Carisma Therapeutics Restructures to Advance Next-Generation Therapies
Carisma Therapeutics is restructuring to focus on its in vivo macrophage engineering platform, discontinuing the development of CT-0525 and reducing its workforce by 34%. This strategic shift aims to prioritize oncology, fibrosis, and autoimmune disease programs to drive long-term growth and innovation.

Carisma Therapeutics (Nasdaq: CARM), a leader in macrophage-based therapies, has unveiled a strategic restructuring aimed at advancing its innovative in vivo macrophage engineering platform. As part of this shift, the company will discontinue the development of its lead candidate, CT-0525, a CAR-monocyte cell therapy targeting HER2-positive solid tumors. In addition, Carisma will reduce its workforce by 34%, affecting 23 full-time employees across its R&D, manufacturing, finance, and corporate functions. This restructuring will enable Carisma to focus its resources on its most promising therapeutic areas, including oncology, fibrosis, and autoimmune diseases, reinforcing the company’s commitment to pioneering therapies that address high unmet medical needs.
Founded in 2016 as a spin-out from the University of Pennsylvania, Carisma was co-founded by Dr. Saar Gill, a key scientific leader and the current Chairman of the company’s Scientific Advisory Board. Dr. Gill is also an Assistant Professor of Medicine at the University of Pennsylvania and an Attending Physician specializing in Hematologic Malignancies at the Hospital of the University of Pennsylvania. In addition, he is a member of the Abramson Cancer Center at Penn.
Strategic Shift Following Sesen Bio Merger
This restructuring follows a broader reassessment of Carisma’s focus and priorities after its reverse merger with Sesen Bio in 2023. The merger significantly strengthened Carisma’s financial position, securing $140 million in cash, which provides operational runway for the next two years. Despite initial resistance from activist investors, Carisma’s leadership successfully aligned shareholder interests, setting the stage for this realignment. The company is now narrowing its focus to high-priority programs that align with its long-term vision of advancing transformative science while maintaining financial sustainability.
Focusing on Macrophage Engineering for Oncology, Fibrosis, and Autoimmune Diseases
Carisma’s approach to oncology has already positioned it as a key innovator, particularly in the treatment of solid tumors, which have historically been difficult for immune-based therapies to address. Unlike traditional CAR-T therapies, which are more effective for hematologic malignancies, Carisma’s CAR-macrophages activate both the innate and adaptive immune systems. This multi-faceted immune response is designed to overcome barriers that have limited the effectiveness of other cell therapies in treating solid tumors. The company’s lead program, CT-0508, is currently in a Phase 1 clinical trial as both a monotherapy and in combination with Merck’s Keytruda, with additional data expected by the end of the year.
In addition to its oncology programs, Carisma is expanding its macrophage engineering platform to treat fibrosis and autoimmune diseases. Early results from preclinical studies in liver fibrosis have shown promise, including reduced inflammation and tissue regeneration. Carisma expects to nominate a development candidate in this area by early 2025. Furthermore, the company’s collaboration with Moderna, Inc. is pivotal in advancing anti-glypican 3 (GPC3) therapies for solid tumors and developing therapies for autoimmune diseases. Moderna has selected four research targets, with more expected as the collaboration progresses.
Workforce Reduction and Executive Departures
As part of its strategic restructuring, Carisma Therapeutics has made the difficult decision to reduce its workforce by 34%, impacting 23 employees, including key executives such as Chief Financial Officer Richard Morris, General Counsel Eric Siegel, and Senior Vice President of Human Resources Terry Shields. The company anticipates a $2.7 million financial impact from the termination benefits associated with these layoffs. Although these changes are difficult, they are essential to realign the company’s resources with its highest-priority programs, ensuring long-term financial sustainability and strategic focus.
In April 2024, Carisma announced plans to reduce its workforce by 37% in the second quarter as part of a broader effort to narrow its research focus and conserve cash. The Philadelphia-based cell therapy developer, which began the year with 107 employees, will reduce its headcount by approximately 40 workers.
Discontinuation of Anti-HER2 Development
Carisma’s decision to discontinue the development of its anti-HER2 program was based on a comprehensive assessment of the competitive landscape in anti-HER2 treatments. This evaluation considered the impact of recently approved anti-HER2 therapies on HER2 antigen loss and downregulation, and how these developments influence the future strategy for any anti-HER2 treatments.
The company has completed patient enrollment for the Phase 1 clinical trial of CT-0525 but will not proceed with the previously planned Cohort 3 of the study. While the data available to date from the anti-HER2 program shows that CAR-M cell therapy is safe, well-tolerated, and feasible to manufacture, Carisma believes it will not be able to deliver meaningful outcomes with this program in its current form. Nonetheless, Carisma remains confident in the potential of CAR-M cell therapy and continues to explore other promising avenues for treatment options for patients with solid tumors.
Leadership Statement on Strategic Decisions
"Following a comprehensive review of our portfolio, we have made the strategic decision to prioritize advancing our in vivo macrophage engineering platform," said Steven Kelly, President and Chief Executive Officer of Carisma. "The compelling data generated by both the Moderna-partnered in vivo CAR-M oncology programs as well as our internal liver fibrosis program underscore the potential to revolutionize treatment paradigms with an innovative and patient-centric approach."
"These strategic initiatives, re-directing our investments to the in vivo macrophage engineering platform, discontinuing development of our anti-HER2 program and reducing our workforce, aim to streamline our operations and reduce operating expenses over time," Kelly continued. "While these decisions are very challenging, they are made in the best interest of our shareholders. We remain deeply grateful for the significant contributions of the employees departing Carisma."
Navigating Industry Challenges and Moving Forward
Carisma’s restructuring comes at a time when many biotech companies in Philadelphia are grappling with broader industry challenges. For example, Kite recently announced the closure of its Philadelphia operations after acquiring Tmunity in 2023. Despite these challenges, Carisma’s leadership remains focused on its mission to deliver transformative therapies. The company’s decision to streamline its operations and focus on its core programs positions it well to make a significant impact in oncology, fibrosis, and autoimmune diseases.
Looking ahead, Carisma is well-positioned to redefine treatment paradigms in these high-need areas. By concentrating on its most promising programs and leveraging its partnerships, Carisma is poised to make breakthrough contributions to the treatment of solid tumors, fibrosis, and autoimmune diseases, ultimately improving patient outcomes.