D cost reduction to preserve capital,” William Blair analysts wrote on May 5 following the company’s first quarter earnings report.
“In terms of clinical catalysts, the focus will be on pivotal Phase II/III data of opakalim in focal onset epilepsy (FOS) and placebo-controlled Phase II data of taldefgrobep alfa in obesity,” they added.
While opakalim struck out in MDD, with this asset too, Biohaven has another shot on goal. Pivotal topline data from a Phase 2/3 trial are due for the potassium channel agonist in epilepsy in the second half of 2026, according to the company’s 2026 key milestones chart.
Ackerman noted that while the FDA’s requirement is sustained weight loss through 48 weeks, the 24-week readout for taldefgrobep in obesity “gives us an opportunity to get an earlier read on the data and get earlier into Phase 3, if we see what we’re hoping to see.”
At ADA, Biohaven will be presenting data supporting its dosing choices for the Phase 2 trial, including the once-monthly option, which “our modeling suggests is very viable,” Ackerman said.
“If we can meet our goals of having significant reductions in fat mass and fat mass reduction on par with . . . a leading agent in the GLP-1–based therapies, we think that that is an attractive proposition for individuals.”
Obesity Davids and Goliaths face off at ADA 2026
The American Diabetes Association’s annual congress will feature a superstar lineup, including weight loss giants Eli Lilly and Novo Nordisk. But several scrappy biotechs will also present obesity candidates with the potential to match—if not outperform—their deep-pocketed competitors.
This weekend, many of the world’s leading metabolic experts will flock to New Orleans to attend the 2026 American Diabetes Association’s Scientific Sessions.
Recent editions of the meeting have unsurprisingly had a heavy focus on obesity. Weight loss has become one of the most lucrative areas across biopharma, with IQVIA forecasting $92 billion in sales of obesity medicines this year and up to $200 billion by 2027 and beyond. And last year, obesity unseated long-reigning oncology as the top contributor of pharma pipeline value, with weight-loss medications accounting for 25% of the overall pharma pipeline value.
Obesity’s ascent has spilled over into conferences like ADA, where many of the most highly anticipated presentations focus on weight control. This is especially true for the 2026 edition of the congress, which features a superstar lineup of companies presenting new data on both approved and investigational drugs.
These include readouts from undisputed weight loss leaders Eli Lilly and Novo Nordisk, as well as from other major pharmas looking to stake their claim in the sector. But ADA 2026 will also see some plucky biotechs stand up to these giants, bringing their own obesity candidates that could give these deep-pocketed counterparts a run for their money.
Frontrunners face off with next-gen obesity bets
All eyes at ADA will be on Lilly and Novo and their next-generation assets as they chart the way forward for the obesity space.
Lilly will present data from the Phase 3 TRIUMPH-1 and TRANSCEND-T2D-1 studies of its triple-G agonist retatrutide in obesity and diabetes, respectively. Lilly has deemed retatrutide part of a “different drug category,” as compared with its current weight-loss drugs, Andy Hsieh, healthcare research analyst at William Blair, told BioSpace in an email.
Hsieh expects the triple-G asset, “given its high potency,” to set itself apart from Lilly’s other obesity products—including the GLP-1/GIP dual agonist Zepbound and small-molecule drug Foundayo. Still, he anticipates that the debate around retatrutide will focus on the tradeoff between its weight loss efficacy and tolerability.
Indeed, data that Lilly has disclosed so far demonstrate impressive weight reduction. Retatrutide generated 28.3% weight loss over 80 weeks in the Phase 3 TRIUMPH-1 study, Lilly announced on May 21, likening the results to those elicited by bariatric surgery. The trial assessed the candidate in patients with obesity but without diabetes.
The Phase 3 TRIUMPH-4 study, reported in December, showed a 26.6% placebo-adjusted weight-loss at 68 weeks in patients who have obesity or are overweight with knee osteoarthritis, results BMO Capital Markets said at the time “help to solidify retatrutide’s profile as an even higher efficacy next generation GLP-1+ asset.”
But the drug’s safety profile has tempered some of the industry’s excitement, with Lilly reporting a signal called dysesthesia—a neurological anomaly characterized by unpleasant or painful sensations—in more than a fifth of patients on the 20-mg dose of retatrutide in TRIUMPH-4. Dysesthesia also occurred in TRIUMPH-1, with rates rising with dose level.
Not to be outdone by its chief competitor, Novo is bringing its own next-generation weight-loss candidate, CagriSema, to ADA 2026. The drug is a fixed-dose combination of its GLP-1 giant semaglutide and long-acting amylin analog cagrilintide.
While the pharma will give several presentations at the conference, William Blair believes investors will be more interested in CagriSema’s data in diabetes—outlined in the Phase 3 REIMAGINE 1, 2 and 3 studies—than in obesity after the asset “failed to demonstrate non-inferiority” versus Lilly’s Zepbound, according to a May 4 note.
In February, data from Novo’s head-to-head REDEFINE-4 study showed that patients on CagriSema lost 23% of their body weight on average at 84 weeks, whereas comparators on Zepbound saw a 25.5% reduction in weight.
Novo remains confident in CagriSema, however, and expects the drug to hit U.S. shelves next year. “When CagriSema will make it to the market early next year as the first amylin-based product, it will have the best weight loss label than any product marketed at that time,” CEO Maziar Mike Doustdar told investors and analysts at the time of the head-to-head readout.
Behind the duopoly, Big Pharmas play for third
With Lilly and Novo firmly in the lead, the rest of biopharma is looking to claim that coveted third place, with Boehringer Ingelheim, Roche and more hustling to get their candidates to the market. Many of these aspirants will be at ADA 2026.
Based on timelines alone, Hsieh told BioSpace, Boehringer appears poised to win the race.
Boehringer is working with Zealand Pharma on survodutide, a dual agonist of the GLP-1 and glucagon receptors, “designed to go beyond weight reduction by targeting pathways relevant to metabolic dysfunction and liver disease,” Vani Manja, global head of Obesity and Liver Health at the German pharma, told BioSpace in an email.
With survodutide, Boehringer is shifting its focus “from weight loss to metabolic health, from single targets to multi‑pathway approaches, and from short‑term outcomes to more durable impact,” Manja said.
At ADA, the company will present detailed data from the Phase 3 SYNCHRONIZE-1 study, a topline readout from which showed a 16.6% drop in weight at 76 weeks, as compared with 3.2% in placebo controls. These numbers “appear less competitive vs other dual target mechanisms,” such as Lilly’s tirzepatide, BMO said in an April 28 note.
Still, survodutide could set itself apart from the current leaders by offering better quality weight loss, BMO added. Indeed, most of the weight reduction in SYNCHRONIZE-1 was due to fat loss. Lean mass accounted for “only a small proportion” of the total weight that participants lost, Zealand said at the time.
William Blair expects to see more detailed data from SYNCHRONIZE-1 at ADA, particularly “additional color from survodutide’s impact on body composition and liver fat,” according to the firm’s May 4 note. These findings, in turn, could have readthroughs to other indications, such as metabolic dysfunction-associated steatotic liver disease (MASH), which survodutide is also targeting, the analysts continued.
Another potential third-placer is Roche. The pharma in late 2023 invested $2.7 billion to acquire Carmot Therapeutics and its pipeline of GLP-1 therapies, including CT-388, which additionally activates the GIP receptor. Phase 2 data for the asset in January demonstrated a 22.5% placebo-adjusted weight reduction at 48 weeks, with no signs of plateauing.
More detailed data from the trial will be presented at ADA, where William Blair will be keeping an eye out for detailed tolerability data, “given the relatively high doses being evaluated,” analysts said on May 4. So far, Roche has only said that CT-388’s safety is “generally consistent with the incretin class of medicines.”
The firm also believes that investors will also be interested in learning about Roche’s plans to combine CT-388 with Zealand’s amylin therapy petrelintide. Roche signed an up to $5.3 billion partnership in March 2025 with the Danish biotech for the asset.
Also gaining ground on the leaders is Amgen, which according to Hsieh is just a bit behind Boehringer in terms of timing. When it comes to weight-loss numbers, Amgen might “have a better chance of catching up to the duopoly,” he said.
Anchoring Amgen’s weight-loss portfolio is MariTide, a bispecific antibody-peptide that targets both GLP-1 and GIP pathways. In November 2024, the pharma released Phase 2 data showing an up to 20% drop in body weight at 52 weeks—findings analysts found disappointing.
Amgen is nevertheless standing by MariTide. During the company’s earnings call in April, Murdo Gordon, executive vice president of global commercial operations, said MariTide has the potential “to be the best monthly or less frequently dosed agent” in obesity.
In addition to weight loss, Amgen is positioning MariTide as a medicine for adjacent indications, such as heart failure, obstructive sleep apnea and elevated liver fat.
“We see the future of care as increasingly connected across obesity and cardiovascular disease as these conditions commonly coexist and can lead to serious outcomes or death, even though they are treatable,” Chief Medical Officer Paul Burton told BioSpace in an email.
Amgen will be at ADA 2026 but will not be presenting MariTide data.
Don’t discount the little guys
Obesity isn’t just an opportunity for the big guys, of course, as many smaller biotechs are also advancing promising candidates.
Structure Therapeutics is working on the GLP-1 pill aleniglipron, a potential competitor to Lilly’s Foundayo and Novo’s oral Wegovy. In December 2025, Structure released data from the Phase 2b ACCESS II study, showing that a 120-mg dose of aleniglipron resulted in an 11.3% placebo-adjusted weight reduction at 36 weeks—findings that BMO in a Dec. 8 note called “highly competitive.”
Additional data in March showed that at the 44-week follow-up, average weight loss improved even further to 16.3% on a placebo-adjusted basis.
Structure will show up at ADA with a detailed presentation of ACCESS II, as well as data from the dose-ranging ACCESS study. The biotech will also have posters looking at a lower starting dose of aleniglipron and a combination regimen of the candidate paired with an amylin asset.
Viking Therapeutics is similarly looking to play alongside the industry giants with its dual GLP-1/GIP agonist VK2735, which the biotech is advancing both as a subcutaneous injection and as a daily pill. In his email to BioSpace, Hsieh also named VK2735 as one of the obesity hopefuls likely to catch up to Lilly and Novo, with a chance to potentially overtake Boehringer.
At the recently concluded European Congress on Obesity last month, Viking presented data from the Phase 2 VENTURE-Oral study, touting placebo-adjusted weight reduction of up to 10.9% for patients on oral VK2735 at 13 weeks. Meanwhile, the weekly subcutaneous injection hit weight loss of up to 13.1% on a placebo-adjusted basis at the same time point, according to Phase 2 data presented in November 2024.
Viking has pushed subcutaneous VK2735 into late-stage development, while the oral formulation is scheduled to enter Phase 3 studies later this year.
https://www.biospace.com/drug-development/obesity-davids-and-goliaths-face-off-at-ada-2026
Japan urges Iran to show ‘maximum flexibility’ for US deal
Japan’s Prime Minister Sanae Takaichi urged Iranian President Masoud Pezeshkian on Monday to show “maximum flexibility” to seize the opportunity for a ceasefire agreement with the United States.
Takaichi told reporters after the call that she also strongly demanded the Strait of Hormuz be reopened soon to ensure free and safe navigation for ships from Asia and other countries.
She did not detail Pezeshkian’s response but said the two leaders agreed to keep close communication.
'Araghchi says Iran-US ceasefire covers Lebanon'
Iranian Foreign Minister Abbas Araghchi said on Monday that the ceasefire between Iran and the United States covered “all fronts,” including Lebanon.
“The ceasefire between Iran and the US is unequivocally a ceasefire on all fronts, including in Lebanon,” he said.
The foreign minister said a violation on one front would amount to a violation of the ceasefire on all fronts.
“The US and Israel are responsible for the consequences of any violation,” Araghchi warned in a post on X.
Israeli Prime Minister Benjamin Netanyahu said in a statement earlier in the day that he had ordered the military to strike targets belonging to Iran-backed Hezbollah in Beirut’s southern suburb of Dahiyeh.