Enabling Novel Cell Therapies by Leveraging Established Blood Stem Cell Transplant Infrastructure

Enabling Novel Cell Therapies by Leveraging Established Blood Stem Cell Transplant Infrastructure

September 09, 2021PAO-09-21-CL-04

The National Marrow Donor Program® (NMDP)/Be The Match® has been managing the harvest and shipment of tens of thousands of blood stem cell donations for transplant — the most widely used cell therapy globally — for over 30 years. Its business unit Be The Match BioTherapies® is focused on helping cell and gene therapy companies speed their novel treatments into the clinic and the market by leveraging its extensive experience and well-established infrastructure.

Long History Delivering Cell Therapies

Hematopoietic stem cell transplant is considered by many to be the original cell therapy, using non-engineered cells most often donated by volunteer anonymous donors. Tens of thousands of donations take place each year, with the donated blood stem cells transported around the world as potentially lifesaving treatments for patients with blood diseases and disorders, such as leukemia and lymphoma.

Our Minneapolis, Minnesota–based nonprofit the National Marrow Donor Program® (NMDP)/Be The Match® was founded in 1986 to operate a registry of volunteer hematopoietic stem cell donors in the United States. We launched an umbilical cord blood transplant program in 1998. We have a long and rich history of efficiently delivering these types of cell therapies globally in very large volumes — larger volumes than any other contemporary cell and gene therapy company.

The NMDP/Be The Match is not generally well known in the biopharma industry, unless someone has been involved with a blood stem cell transplant. However, we are an institution with an unmatched knowledge base in the harvest of potentially therapeutic cells and movement of cellular therapies around the world. In addition, we have built the extensive infrastructure needed to achieve the distribution of massive volumes of cell therapy shipments within very tight timeframes.


Leveraging Blood Stem Cell Transplant Experience

The emergence of a number of high-profile cell therapy companies (e.g., bluebird bio, Juno Therapeutics, Kite Pharma, and others) caught the attention of our leadership team at the NMDP/Be The Match. They realized that there was a lack of awareness about the massive infrastructure the NMDP/Be The Match already possessed for the harvest and delivery of cell therapies. They speculated that the infrastructure could be valuable to the biopharma industry and could help accelerate access to emerging cell and gene therapies.

After significant research and careful consideration, our organization made the decision to launch Be The Match BioTherapies® in 2016. Today, Be The Match BioTherapies has over 45 cell and gene therapy developer clients for which we provide a variety of resources and services. For many companies that may have elected not to develop personalized cell therapies because of the cost associated with building the necessary infrastructure, Be The Match BioTherapies has changed the calculus, because we can provide the infrastructure needed to make development projects feasible in a cost-effective manner.

Transplant vs. Cell Therapy: Patient-Focused

More than 60% of cell therapies are being developed to treat blood diseases, many of which may currently be treated with hematopoietic stem cell transplants. Although transplants can result in a cure for many, there are still significant toxicities associated with the treatment, and transplant is not an option for all patients.  

The NMDP/Be The Match is a patient-focused organization with a mission to save lives through cellular therapy. Through Be The Match BioTherapies, we are able to support the development of new therapies, many of which have the potential to improve outcomes for our transplant patients. We also are able to impact the lives of additional patient populations, broadening our reach into the arenas of solid tumors, autoimmune diseases, genetic disorders, and other indications not traditionally treated via transplant.

The NMDP/Be The Match measures success based on the number of patients we impact.  Hematopoietic stem cell transplants require a genetic match between the donor and recipient. This can be particularly difficult to achieve, as the genetic makeup of the domestic and global populations continues to rapidly change. Many of the newly developed cell therapies reduce the reliance on matching, and as such they can solve one of the major problems around access to lifesaving therapies for genetically diverse populations.

Furthermore, some of these therapies may also be available off-the-shelf, which should simplify the portion of the supply chain used to move products to patients and speed up treatment timelines. Challenges in the supply chain associated with harvesting donor cells and shipping those to manufacturers will continue to exist.

Altogether, cell therapies present an opportunity to substantially increase our ability to impact patient lives. At the NMDP/Be The Match, we are embracing this new technology and applying our institutional knowledge to help shape the development of the evolving cell therapy field from a patient-centric perspective.

Hands-On Clinical Insight

Many companies developing cell therapies do not have the breadth of experience and clinical insight in the treatment of blood cancers, bone marrow diseases, and immune system and genetic disorders, all of which have been treated using transplant for decades.

The NMDP/Be The Match can help these companies bridge that gap in clinical knowledge. We have transplant physicians on staff to provide hands-on clinical insight. We also have many connections within the transplant community and are in daily communication with transplant physicians and their staffs at over 180 transplant centers around the world. This knowledge and network, combined with years of data collection and analysis, can be applied to solve problems for companies developing cell therapies.

The NMDP/Be The Match has been gathering data on and studying allogeneic and autologous transplant for over 30 years. Utilizing this expertise, the NMDP/Be The Match can help design clinical trials, especially in cases where those trials involve comparisons to transplant. We can also support the development of emerging cell therapies by addressing concerns that are common to cell therapy approaches, such as host rejection or sensitivity and efficacy utilizing different conditioning regimens.

Transplant and Cell Therapy Outcomes Data Registries

The Center for International Blood and Marrow Transplant Research® (CIBMTR®) is a 200-person research organization funded equally by the NMDP/Be The Match and the Medical College of Wisconsin. For years, the CIBMTR has collected outcomes data on every allogeneic transplantation performed in the United States. U.S. transplant centers also voluntarily submit autologous transplantation data, and transplant centers worldwide voluntarily submit both autologous and allogeneic transplantation data. As a result, the CIBMTR’s clinical database now contains information from more than 575,000 patients and more than 330 different transplant centers.

The National Cancer Institute awarded the CIBMTR a grant to operate the Cellular Immunotherapy Data Resource (CIDR). This is part of the Cancer Moonshot to accelerate cancer research under the Immuno-Oncology Translational Network (IOTN). The Cancer Moonshot helps scientists in different organizations nationwide to join and quickly develop new immune therapies to prevent or cure cancer.  

Since 2016, the CIBMTR has operated the Cellular Therapy Registry, which collects data on cellular immunotherapies for cancer. Parallel to the CIBMTR’s data infrastructure for hematopoietic cell transplantation (HCT), used mostly to treat blood cancers, the CIDR gathers data on cellular therapies for all cancers, including solid tumors. 

The Cellular Therapy Registry collects essential data on the baseline characteristics of patients, along with pre- and post-infusion data, infusion details, disease response, and outcomes. The data are analyzed and may be used to plan preclinical studies and clinical trials. The CIMBTR is currently collecting data on patients who have received Kymriah® (Novartis), Yescarta® (Gilead Sciences), and three other commercially available cell therapy treatments.

Clinical Trial Experience

The CIBMTR also runs prospective clinical trials through the National Institutes of Health (NIH)-funded Blood and Marrow Transplant Clinical Trials Network (BMT CTN). The BMT CTN was established because of a critical need for multi-institutional clinical trials focused directly on improving survival for patients undergoing HCT. Since 2001, the BMT CTN has opened more than 30 multi-institutional phase II and III trials, involving more than 100 transplant centers and enrolling thousands of patients.

BMT CTN is funded through the NIH and is a collaborative effort of the CIBMTR, the National Marrow Donor Program (NMDP)/Be The Match, and The Emmes Company, together with 20 core transplant centers. Collectively, CIBMTR, NMDP/Be The Match, and The Emmes Company serve as the BMT CTN Data and Coordinating Center to provide administrative, statistical, scientific, and informatics support to all BMT CTN activities.

Two-Part Strategy: Supporting both Autologous and Allogeneic Approaches

Be The Match BioTherapies supports customers developing both autologous and allogeneic cell therapies. The latter may be more intuitive for people that know Be The Match, because we are well known for our ability to locate allogeneic donors for transplant. That experience translates well when it comes to supplying allogeneic donor cells to manufacturers of allogeneic cell therapies, in particular because we are able to leverage the Be The Match Registry, which counts among its membership more than 20 million potential donors.  

Importantly, we do not compensate donors, and we conduct a thorough screening process before a donor can move forward with a donation for a biopharma company. This approach ensures the broadest possible use of eventual therapies and optimizes safety for both donors and patients.

In the autologous setting, the role for Be The Match BioTherapies may be less intuitive. But, upon closer examination, the parallels between the infrastructure required to harvest and deliver a transplant and the infrastructure needed to harvest and deliver an autologous cell therapy are clear. To develop an autologous cell therapy, an initial piece of infrastructure required is a network of centers to harvest the cells. The NMDP/Be The Match manages a national contracted network of 110 cell harvest facilities across the country. Since apheresis is a peculiar niche within the healthcare industry, this expertise is critical.

Another piece of infrastructure that is required that is just as critical is the ability to ship the time- and temperature-sensitive cellular material to a manufacturing location while ensuring that the cells maintain their viability and required attributes. That requires expertise in logistics, customs requirements, and many other capabilities. We have a dedicated team of approximately 70 people that handles 36,000 highly time-sensitive shipments annually, half of which have an international component.

That team is also a crisis management team planning in advance for expected events, contingency planning for unexpected events, and reacting when issues occur. For instance, even though over 83% of commercial flights — the primary means for transporting donated material for transplant — were canceled between March 2020 and March 2021, the NMDP/Be The Match did not miss a single one of over 5,800 fresh transplant deliveries.

Because of our scale, we can support cell therapy developers conducting a 30-patient clinical trial or conducting a commercial launch to address a 10,000-person global patient population.

Bundled Service Offering

Indeed, what Be The Match BioTherapies offers is a comprehensive bundle of services from cell harvest through delivery and through outcomes data collection. We consider cell harvest to be part of the GMP manufacturing process. By building harvest and delivery into a single system, we are reducing risk and assuring consistency of product efficacy.

Through a recently established partnership with Lonza, we are going a step further, combining our gold standard in apheresis and cell delivery with a leading contract manufacturing organization that has state-of-the-art cell and gene therapy manufacturing facilities around the world. The result will be not only reduced risk with respect to quality, but also reduced time to the clinic and the market.  

There is still more work to be done. We are not finished building our ecosystem. We look forward to the future as we partner with more cell and gene therapy companies and service providers and work toward a common goal: to save more lives through cellular therapy.

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