Enlivex Announces Positive Interim Data – Statistically Significant 47.0% Durable and Persistent Pain Reduction At Six Months, in Patients with Moderate to Severe Knee Osteoarthritis

Rhea-AI Summary

Enlivex Therapeutics (NASDAQ: ENLV) has reported positive interim six-month efficacy data from its Phase I/II Allocetra™ trial for moderate to severe knee osteoarthritis treatment. The data showed a statistically significant 47.0% reduction in pain (P=0.0001) compared to baseline, with 83% of patients responding to treatment after 6 months.

Key improvements include a 46% enhancement in joint function and 40% improvement in joint stiffness. The trial demonstrated strong persistence and durability, maintaining the positive effects observed at 3 months. No serious adverse events were reported, with only mild transient discomfort/pain or swelling following injections.

The trial is currently progressing to its Phase II stage, a double-blind, randomized, placebo-controlled study. The company expects topline data readout by Q3 2025, evaluating joint-pain and function compared to placebo at three, six, and 12 months post-treatment.

Positive

• 47.0% statistically significant pain reduction at 6 months (P=0.0001)
• 83% of patients maintained response after 6 months
• 46% improvement in joint function
• 40% improvement in joint stiffness
• No serious adverse events reported
• Strong durability of treatment effects

Negative

• None.

Insights

Biotech Research Analyst

Enlivex's interim 6-month data for Allocetra in knee osteoarthritis delivers compelling evidence of durable therapeutic effect. The 47.0% pain reduction (P=0.0001) represents statistically robust efficacy that has maintained consistency from the 3-month timepoint, addressing one of the most significant challenges in osteoarthritis treatment - durability of response.

The 83% responder rate at 6 months is particularly impressive, suggesting Allocetra's macrophage reprogramming mechanism may offer advantages over current standards of care that typically show waning efficacy. The comprehensive improvement across multiple symptoms (pain, function, stiffness) indicates a therapy potentially addressing the condition's underlying pathology rather than merely masking symptoms.

For context, this data positions Allocetra favorably within the osteoarthritis treatment landscape, where many interventions struggle to maintain efficacy beyond 3 months. The progression to a properly powered, randomized Phase II stage with the anticipated Q3 2025 readout represents the critical next validation step.

For a company with Enlivex's current market footprint, these results constitute a significant milestone that could substantially alter its valuation trajectory if confirmed in the placebo-controlled study. The clean safety profile further enhances the risk-reward proposition for this novel immunotherapy approach in a condition affecting hundreds of millions globally.

Orthopedic Medicine Specialist

The 6-month persistence of Allocetra's therapeutic effect in knee osteoarthritis represents clinically meaningful data. A 47.0% reduction in pain combined with 46% improvement in function and 40% in stiffness indicates comprehensive symptom relief that patients would consider significant in their daily lives.

From a clinical perspective, the durability from 3 to 6 months addresses a important unmet need. Current injectable interventions for moderate-to-severe knee OA (corticosteroids, hyaluronic acid) typically show declining efficacy within 1-3 months, often requiring repeated administrations with diminishing returns. Allocetra's sustained benefit profile suggests potential for extended symptomatic relief with fewer interventions.

The clean safety profile with only mild injection-site reactions is particularly important for chronic conditions requiring long-term management. The absence of serious adverse events supports a favorable risk-benefit ratio that clinicians and patients would find acceptable.

While this data is promising, the upcoming double-blind, placebo-controlled Phase II stage will be essential to definitively establish efficacy. Placebo effects can be substantial in osteoarthritis trials, particularly for injectable therapies. The strongly significant P-value (0.0001) in the open-label phase is encouraging, but blinded confirmation will be important for clinical and regulatory acceptance of Allocetra's novel immunomodulatory approach to osteoarthritis management.

 Nes-Ziona, Israel, March 03, 2025 (GLOBE NEWSWIRE) -- Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the “Company”), a clinical-stage macrophage reprogramming immunotherapy company, today announced positive interim six-month efficacy data from the Phase I stage  of its randomized, multi-country Phase I/II Allocetra™ trial in patients with moderate to severe knee osteoarthritis.

Key highlights:

• Statistically significant 47.0% average reduction of reported pain (P=0.0001) compared to average pain level at baseline
• 46% improvement in joint function and 40% improvement in joint stiffness
• 83% of the patients were still considered as responders to treatment⁴ after 6 months
• No serious adverse events
• Efficacy continues to display strong persistence and durability over time, maintaining the 3-month positive effect

Oren Hershkovitz, Ph.D, CEO of Enlivex, commented, “We are very excited about the 6-month interim results. The substantial and persistent pain reduction in these patients following Allocetra^TM treatment is extremely important. We believe patients with moderate to severe knee osteoarthritis seek treatment offering an immediate, durable and marked improvement in their pain and function, and we believe these results, together with our previously reported Phase I interim results of patients measured three months following the administration of Allocetra™ injections, demonstrate the potential for Allocetra™ to be such a treatment. Our recruitment efforts for the Phase II stage of this trial are going according to plan, and we remain fully committed to assessing Allocetra’s novel mechanism of action as a treatment alternative for patients with moderate to severe knee osteoarthritis.”

The multi-center Phase I/II clinical trial consists of two stages. The first stage, which was successfully completed, was a Phase I safety run-in, open-label dose escalation phase to characterize the safety and tolerability of Allocetra™ injections to the target knee in order to identify the dose and injection regimen for the subsequent Phase II stage described below. This second stage is progressing along the previously announced timeline, and the Company currently expects a topline data readout from the Phase I/II trial by the third quarter of 2025.

The Company previously announced positive 3-month interim safety and efficacy results for the first 12 patients treated in the Phase I stage. The previously announced data demonstrated a marked statistically significant improvements in all key efficacy endpoints, including 50%¹ average pain reduction and 42% and 37% improvement in functionality and stiffness, respectively, compared to the baseline². All 12 patients in the Phase I stage completed the assessment at 6 months following the last injection³, and the data from such assessments showed a statistically significant 47.0% average reduction of reported pain (P=0.0001), compared to the pain level at baseline. The reported reduction in pain was consistent with the data from the WOMAC questionnaire used to assess function and stiffness, in addition to pain, which showed a 51.2% reduction in the WOMAC pain, a 46% improvement in WOMAC function and a 40% improvement in WOMAC stiffness. Similar to the 3-month interim analysis for the Phase I data, 83% of the patients were still considered as responders to treatment⁴. The 6-month interim results have remained consistent with the results reported at 3 months, indicating a durable and substantial improvement in pain and functional capacity up to 6 months following the last injection. Safety profile of Allocetra™ was also consistent with previous report as well, with no serious adverse events while transient events of discomfort/pain or swelling in the knee following injection were reported, mostly mild in severity.

The trial is currently enrolling patients into the Phase II stage, which is a double-blind, randomized, placebo-controlled trial. In addition to evaluating safety, this blinded randomized second stage is statistically powered to assess the efficacy of Allocetra™ injections into the knee. The trial’s key efficacy end points will evaluate joint-pain and joint-function in comparison to placebo at three months, six months and 12 months post treatment.

ABOUT KNEE OSTEOARTHRITIS

Osteoarthritis is by far the most common form of arthritis, affecting more than 32.5 million Americans and more than 300 million individuals worldwide. About half of knees with ACL injuries develop osteoarthritis within 5 to 15 years. 78 million Americans are projected to have osteoarthritis by the year 2040. Symptomatic knee osteoarthritis is particularly prevalent and disabling, with 40% of men and 47% of women developing knee osteoarthritis in their lifetimes. Osteoarthritis accounts for over one million hospitalizations annually in the United States, primarily for total joint replacement. The burden of osteoarthritis is enormous, and the need for treatments that reduce pain and attendant disability for persons with osteoarthritis is critical. There are currently no medications approved by either the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA) that have been demonstrated to arrest, slow or reverse progression of structural damage in the joint.

ABOUT ENLIVEX

Enlivex is a clinical stage macrophage reprogramming immunotherapy company developing Allocetra™, a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Resetting non-homeostatic macrophages into their homeostatic state is critical for immune system rebalancing and resolution of life-threatening and life debilitating conditions. For more information, visit https://enlivex.com/.

Safe Harbor Statement: This press release contains forward-looking statements, which may be identified by words such as “expects,” “plans,” “projects,” “will,” “may,” “anticipates,” “believes,” “should,” “would,” “could,” “intends,” “estimates,” “suggests,” “has the potential to” and other words of similar meaning, including statements regarding expected cash balances, expected clinical trial results, market opportunities for the results of current clinical studies and preclinical experiments, the effectiveness of, and market opportunities for, ALLOCETRA^TM programs. All such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that forward-looking statements involve risks and uncertainties that may affect Enlivex’s business and prospects, including the risks that Enlivex may not succeed in generating any revenues or developing any commercial products; that the products in development may fail, may not achieve the expected results or effectiveness and/or may not generate data that would support the approval or marketing of these products for the indications being studied or for other indications; that ongoing studies may not continue to show substantial or any activity; and other risks and uncertainties that may cause results to differ materially from those set forth in the forward-looking statements. The results of clinical trials in humans may produce results that differ significantly from the results of clinical and other trials in animals. The results of early-stage trials may differ significantly from the results of more developed, later-stage trials. The development of any products using the ALLOCETRA^TM product line could also be affected by a number of other factors, including unexpected safety, efficacy or manufacturing issues, additional time requirements for data analyses and decision making, the impact of pharmaceutical industry regulation, the impact of competitive products and pricing and the impact of patents and other proprietary rights held by competitors and other third parties. In addition to the risk factors described above, investors should consider the economic, competitive, governmental, technological and other factors discussed in Enlivex’s filings with the Securities and Exchange Commission, including in the Company’s most recent Annual Report on Form 20-F filed with the Securities and Exchange Commission. The forward-looking statements contained in this press release speak only as of the date the statements were made, and we do not undertake any obligation to update forward-looking statements, except as required under applicable law.

ENLIVEX CONTACT

Shachar Shlosberger, CFO
Enlivex Therapeutics, Ltd.
shachar@enlivexpharm.com

INVESTOR RELATIONS CONTACT

Dave Gentry, CEO
RedChip Companies Inc.
1-407-644-4256
ENLV@redchip.com

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¹ Percent reduction calculated per patient and then averaged for all patients.
² Function and stiffness were assessed via Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire.
³ One patient received a steroid injection to the target knee 2 months prior to assessment
⁴ According to the OMERACT-OARSI criteria (Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International)
⁵ Source: The Arthritis Foundation, Disease modification in osteoarthritis; pathways to drug approval, Katz et. Al., Osteoarthritis and Cartilage Open (2) (2020)

FAQ

What are the key efficacy results of ENLV's Allocetra trial for knee osteoarthritis at 6 months?

The trial showed 47.0% pain reduction, 46% improvement in joint function, and 40% improvement in stiffness, with 83% of patients responding to treatment after 6 months.

When will Enlivex (ENLV) release the Phase I/II Allocetra trial topline data?

Enlivex expects to release the topline data from the Phase I/II trial by the third quarter of 2025.

What safety profile did Allocetra demonstrate in ENLV's knee osteoarthritis trial?

No serious adverse events were reported, with only mild transient discomfort/pain or swelling following injections.

How does the 6-month data compare to the 3-month results in ENLV's Allocetra trial?

The 6-month results remained consistent with the 3-month data, showing durable and substantial improvements in pain and functional capacity.

What is the design of ENLV's Phase II Allocetra trial for knee osteoarthritis?

The Phase II is a double-blind, randomized, placebo-controlled trial evaluating safety and efficacy of Allocetra injections versus placebo at 3, 6, and 12 months.