HFB200301 / HiFiBiO - LARVOL DELTA

Predictive and generative AI to guide the clinical development of HFB200301, a first-in-class TNFR2 agonist: drug intelligence science (DIS®) (SITC 2024) - P1 | "Results Analysis of our Disease Cell Atlas in the anti-PD-(L)1 refractory setting revealed that TNFR2 is primarily expressed on CD8+ T-cells lacking PD-1 expression, suggesting that agonism may mobilize a distinct set of CD8+T-cells.In our HFB200301 TNFR2 agonist clinical trial (NCT05238883), several tumor types selected by our predictive models, such as anti-PD-(L)1 refractory pleural mesothelioma and EBV+ gastric cancer, have shown either monotherapy or combination anti-tumor activity with the anti-PD-1 inhibitor tislelizumab, which suggests that our predictive models are surfacing the tumor types that will benefit from HFB200301.Moreover, in the same patients exhibiting anti-tumor activity, mIF analysis revealed marked increases in activated CD8+ T-cells following compound treatment, suggesting that the anti-tumor activity results from the on-mechanism action of HFB200301. Conclusions These case studies demonstrate how our multi-modal generative AI and predictive..."

Clinical • IO biomarker • Gastric Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Solid Tumor • CD8

Model-informed dose optimization of HFB200301, a TNFR2 agonist monoclonal antibody (mAb), in monotherapy and in combination with the anti-PD-1 mAb tislelizumab (TIS), in patients (pts) with advanced solid tumors (ESMO 2024) - P1 | "Model-optimized dosing of HFB200301 may provide improved therapeutic activity while maintaining a favorable safety profile in pts with advanced solid tumors. Further dose evaluation is underway with HFB200301 as a monotherapy and in combination with TIS."

Clinical • Combination therapy • Metastases • Monotherapy • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

HiFiBiO Therapeutics to Present Phase 1 Clinical Trial Data for Two Novel Immuno-Oncology Antibodies at the 2024 Annual Congress of the European Society for Medical Oncology (HiFiBiO Press Release) - "HiFiBiO Therapeutics, a clinical stage immune modulation biotechnology company today announced its participation in the 2024 Annual Congress of the European Society for Medical Oncology (ESMO), taking place September 13-17 in Barcelona, Spain....The company will present compelling Phase 1 trial data on two novel monoclonal antibodies: the first-in-class TNFR2 agonist HFB200301 (NCT05238883) and the best-in-class BTLA antagonist HFB200603 (NCT05789069)....HiFiBiO is now applying this strategy to inflammation and immunology, with plans to submit an IND application for a novel BTLA agonist by the end of September."

IND • P1 data • Immunology • Inflammation • Solid Tumor

Phase I dose escalation trial of the first-in-class TNFR2 agonist monoclonal antibody, HFB200301, in monotherapy and in combination with tislelizumab, an anti-PD-1 monoclonal antibody, in adult patients with advanced solid tumors. (ASCO 2024) - P1 | "HFB200301 demonstrates a favorable safety profile, dose-dependent PK, with PD and preliminary clinical activity in monotherapy and in combination with TIS in pts with heavily pre-treated refractory solid tumors."

Clinical • Combination therapy • Metastases • Monotherapy • P1 data • Fatigue • Gastric Cancer • Gastrointestinal Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Movement Disorders • Oncology • Pruritus • Solid Tumor • CD4 • CD8 • PD-L1

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

A Study of HFB200301 as a Single Agent and in Combination With Tislelizumab in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=170 | Recruiting | Sponsor: HiFiBiO Therapeutics | Phase classification: P1a/1b ➔ P1 | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2026

Combination therapy • Metastases • Phase classification • Trial completion date • Trial primary completion date • Cervical Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Germ Cell Tumors • Head and Neck Cancer • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Testicular Cancer • BRAF

HiFiBiO Therapeutics Announces First Patient Dosed with HFB200301 in Combination with tislelizumab in Patients with DIS Selected Advanced Solid Tumors (Businesswire) - "HiFiBiO Therapeutics...announced today that the first patient has been dosed with HiFiBiO’s HFB200301, a first-in-class agonistic anti-TNFR2 monoclonal antibody, in combination with tislelizumab, an investigational anti-PD-1 immune checkpoint inhibitor, for the treatment of advanced solid tumor indications preselected by HiFiBiO’s proprietary Drug Intelligence Science (DIS^®) platform."

Trial status • Cervical Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Kidney Cancer • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Testicular Cancer

A Study of HFB200301 as a Single Agent and in Combination With Tislelizumab in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1a/1b | N=170 | Recruiting | Sponsor: HiFiBiO Therapeutics | Phase classification: P1 ➔ P1a/1b | N=90 ➔ 170 | Trial completion date: Jan 2024 ➔ Dec 2024 | Trial primary completion date: Jan 2024 ➔ Dec 2024

Combination therapy • Enrollment change • Metastases • Phase classification • Trial completion date • Trial primary completion date • Cervical Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Germ Cell Tumors • Head and Neck Cancer • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Testicular Cancer • BRAF

Phase I study of HFB200301, a first-in-class TNFR2 agonist monoclonal antibody in patients with solid tumors selected via Drug Intelligent Science (DIS). (ASCO 2022) - P1 | "Secondary objectives include pharmacokinetic parameters, preliminary evidence of anti-tumor efficacy (e.g., ORR, DCR, DOR) and pharmacodynamic evaluation (e.g., T cell subsets) in the blood and in the tumor. Furthermore, a potential predictive biomarker signature derived based on the DIS single-cell immune profiling approach will be investigated retrospectively."

Clinical • IO biomarker • P1 data • Cervical Cancer • Clear Cell Renal Cell Carcinoma • Cutaneous Melanoma • Epstein-Barr Virus Infections • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Germ Cell Tumors • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Malignant Pleural Mesothelioma • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Testicular Cancer • CD4 • CD8 • PD-L1 • TNFRSF1B

HiFiBiO Therapeutics Announces Clinical Trial Supply Agreement to Evaluate HFB200301 in Combination with Tislelizumab in Patients with DIS Selected Advanced Solid Tumors (Businesswire) - "HiFiBiO Therapeutics...announced today a clinical trial supply agreement with Novartis to evaluate tislelizumab, an anti-PD-1 immune checkpoint inhibitor, in combination with HiFiBiO’s HFB200301, an investigational first-in-class monoclonal anti-TNFR2 agonist antibody for the potential treatment of advanced solid tumor indications preselected by HiFiBiO’s proprietary Drug Intelligence Science (DIS™) platform....Under the terms of the agreement, HiFiBiO Therapeutics will maintain control of the HFB200301 program, including global R&D and commercial rights. Novartis has agreed to supply tislelizumab for use in combination with HFB200301."

Licensing / partnership • Oncology • Solid Tumor

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 HFB200301 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=90 | Recruiting | Sponsor: HiFiBiO Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Cervical Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Germ Cell Tumors • Head and Neck Cancer • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Testicular Cancer • BRAF

A Study of HFB200301 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=90 | Not yet recruiting | Sponsor: HiFiBiO Therapeutics

New P1 trial • Cervical Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Germ Cell Tumors • Head and Neck Cancer • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Testicular Cancer • BRAF

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] Mechanism of action and biomarker strategy for HFB200301, an anti-TNFR2 agonist antibody for the treatment of cancer (AACR 2021) - "These unique T cell profiles may help identifying patients more likely to respond to HFB200301 treatment.In summary, HFB200301 exhibits a unique mechanism of action mainly relying on its agonistic activity on several effector cell types in tumor micro-environment that we expect will benefit a patient population selected with a unique biomarker signature. HFB200301 is currently in preclinical development and a biomarker-driven Phase 1 clinical study is projected for 2021."

Biomarker • IO biomarker • Oncology • CD4 • CD8 • TNFRSF1B