A company developing off-the-shelf CAR-T cell therapies that went from startup phase to an initial public offering in the space of a few months earlier this year made its clinical data debut at the American Society of Hematology.
South San Francisco, California-based Allogene announced Monday presentations of clinical data from its Phase I study of UCART19 in acute lymphoblastic leukemia and preclinical data on ALLO-715 for multiple myeloma.
Allogene made headlines earlier this year when it launched in April with a $300 million Series A round of venture capital funding from several firms and Kite Pharma founders Arie Belldegrun and David Chang at the helm. Five months later, the company raised another $120 million in a private placement, followed by another $324 million in its IPO in October. Its market cap stands at nearly $4 billion.
The Phase I data on UCART19 showed that among 17 patients who received a lymphodepletion regimen of the chemotherapy agents fludarabine and cyclophosphamide with a monoclonal antibody targeting the CD52 antigen, 82 percent achieved a complete remission or a complete remission with incomplete recovery of their blood counts, known as CR/CRi rate. Among those who did not receive the antibody, there was minimal expansion of the CAR-T cells and no response. The 14 patients who achieved a CR/CRi on the triplet lymphodepletion regimen yielded a response rate of 67 percent, out of 21 total patients. Lymphodepletion is the process of destroying lymphocytes and T cells in order to make room for CAR-T cells to expand.
There are currently two CAR-T therapies with Food and Drug Administration approval: Novartis’ Kymriah (tisagenlecleucel), for pediatric and young adult acute lymphoblastic leukemia and adult diffuse large B-cell lymphoma; and Gilead Sciences’ Yescarta (axicabtagene ciloleucel) for DLBCL. Like both of those products, UCART19 works by targeting the CD19 antigen on the surface of cancer cells.
But Kymriah and Yescarta are autologous CAR-Ts made from the patient’s own harvested and modified T cells. In contrast, Allogene – and companies such as fellow South San Francisco firm Atara Biotherapeutics and Belgium’s Celyad – are developing allogeneic CAR-Ts derived from donor cells, hence their being called “off-the-shelf.”
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
Whereas autologous CAR-Ts carry potentially dangerous toxicities such as neurological side effects and cytokine release syndrome, an additional potential complication of allogeneic CAR-Ts – given their nature as being made from donor cells – is graft-versus-host disease, or GvHD. However, Allogene said there was no evidence of GvHD or severe neurotoxicity in its study.
In addition to the anti-CD19 CAR-T, Allogene presented data on ALLO-715, which targets the antigen BCMA and is in preclinical testing as a potential therapy for multiple myeloma. According to the data, the therapy showed potent cytotoxic activity against multiple myeloma cell lines and was effective in animal models at a single dose. The company plans to start Phase I clinical testing next year. Like UCART19, ALLO-715 will be up against competition from autologous CAR-T therapies targeting the same antigen. In this case, it will be bluebird bio and Celgene’s bb2121 and bb21217, as well as Janssen and China-based Legend Biotech’s LCAR-B38M.
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