Radella Pharmaceuticals Announces New Obesity Trial Data Showing Statistically Significant Weight Loss and Broader Cardiometabolic Benefits

First‑in‑class, PTP1B‑modulating peptide reduced body weight, improved insulin sensitivity and lowered LDL cholesterol without tolerability issues

NEW YORK, July 31, 2025 /PRNewswire/ -- Radella Pharmaceuticals, LLC, a clinical-stage biopharmaceutical company developing innovative therapies for cardiometabolic disorders, today announced that its Phase 1b clinical trial of MD-18 targeting obesity and type 2 diabetes met its objectives, achieving statistically significant weight loss and broader cardiometabolic improvements in healthy volunteers, with a clean safety and tolerability profile.

The first-in-class peptide utilizes a dual-pronged approach to increase insulin sensitivity and increase energy expenditure by reactivating leptin signaling, a pathway often impaired in obesity, through precise modulation of the enzyme PTP1B. The company believes MD-18 prompts the body to use more of the calories it has already stored, enabling weight loss while preserving lean muscle mass. This differs from glucagon-like peptide-1 receptor agonists (GLP-1 RAs), which primarily induce weight loss through appetite suppression, and are associated with lean mass loss and tolerability issues.

"These data validate MD-18 as a next-generation approach to cardiovascular and metabolic health," said Daniel Cohen, Founder and Chief Executive Officer of Radella. "Participants lost weight and waist circumference, and saw improvements in cholesterol and insulin measures. These findings indicate that MD-18 may offer pan-cardiometabolic benefits for common obesity co-morbidities, including heart disease and diabetes."

Study Design and Results

The double‑blind, placebo‑controlled multiple ascending dose (MAD) Phase 1b trial enrolled healthy volunteers [n=36] with an average body‑mass index (BMI) of 28.8 +2.5 in the MD-18 arm. Participants received either placebo or escalating weekly doses of MD‑18 for four weeks without titration. The study was conducted in the early phase clinical trial facility in Sheba Medical Center, Israel.

Topline results from the initial six cohorts in the Phase 1b trial include:

• Significant weight loss of up to 2.7% in otherwise healthy volunteers in 28 days of treatment. These results were seen in primarily non-obese subjects and were accompanied by a 2.2% decrease in waist circumference with weekly administration. The data suggest greater weight loss would be observed in obese individuals.
• Data are consistent with lean mass preservation. As expected with the drug's novel mechanism of action and nonclinical data indicating the ability to preserve lean mass, the data are in line with expectations for a next-generation cardiometabolic therapeutic. Unlike other therapies that optimize weight loss primarily via anorexic effect, MD-18 holds the potential to achieve sustainable adipose tissue loss while preserving muscle mass.
• Significant reductions in key cardiovascular biomarkers. In healthy subjects with elevated LDL cholesterol levels, MD-18 demonstrated a statistically significant decrease in LDL cholesterol vs. placebo. Further, MD-18 demonstrated a statistically significant decrease in alanine aminotransferase (ALT) levels vs. placebo, suggesting the potential to reduce liver fat content.
• No safety signals and best-in-class tolerability profile. All drug related adverse events (AEs) were mild (Grade 1) and most AEs, including gastrointestinal events, were similar between MD-18 and placebo.

How MD-18 differs from GLP-1 therapies

Current GLP-1 therapies promote weight loss primarily via appetite reduction, and a recent meta-analysis showed that approximately 25% of weight lost with these drugs is lean muscle mass¹. These medications are also associated with side effects such as nausea and other gastrointestinal issues. According to a 2025 study in JAMA Network Open, nearly two-thirds of adults without type 2 diabetes and nearly half of those with diabetes discontinued GLP-1 therapy within one year, primarily due to tolerability concerns².

In contrast, MD-18's approach aims to restore metabolic signaling through targeted PTP1B modulation. In both preclinical models and clinical trials, MD-18 has demonstrated improved insulin sensitivity, lower cholesterol, and reduced ALT levels, a marker of liver health. These are important biomarkers, as more than two in five American adults with obesity also have other chronic conditions, including high blood pressure, heart disease, and diabetes, according to the CDC³.

"We believe MD-18 is better positioned to maintain weight loss long term," said Amir Tirosh, MD, PhD, Chief Medical Officer at Radella. "The cardiometabolic signals we're seeing, which include not just weight loss but also improved lipids, insulin and liver enzymes, point to a therapy that treats the whole patient, not just the numbers on the scale. In addition, with MD-18 we may be able to finally enter an era of highly effective combination therapy in obesity, in which MD-18 may also be used with GLP-1 therapies."

PTP1B and Leptin as a Target

PTP1B is well understood to modulate insulin sensitivity and energy expenditure via the leptin pathway. Leptin plays a crucial role in regulating body weight, but in people with obesity, resistance to the hormone leads to lower energy expenditure and increased fat storage. Early attempts to restore leptin sensitivity or deliver leptin directly in humans failed, producing unintended effects such as hypoglycemia, immune dysfunction, and other toxicities, often due to drugs that indiscriminately blocked enzymes throughout the body.

Radella's approach is different: MD-18 is a small peptide that disrupts with high specificity a key protein-protein interaction in the leptin signaling pathway, avoiding the off-target effects seen with earlier therapeutic approaches targeting PTP1B.

Next Steps

Based on these topline results from the six cohorts in the MAD portion of the Phase 1b study, Radella will initiate two additional cohorts in the intent-to-treat population, including obese patients without type 2 diabetes and overweight and obese patients with type 2 diabetes. In each cohort patients will receive either placebo or once weekly injections of MD-18 for 12 weeks.

The company expects to report topline data from these cohorts in Q1 2026.

About Radella Pharmaceuticals

Radella Pharmaceuticals, LLC, headquartered in New York, NY, with operations in Aberdeen, Scotland and Tel Aviv, Israel, is a privately backed, clinical-stage biopharmaceutical company developing transformative therapies in cardiometabolic disease and beyond. Singularly focused on delivering curative solutions to patients and bettering human health, the company has successfully advanced its lead asset, MD-18, into clinical trials, developing a pipeline of follow-on assets targeting unmet needs in other large therapeutic areas, including neurodegenerative and fatty liver disease. MD-18 is a first-in-class peptide that targets multiple pathways involved in obesity and related metabolic conditions. MD-18 demonstrates a breakthrough in targeting protein-tyrosine phosphatase 1B (PTP1B), a historically challenging therapeutic target that plays a crucial role in metabolic regulation. MD-18's unique mechanism of action, which targets both insulin sensitivity and energy expenditure through PTP1B regulation and the leptin pathway, represents a potentially transformative approach for patients with cardiometabolic disease and its adjacencies. For more information on Radella's clinical program and current trials, visit radellapharma.com.

Contacts

Company Contact
Philip Lehman
Radella Pharmaceuticals, LLC.
Chief Operating Officer & Head of Business Development
[email protected]

Media Contact
Ryan Flinn
In Like Flinn Communications
[email protected]

Citations

¹ Effect of glucagon-like peptide-1 receptor agonists and co-agonists on body composition: Systematic review and network meta-analysis Karakasis, Paschalis et al. Metabolism - Clinical and Experimental, Volume 164, 156113. https://www.metabolismjournal.com/article/S0026-0495(24)00341-X/abstract
² Rodriguez PJ, Zhang V, Gratzl S, et al. Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity. JAMA Netw Open. 2025;8(1):e2457349. doi:10.1001/jamanetworkopen.2024.57349. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2829779
³ CDC Website, Adult Obesity Facts. https://www.cdc.gov/obesity/adult-obesity-facts/index.html

SOURCE Radella Pharmaceuticals