More tolerable PWS hunger therapies slated for new human trials next year

Palatin Technologies expects to begin early-stage clinical trials next year for two experimental treatments designed to curb extreme hunger in people with Prader-Willi syndrome (PWS) and other rare obesity conditions.

While Palatin previously anticipated launching these Phase 1 trials this year, the company has pushed the start date to 2027. Data readouts are expected in the second half of 2027 and the first half of 2028.

Both therapy candidates — one an under-the-skin injection and the other an oral pill — aim to reduce hyperphagia, a common symptom of PWS marked by a constant, overpowering sense of hunger that leaves individuals unable to feel full after eating.

Palatin is developing three potential hunger-reducing treatment approaches. They work by targeting and activating the melanocortin-4 receptor (MC4R), a protein involved in signaling to regulate appetite. While existing MC4R-targeting drugs can control hunger, they often trigger side effects like severe nausea and hyperpigmentation (skin darkening). Palatin’s goal is to create next-generation treatments that provide the same hunger relief without these long-term issues.

“While currently available and emerging therapies [activating MC4R] have demonstrated meaningful efficacy, gastrointestinal adverse events and hyperpigmentation remain important challenges for patients requiring long-term treatment,” Carl Spana, PhD, Palatin’s president and CEO, said in a company press release announcing the latest financial results and business updates. “Our objective is to develop MC4R therapies that deliver comparable or greater efficacy with improved tolerability, little to no hyperpigmentation, and product profiles suitable for lifelong use.”

Recommended Reading

Sept. 22, 2025 by Janet Favorite

How hyperphagia affects patients and their families

Developing safer appetite treatments

With that in mind, Palatin’s candidates are designed to have little to no effect on MC1R, an MC4R-related protein whose inadvertent activation is thought to underlie the hyperpigmentation reported with currently available MC4R-activating therapies.

That is a known issue for setmelanotide, an MCR4 activator currently approved under the brand name Imcivree to treat certain rare genetic obesity conditions. The therapy has also shown promise in reducing PWS-related hunger.

“MC4R agonism [activation] is now clinically and commercially validated in multiple rare and syndromic obesity disorders, establishing a strong foundation for the development of next-generation therapies,” Spana said.

Two of Palatin’s investigational therapies are peptides — short sequences of amino acids, the building blocks of proteins — designed to be administered via under-the-skin (subcutaneous) injection. Both have been shown to activate MC4R, but not MC1R, in preclinical studies.

The lead peptide candidate, called PL2000, is a lipidated molecule, meaning that certain fatty molecules have been attached to the peptide. According to Palatin, the lipidated therapy significantly reduced food intake and body weight in a mouse model of diet-driven obesity.

To support an investigational new drug application — the formal request needed to begin U.S. human clinical trials — Palatin is finishing preclinical studies and manufacturing for PL2000, a candidate that could be dosed once weekly or less frequently.

Alongside PL2000, the company is developing a controlled-release version of its nonlipidated candidate, PL1000, as well as an oral MC4R activator. For the oral pill, Palatin is pairing artificial intelligence with insights from an earlier candidate, PL7737, to design a treatment that curbs hunger without causing hyperpigmentation.

All planned development activities, clinical studies, and timelines remain dependent on the company securing appropriate funding, according to the release.