Carisma Therapeutics, Novartis, And Contract Manufacturing

By Erin Harris, Editor-In-Chief, Cell & Gene
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Philadelphia-based Carisma Therapeutics, known for its novel CAR-M technology, which was developed by and licensed from scientists at the University of Pennsylvania, has partnered with Novartis for the manufacturing of the biopharma’s HER 2 targeted CAR-M cell therapy. Clinical manufacturing is planned to begin in 2023. Steven Kelly, President and CEO at Carisma Therapeutics and I sat down to talk more about Carisma’s HER2 targeted CAR-M therapy as well as the decision to ink a contract manufacturing partnership with Novartis.

Explain Carisma’s CT-0508, the lead HER2 targeted CAR-M therapy.

CT-0508 is a human epidermal growth factor receptor 2 (HER2) targeted chimeric antigen receptor macrophage (CAR-M) for the treatment of patients with solid tumors. We are currently evaluating it in a landmark Phase 1 multi-center clinical trial that focuses on patients with recurrent or metastatic HER2-overexpressing solid tumors whose cancers do not have approved HER2-targeted therapies or who do not respond to treatment.

Our investigation of 0508 to date has already shown the potential of the CAR-M platform, which has applicability across multiple therapeutic areas.

At the Society for Immunotherapy of Cancer’s (SITC) 36th Annual Meeting, we presented early data from the first-ever clinical study with genetically engineered macrophages in humans. The preliminary findings demonstrate that:

• CT-0508 was well tolerated after infusion and there were no dose limiting toxicities.
• CT-0508 was also successfully manufactured from heavily pre-treated, advanced solid tumor patients and shows high CAR expression, viability, and purity.
• The data also demonstrate that CT-0508 remodeled the solid tumor microenvironment (TME) and mediated expansion/activation of T cells within the tumors.

We are continuing to enroll patients in the clinical trial of CT-0508 to make additional observations about how CAR-M therapy can potentially address the unmet needs of patients.

In general, what major advancements have been made in CAR-M therapy over the last few years?

Since it was founded by pioneers in cell therapy from the University of Pennsylvania, Carisma has been at the forefront of developing the new CAR-M technology. In addition to starting the first-of-its-kind clinical trial in HER2 positive cancer in 2021, Carisma has continued to advance the engineered macrophage platform through combination approaches (data demonstrating synergy with anti-PD1 was presented at SITC in 2021), advancing a monocyte based platform with a 1 day processing time, and advancing new methods to engineer the cells including next next-generation CAR designs, novel viral vectors, CRISPR editing, and in-vivo targeting with mRNA/ LNPs (in partnership with Moderna).

Novartis has penned an initial deal to manufacture Carisma Therapeutics’ HER2-targeted CAR-M cell therapy, which is currently in initial studies to treat solid tumors. Why Novartis?

We chose Novartis as our partner because of their proven ability to manufacture complex cell-based therapeutics through commercialization, a highly skilled and well trained employee base, capacity to meet our clinical trial demands and competitive economics.

As a result of this collaboration, we will soon have expanded capacity for manufacturing of the cell therapy product for the CT-0508 clinical study.

This collaboration also reinforces an overarching strategy for our company as we strive to work with best-in-class companies. We seek to work with companies that have complementary capabilities and expertise to our own to further our pipeline and uncover potentially life-saving therapies to patients. For example, our recent partnership with Moderna to develop in-vivo macrophage targeted therapies using mRNA/ LNPs, is another example of this.

Carisma is headquartered in Philadelphia while Novartis’ cell therapy site is in Morris Plains, NJ. Does proximity play a role in the success of the partnership and the manufacturing process?

While the proximity is a benefit, we chose Novartis because of their proven expertise in manufacturing GMP cell therapy. Their Morris Plans facility has also been inspected by regulatory agencies including US, EU, UK and Japan.  We will also continue to work with our other cell therapy manufacturing partner, on CT-0508, in addition to establishing a new platform for the manufacturing of CAR-Monocytes.

Did Carisma consider in-house manufacture?

Ultimately, we would like to bring manufacturing in house to allow greater control over the process and access to dedicated facilities. Given the significant capital investment required to build such a facility it makes more sense for us, in the short term, to partner with leaders in the space, such as Novartis.