Rethinking Clinical Development In The Age Of Synthetic Cell Therapy

By Sanjeev Luther, president and CEO, Ernexa Therapeutics

I have been fortunate to spend the better part of my career at the intersection of cutting-edge science and clinical development. I watched breakthroughs move from bench to bedside, and sometimes stall along the way. I saw what happens when innovation outpaces infrastructure. Cell therapy holds immense potential, and it is on us as clinical developers to rise to its demands and better shape its future.

One area that is particularly reshaping the playbook is synthetic biology, especially when applied to engineered stem cells, such as induced mesenchymal stem cells (iMSCs), a more specialized type of stem cell that has a unique ability to migrate toward tumors or areas of inflammation. These are not your traditional MSCs pulled from a donor and infused into a patient. These are programmable, living therapies engineered to home in on tumors or inflamed tissues, delivering cytokines precisely where they are needed, with greater consistency and control than ever before.

They represent a new frontier. But to get them to patients, we need to reimagine how we develop and evaluate them.

Not Just a New Therapy, A New Therapeutic Model

The promise of synthetic, allogeneic iMSCs is immense. Because they are derived from a single donor source and bioengineered for function, they can be manufactured at scale and stored for off-the-shelf use. This solves many of the practical hurdles that have long held cell therapy back, like the need for patient-specific cell harvesting and weeks-long production timelines.

But here is the catch: While these therapies may solve old problems, they introduce new ones. And those problems land squarely on the desks of clinical teams.

Take dosage, for example. When you are dealing with a living therapeutic, especially one that can persist and interact with the immune system, the “more is better” logic of small molecules does not apply. Too much, and you risk an immune response. Too little, and the therapy may not take hold. We are no longer just looking at safety and tolerability. We are watching for real-time biological activity.

This is where pharmacodynamic markers become essential. We need to understand how the cells behave in the body, how long they last, and what kind of immune activation they generate. In engineered iMSCs designed to release IL-7 and IL-15, for instance, the goal is to kickstart a T cell response in the tumor microenvironment, not to flood the entire system with cytokines. That is a delicate balance, and one we can only achieve by measuring the right biomarkers at the right time.

The Right Trial Design

In early-phase trials, traditional dose escalation approaches may not work here. Instead, we may need to move toward adaptive designs that allow us to course-correct in real time, based on what we learn from each cohort — not just in terms of safety but in terms of cell persistence, cytokine expression, and evidence of immune modulation.

And we cannot rely solely on tumor shrinkage or symptom scores as our endpoints. In cell therapy, benefit may emerge gradually or manifest in the form of immune reprogramming that does not immediately translate to radiographic response. That makes endpoint selection more complicated but also more important.

We should also consider integrating patient-reported outcomes, especially in diseases like autoimmune disorders, where flare patterns are unpredictable and the patient experience can be difficult to quantify. Patients often know before we do when a treatment is working — or, unfortunately, when it is not.

The Consent Conversation Is Changing

I want to pause here to talk about something that does not often receive enough attention in clinical discussions: the informed consent process. These therapies are complicated. They involve donor cells, genetic reprogramming, immune system modulation, and a level of novelty that can overwhelm even the most well-informed patient.

We owe it to patients to explain, in plain language, what we are asking of them. Not just the mechanics of participation, but the "why" behind our approach: why we chose the endpoints we did, why we believe in the science, and what we hope their contribution will mean — not just for them but for future patients.

For those who have cycled through failed therapies or watched loved ones do the same, that conversation can be deeply emotional. It should be. We are asking them to place their trust in something that has not yet proven itself, and that trust must be earned with empathy, transparency, and humility.

Regulators Are Listening. Let’s Talk to Them Early.

The regulatory path for synthetic cell therapies is evolving, and that is both a challenge and an opportunity. Agencies are open to new ideas, but they need us to come prepared. That means a clear rationale for our trial design, robust data on manufacturing consistency, and a plan for how we will monitor long-term safety.

Potency assays, release criteria, and immune monitoring all require a new level of precision. We are no longer just making a product; we are orchestrating a living system.

That is why early and ongoing dialogue with regulators is so critical. This is not to check a box; it is a collaboration. And when done right, it can shape smarter, more efficient development paths that benefit everyone, most of all the patient.

Meeting The Moment

There is a quiet revolution happening in cell therapy. We are moving from artisan-level cell crafting to industrial-scale precision engineering and from a patchwork of bespoke protocols to platforms that can be replicated and deployed across indications.

But with that leap forward comes responsibility. As clinical developers, we are no longer just stewards of trials. We are architects of a new clinical paradigm. We must think differently. Move faster. Communicate better. And above all, stay grounded in what brought us here: a desire to bring hope, healing, and new options to patients who have waited far too long.

Synthetic biology will not just change what we treat; it will change how we think about treatment. Let’s make sure our clinical development models evolve with it.

About The Author:

Sanjeev Luther is the president and CEO of Ernexa Therapeutics and a member of the Board of Directors. Sanjeev is a seasoned pharmaceutical executive with over 30 years in leadership roles at organizations including Cornerstone Pharmaceuticals, Bristol Myers Squibb, Novartis, Bausch and Lomb, and GE Healthcare.

Ernexa Therapeutics is developing innovative cell therapies for the treatment of advanced cancer and autoimmune disease. Its lead cell therapy product, ERNA-101, is being developed for the treatment of ovarian cancer, and ERNA-201 for autoimmune disease.