BlueSphere Bio Announces IND Clearance for First Human Candidate and New Cell Therapy for High-Risk Leukemia

BlueSphere Bio, a Pittsburgh-based drug development company, has announced that the FDA has approved its Investigational New Drug (IND) application for a Phase 1/2a clinical trial, named TCX-101. The trial will focus on their first-in-human product candidate, BSB-1001, targeting patients with relapsed or refractory acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and myeloid dysplastic syndrome (MDS). This therapy will be administered in conjunction with allogeneic hematopoietic stem cell transplantation (alloHSCT). The company expects to enroll the first patient by the fourth quarter of 2024.

The TCX-101 trial is designed to include patients with active morphological disease or cytogenetic features that put them at a high risk of relapse. These patients will receive simultaneous administration of BSB-1001 along with alloHSCT, aiming to target residual leukemia cells without using immunosuppressive drugs. BSB-1001 is a TCR T-cell therapy that targets HA-1, a minor histocompatibility antigen restricted to blood cells. It is the first TCR-T cell therapy candidate produced using the company’s TCXpress™ platform, which enables rapid TCR discovery and screening.

In addition to BSB-1001, BlueSphere has announced three other blood-restricted minor histocompatibility antigen TCR product candidates, all discovered with the TCXpress™ platform. These candidates position BlueSphere’s portfolio to offer extensive HLA coverage in hematologic conditions.

Speaking on the development, Keir Loiacono, CEO of BlueSphere, expressed enthusiasm about starting the TCX-101 trial. He highlighted the unique approach of using TCR-based therapies in conjunction with alloHSCT, which could offer new treatment options for patients unable to undergo alloHSCT due to active leukemia.

Expanding its reach, BlueSphere has also broadened its pipeline to target AML patients with the NPM1 mutation through a program named TCX-102. The NPM1 mutation is present in about 30% of AML patients throughout the disease’s duration, making it an ideal target for TCR-based therapy. Utilizing the TCXpress™ platform, BlueSphere identified a lead TCR reactive against mutant NPM-1. The company screened approximately 700 million T cells to select three lead candidates within six months, eventually nominating one TCR for clinical development. IND enabling work is ongoing, with a filing expected in the second quarter of 2025. Unlike TCX-101, the TCX-102 trial will be an autologous program not combined with alloHSCT.

Dr. Erkut Bahceci, Chief Medical Officer of BlueSphere, emphasized that the NPM1 mutation’s prevalence and persistence in AML patients make it an exceptional target for TCR-based therapies. He noted that the advancement of the TCX-102 program underscores the potency and efficiency of the TCXpress™ platform in discovering rare TCR candidates.

Founded by UPMC Enterprises, BlueSphere Bio focuses on TCR-based therapies. The company’s proprietary TCXpress™ platform can rapidly isolate and characterize TCRs for use in various clinical settings. While initially focusing on oncology, the platform has the potential for broader therapeutic applications.

BlueSphere aims to leverage the TCXpress™ platform to develop a portfolio of TCR-based assets, initially targeting AML, ALL, and MDS. BSB-1001, the leading candidate in the TCX-101 program, will be administered alongside alloHSCT, with patient enrollment anticipated to begin in the fourth quarter of 2024.