FB849 / 1ST Bio - LARVOL DELTA

FB849, a highly selective HPK1 inhibitor, reshapes the tumor immune microenvironment by modulating various immune cells (AACR 2025) - P1/2 | "We hypothesize that the intra-tumoral expansion of CXCL13+ CD8+ T cells enhance interactions between T cells and various non-T cells including B cells and dendritic cells, potentially driving tertiary lymphoid structure (TLS) formation via the CXCL13 chemokine secretion, which warrants further validation in preclinical and clinical research. Altogether, our work represents a promising approach to modulate a broad spectrum of immune cells simultaneously and enhance their crosstalk, paving the way for durable clinical activity and supporting further development in the clinic."

Immune cell • IO biomarker • Oncology • Renal Cell Carcinoma • Solid Tumor • CD8 • CD80 • CD86 • CTAG1B • CXCL13 • CXCL8 • IFNG • IL12A • IL1B • IL2 • IL6

First Bio, collaboration with world-class cancer research institute 'Mofit'∙∙∙Global clinical development of next-generation immune anticancer drugs accelerates [Google translation] (BioTimes) - "First Biotherapeutics...announced on the 11th that it has signed a strategic partnership with the Moffitt Cancer Center, a world-renowned cancer research and treatment institution. The two companies will accelerate the global clinical development of the next-generation immune anticancer drug 'FB849' and jointly pursue intermediary research and development of tumor-infiltrating lymphocyte (TIL) cell therapy....The two companies will accelerate the clinical development of FB849 and explore new possibilities for anticancer treatment based on long-term collaboration leading to late-stage clinical trials. First, they will secure clinical proof-of-concept (PoC) data by evaluating the efficacy and safety of FB849 in specific cancers such as renal cell cancer, and conduct intermediary research using patient samples."

Licensing / partnership • Renal Cell Carcinoma

First Bio selects national new drug development project for immunotherapy drug 'FB849' [Google translation] (HIT News) - "First Biotherapeutics...is developing a new drug, 'FB849', which is being developed as an immuno-anticancer drug, in clinical development for the '2024 1st National New Drug Development Project' hosted by the National New Drug Development Project (Director Park Young-min, hereinafter referred to as the project group). It was announced on the 19th that it was finally selected for the 'New Support Project' and signed a business agreement with the business group....With support from the business group, First Bio plans to confirm the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary effectiveness of FB849 monotherapy in patients with advanced solid tumors who have developed resistance to existing standard treatments in phase 1 clinical trials. At the same time, the company plans to independently conduct combination therapy with pembrolizumab (product name Keytruda)."

Licensing / partnership • Oncology • Solid Tumor

HPK1 inhibitor reinvigorates exhausted tumor-infiltrating CD8 T cells and synergizes with anti-PD-1 blockade in gynecologic malignancies (AACR 2024) - "However, there was no synergistic effect of FB849 + anti-PD-1 in terms of proliferative capacity in ovarian cancer. Overall, the results of our present study provide a rationale for clinical trials investigating the anti-tumor efficacy of FB849 ± anti-PD-1 tailored to the respective properties of gynecologic malignancies."

IO biomarker • Colorectal Cancer • Endometrial Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • CD8 • LCP2

Integrative analysis of proteomic alterations in human PBMC's treated by HPK1 inhibitor FB849 reveals enriched pathways from various immune cells leading to potential novel biomarker discovery (AACR 2024) - P1/2 | "Together, this work reveals genome-wide alterations in the proteomic and phosphoproteomic landscape by FB849 in both mouse PBMC's and human PBMC's with clear pathway enrichment potentially from various immune cell lineages. Further exploration of the differential expression of each protein and/or phosphoproteins especially in T cell-, B cell-, and monocyte-enriched biomarkers which link to HPK1-relevant signal transduction is needed to find out their clinical implication and to highlight new understanding of HPK1 signaling network in cancer immunity."

Biomarker • Immune cell • Oncology

A selective HPK1 inhibitor FB849 reprograms intratumoral immune cells and elicits strong anti-cancer immunity (AACR 2024) - "These data from patient TIL's together with mouse TIL's pinpoint unprecedented anti-tumor mechanism by FB849 through modulation of exhausted T cells as well as myeloid cells. Altogether, this study supports the planned clinical development of FB849 as a promising immuno-oncology agent as a monotherapy in the selected cancer types and as post-ICI combination with a PD-1 antagonist."

Immune cell • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD8 • FOXP3 • IL2RA • LAG3 • PD-1

KEYNOTE-F25: A Phase I/II, Open-label Study to Investigate the Safety, Tolerability, PK, and Preliminary Efficacy of FB849 (clinicaltrials.gov) - P1/2 | N=121 | Recruiting | Sponsor: 1ST Biotherapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor

1ST Biotherapeutics, Inc. Announces First Patient Dosed in Phase I/II Study of HPK1 Inhibitor FB849 in Patients with Advanced Solid Tumors (BioSpace) - "1ST Biotherapeutics, Inc...announced the first patient dosing in the clinical Phase I/II trial evaluating FB849 in patients with advanced solid tumors....The clinical Phase I/II trial is an open-label study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of FB849 as a monotherapy and in combination with KEYTRUDA for the treatment of advanced solid tumors (NCT05761223)."

Trial status • Oncology • Solid Tumor

1ST Biotherapeutics Announces Clinical Trial Collaboration and Supply Agreement with MSD to Evaluate FB849 in Combination With KEYTRUDA (pembrolizumab) (GlobeNewswire) - "1ST Biotherapeutics, Inc...announced a Clinical Trial Collaboration and Supply Agreement (CTCSA) with MSD, a tradename of Merck & Co., Inc., Rahway, NJ, USA, to evaluate FB849 in combination with MSD’s anti-PD-1 therapy KEYTRUDA^® (pembrolizumab) in a Phase I/II clinical trial for the treatment of patients with advanced solid tumors....Under the terms of the agreement, MSD will provide KEYTRUDA to be used in combination with FB849 for the planned Phase I/II study....The Phase I/II study (NCT05761223) is a first-in-human, multicenter, open-label study to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of FB849 alone as a monotherapy and in combination with KEYTRUDA for the treatment of advanced solid tumors. The recruitment in the clinical study is expected in the second half of 2023."

Licensing / partnership • Trial status • Oncology • Solid Tumor

A Phase I/II, Open-label Study to Investigate the Safety, Tolerability, PK, and Preliminary Efficacy of FB849 (clinicaltrials.gov) - P1/2 | N=121 | Not yet recruiting | Sponsor: 1ST Biotherapeutics, Inc. | Initiation date: May 2023 ➔ Nov 2023

Combination therapy • Metastases • Trial initiation date • Oncology • Solid Tumor

A Phase I/II, Open-label Study to Investigate the Safety, Tolerability, PK, and Preliminary Efficacy of FB849 (clinicaltrials.gov) - P1/2 | N=121 | Not yet recruiting | Sponsor: 1ST Biotherapeutics, Inc.

New P1/2 trial • Oncology • Solid Tumor

1ST Biotherapeutics, Inc., Announces FDA Clearance of IND Application for Phase 1/2 Study of FB849 to Treat Patients with Advanced Solid Tumors (GlobeNewswire) - 1ST Biotherapeutics, Inc...announced that the U.S. Food and Drug Administration (FDA) has accepted its Investigational New Drug (IND) application to evaluate FB849, a small-molecule hematopoietic progenitor kinase 1 (HPK1) inhibitor, in patients with advanced solid tumors. Harnessing multiple components in the immune system while avoiding interfering with essential immune function is a significant challenge in immuno-oncology. FB849 as a highly selective HPK1 inhibitor has the potential to overcome these challenges....The Phase 1/2 study will be a multicenter and open-label study to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of FB849 as a monotherapy and in combination with currently approved checkpoint inhibitors for the treatment of advanced solid tumors. The study preparation is under way."

IND • Oncology • Solid Tumor