Clinical Translation of Zemcelpro® Hematopoietic Cell Therapy

Congratulations on your huge milestone! Can you tell us about the origins of the UM171 cell therapy program?

Nathalie: UM171 discovery and development occurred between 2013 and 2014. ExCellThera, a spin-off from the Université de Montréal, was founded by Guy Sauvageau, a world-renowned hematologist, and Anne Marinier, an experienced chemist whose team developed the small molecule in close collaboration with the Guy Sauvageau Laboratory. This well-established academic laboratory focuses on fundamental research and product characterization. In 2014, following the demonstration of UM171’s ability to effectively expand hematopoietic stem cells, the program advanced into clinical development.

In 2016, a first-in-class clinical protocol using UM171 to expand cord blood-derived hematopoietic stem cells was evaluated in an initial Phase I/II clinical trial at Hôpital Maisonneuve-Rosemont in Montréal. Encouraging early results in adult patients with hematologic malignancies who lacked access to a suitable donor demonstrated meaningful clinical benefit and led to the development of the ECT-001-CB clinical program, resulting in the completion of five clinical studies. These findings also supported further evaluation of the cell therapy in high-risk acute leukemia, a setting in which engraftment outcomes remain suboptimal despite standard-of-care therapies, highlighting a significant unmet medical need.

What were the biggest technical or process challenges in bringing Zemcelpro® to commercialization?

Fannie: One of the major challenges in advancing Zemcelpro® toward commercialization was transitioning from a fresh product to a fully cryopreserved formulation, which constituted a significant change to the manufacturing process. A critical requirement was to demonstrate that freezing and thawing did not adversely affect hematopoietic stem cell quality, viability, potency, or overall safety. This transition also introduced additional logistical complexity, as cryopreserved cell therapies require specialized shipping and storage conditions, as well as standardized thawing procedures at clinical sites.

Regulatory expectations for such a change were high, necessitating extensive comparability data to demonstrate that the cryopreserved product was equivalent to the fresh formulation. In parallel, the development and validation of robust quality control assays—particularly to evaluate identity, viability, and potency of expanded CD34+ cells—were essential and required specialized expertise. To address this need, ExCellThera developed a custom colony-forming unit (CFU) assay using MethoCult™ and the automated STEMvision™ system, both from STEMCELL Technologies, to reliably assess product potency.

How did your team approach regulatory interactions, particularly around ancillary materials or potency testing? Were there any hurdles?

Nathalie: Our team engaged early with multiple regulatory authorities to discuss the development of the product, including the regulatory classification of UM171 as an ancillary/raw material (reagent). By way of background, the patented small molecule is used to expand and rejuvenate hematopoietic stem cells ex vivo and is removed from the final product infused in patients. As such, ancillary materials generally require less documentation than active drug substances. However, we built a robust regulatory file due to the novel nature of this small molecule.

We held several interactions with the European Medicines Agency (EMA), including a Scientific Advice meeting early in the submission process and a full pre-marketing authorization application (MAA) meeting. These exchanges helped establish a collaborative relationship with the EMA and clarified regulatory expectations for ancillary materials as well as for product potency testing. Following dossier submission, we continued discussions with the EMA through formal clarification meetings.

Has ExCellThera leveraged any expedited pathways as part of the regulatory strategy?

Nathalie: ExCellThera/Cordex successfully requested an accelerated assessment from the EMA, which was granted in recognition of the substantial unmet medical need in Europe for patients lacking suitable donors, together with the product’s orphan drug designation and the innovative nature of Zemcelpro®, which offers the potential for a curative therapeutic option.

Was early interaction with the regulatory body helpful in shaping the direction of your project? What advice would you give to others going through this process?

Nathalie: Yes, engaging with the regulatory body early on was tremendously helpful. It allowed us to understand their perspective from the beginning and helped us shape our development strategy accordingly. More importantly, it gave us the opportunity to build an ongoing collaborative relationship. That dialogue created a climate of understanding and trust, which made it much easier to provide the information they needed as the process evolved. That relationship is actually still ongoing.

We asked a lot of questions throughout the process. At times, we received pushback from advisors who suggested that asking too many questions might make us look like we didn’t know what we were doing. But the truth was we didn’t know everything. So we asked. And they answered.

My advice would be: Don’t be afraid to ask questions. Early clarity and open communication are far more valuable than trying to appear overly confident.

What qualities or capabilities did you look for in partners or suppliers during product development?

Nathalie: As a pre-revenue biotech we sought partners and suppliers capable of thinking creatively and pragmatically to develop solutions tailored to our needs. We maintained lean processes and focused on the parameters most critical to product quality and regulatory success. Open communication and transparency with our partners and suppliers were key enablers, allowing us to clearly define priorities and efficiently align on requirements.

Were there any collaborations or tools that helped streamline your workflow or mitigate risk?

Nathalie: Strong internal, cross-functional collaboration was central to streamlining workflows and managing risk throughout the development of the Zemcelpro®. Close coordination among Manufacturing, Quality Control (QC), Quality Assurance (QA), Regulatory Affairs (RA), Research and Development (R&D), and clinical teams—including experienced hematologists—enabled early identification of issues and rapid alignment on effective solutions.

We also engaged specialized external collaborators in areas such as analytical method development and regulatory strategy, which helped accelerate method validation and reduce technical and regulatory uncertainty. In parallel, the systematic collection and review of manufacturing data supported ongoing trend analysis, early detection of potential issues, and continuous strengthening of process controls over time.

In what ways, if any, did STEMCELL support your regulatory filings and other clinical activities?

Fannie: STEMCELL Technologies was highly responsive to ExCellThera’s specific needs and provided critical support during the transition from a custom expansion medium to a GMP-compliant, off-the-shelf product. In the initial phase, STEMCELL supported the custom media stability studies and, subsequently, assisted with the introduction of the GMP StemSpan™-AOF medium through the preparation of regulatory documentation.

The collaboration between STEMCELL and ExCellThera was structured around regular periodic meetings, during which both parties shared progress updates, exchanged technical expertise, and coordinated timelines to ensure alignment with project requirements.

Future Opportunities for HSPC-Based Therapies

Where do you see the most opportunity for innovation in HSPC-based or -related therapies?

Shanti: There are significant opportunities for innovation across multiple aspects of hematopoietic stem and progenitor cell (HSPC)-based therapies. Further advances in hematopoietic stem cell expansion technologies could improve scalability and enable broader clinical use. In parallel, gene-modified HSPCs represent a rapidly evolving area, where improvements in gene-editing tools and safer, more efficient delivery methods have the potential to expand the range of treatable diseases.

We see significant opportunities for innovation at the level of ex vivo manipulation and manufacturing robustness of HSPC-based therapies. UM171 serves as a powerful enabling technology across multiple HSPC-derived approaches, and ExCellThera has adopted a collaborative model with partners developing cell and gene therapies. By improving cell yields and mitigating cellular exhaustion during ex vivo expansion, this small molecule helps address key manufacturing bottlenecks and supports the generation of more potent and durable HSPCs, including gene-modified cell populations. This can translate into greater manufacturing consistency and reduced overall cost of goods.

From a regulatory perspective, UM171 can often be integrated into existing manufacturing workflows as an ancillary material that is not present in the final drug product and is supported by a Drug Master File (DMF), facilitating adoption without fundamentally altering the regulatory profile of the therapy.

What advice would you give to teams entering clinical development for the first time?

Nathalie: One of the most important success factors is establishing strong documentation practices from the outset. Even during early research and process development, data, decisions, experimental conditions, and scientific rationales should be recorded in a clear and consistent manner. Robust documentation not only supports future regulatory submissions and inspections, but also facilitates internal alignment, reproducibility, and effective knowledge transfer as teams evolve.

It is equally critical to consider GMP requirements early, well before the start of formal clinical manufacturing. This includes designing processes and assays with scalability and regulatory expectations in mind, implementing quality systems that are appropriate to the development stage, and becoming familiar with requirements related to raw materials, traceability, batch records, and release testing. Early planning in these areas helps avoid costly rework and accelerates the transition to clinical-grade and commercial manufacturing.

Finally, early and ongoing engagement with regulatory authorities is essential. Seeking scientific advice and proactively discussing challenges or uncertainties foster transparency and alignment on expectations. Such dialogue reduces regulatory risk, supports more efficient development pathways, and is far preferable to making assumptions that require correction later.

It sounds like you’re very passionate about your work. Will you continue to innovate and keep pushing forward scientifically?

Shanti: Absolutely. There’s still a great deal of new science and ongoing discussion. We’re very much focused on advancing the work. While the past year has required intense effort, particularly around EMA applications, innovation is still a key priority.

Our collaboration with the Sauvageau Lab, which is literally one floor below us, has been especially valuable. The lab brings deep expertise in stem cell biology and related disciplines, creating a highly collaborative scientific environment. We meet several times a year to exchange perspectives on emerging discoveries, evolving scientific questions, and new directions in the field.

When promising concepts align with our development priorities, ExCellThera’s R&D team evaluates them using standardized methods and quality frameworks consistent with our product development processes. This allows us to assess reproducibility, evaluate new molecules or procedures against existing approaches, and determine their translational potential. The collaboration helps us stay closely connected to cutting-edge science while maintaining the rigor required for therapeutic development.

On a final note, how has the Montréal biotech community influenced your work? Do you feel supported locally?

Nathalie: Montréal has a very strong scientific ecosystem, particularly in stem cell research. Being located within a research institute means we are constantly exposed to discoveries and emerging ideas across multiple areas of biomedical research. Over the past year, our regulatory commitments have limited our participation in conferences and broader networking events. However, we continue to be part of a close community that includes academic groups and clinical collaborators. For example, we have strong relationships with hematologists who have used our product in clinical trials. They are an important part of our extended community.

We’ve also recently started engaging more with industry groups such as BIOQuébec and others. We’re not only sharing updates on our progress, but also discussing the challenges we face—particularly regulatory challenges. It’s important for us to be more vocal, both to contribute to the broader conversation and to help strengthen the ecosystem we’re part of.