On June 3, 2024 BlueSphere Bio, a drug development company focused on the discovery of novel T-Cell receptor (TCR) based therapies, reported that the Food and Drug Administration (FDA) has cleared BlueSphere’s Investigational New Drug application (IND) for a Phase 1/2a trial (TCX-101) of its first-in-human (BSB-1001) product candidate for patients with relapsed or refractory acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and myeloid dysplastic syndrome (MDS), in conjunction with allogeneic hematopoietic stem cell transplantation (alloHSCT) (Press release, BlueSphere Bio, JUN 3, 2024, View Source [SID1234644080]). The Company anticipates enrolling the first patient in this multi-center, open-label study in 4Q2024. Notably, because of the unique product and trial design, the TCX-101 trial will enroll patients with active morphologic disease or cytogenetic features placing them at high risk of relapse. Additionally, patients will receive simultaneous administration of BSB-1001 with alloHSCT to optimally target residual leukemia, without the use of immunosuppressive drugs.

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BSB-1001 targets HA-1, a blood-restricted minor histocompatibility antigen (miHA) and is the first TCR-T cell therapy candidate generated using the Company’s TCXpress platform. TCXpress is an integrated, high-throughput TCR identification and screening platform that enables efficient TCR discovery with a competitive timeline. While BlueSphere is also developing assets for solid tumors and non-oncology indications, it has chosen to prioritize its high-risk leukemia programs in the clinic.

Simultaneously, BlueSphere also announced three additional blood-restricted miHA TCR product candidates that are ready for clinical development – all discovered utilizing the TCXpress platform. Together, these four TCR T-cell therapy candidates comprising the TCX-101 program positions the Company’s miHA portfolio with best-in-class HLA coverage in these hematologic indications.

"We are eager to begin treating patients in our TCX-101 trial," said Keir Loiacono, Esq., Chief Executive Officer of BlueSphere. "Our team is focused on accelerated identification, development and translation of novel products to the clinic. While alloHSCT provides a chance of a cure for patients, a large fraction of patients will still relapse or do not have it as an option because of active leukemia. Deploying a TCR-based approach to blood restricted antigens – like miHAs combined with alloHSCT – could provide new options for these patients. We believe that BlueSphere’s unique approach to product and trial design will, among other things, enable us to treat patients who previously were unable to receive alloHSCT because of the presence of active leukemia."

To further expand the reach of our TCR-based portfolio, BlueSphere has broadened its pipeline to address an additional subset of AML patients having mutated NPM1. Utilizing TCXpress, the Company identified and subsequently nominated a single lead TCR reactive against mutant NPM-1 for the TCX-102 program. As a testament to the power of our TCXpress platform and ability to accelerate translation to the clinic, the Company screened close to 700 million T cells and was able to select three (3) lead candidates in under six months, ultimately nominating a single TCR for clinical development. IND enabling work is underway with an IND filing anticipated in 2Q2025. The TCX-102 trial will be an autologous program and will not be given in combination with alloHSCT.

"The NPM1 mutation is a founder mutation present in approximately 30% of AML patients and is present throughout the duration of the disease, making it an ideal target for TCR-based therapy," said Erkut Bahceci, MD, Chief Medical Officer of BlueSphere. "The advancement of the TCX-102 program in patients with mutant NPM1 demonstrates our commitment to this disease space and underscores the power of our TCR discovery platform to discover rare and potent TCR candidates."