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Carisma Unveils Promising Pre-Clinical Data on Anti-GPC3 In Vivo CAR-M Therapy for Hepatocellular Carcinoma

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Carisma Therapeutics (NASDAQ: CARM) announced positive pre-clinical data for its anti-GPC3 in vivo CAR-M therapy for hepatocellular carcinoma (HCC), developed with Moderna. The therapy demonstrated ability to create CAR-M directly in vivo, reprogramming myeloid cells to target GPC3-expressing cancer cells. Pre-clinical results showed specificity for GPC3 tumor antigen with dose-dependent cytotoxicity against GPC3+ tumor cells. In both syngeneic and humanized tumor models, the therapy significantly reduced tumor burden and suppressed liver metastasis. The treatment was well-tolerated in mouse models, showing promise as an off-the-shelf treatment for GPC3+ solid tumors, including HCC.

Carisma Therapeutics (NASDAQ: CARM) ha annunciato dati preclinici positivi per la sua terapia CAR-M anti-GPC3 in vivo per il carcinoma epatocellulare (HCC), sviluppata in collaborazione con Moderna. La terapia ha dimostrato di avere la capacità di creare CAR-M direttamente in vivo, riprogrammando le cellule mieloidi per mirare alle cellule tumorali che esprimono GPC3. I risultati preclinici hanno mostrato specificità per l'antigene tumorale GPC3 con una citotossicità dose-dipendente contro le cellule tumorali GPC3+. In modelli tumorali sia singeneici che umanizzati, la terapia ha significativamente ridotto il carico tumorale e ha soppressato le metastasi epatiche. Il trattamento è stato ben tollerato nei modelli murini, mostrando promettente come trattamento pronto all'uso per i tumori solidi GPC3+, incluso l'HCC.

Carisma Therapeutics (NASDAQ: CARM) anunció datos preclínicos positivos para su terapia CAR-M anti-GPC3 in vivo para el carcinoma hepatocelular (HCC), desarrollada junto a Moderna. La terapia demostró la capacidad de crear CAR-M directamente in vivo, reprogramando las células mieloides para dirigirse a las células cancerosas que expresan GPC3. Los resultados preclínicos mostraron especificidad por el antígeno tumoral GPC3 con citotoxicidad dependiente de la dosis contra las células tumorales GPC3+. En modelos tumorales sin génicos y humanizados, la terapia redujo significativamente la carga tumoral y suprimió las metástasis hepáticas. El tratamiento fue bien tolerado en modelos de ratones, mostrando promesas como una terapia lista para usar para tumores sólidos GPC3+, incluido el HCC.

카리머 테라퓨틱스(NASDAQ: CARM)는 모더나와 함께 개발한 간세포암(HCC) 치료를 위한 항 GPC3 CAR-M 요법에 대한 긍정적인 전임상 데이터를 발표했습니다. 이 요법은 GPC3를 발현하는 암세포를 목표로 하기 위해 골수세포를 재프로그램하여 CAR-M을 직접 in vivo에서 생성할 수 있는 능력을 입증했습니다. 전임상 결과는 GPC3 종양 항원에 대한 특이성을 보여주며 GPC3+ 종양 세포에 대해 용량 의존적 세포 사멸성을 나타냈습니다. 자가 이식 및 인간화된 종양 모델 모두에서 이 요법은 종양 부하를 상당히 줄이고 간 전이를 억제했습니다. 이 치료는 쥐 모델에서 잘 견디어져 GPC3+ 고형 종양, 특히 HCC를 위한 즉시 사용 가능한 치료법으로서 유망한 결과를 보였습니다.

Carisma Therapeutics (NASDAQ: CARM) a annoncé des données précliniques positives pour sa thérapie CAR-M anti-GPC3 in vivo contre le carcinome hépatocellulaire (HCC), développée avec Moderna. La thérapie a démontré sa capacité à créer des CAR-M directement in vivo, en reprogrammant les cellules myéloïdes pour cibler les cellules cancéreuses exprimant GPC3. Les résultats précliniques ont montré une spécificité pour l'antigène tumoral GPC3 avec une cytotoxicité dépendant de la dose contre les cellules tumorales GPC3+. Dans des modèles tumoraux syngéniques et humanisés, la thérapie a significativement réduit la charge tumorale et supprimé les métastases hépatiques. Le traitement a été bien toléré dans les modèles murins, montrant des promesses en tant que traitement prêt à l'emploi pour les tumeurs solides GPC3+, y compris le HCC.

Carisma Therapeutics (NASDAQ: CARM) hat positive präklinische Daten zu seiner in vivo CAR-M Therapie gegen GPC3 für das hepatozelluläre Karzinom (HCC), das gemeinsam mit Moderna entwickelt wurde, veröffentlicht. Die Therapie zeigte die Fähigkeit, CAR-M direkt in vivo zu erzeugen, indem myeloische Zellen umprogrammiert wurden, um GPC3-exprimierende Krebszellen anzugreifen. Die präklinischen Ergebnisse zeigten eine Spezifität für das GPC3 Tumorantigen mit dosisabhängiger Zytotoxizität gegen GPC3+ Tumorzellen. In sowohl syngeneischen als auch humanisierten Tumormodellen reduzierte die Therapie signifikant die Tumorbürde und unterdrückte Lebermetastasen. Die Behandlung wurde in Mausmodellen gut vertragen und zeigt vielversprechend das Potenzial als sofort verfügbare Behandlung für GPC3+ solide Tumoren, einschließlich HCC.

Positive
  • Successful pre-clinical results showing tumor reduction and metastasis suppression
  • Demonstrated dose-dependent cytotoxicity against target cells
  • Well-tolerated safety profile in mouse models
  • Potential for off-the-shelf treatment development
Negative
  • Still in early pre-clinical stage, far from commercialization
  • Results to animal models, human efficacy yet to be proven

Insights

The preclinical data for Carisma's anti-GPC3 CAR-M therapy represents a significant scientific advancement in liver cancer treatment. The therapy demonstrates three important elements: successful in vivo reprogramming of immune cells, specific targeting of GPC3-positive tumors and significant tumor reduction with metastasis suppression.

The collaboration with Moderna leverages their mRNA/LNP platform technology, potentially offering a more accessible and scalable treatment approach compared to traditional cell therapies. The data showing both tumor reduction and good tolerability in preclinical models suggests a favorable therapeutic window. However, investors should note that translation from mouse models to human clinical trials often faces challenges and success is not guaranteed.

This development strengthens Carisma's position in the competitive cell therapy landscape, particularly for solid tumors where many current approaches struggle. The collaboration with Moderna adds significant credibility and technological support to the program. For a company with a market cap of $42.8M, successful development of an off-the-shelf treatment for liver cancer represents substantial upside potential.

The focus on hepatocellular carcinoma is strategically sound, as it's a market with high unmet need and growing incidence rates globally. The off-the-shelf nature of the therapy could provide significant cost advantages over personalized cell therapies, potentially leading to better market penetration if approved.

New findings showcase the potential of in vivo CAR-M technology as an effective, off-the-shelf treatment for hepatocellular carcinoma (HCC)

PHILADELPHIA, Nov. 8, 2024 /PRNewswire/ -- Carisma Therapeutics Inc. (Nasdaq: CARM) ("Carisma" or the "Company"), a clinical-stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, today announced positive pre-clinical data on its anti-GPC3 in vivo chimeric antigen receptor macrophage and monocyte (together, "CAR-M") therapy for hepatocellular carcinoma ("HCC"), developed in collaboration with Moderna, Inc. (Nasdaq: MRNA). The data demonstrated that the development candidate can successfully create CAR-M directly in vivo, reprogramming endogenous myeloid cells to target and destroy Glypican-3 ("GPC3"), expressing cancer cells.

Pre-clinical results showed that the novel in vivo anti-GPC3 CAR-M therapy exhibits specificity for the GPC3 tumor antigen, driving potent dose-dependent cytotoxicity against GPC3+ tumor cells. Additionally, the CAR-M produced pro-inflammatory cytokines and adopted an inflammatory, activated macrophage phenotype upon antigen engagement. In both syngeneic and humanized tumor models, systemic administration of anti-GPC3 CAR mRNA/LNP significantly reduced tumor burden and suppressed metastasis to the liver. The therapy was well tolerated in mouse models, highlighting its potential as an off-the-shelf treatment for GPC3+ solid tumors, including HCC.

"The data demonstrate our ability to generate anti-GPC3 CAR-M cells directly in vivo using mRNA/LNP technology, leading to significant tumor reduction in translationally relevant pre-clinical models," said Michael Klichinsky, PharmD, PhD, Co-Founder and Chief Scientific Officer at Carisma. "This novel off-the-shelf approach offers a promising new strategy for treating hepatocellular carcinoma, and we are eager to advance it toward clinical development."

"These preclinical data highlights the successful application of our mRNA/LNP platform in enabling in vivo cell therapy," said Lin Guey, PhD, CSO of Therapeutic Research Ventures, Moderna. "We look forward to further advancing the anti-GPC3 in vivo CAR-M therapy for HCC patients and continuing our collaboration with Carisma to bring innovative treatments to those patients with solid tumors."

About Carisma Therapeutics

Carisma Therapeutics Inc. is a clinical-stage biopharmaceutical company focused on utilizing our proprietary macrophage and monocyte cell engineering platform to develop transformative immunotherapies to treat cancer and other serious diseases. We have created a comprehensive, differentiated proprietary cell therapy platform focused on engineered macrophages and monocytes, cells that play a crucial role in both the innate and adaptive immune response. Carisma is headquartered in Philadelphia, PA. For more information, please visit www.carismatx.com.

Cautionary Note on Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, anticipated discovery, preclinical and clinical development activities for Carisma's product candidates, the potential safety, efficacy, benefits and addressable market for Carisma's product candidates, and clinical trial results for Carisma's product candidates. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The words "believes," "anticipates," "estimates," "plans," "expects," "intends," "may," "could," "should," "potential," "likely," "projects," "continue," "will," "schedule," and "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are predictions based on the Company's current expectations and projections about future events and various assumptions. Although Carisma believes that the expectations reflected in such forward-looking statements are reasonable, Carisma cannot guarantee future events, results, actions, levels of activity, performance or achievements, and the timing and results of biotechnology development and potential regulatory approval is inherently uncertain. Forward-looking statements are subject to risks and uncertainties that may cause Carisma's actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties related to Carisma's ability to advance its product candidates, the receipt and timing of potential regulatory designations, approvals and commercialization of product candidates, clinical trial sites and our ability to enroll eligible patients, supply chain and manufacturing facilities, Carisma's ability to maintain and recognize the benefits of certain designations received by product candidates, the timing and results of preclinical and clinical trials, Carisma's ability to fund development activities and achieve development goals, Carisma's ability to protect intellectual property, and other risks and uncertainties described under the heading "Risk Factors" in Carisma's Annual Report on Form 10-K for the year ended December 31, 2023, its Quarterly Reports on Form 10-Q and other documents that Carisma files from time to time with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release, and Carisma undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof, except as may be required by law.

Investors:
Shveta Dighe
Head of Investor Relations
investors@carismatx.com

Media Contact:
Julia Stern
(763) 350-5223
jstern@realchemistry.com

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SOURCE Carisma Therapeutics Inc.

FAQ

What are the key findings of Carisma's (CARM) anti-GPC3 CAR-M therapy pre-clinical trials?

The pre-clinical trials showed the therapy successfully creates CAR-M cells in vivo, demonstrates specificity for GPC3 tumor antigen, reduces tumor burden, and suppresses liver metastasis, while showing good tolerance in mouse models.

How does Carisma's (CARM) anti-GPC3 CAR-M therapy work against hepatocellular carcinoma?

The therapy reprograms endogenous myeloid cells to target and destroy GPC3-expressing cancer cells, producing pro-inflammatory cytokines and adopting an inflammatory, activated macrophage phenotype upon antigen engagement.

What is the collaboration between Carisma (CARM) and Moderna for the CAR-M therapy?

Carisma and Moderna are collaborating to develop the anti-GPC3 in vivo CAR-M therapy using Moderna's mRNA/LNP technology platform for treating hepatocellular carcinoma.

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