Zealand Pharma may be gearing up for a high-stakes year of obesity readouts, but the Danish biopharma thinks the brain could hold the key to the company’s long-term success.
In fact, Zealand is already on the hunt for partners who can help develop weight loss treatments that target the brain, according to the company’s Chief Scientific Officer, Utpal Singh, Ph.D.
“Right now, the emerging data is suggesting that all of metabolic control and even immune system control is happening via the brain,” Singh told Fierce in an interview. “Even GLP therapies are working through the brain, so [we’re] starting to develop partnerships and tools to take therapies directly to the brain.”
These partnerships could involve developing combination regimens that include Zealand’s existing investigational weight loss drugs or collaborating on entirely new treatments. One area of focus will be using shuttle technology to enable therapies to cross the blood-brain barrier.
Roche, which is already partnering with Zealand on its phase 2-stage amylin analogue, petrelintide, has been exploring ways to shuttle drugs across the blood-brain barrier for well over a decade. Has Zealand reached out to the Swiss pharma about stretching their collaboration into this area?
“We’ve talked to them, and we've talked to a number of folks along those lines, absolutely,” Singh responded.
“Some of the things that we want to do around the brain are moonshots,” he pointed out. “They're going to be really hard, but I think could be transformational.”
A big factor in metabolic health is hypothalamic resistance, where “your brain is no longer responding to leptin and insulin the way it does under normal physiological conditions,” Singh explained.
“There's some novel targets that could help improve that and increase the sensitivity of the brain to those peripheral signals,” he added. “So some of those may be small molecules; some may require shuttling technologies into the brain.”
It’s not only accessing the brain where Zealand is seeking partners. Last week, the company announced it is handing over $20 million—potentially rising to $30 million—in upfront cash to OTR Therapeutics to use the Chinese biotech’s oral small-molecule platform to “discover and develop novel therapeutics for multiple targets in metabolic diseases.”
Shanghai-based OTR, which just launched in March, has kept its own pipeline under wraps, making it hard from the outside to see what attracted Zealand to the deal. As Singh tells it, the collaboration is as much about OTR’s expertise as it is about their oral platform.
In fact, Singh—who moved to Zealand in April after serving as Eli Lilly’s senior vice president of small molecule discovery—had previously worked with both OTR’s CEO Zhui Chen, Ph.D., and Chief Scientific Officer Yuan Shi, Ph.D.
“Their CSO was someone I had an opportunity to partner with when he was at Lilly,” Singh explained. “They [both] have a track record of being able to find very highly selective molecules and put them in the clinic.”
“So it’s a combination of the leadership expertise and the scale and agility that they can access in that ecosystem that for us would take years to replicate internally,” he added.
Zealand’s existing pipeline consists entirely of injectables, so it’s perhaps unsurprising that the company sought out an oral-focused collaboration with the likes of OTR. Recent months have seen a stream of readouts in the hotly contested race to get an oral obesity med to market.
Novo Nordisk currently awaits an FDA approval decision for the oral version of its blockbuster obesity injection Wegovy. Does Zealand think it can compete with its more established Danish counterpart?
“As a scientist, I don't want to over-promise and under-deliver,” Singh said. “But I think we would not be investing in a program like this if we didn't believe that it could be better than the current standard of care.”
Singh spoke to Fierce in London on the morning after the company decamped to the U.K. capital to unveil its “Metabolic Frontier 2030.” The road map involves targeting five product launches by 2030, including petrelintide.
Phase 2 data for the Roche-partnered amylin analogue is expected in the first half of 2026. A phase 1b study last year tied the asset to a 8.6% reduction in mean body mass at 16 weeks, although one of the biggest potential selling points is the lower rate of gastrointestinal adverse events compared to approved GLP-1 drugs.
It means Zealand has been pitching petrelintide as a potential option for patients who cannot tolerate GLP-1 meds and to people who want an alternate, more tolerable treatment for maintaining weight loss on drugs such as Novo’s Wegovy.
There’s also survodutide, a Boehringer Ingelheim-partnered dual agonist for GLP-1/glucagon in a range of phase 3 studies for both obesity and metabolic dysfunction-associated steatohepatitis (MASH).
Beyond obesity, Zealand is banking on approvals for glepaglutide, a GLP-2 analog being investigated for short bowel syndrome, and dasiglucagon, a continuous infusion glucagon analog being lined up for congenital hyperinsulinism.
While the rewards of becoming a top obesity player are astronomical, the elevated expectations from investors and analysts bring their own problems. Novo experienced this first-hand this year, losing its CEO and chief scientific officer in the wake of some disappointing sales figures and clinical readouts.
With Zealand proclaiming at its strategy day that it’s set on becoming a “generational biotech leader in obesity and metabolic health,” is Singh having any sleepless nights about a poor readout from one of its own weight loss drugs?
“The short answer is no,” he said. “Because I think we have the expertise; we have the financial capital where we can actually make [the] right investments; and we can learn.”
Those hoped-for commercial launches in the coming years are only the first stage of what Singh described as “waves of innovation” at Zealand. The next stage is “starting to look at weight-independent insulin sensitization,” which will be followed by the plans to “modulate receptors directly in the brain.”
It’s an ambitious strategy, but Zealand is gearing up for the challenge. The company’s headcount recently reached 500 employees, most of whom are based in Denmark. The biopharma also announced a new research site in Boston, which the company expects to house around 100 employees by the end of the decade, primarily focused on AI-driven drug creation and automation.
With Zealand’s promising pipeline and bold ambitions, it’s a surprise Roche hasn’t offered to buy out its partner in its entirety. Has that possibility been brought up?
“We'll see what happens,” said Singh. “But I didn't come here to be a flash in the pan.”
“I want to build a legacy that 25 years from now, people look back and say, ‘There were some key decisions we made that were fundamental to making an impact in human health and keeping this company on steady ground.’”