- A biotechnology startup has raised $200 million from a group of blue-chip investors to develop a new kind of cancer cell therapy for people with lymphoma whose cancer has relapsed or grown resistant to existing cellular treatments.
- The cash influx will allow the startup, Cargo Therapeutics, to advance its therapy into a Phase 2 study later this year, as well as support the associated manufacturing work such a trial will require.
- Cargo’s experimental treatment is a form of personalized cell therapy known as CAR-T. While several CAR-T therapies are approved in the U.S. to treat lymphoma, they all are aimed at a protein called CD19. Cargo’s therapy targets another protein called CD22 instead, which its backers see as a way around cancers that have returned or learned to evade CD19-directed treatment.
CAR-T therapy is now an important treatment option for several kinds of lymphoma, as well as certain leukemias and multiple myeloma. The treatments approved in the U.S. have mostly been reserved for use after multiple other drugs have failed to curb the cancer’s growth, although recent studies have proven CAR-T therapy’s benefit earlier and led to expanded clearances.
While some patients benefit greatly from CAR-T therapy, a good portion don’t, either never responding to treatment or having their cancer recede only to come back months later.
With lymphoma, for example, cancerous cells sometimes “escape,” losing the CD19 protein flag that CAR-T cells are trained to spot. When this happens, those cells can survive and grow without detection by the souped-up immune cell defenders.
Cargo is testing a different approach, focusing on the CD22 protein, or antigen, which is also expressed on cancerous B cells. “Targeting alternative antigens represents an important therapeutic strategy for patients who are [relapsed or refractory] to CAR19, including those with CD19 loss or downregulation,” wrote Gina Chapman, Cargo’s CEO, in an email.
In comparison to many new biotechs just starting out, Cargo has a leg up. Its treatment, dubbed CRG-022, has already been studied in a Phase 1 clinical trial and showed promise treating large B cell lymphoma that’s relapsed or resistant to CD19-directed CAR-T therapy.
Results from that trial were reported at a medical meeting in February and showed 68% of the 38 patients who were infused with Cargo’s therapy responded to treatment. Just over half went into remission, only one of whom has since relapsed.
Overall, patients lived a median of 22.5 months following treatment, according to an interim analysis of the data cited by Cargo.
The company is planning to advance its treatment into a larger study across multiple trial centers this year, which could potentially serve as the basis of an approval application should it succeed. “Given Cargo’s progress to date and its experienced leadership team, Cargo is well-positioned to be first-to-market with an autologous CD22 CAR T-cell therapy,” said Reid Huber, a partner at Third Rock Ventures, which joined a dozen venture capital firms and other investors to fund the biotech.
Other groups are also trying to develop CD22-targeting CAR-T therapies. A federal database of clinical trials shows a number of studies ongoing testing various cellular treatments aimed at that protein, many by research hospitals in China. Four studies run by the National Cancer Institute in the U.S. are recruiting participants, while the British biotech Autolus lists a CAR-T therapy aimed at both CD19 and CD22 in early-stage development.
Cargo claims its treatment has a shot at being the best of its type, citing several design features that Chapman said could help improve T cell function, activation and persistence in the body.
While no CD22 CAR-T therapies are yet approved in the U.S., the Food and Drug Administration has cleared two drugs that target the protein: AstraZeneca’s Lumoxiti for a type of leukemia and Pfizer’s Besponsa for another type of the blood cancer. (AstraZeneca will soon withdraw Lumoxiti due to its low uptake.)
CAR-T therapies come with many side effects, some of which can be severe, and CRG-022 is likely to be no different. CD22 is also expressed on non-cancerous cells, so targeting the protein may result in what’s known as B cell aplasia, or extremely low B cell counts.
In addition to large B cell lymphoma, Cargo also plans to study CRG-022 in pediatric B-cell acute lymphoblastic leukemia.
Previously known as Syncopation Life Sciences, Cargo was launched in 2021. It was founded by Crystal Mackall, the founding director of the Stanford University Center for Cancer Cell Therapy; Robbie Majzner, an assistant professor of pediatrics there whose research has focused on CAR-T therapy; and Nancy Goodman, the CEO of Kids V Cancer, a pediatric cancer think tank.
The three collaborated with Samsara BioCapital to get Cargo off the ground. The most recent funding was led by Third Rock, RTW Investments and Perceptive Xontogeny Venture Fund, which were joined by seven new investors, Samsara, and the existing seed investors Red Tree Venture Capital and Emerson Collective.