iBio’s First-in-Class Activin E Antibody Achieves >26% Fat Reduction Without Muscle Loss and Shows Synergy with GLP-1s in Preclinical Model

Rhea-AI Summary

iBio (NASDAQ: IBIO) has announced promising preclinical results for its first-in-class Activin E antibody in treating obesity. In a 4-week study with obese mice, the antibody achieved a 26% reduction in fat mass while preserving muscle mass. The treatment demonstrated significant reductions in various fat deposits: 31% in subcutaneous fat and 34-37% in visceral fat depots linked to cardiometabolic disease risk.

When combined with a GLP-1 receptor agonist, the Activin E antibody showed remarkable synergy, achieving a 77% reduction in total fat mass and total weight loss of 35.3% - surpassing GLP-1 alone by 7.5%. Unlike current obesity drugs that may reduce muscle mass, iBio's approach focuses on fat-specific weight loss, potentially offering a more effective solution for obesity treatment while maintaining physical function and healthy metabolism.

Positive

• Achieved 26% fat mass reduction while fully preserving muscle mass
• Demonstrated 34-37% reduction in visceral fat deposits linked to cardiometabolic diseases
• Showed 77% fat mass reduction when combined with GLP-1 receptor agonist
• Achieved 7.5% greater total weight loss compared to GLP-1 alone
• Offers potential advantage over current obesity drugs that can reduce muscle mass

Negative

• Results are only from preclinical mouse studies, requiring further validation in humans
• Early-stage development with no human trial data yet

Insights

Biotechnology Analyst

iBio's novel Activin E antibody shows promising preclinical results for obesity treatment, offering targeted fat reduction while preserving muscle mass, unlike current GLP-1 therapies.

The new preclinical data from iBio's Activin E antibody program represents a potentially significant advancement in obesity therapeutics. The 26% reduction in fat mass without muscle loss demonstrates a differentiated mechanism compared to GLP-1 receptor agonists, which typically cause both fat and muscle reduction. This selective targeting could address a key limitation in current obesity treatments.

Particularly noteworthy is the antibody's ability to reduce visceral fat deposits—with 34% and 37% reductions in epididymal and retroperitoneal fat depots—as these fat types are most strongly associated with cardiometabolic disease risk. The preservation of muscle mass is metabolically significant, potentially supporting better long-term outcomes by maintaining basal metabolic rate and physical function.

The synergistic effect when combined with GLP-1 receptor agonists—achieving 77% fat mass reduction and 35.3% total weight loss—suggests this could be developed as either a standalone therapy or as a complementary treatment to enhance the efficacy of existing blockbuster GLP-1 drugs. This positions iBio's candidate as potentially valuable in the rapidly growing obesity market.

While these mouse model results are promising, significant development hurdles remain. As a first-in-class antibody targeting Activin E, this represents an entirely novel approach to obesity treatment, which carries both unique opportunities and development risks. The next critical milestone will be translating these preclinical findings to human studies.

Endocrinology & Metabolism Specialist

iBio's Activin E antibody achieves metabolically favorable fat-specific weight loss and shows significant synergy with GLP-1s, potentially addressing key limitations of current obesity treatments.

These preclinical results highlight a potentially important advancement in obesity therapeutics. Current GLP-1 receptor agonists induce weight loss but often at the expense of lean muscle mass, which can compromise metabolic health and physical function. iBio's approach demonstrates a more selective targeting of adipose tissue, achieving 26% fat reduction while fully preserving muscle mass—a distinction that could translate to more favorable metabolic outcomes.

The specific reductions in visceral fat compartments are clinically significant. Visceral fat, particularly the epididymal and retroperitoneal depots targeted in this study (34% and 37% reductions), is metabolically active tissue strongly associated with insulin resistance, systemic inflammation, and cardiovascular disease risk. Selectively reducing these depots while preserving muscle could potentially deliver cardiometabolic benefits beyond those achieved through general weight loss.

The synergistic effect when combined with GLP-1 receptor agonists is particularly intriguing from a therapeutic perspective. The 77% fat mass reduction and enhanced total weight loss (35.3% versus 27.8% with GLP-1 alone) suggests a complementary mechanism that could overcome some limitations of single-agent approaches.

This concept of "quality weight loss" that preserves metabolically beneficial tissues while reducing pathogenic fat depots represents an important direction in obesity medicine. If these findings translate to humans, this approach could potentially address some of the muscle-related concerns that have emerged with widespread GLP-1 use in clinical practice.

• Activin E antibody demonstrates significant decrease in fat in obese mice by reducing visceral fat depots, which are strongly linked to increased risk of cardiovascular and metabolic diseases, resulting in a 26% reduction in fat mass with no loss in muscle
• Strong synergistic effect on fat mass (77% reduction) was observed when the Activin E antibody was combined with a GLP-1 receptor agonist, resulting in total weight loss of 35.3%, 7.5% greater than GLP-1 alone
  

SAN DIEGO, May 05, 2025 (GLOBE NEWSWIRE) -- iBio, Inc. (Nasdaq: IBIO), an AI-driven innovator of precision antibody therapies, today announced new promising preclinical data for its first-in-class Activin E antibody unveiled in January. Data from the recently completed 4-week study in diet-induced obese mice show a 26% reduction in fat mass following treatment with the Activin E antibody, with muscle mass fully preserved. These findings highlight a significant fat loss can be achieved without the double-digit weight reductions typically required by other obesity drugs.

GLP-1 receptor agonists are effective at promoting weight loss. However, they can also reduce lean body mass, including muscle, which may limit some of the intended health benefits. In contrast, fat-specific weight loss is considered a higher-quality form of weight loss. It reduces fat—linked to lower risk of heart and metabolic diseases—while preserving muscle, which helps maintain strength, supports a healthy metabolism, and may prevent or reduce weight regain over time.

“We believe achieving high-quality weight loss, by reducing fat mass while preserving muscle, is essential in addressing the obesity epidemic,” said Martin Brenner, DVM, PhD, Chief Executive Officer and Chief Scientific Officer of iBio. “For example, a person with a BMI of 30 is classified as obese and often has a body fat percentage exceeding 25%. Reducing fat by 25% while maintaining muscle mass and strength could shift them into a healthier weight category without compromising physical function.”

The study also analyzed specific fat depots in obese mice and found a significant 31% reduction in subcutaneous fat. More notably, reductions of 34% and 37% were observed in the epididymal and retroperitoneal fat depots, respectively—both of which are forms of visceral fat closely linked to increased risk of cardiometabolic disease. When combined with a GLP-1 receptor agonist, the Activin E antibody produced additive effects, reducing total fat mass by 77%. Subcutaneous fat loss increased to 74%, while visceral fat depots—epididymal and retroperitoneal—were reduced by 69% and 81%, respectively. The data was presented at the 14th International BMP Conference that occurred May 2–6 in Philadelphia, Pennsylvania.

About iBio, Inc.

iBio (Nasdaq: IBIO) is a cutting-edge biotech company leveraging AI and advanced computational biology to develop next-generation biopharmaceuticals for cardiometabolic diseases, obesity, cancer and other hard-to-treat diseases. By combining proprietary 3D modeling with innovative drug discovery platforms, iBio is creating a pipeline of breakthrough antibody treatments to address significant unmet medical needs. Our mission is to transform drug discovery, accelerate development timelines, and unlock new possibilities in precision medicine.  For more information, visit www.ibioinc.com or follow us on LinkedIn.

Forward-Looking Statements

Certain statements in this press release constitute "forward-looking statements" within the meaning of the federal securities laws. Words such as "may," "might," "will," "should," "believe," "expect," "anticipate," "estimate," "continue," "predict," "forecast," "project," "plan," "intend" or similar expressions, or statements regarding intent, belief, or current expectations, are forward-looking statements. These forward-looking statements are based upon current estimates and assumptions and include statements regarding the therapeutic potential of Activin E as a target for cardiometabolic disorders and obesity; Activin E being a promising novel therapeutic target whose inhibition is believed to induce fat-selective weight loss and offer protection against obesity and cardiometabolic disease; plans to rapidly advance testing of the antibody in more complex models; the in-licensed antibody being the first functional inhibitor of Activin E; inhibiting Activin E-mediated signaling offering a novel therapeutic strategy to reduce internal abdominal fat while preserving muscle mass potentially reversing obesity, preventing diabetes, and improving overall cardiometabolic health. As one of several cellular components involved in cardiometabolic regulation; Activin E, along with amylin, GLP-1 and others, having the potential to be targeted simultaneously to yield synergistic benefits for patients; and the antibody having the potential to deliver meaningful benefits to patients. While iBio believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements, which are based on information available to us on the date of this release. These forward-looking statements are subject to various risks and uncertainties, many of which are difficult to predict that could cause actual results to differ materially from current expectations and assumptions from those set forth or implied by any forward-looking statements. Important factors that could cause actual results to differ materially from current expectations include, among others, the ability of Activin E to be a successful target for cardiometabolic disorders and obesity and iBio’s antibody to induce fat-selective weight loss and offer protection against obesity and cardiometabolic disease; iBio’s ability to obtain regulatory approvals for commercialization of its product candidates, or to comply with ongoing regulatory requirements; regulatory limitations relating to iBio’s ability to promote or commercialize its product candidates for specific indications; acceptance of iBio’s product candidates in the marketplace and the successful development, marketing or sale of products; and whether iBio will incur unforeseen expenses or liabilities or other market factors; and the other factors discussed in iBio’s filings with the SEC including its Annual Report on Form 10-K for the year ended June 30, 2024 and its subsequent filings with the SEC on Forms 10-Q and 8-K. The information in this release is provided only as of the date of this release, and iBio undertakes no obligation to update any forward-looking statements contained in this release on account of new information, future events, or otherwise, except as required by law.

Corporate Contact:
iBio, Inc.
Investor Relations
ir@ibioinc.com

Media Contacts:
Ignacio Guerrero-Ros, Ph.D., or David Schull
Russo Partners, LLC
Ignacio.guerrero-ros@russopartnersllc.com
David.schull@russopartnersllc.com
(858) 717-2310 or (646) 942-5604

FAQ

What are the key results of iBio's (IBIO) Activin E antibody in obesity treatment?

iBio's Activin E antibody achieved 26% fat mass reduction while preserving muscle mass in obese mice, and when combined with GLP-1 agonists, showed 77% fat mass reduction and 35.3% total weight loss.

How does iBio's (IBIO) Activin E antibody differ from current obesity treatments?

Unlike current obesity drugs that may reduce muscle mass, iBio's Activin E antibody specifically targets fat reduction while preserving muscle mass, potentially offering better quality weight loss.

What was the effect of iBio's (IBIO) Activin E antibody on visceral fat?

The antibody reduced epididymal and retroperitoneal visceral fat deposits by 34% and 37% respectively, which are strongly linked to cardiometabolic disease risk.

How does iBio's (IBIO) Activin E antibody perform when combined with GLP-1 drugs?

When combined with GLP-1 receptor agonists, the antibody showed synergistic effects, achieving 77% total fat mass reduction and 35.3% total weight loss, exceeding GLP-1 alone by 7.5%.

What stage of development is iBio's (IBIO) Activin E antibody in?

The Activin E antibody is in preclinical development, with results from a 4-week study in diet-induced obese mice recently completed.