TNF Pharmaceuticals Initiates Phase 2b Clinical Trial of First Oral TNF-Alpha Inhibitor

Rhea-AI Summary

TNF Pharmaceuticals (NASDAQ: TNFA) has initiated a Phase 2b clinical trial for isomyosamine, their oral TNF-alpha inhibitor drug candidate, targeting chronic inflammation associated with muscle loss in post-surgical hip/femur fracture patients.

The fully funded, randomized, placebo-controlled study at the University of Florida will evaluate 60 patients for up to 90 days post-surgery. The trial builds on previous positive Phase 2a results and aims to explore isomyosamine's efficacy in preventing progressive muscle loss and frailty.

Key advantages of isomyosamine include:

• Oral administration versus current injection/infusion-only options
• Selective TNF-α blocking where overactivated
• Ability to cross blood-brain barrier
• Lower risk of serious side effects compared to traditional treatments

The target market is substantial:

• TNF-alpha inhibitor market: $39.7B (2024), expected to reach $47.3B by 2029
• Sarcopenia affects 10-16% of elderly population
• Sarcopenia treatment market: $3.07B (2024), projected to reach $4.0B by 2029

Positive

• First oral TNF-alpha inhibitor in $40B+ market
• Fully funded Phase 2b trial initiated
• Built on positive Phase 2a results
• Unique advantages: oral administration, selective blocking, brain barrier penetration
• Large market opportunity: sarcopenia affects 10-16% of elderly
• No FDA-approved treatments for sarcopenia currently

Negative

• Early-stage clinical trial - no guaranteed success
• Faces competition in $40B+ TNF inhibitor market
• patient size (60) in Phase 2b trial

Insights

Pharmaceutical Research Analyst

TNF Pharmaceuticals has initiated a fully funded Phase 2b clinical trial for isomyosamine, potentially the first oral TNF-alpha inhibitor, targeting muscle loss in post-surgical hip fracture patients. This development represents a significant milestone in the company's clinical program and warrants careful investor attention.

The advancement to Phase 2b follows positive Phase 2a results and positions TNFA to potentially disrupt the $40+ billion TNF inhibitor market. What makes this particularly compelling is the current landscape where all existing TNF-alpha inhibitors require injection or infusion—a substantial barrier to patient compliance and quality of life. An effective oral alternative would represent a paradigm shift in treatment approach.

The sarcopenia indication is strategically chosen and commercially significant. With 50+ million affected patients globally and projections exceeding 200 million in the coming decades, sarcopenia represents a $3.07 billion market growing at 4.5% CAGR. More importantly, there are currently no FDA-approved treatments specifically for sarcopenia despite its $40+ billion burden on healthcare systems—creating a clear unmet medical need and regulatory opportunity.

Isomyosamine's differentiated profile extends beyond its oral administration. Its selective blocking mechanism targets overactive TNF-alpha while preserving normal immune function, potentially avoiding the serious side effects that plague current immunosuppressive therapies. Additionally, its ability to cross the blood-brain barrier could open therapeutic avenues for neuroinflammatory conditions in the future.

The Phase 2b trial design includes several noteworthy elements: the 90-day treatment duration will provide robust data on sustained efficacy; the focus on functional improvement aligns with FDA's preference for clinically meaningful endpoints; and the involvement of the University of Florida adds institutional credibility.

For investors, the risk/reward profile here is compelling given TNFA's current $1.18 million market capitalization relative to the multi-billion dollar market opportunity. However, this disparity also reflects the significant development and regulatory hurdles that remain. The 60-patient sample size, while appropriate for Phase 2b, means larger pivotal trials will be necessary before commercialization.

The "fully funded" trial status suggests adequate near-term cash runway, but investors should monitor burn rate and potential future capital needs as development progresses toward more expensive late-stage trials.

Biotechnology Development Specialist

TNF Pharmaceuticals' initiation of a Phase 2b trial for isomyosamine represents a potential inflection point in both the company's development trajectory and the broader TNF-alpha inhibitor landscape. The significance of this milestone extends beyond the immediate clinical program.

The blood-brain barrier penetration capability of isomyosamine isn't just a technical achievement—it's a fundamental differentiator that could unlock therapeutic applications for neuroinflammatory conditions that remain largely untreatable with current biologics. This property, combined with its selective inhibition mechanism, suggests a potential safety advantage over existing treatments that cause systemic immunosuppression.

From a development perspective, advancing to Phase 2b following positive Phase 2a results marks a critical risk-reduction milestone. However, investors should note that Phase 2b success typically translates to approximately 30-40% probability of eventual FDA approval—substantial progress, but significant hurdles remain. The 60-patient trial size, while appropriate for this stage, means larger pivotal studies of 200-300+ patients would likely be required before regulatory submission.

The strategic focus on sarcopenia is particularly astute. This condition affects 10-16% of elderly worldwide with projections reaching 200+ million patients in coming decades. More importantly, despite its $40+ billion burden on healthcare systems, sarcopenia lacks FDA-approved treatments—creating a regulatory pathway with potentially fewer competitive obstacles than established inflammatory indications.

The economic case is compelling. Currently, TNF-alpha inhibitors like adalimumab (Humira) and etanercept (Enbrel) command premium pricing despite their injection requirements. An oral alternative with comparable efficacy could command similar pricing while expanding the addressable patient population unwilling to accept injections. This positions isomyosamine as potentially both a market-expanding and market-share-capturing agent.

The disconnect between TNFA's $1.18 million market capitalization and the $40+ billion TNF inhibitor market represents either significant undervaluation or appropriate risk adjustment. For context, even capturing 1% of the TNF inhibitor market would represent $400+ million in annual revenue potential—highlighting the asymmetric risk/reward profile.

The "fully funded" trial status is noteworthy but requires context. Phase 2b trials typically cost $5-15 million, suggesting either substantial cash reserves relative to market cap or strategic partnerships providing non-dilutive funding. Investors should monitor cash runway closely as Phase 3 trials would require significantly greater capital.

Success in this trial could position TNF Pharmaceuticals as an attractive acquisition target for larger pharmaceutical companies seeking to protect existing TNF inhibitor franchises facing biosimilar competition.

Fully funded multi-center study initiated at University of Florida to further explore efficacy of isomyosamine for preventing progressive muscle loss and frailty

Study builds on positive results achieved in earlier Phase 2a trial

TNF-alpha inhibitor market estimated at $40+ billion with no FDA-approved oral treatments

BALTIMORE--(BUSINESS WIRE)-- TNF Pharmaceuticals, Inc. (Nasdaq: TNFA) (“TNF” or the “Company”), a clinical stage biopharmaceutical company committed to developing novel therapies for autoimmune and inflammatory conditions, today announced the initiation of a fully funded Phase 2b clinical trial evaluating oral TNF-alpha (TNF-α) inhibitor drug candidate isomyosamine as a treatment for chronic inflammation associated with muscle loss (frailty or sarcopenia) in patients who have undergone hip or femur fracture repair surgery.

“The initiation of our Phase 2b isomyosamine trial marks an important milestone in our mission to develop a novel science for immuno-metabolic regulation and increased longevity,” said Mitchell Glass, M.D., President and Chief Medical Officer of TNF. “A deeper exploration of isomyosamine’s efficacy will be studied in patients with acute post-surgical inflammation and complications from hip or femur fractures. In addition to further functional decline, these patients face a higher likelihood of complications that can compromise or delay recovery and are associated with higher healthcare costs.”

According to Jay Magaziner, Ph.D., Director of the Center for Research on Aging at the University of Maryland and founder of the Baltimore Hip Studies project that evaluates outcomes after hip fractures in older patients, “After hip fracture, older patients can precipitously lose bone, muscle, and function, which is associated with a systemic inflammatory response. If we can block this inflammatory response, we have a chance to reduce the amount of muscle loss and the associated functional loss, leading to better outcomes in hip fracture among older persons.”

The upcoming Phase 2b trial to be initiated at the University of Florida is a randomized, placebo-controlled, double-blind study evaluating the efficacy and safety of isomyosamine in reducing inflammation in patients with sarcopenia undergoing fracture repair. Sixty patients will be treated with isomyosamine or placebo for up to 90 days after surgery. The study will measure the extent and time course of recovery to evaluate functional improvement, comparing active dosing to placebo.

The site’s principal investigator is Porter Young, M.D., an assistant professor of orthopaedic surgery and rehabilitation at the University of Florida. His research centers on acetabulum fractures, pelvis fractures, periarticular fractures and management of polytrauma patients.

Isomyosamine is an oral, next-generation TNF-α inhibitor with the potential to transform the way TNF-α based diseases are treated due to its selectivity and ability to cross the blood brain barrier. Its ease of oral dosing is a significant differentiator compared to currently available TNF-α inhibitors, all of which require delivery by injection or infusion. Isomyosamine has also been shown to selectively block TNF-α action where it is overactivated without preventing it from doing its normal job of responding to routine infection. In addition, in early clinical studies it has not been associated with serious side effects known to occur with traditional immunosuppressive therapies that treat inflammation.

Burden of Sarcopenia

Sarcopenia (ICD-10-CM code M62.84) affects approximately 10% to 16% of the elderly worldwide.¹ It is also estimated to affect more than 1 in every 10 young adults of most ethnicities.² Based on conservative calculations, at least 50 million people were affected by sarcopenia in 2018, and the disease is projected to affect over 200 million over the next four decades due to the growing elderly population.³

The sarcopenia treatment market is estimated to be $3.07 billion in 2024 and is expected to grow at a compound annual growth rate (CAGR) of 4.5% to $4.0 billion by 2029.⁴ With no FDA-approved treatments for sarcopenia, the estimated $40+ billion in related hospitalization costs is a considerable economic burden on the U.S. healthcare system.⁵

The global market value for TNF inhibitor drugs was estimated to be $39.7 billion in 2024. Growing at an expected CAGR of 3.6% for the next five years, the TNF inhibitor market is expected to reach $47.3 billion by 2029.⁶

About Isomyosamine

Isomyosamine is a novel plant alkaloid small molecule shown to regulate the immuno-metabolic system through the modulation of numerous pro-inflammatory cytokines including TNF-alpha (TNF-α), an immune cell signaling protein and inflammatory cytokine responsible for inducing and maintaining the inflammatory process. TNF-α is located upstream of a cascade of molecular signals that induces inflammation and helps activate the process of aging. Many in vivo and in vitro studies have shown that TNF-α plays a causative role in the pathogenesis of various age-related diseases.

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¹ Metabolism journal, Epidemiology of sarcopenia: Prevalence, risk factors, and consequences (2023)
² Metabolism journal, Sarcopenia in youth (2023)
³ Biology, Sarcopenia Is Associated with an Increased Risk of Postoperative Complications… (2023)
⁴ Mordor Intelligence, Sarcopenia Treatment Market Size & Share Analysis - Growth Trends & Forecasts (2024 - 2029)
⁵ Journal of Frailty & Aging, Economic Impact of Hospitalizations in US Adults with Sarcopenia (2019)
⁶ Mordor Intelligence, TNF Inhibitors Market Size (2024 - 2029)

About TNF Pharmaceuticals, Inc.

TNF Pharmaceuticals, Inc. (Nasdaq: TNFA), a clinical stage pharmaceutical company committed to extending healthy lifespan, is focused on developing two novel therapeutic platforms that treat the causes of disease rather than only addressing the symptoms. Isomyosamine is a drug platform based on a clinical stage small molecule that regulates the immune system to control TNF-α, which drives chronic inflammation and other pro-inflammatory cell signaling cytokines. Isomyosamine is being developed to treat diseases and disorders marked by acute or chronic inflammation. The Company’s second drug platform, Supera-CBD, is being developed to treat chronic pain, addiction and epilepsy. Supera-CBD is a novel synthetic derivative of cannabidiol (CBD) and is being developed to address and improve upon the rapidly growing CBD market, which includes both FDA approved drugs and CBD products not currently regulated as drugs. For more information, visit www.tnfpharma.com.

About the University of Florida

The University of Florida is a premier academic institution that has repeatedly ranked as one of the top five public universities in the country, according to U.S. News & World Report. With campuses in Gainesville and Jacksonville, UF’s health sciences centers and colleges attract the brightest students, scholars, scientists and health care providers from across the country and abroad.

UF faculty conducted a record $1.26 billion in research in fiscal year 2024.

Cautionary Statement Regarding Forward-Looking Statements

This press release may contain forward-looking statements. These forward-looking statements involve known and unknown risks, uncertainties and other factors which may cause actual results, performance or achievements to be materially different from any expected future results, performance, or achievements. Forward-looking statements speak only as of the date they are made and neither the Company nor its affiliates assume any duty to update forward-looking statements. Words such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “may,” “plan,” “will,” “would’’ and other similar expressions are intended to identify these forward-looking statements. Examples of such statements include, but are not limited to, statements regarding the Company’s ability to launch, the success and timing of, the Company’s planned trial of isomyosamine (MYMD-1®) as a treatment for GLP-1-induced sarcopenia and frailty. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements include, without limitation: the Company’s ability to maintain compliance with the Nasdaq Stock Market’s listing standards; the timing of, and the Company’s ability to, obtain and maintain regulatory approvals for clinical trials of the Company’s pharmaceutical candidates; the timing and results of the Company’s planned clinical trials for its pharmaceutical candidates; the amount of funds the Company requires for its pharmaceutical candidates; increased levels of competition; changes in political, economic or regulatory conditions generally and in the markets in which the Company operates; the Company’s ability to retain and attract senior management and other key employees; the Company’s ability to quickly and effectively respond to new technological developments; and the Company’s ability to protect its trade secrets or other proprietary rights, operate without infringing upon the proprietary rights of others and prevent others from infringing on the Company’s proprietary rights. A discussion of these and other factors with respect to the Company is set forth in the Company’s Annual Report on Form 10-K for the year ended December 31, 2023, filed by the Company on April 1, 2024, and subsequent reports that the Company files with the Securities and Exchange Commission. Forward-looking statements speak only as of the date they are made, and the Company disclaims any intention or obligation to revise any forward-looking statements, whether as a result of new information, future events or otherwise.

View source version on businesswire.com: https://www.businesswire.com/news/home/20250225405912/en/

Investor Contact:

Robert Schatz

(646) 421-9523

rschatz@tnfpharma.com

www.tnfpharma.com

Source: TNF Pharmaceuticals, Inc.

FAQ

What are the key advantages of TNFA's isomyosamine over current TNF-alpha inhibitors?

Isomyosamine is oral (vs. injection/infusion), selectively blocks TNF-α, crosses blood-brain barrier, and shows fewer serious side effects than traditional treatments.

How many patients will be enrolled in TNFA's Phase 2b isomyosamine trial?

60 patients will be treated with isomyosamine or placebo for up to 90 days after surgery.

What is the market size for TNF inhibitors in 2024 and its growth projection?

The TNF inhibitor market is $39.7B in 2024, expected to reach $47.3B by 2029 (3.6% CAGR).

What is the prevalence of sarcopenia and its market potential for TNFA?

Sarcopenia affects 10-16% of elderly globally, with a treatment market of $3.07B in 2024, growing to $4.0B by 2029.

Where is TNFA conducting its Phase 2b trial for isomyosamine?

The trial is being conducted at the University of Florida under PI Porter Young, M.D.