Inside Mesoblast's Playbook For Making Allogeneic Cell Therapy Real

By Erin Harris, Editor-In-Chief, Cell & Gene
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Mesoblast has spent nearly two decades doing the slow, unglamorous work that turns allogeneic cell therapies from concept into commercial reality. I sat down with Mesoblast’s CEO Silviu Itescu to learn how the company built its mesenchymal stromal cell (MSC) platform, secured the first and only FDA‑approved MSC product in the U.S., and is now leveraging that foundation across a suite of high‑need inflammatory indications. At the heart of the story is a simple throughline: rigor. Mesoblast’s choices reveal a deliberate strategy for making complex cellular medicines consistent, potent, and economically sustainable.

The clearest proof point is RYONCIL, Mesoblast’s first‑generation, allogeneic bone marrow-derived MSC product for steroid-refractory, acute Graft-versus-Host-Disease (GvHD) in children. Itescu emphasized that the program’s success came from aligning deep biology with industrial discipline. The team invested early in understanding how MSCs modulate excessive inflammation in settings where small molecules and monoclonal antibodies have repeatedly failed, then built a manufacturing process capable of delivering batch‑to‑batch identical vials at commercial scale. That rigor translated into outcomes; in a pivotal Phase 3 trial, RYONCIL achieved a 70% response rate at 28 days in a pediatric population that previously had no FDA‑approved options, where survival with unapproved therapies hovered around 20–30%. “Responders at day 28 saw more than 70% survival at six months, and most of those children remained alive five years later, with only about 14% mortality from acute GvHD over that period,” Itescu said. “For a fragile, high‑risk cohort, this is effectively a path to long‑term, disease‑free outcomes rooted in great science and uncompromising control over product consistency.”

The Regulatory Path to RYONCIL

Mesoblast’s experience has also given it a distinctive perspective on global regulatory divergence. Itescu was candid that harmonization in cell and gene therapy cannot be reduced to aligning guidance documents. Instead, he framed it as a broader meeting of executives that spans scientific language, clinical trial requirements, GMP and quality standards, health‑system readiness, reimbursement structures, and investor incentives. Advanced therapies are capital‑intensive and technically demanding; there are, as Itescu put it, no shortcuts. For a publicly listed company operating under FDA and other regulators, harmonization must include robust intellectual property protection, commercial protection, and reimbursement models that both keep therapies accessible and justify the high upfront investment required to meet these standards. “The U.S. environment has evolved in a way that meaningfully rewards this level of rigor and innovation, and I’d like to see European and Asian jurisdictions raise the bar to create a more even global playing field for MSC and other advanced therapies.”

Underpinning Mesoblast’s pipeline is a clear strategic bet on allogeneic MSCs as an industrial platform rather than a series of one‑off products. He shared that the company viewed autologous approaches as fundamentally constrained by scalability and variable quality, particularly when starting from older or diseased patients whose cells are harder to manufacture and potentially less effective. MSCs, by contrast, lend themselves to scalability and off‑the‑shelf use because of their underlying biological properties. Mesoblast first established a scalable, first‑generation manufacturing process that isolates and expands cells in a specific, tightly controlled way, yielding RYONCIL for intravenous use in orphan inflammatory indications, such as pediatric acute GvHD.

In parallel, the company has developed a second‑generation platform, rexlemistrocel, which uses monoclonal antibodies to isolate earlier, more potent mesenchymal precursors. This second‑generation product is formulated for local delivery at different doses and concentrations, enabling programs in broader, inflammation‑driven diseases such as chronic low back pain and cardiovascular disease. That platform thinking manifests in how Mesoblast sequences its indications and product configurations. RYONCIL, as the first‑generation product, is being expanded via potential label extensions into additional inflammatory conditions where the same IV dosing and mechanism of dampening systemic inflammation can deliver value. Rexlemistrocel, by contrast, is deployed where local, high‑potency anti‑inflammatory effects are needed.

Targeting High-Need Inflammatory Diseases

In chronic low back pain, a microdose of six million cells is injected into the intervertebral disc in patients with severe, refractory pain; in an initial Phase 3 trial, a single injection produced significant, durable pain reduction out to at least three years. A second trial is fully enrolling, with a 12‑month pain endpoint that the FDA has indicated could be approvable if positive. In progressive heart failure, where biomarkers like CRP, interleukin‑1, and interleukin‑6 predict both disease progression and mortality, Mesoblast’s 500‑patient randomized study showed that a single, higher‑dose catheter‑based injection of rexlemistrocel into the myocardium reduced heart attacks, strokes, and death for at least three years in patients with inflammatory signatures. By matching product generation, dose, route, and disease biology, the company is rolling out a portfolio of MSC medicines targeted at populations with few or no alternatives and poor outcomes, moving away from add‑on therapy and toward interventions that can materially change the trajectory of disease.

“None of this would have been possible without hard‑won lessons in manufacturing strategy and late‑stage trial design,” Itescu said. One of his central messages for other cell therapy developers is to enter Phase 3 with the commercial product, not a transitional version. “If key aspects of the product (i.e. manufacturing process, potency assays, release specifications) change after pivotal data are generated, you effectively have a new product and jeopardize the connection between clinical outcomes and what will be sold,” he said. Mesoblast learned this through years of iterative interaction with the FDA, a process that likely delayed approval by several years but ultimately produced a robust, approvable package. The company now locks down its manufacturing process and analytical toolkit before Phase 3 and is leveraging those lessons across its second‑generation programs and larger indications.

At the same time, Itescu notes that truly innovative therapies can deliver outcomes that weren’t anticipated when trials were designed. “In heart failure, for example, traditional endpoints focused on shortness of breath and hospitalization, but our technology drove unexpected improvements in mortality and major adverse cardiac events, benefits far beyond what current small‑molecule therapies typically achieve,” he said. “Going forward, confirmatory studies are being built around these more transformative endpoints, reflecting a belief that next‑generation cell therapies should aim for disease‑changing outcomes, even if that means thinking differently when defining primary endpoints.”

In the next 12 to 24 months, Mesoblast plans to execute on commercial growth, label expansion, and late‑stage development. Early launch metrics for RYONCIL have been strong, easing concerns about market adoption, pricing, and coverage. The product is now reimbursed by commercial insurers as well as Medicare and Medicaid, positioning revenues to continue growing as usage expands. On the clinical front, an NIH‑sponsored Bone Marrow Transplant Clinical Trials Network study in adult acute GvHD is about to start, spanning roughly 45 major U.S. sites and enrolling around 170 patients. If the adult randomized data mirror the pediatric results, RYONCIL could become standard second‑line care after steroids in adults, a market estimated to be roughly three times larger than the pediatric segment.