On August 2, 2021 T-knife Therapeutics, Inc., a next-generation T-cell receptor company developing a pipeline of innovative therapeutics for solid tumor patients, reported the successful completion of a $110 million Series B financing (Press release, T-Knife, AUG 2, 2021, View Source [SID1234585519]). The financing was led by Fidelity Management & Research Company, LLC., with participation from other new investors including, LSP, Qatar Investment Authority (QIA), Casdin Capital, Sixty Degree Capital, and CaaS Capital, along with existing investors RA Capital Management, Versant Ventures and founding investor Andera Partners. The company plans to use proceeds from the financing to expand its scientific team, increase manufacturing capacity and advance its pipeline of T-cell receptor (TCR) engineered T cell therapies (TCR-T).
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"Over the past year we have made substantial progress toward our goal of building a leading TCR-T company focused on delivering clinically meaningful benefits for patients with solid tumors," stated Thomas M. Soloway, Chief Executive Officer of T-knife. "We are excited to have the support of this group of dedicated life sciences investors to help us fulfill our mission, and we welcome Dr. Karin Kleinhans of LSP to our board of directors."
"T-knife has an elegant and differentiated approach to identifying potent, cancer-specific TCRs with naturally optimized affinity and specificity profiles, creating a next-generation platform for this promising therapeutic field," said Alex Mayweg, Chairman of T-knife and Managing Director at Versant Ventures. "We are pleased to be progressing TK-8001 toward the clinic and to advance our broader portfolio of product candidates."
T-knife is leveraging its proprietary HuTCR transgenic mouse platform to discover and develop a portfolio of TCR-T programs to treat patients with solid tumors. T-knife’s lead program, TK-8001, is a novel TCR-T product candidate targeting MAGE-A1 positive cancers. T-knife plans to begin enrolling patients in the TK-8001 IMAG1NE Phase 1/2 clinical study in the fourth quarter of 2021 and is planning to submit INDs/CTAs for additional product candidates in 2022.
"The field of TCR-T holds significant promise to change the treatment paradigm for many cancer patients," said Karin Kleinhans, PhD, Partner at LSP who joined T-Knife’s board in connection with the Series B financing. "We are highly encouraged by the progress being made at T-knife to advance its important next-generation therapies."
Olivier Litzka, Partner at Andera Partners, commented, "As a founding investor, it is gratifying to witness the continued success at T-knife. The completion of the Series B financing is an important milestone that will enable us to execute on our vision of building a leading transatlantic immuno-oncology company."
About the HuTCR platform
T cells play a key role in the immune response by directly recognizing and eliminating infected, foreign or altered cells, such as cancer cells. To do this, they use their T-cell receptors (TCRs) to scan the surface of other cells for foreign antigens presented on Human Leukocyte Antigen (HLA) complexes. Cancer cells can be recognized by mutated or viral antigens expressed only in the tumor, or self-antigens normally expressed during embryonic development and in non-somatic adult tissues. Genetic engineering of T cells with TCRs recognizing antigens aberrantly or over-expressed in cancers can redirect these T cells to the tumor, potentially offering curative responses to cancer patients.
The ability to identify potent cancer-specific TCRs has been limiting for the field of TCR-T. In the case of self-antigens, T cells bearing those TCRs are eliminated during T cell development to avoid recognition and attack of healthy tissues. For non-self tumor antigens, such as those derived from viral sequences or mutations, the very low T cell frequency in the blood has limited TCR discovery efforts.
To overcome these challenges, T-knife has developed transgenic mice (HuTCR mice) carrying the human TCRαβ gene loci and expressing multiple human HLAs. Immunizing HuTCR mice with human tumor antigens, for which mice are not tolerant, allows for the identification of both CD4+ and CD8+ T cells with TCRs that have optimized affinity / specificity profiles capable of mediating significant anti-tumor activity. The TCRs from HuTCR mice are of higher affinity for tumor self-antigens than TCRs isolated from human donors and are naturally optimized to maintain a high specificity profile, making HuTCR mice a powerful high-throughput platform for rapidly generating TCRs with best-in-class potential.