Developer planning clinical trials for 2 next-gen obesity-targeting drugs
New therapies for BBS, hypothalamic obesity also aim to ease skin side effects
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Scales and measuring tapes are used as tools in assessing obesity-targeting drugs in clinical trials. (Photo by iStock)
Palatin Technologies plans to move two experimental obesity-targeting therapies into clinical testing for Bardet-Biedl syndrome (BBS) and hypothalamic obesity (HO) over the next two years, with the launch of early trials involving people with BBS and HO.
The drug candidates will also be developed as potential treatments for people with Prader-Willi syndrome (PWS), a rare disorder that, like BBS and HO, is marked by excessive hunger, known as hyperphagia, and obesity. The developer said it’s hoping these two next-generation candidates can ease “off-target effects,” such as skin darkening, that are sometimes seen with certain obesity drugs.
The two therapies are designed to activate the melanocortin-4 receptor (MC4R), a protein that helps regulate appetite and energy expenditure. Palatin is developing a once-weekly injectable peptide therapy and an oral therapy designed to more selectively target MC4R than its earlier oral candidate, PL7737. Peptides are short chains of amino acids, the building blocks of proteins.
“Our once-weekly [injectable] MC4R selective peptide agonist [activator] program remains on track for an IND [investigational new drug] submission in the [last three months of the year],” Carl Spana, PhD, Palatin’s president and CEO, said in a press release announcing the company’s latest financial results and providing corporate updates.
“In our oral MC4R selective agonist program, we have used data from PL7737 and broader program insights to develop next-generation highly selective MC4R candidates, targeting an IND submission for the first half of calendar 2027,” Spana said.
IND applications, which are filed with the U.S. Food and Drug Administration (FDA), seek clearance to begin testing experimental therapies in clinical trials. Upon clearance of those applications, Palatin expects to rapidly launch two Phase 1 trials to test increasing single and multiple doses of the injectable and oral candidates.
BBS and HO are rare obesity disorders. BBS is caused by genetic mutations that, in addition to obesity, can lead to a wide range of symptoms, such as progressive vision loss, kidney problems, and learning difficulties.
HO occurs due to problems in the hypothalamus, a brain region involved in regulating appetite, metabolism, and energy use. Acquired hypothalamic obesity (aHO), its most common form, is caused by damage to the hypothalamus due to brain tumors, trauma, or treatments such as surgery or radiation therapy.
Available obesity drugs can cause skin darkening
Although the underlying causes differ, disruption of MC4R signaling is believed to play a key role in driving severe hyperphagia, a hallmark feature of both conditions. As such, therapies designed to restore MC4R signaling have emerged as a promising strategy to treat obesity in both conditions.
MRC4 agonists work by binding to and activating the receptor protein, MC4R, which is found on nerve cells of the hypothalamus. By restoring signaling through this pathway, the therapies are expected to increase feelings of fullness, lower food intake, and help limit weight gain.
Imcivree (setmelanotide), an MC4R agonist developed by Rhythm Pharmaceuticals, is already approved in the U.S for several forms of genetic obesity, including BBS and aHO. However, currently available MC4R agonists can be associated with side effects such as nausea, vomiting, and hyperpigmentation, or skin darkening.
“Available therapies for rare obesity disorders often present challenges for long-term use,” Spana said, adding that the company’s “goal is to develop best-in-class MC4R agonists.”
Palatin is developing optimized MC4R agonists that have the potential to reduce the risk of hyperpigmentation. According to the company, this is being achieved by improving the ability of its candidate therapies to selectively target MC4R while reducing activation of other melanocortin receptor proteins, particularly MC1R.
Activation of MC1R, which is involved in skin and hair pigmentation, has been linked to so-called off-target effects — unwanted impacts from activating molecules other than the intended target — such as hyperpigmentation seen with currently available MC4R agonists.
“Our once-weekly injectable peptide lead and next-generation oral small molecule candidates are highly selective for MC4R, which we believe could result in a meaningful reduction in off-target effects associated with MC1R activity, with the potential to eliminate hyperpigmentation,” Spana said.
Available therapies for rare obesity disorders often present challenges for long-term use. … [Palatin’s] goal is to develop best-in-class MC4R agonists.
Preclinical data for Palatin’s once-weekly injectable candidate support sustained effectiveness and tolerability with repeat dosing, according to the company. Its next-generation oral candidate was developed using insights gained from PL7737, which previously demonstrated the ability to significantly reduce weight in animal models of obesity.
According to Palatin, the newer candidates also showed improved MC4R selectivity in preclinical models, suggesting the potential for long-term tolerability, usability, and patient adherence.
