iPSC

Looking back at the headlines in advancements in cell and gene therapy in 2019, one theme that comes to mind is collaboration. New partnerships have encouraged progress in the field. One example is the recently announced alliance between Harvard and MIT to develop a Center for Advanced Biological Innovation and Manufacturing. And cooperation between stakeholder groups—from cell collection centers to drug developers to CROs—remains an essential factor in expediting patient access to life-saving therapies. As we enter a new decade of cell and gene therapy research, collaboration continues to be central to our work at Be The Match BioTherapies®. We’re optimistic that our collective efforts will enable further advancements in cell and gene therapy to serve patients and families worldwide. Progress and evolution in CAR-T research In 2019, we saw CAR-T cell therapies continue to advance at a dramatic rate. While results in hematologic malignancies have historically been most robust, researchers are now exploring how CAR-T therapies may be used to treat solid tumors. Despite the new challenges this approach presents, results in early trials have been promising. One option being explored to overcome the immunosuppressive microenvironment in solid tumors is the use of TRUCKs, or T Cell Redirected Universal Cytokine Killing. This describes the process by which CAR-T cells are used as a vehicle for administering cytokines that stimulate an immune response. Additionally, companies like Editas Medicine, GammaDelta Therapeutics and others are pursuing how gamma-delta cells can be used as immunotherapies for solid tumors and other cancer indications beyond lymphoma. Efficacy of CAR-T treatments are also being explored in indications outside of oncology, including cardiovascular disease. The many strides made this year—and the questions that remain—suggest that the CAR-T field will continue to evolve rapidly in the coming years. Off-the-shelf cancer therapies are on the rise Much of the latest progress in CAR-T represents a movement toward “off-the-shelf” cell therapies, rather than therapies which engineer cells from a patient. In our 2018 year-in-review, we noted that these allogeneic therapies were a growing area of exploration within the biotech space. This past year has seen this growth increase exponentially, with off-the-shelf therapies lauded as “the next frontier” of cell therapy development. In September 2019, Be The Match BioTherapies announced a collaboration with EU-based biotech Celyad. Be The Match BioTherapies will provide high-quality starting material for the development of the company’s CAR-T cell therapy pipeline. Celyad is among the companies pioneering development of non-gene edited allogeneic cell therapies. Induced pluripotent stem cell (iPSC) therapies are also being touted as an off-the-shelf option for cancer patients. Among other milestones, 2019 saw the launch of many such self-renewing therapies. Two examples include Century Therapeutics’ iPSC-derived immune-cell therapies and Fate Therapeutics’ pipeline of iPSC-derived immune cell therapies, which were unveiled at the American Society of Hematology (ASH) conference in December. As cell and gene therapy developers explore the use of natural killer (NK) cells as a potentially safer alternative to CAR-T cells, there is a possibility of greater efficacy in treating solid tumors. Off-the-shelf allogeneic and iPSC therapies have the potential to be much less resource-intensive than autologous therapies. But they also present new challenges, like finding the right donor to deliver cells to cancer patients. Through our parent organization, the National Marrow Donor Program® (NMDP)/Be The Match®, we enable precise therapy-matching services to our pharmaceutical clients. This gives companies more ease and precision in navigating the uncertainty of matching donors with patient cells. Cell therapy donors, in turn, are developing an increased understanding of the value their contributions provide to patients. In an August 2019 Cell Lines Blog post, we shared the story of Leah, an allogeneic cell therapy donor for Be The Match BioTherapies. “To think that my cells could be developed into a therapy that would help many patients … it’s pretty amazing,” Leah wrote of her experience. Growing popularity of CAR-T therapies reveals new questions and considerations for providers, policymakers and pharmaceutical companies With the exponential increase of CAR-T therapies being both developed by pharma companies and used by patients, previously unexplored questions surrounding efficacy, ethics and intellectual property have cropped up across the industry landscape throughout 2019. As companies compete to be first-in-line to bring new forms of CAR-T technology to market, questions regarding intellectual property rights and discovery ownership have revealed themselves. In the race to patent and brand new CAR-T constructs, companies have found themselves in ethical grey areas where the rights to intellectual discoveries can be unclear. In December 2019, jurors in California ordered Kite Therapeutics—a subsidiary of Gilead—to pay over $752 million to Juno Therapeutics (now part of Bristol-Myers Squibb) and the Memorial Sloan Kettering Cancer Center over allegations that the company’s flagship CAR-T therapy, YESCARTA®, violated an MSKCC patent licensed by its competitor. As the only other marketed CAR-T therapy is Novartis’ KYMRIAH® (tisagenlecleucel), this event was a significant blow to the CAR-T therapy market as a whole. Agreement between cell therapy developers and policymakers on how to best track the long-term impact of CAR-T therapies has also proven elusive. In February, the U.S. Centers for Medicare & Medicaid Services (CMS) proposed that coverage of CAR-T therapies should include a clinical study monitoring how patients are doing at least two years following treatment. This approach raised concerns that CAR-T administration would be limited to larger cancer centers. That could limit the number of patients who would have access to the therapies they need. In August, CMS finalized a decision to cover administration of FDA-approved CAR-T therapies for those receiving Medicare benefits. The final decision—arriving after significant delays— removed the stringent outcomes data tracking first proposed earlier in the year, but the initial promise to monitor patient outcomes remained. While manufacturers endorsed this decision as an important stride toward enabling patient access to CAR-T therapies, concerns about cost remain. To improve patient access to CAR-T therapies in 2020 and beyond, additional research into patient outcomes data is required if lower costs and improved rates of coverage are to be reached. Through our research partner, the CIBMTR® (Center for International Blood and Marrow Transplant Research®), we facilitate critical observational and interventional research, resulting in industry-leading data collection and analysis on over 500,000 patient outcomes. Currently, the CIBMTR is the trusted research and outcomes partner for Kite Therapeutics (YESCARTA®) and Novartis (KYMRIAH®). Broadened indications and delivery approaches in gene therapy As the cell therapy landscape has shifted and evolved over the past year, so has progress in gene therapy. As of December 2019, at least nine gene therapies have been approved and are already having an impact on patients’ lives. Though therapies delivered via adeno-associated viruses (AAV) continue to dominate the gene therapy landscape, researchers are actively exploring non-viral methods. Be The Match BioTherapies’ partner Poseida Therapeutics is exploring a system called PiggyBac, which delivers DNA via a transposon with inverted terminal repeat sequences to advance the liver-directed gene therapies and ex vivo therapies in its pipeline. Over the summer, the gene therapy industry was dominated by the approval of Zolgensma®, a gene therapy for spinal muscular atrophy developed by Novartis. More recently, development of gene therapies for sickle cell disease has moved to the forefront, with bluebird bio’s LentiGlobin leading the pack. Though the science is advancing rapidly, treating sickle cell disease with gene therapy presents logistical challenges, not least because the disease is concentrated in areas of sub-Saharan Africa, India and the Caribbean, which currently have limited access to costly genetic therapies. Working toward standardized cell and gene therapy development As various research directions are pursued within the cell and gene therapy industry, standardization of how those therapies are manufactured, distributed and regulated remains an important unifying discussion. In May 2019, Be The Match BioTherapies hosted its second annual Accellerate Summit, which gathered more than 80 stakeholders across the biopharma and healthcare industries. The goal: to address challenges in cell collection, understand efficiencies enabled by standardized data capture, and explore opportunities to integrate IT applications to track chain of custody throughout manufacture. As the next generation of cell and gene therapies continues to advance, discussion among stakeholder groups is critical. “Biopharma, apheresis centers and healthcare providers must work together to ensure that the production and administration of these medicines are efficient and scalable as the field grows,” said Greg Whitehead of Rubius Therapeutics. Be The Match BioTherapies is also partnering with TrakCel in order to enable standardization across the cell and gene therapy supply chain. The collaboration will allow for development of an integrated suite of services and technology platforms. This will help ensure efficiencies in future development of cell and gene therapies, despite the uncertainties that persist. As Jamie Margolis, PhD, Senior Vice President of Donor Services for NMDP/Be The Match, wrote in a recent article for Cell & Gene, “The future of cell and gene therapies is deeply exciting for all of us…. To bring about this future, though, we must begin to build the standards, practices and principles that will strengthen the cell and gene therapy manufacturing process and prepare it for what’s to come.” Significant advancements in cell and gene therapy occurred industry wide throughout 2019. We’re excited to be at the forefront to continue this rapid progress going into 2020. Here’s to another decade of advancements in cell and gene therapy. Whether your therapy is in research, pre-clinical or clinical studies, or commercially available, Be The Match BioTherapies has the unparalleled industry expertise in designing valuable solutions to advance your therapy. Discover your solution >

iPSC

Advancements in cell and gene therapy: 2019 year-in-review