6 month findings from ENX-CL-05-001: A phase 2a study of Allocetra in knee osteoarthritis

Positive phase 2a data support the further development of allogeneic cell therapy, Allocetra, for knee osteoarthritis.

ENX-CL-05-001 (NCT06233474) is a randomized, double-blind, placebo-controlled phase 2a study investigating intra-articular Allocetra in patients with symptomatic moderate-severe knee osteoarthritis.

We spoke with Prof. Philip Conaghan (University of Leeds, Leeds, UK) around the clinical burden and risk factors associated with OA, and the mechanism of action of Allocetra. Prof. Conaghan also discusses the aims and design of the phase 2a study, the efficacy and safety findings at 6 months, and the next steps in the development of Allocetra.

Abstract: Durable efficacy at 6 months using an innovative intra-articular apoptotic cell therapy in knee osteoarthritis: Data from a phase IIA RCT. EULAR 2026, June 3– 6, London, UK.

touchIMMUNOLOGY coverage of EULAR 2026

My name is Philip Conaghan, I am an MD, PhD from the University of Leeds in the UK, where I am also Director of the NIHR Biomedical Research Centre.

Could you tell us about the clinical burden and risk factors associated with knee osteoarthritis?

It is generally well recognized that osteoarthritis presents a significant global burden, with knee osteoarthritis accounting for a large, and perhaps the largest, part of that burden. Globally, more than 600 million people are estimated to be affected by osteoarthritis. We know that around one-third of these individuals experience moderate to severe symptoms and are the group most actively seeking additional treatment options.

The major challenge we face is that current osteoarthritis management consists of a combination of non-pharmacological and pharmacological therapies. The non-pharmacological approaches that are generally effective include muscle strengthening or physiotherapy and weight loss, which is entering a new era with additional therapies coming to market.

On the pharmacological side, we have not had a new effective therapy for many years. Current standard pharmacological therapy typically consists of topical or oral anti-inflammatory drugs, along with occasional intra-articular steroid injections. We also know that many people cannot tolerate or use anti-inflammatory drugs, and there are limits to how many steroid injections an individual can receive, as well as limits on the healthcare system’s capacity to provide them. As a result, there is a clear and urgent need for new therapies.

What is the mechanism of action of Allocetra?

In osteoarthritis, the synovium contains large numbers of activated macrophages that drive the inflammatory process and are associated with pain. We also know that, with immunosenescence and aging, macrophages increasingly adopt a pro-inflammatory phenotype.

We have known for many years that apoptotic cells have immunomodulatory properties and can reduce inflammation through their uptake by activated macrophages. This allogeneic cell therapy, Allocetra, harnesses the natural properties of apoptotic cells by taking human volunteer mononuclear cells and creating an apoptotic cell phenotype. These cells are then taken up by macrophages in inflamed joint tissues, promoting a homeostatic, or much less inflammatory, environment.

Could you describe the aims and design of the phase 2a study?

The study we have recently reported on in meetings was a phase 1/2a study. The phase 1 part was a dose ranging study and the phase 2a part looked at safety as the primary outcome. Then the secondary outcomes were assessing efficacy and biomarkers to predict efficacy. There was also a pre-specified, machine learning-driven analysis that looked for responders. In most trials we try to identify the populations that are most responsive to therapy, and in this case, we did that with a machine learning approach.

What were the efficacy and safety findings at 6 months?

In terms of the trial outcomes, we previously reported the 3-month data, and the 6-month data comfortingly looks very much the same. Firstly, in terms of the primary outcome, which was safety, there were no new safety events reported. Although there were more safety events in the Allocetra arm compared to placebo, most of these seemed to be swollen, tender and painful joints, which were short-lived and mostly managed with conservative therapy.

In terms of the secondary outcomes of efficacy in the modified intention-to-treat (mITT) analysis, we didn’t see a statistical benefit for the therapy over placebo, but there was a numeric benefit. In the predefined machine learning subset, we observed a signal of increasing benefit, in terms of reduced pain and improved function, with increasing age. The first signal emerged in patients over 60 years of age, who represented about half of the study population, and the signal became stronger in older age groups, such as those over 64 years of age. The limitation was that the number of patients decreased as we moved into subsets; however, these findings were consistent with the proposed immunomodulatory mechanism of Allocetra.

What will be the next steps towards realizing the potential of Allocetra?

We now need a larger study in the correct population, and a phase 2b trial is currently underway to explore if this mechanism holds up in an older age population of osteoarthritis.