CAR-T Pioneer Carl June-Led Verismo Therapeutics Doses First Patient in Phase 1 Trial of Novel Dual-Chain CAR-T Therapy SynKIR-110 Following $7M Series A Financing

SynKIR-110 is a double-chain CAR-T cell therapy based on the KIR-CAR technology platform., for the treatment of ovarian cancer, mesothelioma, and cholangiocarcinoma expressing mesothelin.Verismo's KIR-CAR core technology originates from Carl June's team at the University of Pennsylvania, known as the father of CAR-T.Compared with the second-generation CAR traditionally designed with scFv single-chain, KIR-CAR adopts a multi-chain receptor design that mimics natural structures, utilizing KIR (killer cell immunoglobulin-like receptor), a conjugate of T cells/NK cells, to stimulate antigen-cell contact, thereby activating and prompting immune cells to kill tumor cells. It provides T cells with a natural switch stimulus while enhancing surface stability to improve the performance of T cells in the harsh microenvironment of solid tumors, thus reducing T-cell exhaustion.

▲ Difference Between Traditional CAR and KIR-CAR

(Source: Verismo official website)

In addition, KIR-CAR can interact with the DAP12 protein to transmit crucial signals to T cells, promoting T cell proliferation, cytokine secretion, and enhanced cytotoxicity. In preclinical models, KIR-CAR-based cell therapy has demonstrated the ability to maintain anti-tumor activity in solid tumor environments, exhibiting higher tumor-killing capacity compared to conventional CAR-T therapies.

"This is an important milestone for our company, and we are proud to collaborate with the outstanding team at the University of Pennsylvania to bring our SynKIR-110 therapy out of the lab and to patients with unmet medical needs," said Dr. Bryan Kim, co-founder and CEO of Verismo Therapeutics.

It is worth mentioning that,In March this year, Verismo Therapeutics announced the completion of a $7 million Series A financing round.The funding will be used to continue advancing the clinical trials of SynKIR-110 for the treatment of solid tumors, as well as the preclinical development of another cell therapy drug, SynKIR-310, for hematological tumors. In June, Verismo Therapeutics also entered into a collaboration with the Center for Vaccine and Cellular Production (CVFP) at the University of Pennsylvania, which will manufacture SynKIR-110 to advance this therapy into clinical trials.

In addition to leading the development of SynKIR-110, Carl June, the father of CAR-T, has made significant contributions to the field of CAR-T therapy and founded two biotechs, Tmunity and Capstan.

Tmunity

Tmunity, founded in 2015, focuses on developing CAR-T therapies for solid tumors, targeting peripheral solid tumors such as prostate cancer, pancreatic cancer, non-small cell lung cancer, breast cancer, ovarian cancer, as well as central nervous system tumors like glioblastoma.

For solid tumors,Tmunity’s strategy is “Antigen + Co-stimulatory Domain + Armor”. In antigen recognition,Tmunity uses a proprietary binder to recognize a range of targets., while also supporting the loading of multiple binders in a single cell; in terms of co-stimulatory structure selection,Tmunity will conduct combination screening on different co-stimulatory modules such as CD2, 4-1BB, ICOS, and CD27 to create CAR-T with optimal efficacy, safety, and persistence.；On armored elements,TmunityDeveloped a series of modular vectors that can conferCAR-TDifferent Cells“Combat Weapons”, includingCytokine Enhancer/Blockers,PD-1/CD28Switch Receptoretc.These modifications can helpCAR-TTherapy addresses the suppressive tumor microenvironment in solid tumors,ImproveCAR-TAntitumor Activity。

Tmunity has successfully advanced multiple candidate therapies into clinical stages. However, in 2021, two patients died after receiving the PSMA-targeted CAR-T product TmPSMA-01 due to the induction of fatal neurotoxicity. In response, Tmunity redesigned a modified CAR and plans to advance it into clinical trials.

In December 2022, Gilead, one of Tmunity's investors, announced the acquisition of Tmunity. Carl June will serve as a senior scientific advisor to Kite. However, the PSMA-targeted pipeline, as one of the company’s most advanced programs, was not included in the acquisition and was spun off and retained, which also reflects Carl June’s commitment to his original entrepreneurial vision.

Capstan

Capstan, co-founded by Carl June and mRNA pioneer Drew Weissman, focuses on developing in vivo CAR-T therapies using mRNA. It completed a $102 million Series A financing round in September 2022 and made its debut.

Capstan's core technology consists of three interconnected technologies — non-viral delivery systems, cell-specific targeting molecules, and payloads designed for diseases.The integration of these three technologies can not only target T cells for the treatment of hematological tumors, solid tumors, fibrotic diseases, and autoimmune diseases but also target hematopoietic stem cells for the treatment of hereditary blood disorders. This precise in vivo cellular engineering technology gives Capstan a potential competitive edge in drug development, such as the ability to adjust according to disease type to achieve optimal safety and efficacy, flexible administration routes that enable treatment in an outpatient setting, and the capability to combine different mRNA payloads for various therapeutic purposes to achieve superior treatment outcomes.

Carl June once stated in an interview that one of the reasons for creating Capstan was the lesson learned from Tmunity: no biotech company can handle three or more projects simultaneously. Tmunity could not manage what Capstan is about to undertake, necessitating the creation of a separate company. Currently, Capstan’s pipeline is still in the preclinical research stage.

Carl June, the father of CAR-T, has always been at the forefront of this field. His innovative research and trials also represent one of the major trends in the potential development of this field. Now, the dual-chain CAR-T therapy he leads has entered clinical trials, and we look forward to its performance in solid tumor clinical trials.

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