Company Overview
Carisma Therapeutics Inc. (CARM) is a clinical-stage biopharmaceutical company at the forefront of developing transformative immunotherapies using its proprietary macrophage and monocyte cell engineering platform. Founded in 2016 and headquartered in Philadelphia, Carisma has made significant strides in advancing its pipeline of novel cell therapies to treat cancer and other serious diseases.
History and Background
The company's origins can be traced back to April 2016 when it was formed as Carma Therapeutics LLC, a Pennsylvania limited liability company. In May 2017, the company converted to a Delaware corporation under the name CARISMA Therapeutics Inc. In March 2023, CARISMA Therapeutics Inc. merged with a wholly-owned subsidiary of Sesen Bio, with the combined entity retaining the Carisma Therapeutics Inc. name and ticker symbol CARM. This merger allowed Carisma to become a publicly traded company. Prior to the merger, Carisma's operations had been focused on organizing and staffing the company, business planning, capital raising, establishing and maintaining its intellectual property portfolio, building a pipeline of product candidates, conducting drug discovery activities, undertaking pre-clinical studies, manufacturing process development studies, and conducting early-stage clinical trials.
Technology and Focus
Carisma's core focus is on engineering macrophages and monocytes, cells that play a crucial role in both the innate and adaptive immune response. The company has created a comprehensive, differentiated proprietary cell therapy platform that leverages these myeloid cells to develop novel immunotherapies. This unique approach sets Carisma apart from traditional T-cell focused cell therapies, offering the potential to address a broader range of diseases beyond oncology.
Lead Product Candidate
Carisma's lead product candidate, CT-0525, is a first-in-class, ex vivo gene-modified autologous chimeric antigen receptor-monocyte (CAR-Monocyte) cellular therapy intended to treat solid tumors that overexpress human epidermal growth factor receptor 2 (HER2). In May 2024, the company announced that the first patient was dosed in its Phase 1 clinical trial evaluating CT-0525. In June 2024, the FDA granted Fast Track designation for CT-0525, recognizing the serious and life-threatening nature of HER2-overexpressing solid tumors and the potential of CT-0525 to address this critical unmet medical need. Carisma expects to report initial data from the Phase 1 trial by the end of 2024.
Collaborations and Partnerships
In addition to its ex vivo oncology program, Carisma has an in vivo CAR-M program in collaboration with Moderna, Inc. (MRNA). In June 2024, the companies announced the nomination of the first development candidate, an in vivo CAR-M targeting Glypican-3 (GPC3) for the treatment of solid tumors, including hepatocellular carcinoma (HCC). This milestone marked a significant step forward in the partnership, which leverages Carisma's CAR-M expertise and Moderna's mRNA and lipid nanoparticle platform to develop novel off-the-shelf cell therapies.
Financials and Liquidity
Carisma's financial position as of September 30, 2024, shows cash and cash equivalents of $26.9 million, which the company believes are sufficient to sustain its planned operations into the third quarter of 2025. The company reported a net loss of $42.8 million for the nine months ended September 30, 2024, reflecting its ongoing investment in research and development activities.
In terms of financial performance, Carisma generated collaboration revenues of $15.98 million for the nine months ended September 30, 2024, primarily from its partnership with Moderna. Research and development expenses for the same period were $44.09 million, while general and administrative expenses were $16.21 million.
For the most recent quarter ended September 30, 2024, Carisma reported revenue of $3.39 million and a net loss of $12.70 million. The company's operating cash flow for the quarter was negative $28.71 million, with free cash flow at negative $28.70 million. The decrease in revenue and increase in net loss, operating cash flow, and free cash flow compared to the prior year quarter were primarily due to the company's increased investment in research and development as it advances CT-0525 and other pipeline programs.
As of September 30, 2024, Carisma's current ratio and quick ratio both stood at 3.233, indicating a strong short-term liquidity position. The company has not disclosed any available credit line.
Strategic Initiatives
The company's revised operating plan, approved in March 2024, has prioritized the advancement of CT-0525 as the lead product candidate, while pausing further development of CT-1119 and ceasing the development of CT-0508. This strategic decision aims to conserve cash and focus the company's resources on its core clinical programs. As part of this plan, Carisma reduced its workforce by 37% and decreased spending on other non-essential activities.
Legal Challenges
Carisma's journey has not been without its challenges. In December 2022, a putative class action complaint was filed against the company and its then-members of the board of directors, alleging false and misleading statements in the company's proxy statement/prospectus related to the Merger. However, the plaintiff voluntarily dismissed the action as moot in February 2023, and the court subsequently entered an order closing the case.
Future Outlook
Despite the obstacles, Carisma remains committed to its mission of developing innovative immunotherapies. The company's unique approach to engineering macrophages and monocytes holds promise in addressing a wide range of diseases, and its progress in both its ex vivo oncology and in vivo programs demonstrates its ability to execute on its strategic priorities.
As Carisma continues to navigate the clinical development landscape, investors will closely follow the company's ability to replicate the positive results from its preclinical studies in larger-scale clinical trials, obtain regulatory approvals, and ultimately bring its transformative therapies to patients in need. The company's success in these endeavors will be critical in determining its long-term trajectory and potential to disrupt the field of cell-based immunotherapies.
Additional Information
It's worth noting that prior to the merger and subsequent strategic shift, Carisma's lead product candidate was CT-0508, which was the first CAR-Macrophage to be evaluated in a human clinical trial. The company enrolled six patients in a sub-study evaluating the co-administration of CT-0508 and pembrolizumab, a programmed cell death protein 1 checkpoint inhibitor. The study met its primary endpoints of safety, tolerability and manufacturing feasibility of CT-0508. However, as part of the revised operating plan in 2024, Carisma decided to cease further development of CT-0508 to focus resources on CT-0525.
In addition to its oncology programs, Carisma has also achieved pre-clinical proof of concept with its engineered macrophages for the treatment of liver fibrosis, demonstrating the potential versatility of its platform beyond cancer therapies. The company expects to nominate a development candidate for its fibrosis program in the first quarter of 2025.
Carisma's product pipeline consists of two main segments: an ex vivo oncology program and an in vivo program. The ex vivo oncology program is centered around CT-0525, which utilizes a novel approach to CAR-M therapy by engineering patients' monocytes directly, without ex vivo differentiation into macrophages. This CAR-Monocyte approach has shown potential to improve upon the anti-tumor effect seen with traditional CAR-Macrophage approaches.
The in vivo program, conducted in partnership with Moderna, leverages Moderna's mRNA-LNP technology and Carisma's CAR-M platform to create novel in vivo off-the-shelf gene therapy products. In November 2023, the companies announced pre-clinical proof of concept with this approach, and in December 2023, they nominated the first lead candidate under the collaboration. The nomination of the development candidate targeting Glypican-3 for hepatocellular carcinoma in June 2024 triggered a $2 million milestone payment from Moderna to Carisma.
As Carisma Therapeutics continues to evolve and adapt its strategy, it remains focused on leveraging its unique cell engineering platform to develop innovative therapies that have the potential to address significant unmet medical needs across a range of diseases. The company's progress in both its ex vivo and in vivo programs, along with its strategic focus on CT-0525 and the fibrosis program, positions it well to potentially make significant contributions to the field of cell-based immunotherapies in the coming years.