“Manufacturing is not a downstream operational detail in CAR-T; it is part of the science. The process shapes the product.”
John Maher is Chief Scientific Officer of Leucid Bio, a clinical-stage biotech founded to translate more than 20 years of pioneering CAR-T research conducted at King’s College London. Leucid’s Lateral CAR platform was built on the principle of placing key functional components in a more physiological position next to the plasma membrane and is currently in Phase I/IIa clinical evaluation with lead asset LEU011 in relapsed/refractory solid tumors.
For biotech CEOs navigating CAR-T development, the manufacturing decision rarely gets the scientific scrutiny it deserves. It tends to surface as a capacity question late in the process after platform choices have already been made. John Maher thinks that sequencing is backwards. As the field confronts the limits of conventional CAR design in solid tumors, he argues that how you manufacture is inseparable from what you manufacture. The CDMO decisions you make today will determine whether your biology reaches patients at all.
Process Is Product: Why CAR-T Manufacturing Requires Scientific Discipline
Most biotech CEOs have encountered the phrase ‘the process is the product’ in the context of biologics. In CAR-T, John argues, the stakes are higher and the complexity compounds at every step.
“Culture conditions, activation methods, vector exposure, expansion duration, cryopreservation, and release assays can all influence phenotype, potency, and clinical performance. Small process changes can have meaningful biological consequences.”
— John Maher, Leucid Bio
This has shaped how Leucid structures its own manufacturing operations. The company runs an in-house CAR-T manufacturing team at Great Ormond Street Hospital, deliberately keeping the science and the manufacturing function in close contact.
“It means our scientists, clinicians, translational teams, and manufacturing specialists can work together in a highly integrated way,” John explains. “For an early-stage, differentiated platform like lateral CAR, that is extremely valuable because we are not trying to manufacture a generic CAR-T product. We are trying to preserve a very specific biology.”
The practical implication for biotech leaders is this: if your platform is scientifically differentiated, your manufacturing approach needs to reflect that differentiation from day one. The biology you are trying to preserve will not survive a manufacturing process designed for someone else’s product.
Selecting a CDMO: Five Questions That Go Beyond Capacity
When it comes to CDMO selection, John’s starting point is not capacity. Capacity matters, but it is a poor proxy for fit.
“Do not choose a CDMO on capacity alone. Capacity matters, but it is not sufficient. You need a partner whose capabilities match the biology, stage, and risk profile of your product.”
John Maher, Leucid Bio
He identifies five areas that biotech leaders should probe systematically:
- Technical fit: Has the CDMO worked with comparable autologous or engineered T-cell products? Can they support your vector system, analytics, potency assays, and release timelines? Are they strong in tech transfer, deviation management, and comparability?
- Cultural fit: In cell therapy, things go wrong. Starting material varies. Assays need refinement. Regulators ask hard questions. You need a partner that communicates transparently and solves problems scientifically, not one that reports issues after the fact.
- Forward planning: The CDMO right for a Phase I study may not be right for pivotal development or commercial supply. Map the manufacturing journey early: clinical supply, process optimization, automation, analytical validation, scale-out, regional supply, and commercial readiness.
- Scientific understanding of your platform: Any CDMO partner needs to understand autologous cell therapy, chain of identity, chain of custody, release testing, and regulatory expectations. But critically, they also need to understand why small process changes matter for your specific biology.
- Patient urgency: CAR-T patients are often very unwell with limited time. The right partner treats every batch as a patient-specific medicine, not just a production run.
That final point, patient urgency, is the one John returns to most consistently. It is not rhetorical. It describes a concrete operational requirement: a CDMO that understands the human cost of a delayed or failed batch will make different decisions under pressure than one that views the relationship as a contract manufacturing arrangement.
Internal Manufacturing as Strategic Advantage
A common assumption among biotech leaders is that internal manufacturing is a transitional phase that is necessary early, but eventually replaced by CDMO relationships as the company scales. John pushes back on that.
“The model is not ‘internal manufacturing versus CDMO.’ It is an integrated pathway. Internal manufacturing gives us control, learning, and scientific intimacy with the product. CDMO partnerships, when chosen carefully, help us scale that knowledge responsibly.”
John Maher, Leucid Bio
Leucid’s internal capability at Great Ormond Street serves a specific strategic function. It gives the team a deep practical understanding of what matters before any CDMO conversation begins. That understanding defines the terms of engagement. When Leucid approaches a CDMO partner, it can specify which critical quality attributes matter, why they matter, and how to test for them.
For biotech CEOs who do not have (and cannot afford) internal manufacturing infrastructure, the challenge is structuring CDMO relationships to perform the same function. That means embedding scientific discipline into the partnership: shared ownership of process development data, collaborative deviation analysis, meaningful comparability protocols rather than checkbox exercises.
John also addresses the emerging question of in vivo CAR-T engineering. Leucid announced a collaboration with Syenex in December 2025 to explore in vivo delivery of its CAR constructs using the VivoCell platform. He explains that this is not a replacement for ex vivo manufacturing but as a parallel track that may eventually address access and scalability constraints. “The field will need both,” he says. “The key is to match the engineering modality to the biology of the disease and the risk profile of the patient population.” For now, the manufacturing discipline required for ex vivo autologous cell therapy remains the defining challenge for most clinical-stage biotechs.
The Solid Tumor Problem: Why Architecture Matters in Manufacturing and Biology
Leucid’s Lateral CAR platform is a response to one of the field’s most persistent failures: CAR-T has not worked in solid tumors.
“CAR-T has failed thus far in solid tumors. The challenges include safe target antigen selection, tumor antigen heterogeneity, physical exclusion, and inadequate drug delivery to solid tumor deposits, and the hostile and highly immunosuppressive microenvironment that solid tumors establish.”
The lateral CAR architecture, placing activating and co-stimulatory functions side by side rather than in a linear chain, is designed to deliver more balanced and durable T-cell activation in precisely these conditions. LEU011, the first clinical program from this platform, targets NKG2D stress ligands and incorporates CXCR2 co-expression to support tumor trafficking. In the AERIAL Phase I/IIa trial, early data reported in November 2025 showed disease control in multiple patients at the lowest evaluated dose, with tumor infiltration confirmed in post-treatment biopsies.
