HFB301001 / HiFiBiO - LARVOL DELTA

Integrating public single-cell transcriptomics and patient profiles to guide clinical development (AACR 2024) - P1 | "We have presented an AI/ML guided approach to address the key challenge of integrating single-cell data across platforms and demonstrated that relevant disease biology is retained upon integration. We outline a path for deploying this solution at scale for bench and computational scientists to guide target as well as indication selection, as was done for our ongoing clinical programs, including our first-in-class TNFR2 agonist (HFB200301, NCT05238883) and second-generation OX40 agonist (HFB301001, NCT05229601)."

Clinical • IO biomarker • Oncology • CTLA4 • PD-1

HFB301001, an OX40-based immunotherapy, drives Treg clearance and CTL activation through optimized OX40 receptor clustering. (PubMed, J Immunother Cancer) - P1 | "The reduced-affinity strategy represents a promising framework for the clinical development of OX40-targeted cancer immunotherapies. Currently, HFB301001 is concluding in a phase I clinical study involving patients with advanced solid tumors (NCT05229601)."

IO biomarker • Journal • Oncology • Solid Tumor

HFB-301001-01: A Study of HFB301001 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=31 | Terminated | Sponsor: HiFiBiO Therapeutics | N=84 ➔ 31 | Active, not recruiting ➔ Terminated; The decision to discontinue the trial was made as part of a strategic review of the Sponsor's global development portfolio. It is not related to any safety concerns, efficacy findings, recruitment difficulties, or issues with trial conduct.

Enrollment change • Trial termination • Carcinosarcoma • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Uterine Cancer • BRAF

HFB-301001-01: A Study of HFB301001 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=84 | Active, not recruiting | Sponsor: HiFiBiO Therapeutics | Trial completion date: Jan 2025 ➔ Aug 2026 | Trial primary completion date: Jan 2025 ➔ May 2024

Trial completion date • Trial primary completion date • Carcinosarcoma • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Uterine Cancer • BRAF

A phase I monotherapy dose escalation study of HFB301001, a novel next generation OX40 agonist monoclonal antibody, in adult patients with advanced solid tumors. (ASCO 2024) - P1 | "HFB301001 demonstrates a favorable safety profile, dose-dependent PK and PD immunomodulation, and DCR in heavily pretreated solid tumors. HFB301001 warrants further evaluation and expansion in specific tumor types is planned."

Clinical • IO biomarker • Metastases • Monotherapy • P1 data • Genito-urinary Cancer • Immunology • Musculoskeletal Pain • Oncology • Pruritus • Renal Cell Carcinoma • Solid Tumor • CD4 • CD8 • TNFSF4

HFB-301001-01: A Study of HFB301001 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=84 | Active, not recruiting | Sponsor: HiFiBiO Therapeutics | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2024 ➔ Jan 2025 | Trial primary completion date: Jan 2024 ➔ Jan 2025

Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Uterine Cancer • BRAF

Phase I study of HFB301001, a novel OX40 agonist monoclonal antibody, in patients with solid tumors selected via Drug Intelligence Science (DIS) (ESMO 2022) - P1 | "Secondary objectives include pharmacokinetic parameters, preliminary evidence of anti-tumor efficacy, and pharmacodynamic evaluation in blood and tumor. Furthermore, a potential predictive biomarker signature derived based on the DIS™ single-cell immune profiling platform will be investigated."

Clinical • IO biomarker • P1 data • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A Study of HFB301001 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=84 | Recruiting | Sponsor: HiFiBiO Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Uterine Cancer

Discovery of predictive biomarkers of response to T cell-targeting biologics using ex vivo single-cell profiling coupled with TCR clonotype characterization (AACR 2022) - "Comparing the baseline gene expression profiles between T cell clonotypes that responded to the treatment and those that did not allows the discovery of gene expression signatures that can predict response.We processed over 20 tumor samples obtained from cancer patients and treated them ex vivo with two novel biologics currently under clinical development - HFB301001, a potentially best-in-class 2nd generation OX40 agonist, and HFB200301, a potentially first-in-class TNFR2 agonist. Application of these predictive response signatures to bulk transcriptomic data from TCGA was able to stratify patients across cancer indications by predicted likelihood of response to individual treatments or combinations. The predictive biomarkers of response for the novel OX40 and TNFR2 agonist antibodies will be validated in our Phase I clinical trials.Ex vivo single-cell profiling coupled with TCR clonotype characterization enabled the discovery of predictive response signatures that..."

IO biomarker • Preclinical • Oncology • TNFRSF1B

A Study of HFB301001 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=84 | Not yet recruiting | Sponsor: HiFiBiO Therapeutics

New P1 trial • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Uterine Cancer

"#HiFiBiOTherapeutics Receives #FDA Clearance of #IND Application for #HFB301001 https://t.co/kHZLMwQA0a" (,@1stOncology)

FDA event

HiFiBiO Therapeutics Closes $75 Million Series D Financing to Accelerate Pipeline With Two Lead Immuno-Oncology Programs and Validate Its DIS Approach in the Clinic (Businesswire) - “HiFiBiO Therapeutics…announced the completion of an oversubscribed $75M Series D financing round….HiFiBiO Therapeutics will use the proceeds from the financing to advance two lead antibody oncology assets into Phase I clinical trials - HFB200301, a novel anti-TNFR2 antibody and HFB301001, a differentiated second generation anti-OX-40 antibody.”

Commercial • Oncology

[VIRTUAL] Clinical approach and biomarker strategy for HFB301001, a novel OX40 agonistic antibody (AACR 2021) - "Finally, we show here our phase I trial design for HFB301001 that implements these findings.In conclusion, HFB301001 is a highly differentiated therapeutic antibody which is well positioned to enter a global, multi-center Phase I clinical trial to explore optimal biologically active dose and evaluate predictive biomarker hypotheses. Here, we present results supporting the rationale for indication selection, biomarker identification, dose selection, and phase I clinical trial design."

Biomarker • Clinical • IO biomarker • Oncology