HX-009 / Waterstone Hanxbio, HanX Biopharma - LARVOL DELTA

A phase 1b study investigating the safety, tolerability and preliminary efficacy of HX009 in post-immune checkpoint inhibitor (CPI) therapy advanced melanoma patients. (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT05731752 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Checkpoint inhibition • Clinical • Metastases • P1 data • Melanoma • Oncology • Solid Tumor

HanX Biopharma Announces HX009 TNBC Combination Therapy IND Approved by the National Medical Products Administration (bydrug.pharmcube.com) - "HanX Biopharma's application for the combination of HX009 and ADC meets the relevant requirements for drug registration and agrees to conduct a Phase 2 clinical trial of the combination therapy for triple-negative breast cancer (TNBC)."

New P2 trial • Triple Negative Breast Cancer

HX009+ IN10018 with or Without Standard Chemotherapy for Advanced Solid Tumours (clinicaltrials.gov) - P1/2 | N=124 | Recruiting | Sponsor: Hangzhou Hanx Biopharmaceuticals, Ltd. | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2027 ➔ Dec 2028 | Trial primary completion date: Dec 2025 ➔ Dec 2027

Enrollment open • Trial completion date • Trial primary completion date • Biliary Cancer • Biliary Tract Cancer • Melanoma • Oncology • Solid Tumor

A Phase Ib Clinical Trial Investigating the Safety, Tolerability, and Pharmacokinetics of HX009,a Novel Bsab Dual Targeting PD-1 x CD47,in Patients with EBV+ Non-Hodgkin Lymphoma (NHL) (ASH 2024) - P1, P1/2, P2 | "Conclusions : In summary, HX009 single agent at 10mg/kg Q2W dose level is well tolerated with manageable safety profile, and anti-tumor activity has been demonstrated in treating patients with R/R EBV+ NHL. Further clinical investigation of HX009, either in single agent or in combination settings, is warranted."

Clinical • P1 data • PK/PD data • Anemia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • PD-1

HX009+ IN10018 With or Without Standard Chemotherapy for Advanced Solid Tumours (clinicaltrials.gov) - P1/2 | N=124 | Not yet recruiting | Sponsor: Hangzhou Hanx Biopharmaceuticals, Ltd.

Metastases • New P1/2 trial • Biliary Cancer • Biliary Tract Cancer • Melanoma • Oncology • Solid Tumor

Preclinical pharmacology characterization of HX009, a novel PD1 x CD47 Bi-specific antibody. (PubMed, Sci Rep) - "We report a new rationally-designed bispecific-antibody (BsAb), HX009, simultaneously targeting PD1 and CD47 to improve both the efficacy and safety over the respective single-targeting agents by grafting the extracellular domain of SIRPα onto the parental anti-PD1-monoclonal antibody, HX008. The IV single-dose toxicology study with a 14-day observation revealed a maximum tolerated dose of 150 mg/kg, while the repeated-dose (once weekly for 4 weeks, 5 doses in total) study showed a highest non-severely toxic dose (HNSTD) of 15 mg/kg. The desired preclinical PK and safety profiles, along with its antitumor activity, support HX009's candidacy for its clinical development."

IO biomarker • Journal • Preclinical • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • PD-1 • SIRPA • TNFRSF4

Preclinical pharmacology characterization of HX009, a novel PD1 x CD47 Bi-specific antibody (Nature) - "We report a new rationally-designed bispecific-antibody (BsAb), HX009, simultaneously targeting PD1 and CD47 to improve both the efficacy and safety over the respective single-targeting agents by grafting the extracellular domain of SIRPα onto the parental anti-PD1-monoclonal antibody, HX008.... The IV single-dose toxicology study with a 14-day observation revealed a maximum tolerated dose of 150 mg/kg, while the repeated-dose (once weekly for 4 weeks, 5 doses in total) study showed a highest non-severely toxic dose (HNSTD) of 15 mg/kg. The desired preclinical PK and safety profiles, along with its antitumor activity, support HX009’s candidacy for its clinical development."

Preclinical • Oncology

Recombinant Humanized Anti-CD47/PD-1 Bifunctional Antibody HX009 in Patients With Relapsed/Refractory Lymphoma (clinicaltrials.gov) - P1/2 | N=99 | Recruiting | Sponsor: Hangzhou Hanx Biopharmaceuticals, Ltd. | Trial completion date: Aug 2023 ➔ Dec 2026 | Trial primary completion date: Dec 2022 ➔ Dec 2025

Trial completion date • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Marginal Zone Lymphoma • Oncology • Peripheral T-cell Lymphoma

Hanseitai Announces that the First HX009 Combination Therapy IND Has Been Approved by the National Medical Products Administration [Google translation] (HanX Bio Press Release) - "On September 5 , 2024 , Hansaitai announced that the first HX009 combination therapy Phase 2 clinical trial received the drug clinical trial approval notice from the National Medical Products Administration. Hansaitai's application meets the relevant requirements for drug registration and agrees to conduct a Phase 2 clinical trial of this product in combination therapy for biliary malignancies (BTC)....'We look forward to quickly advancing this clinical trial and providing patients with new treatment options as soon as possible.'"

New P2 trial • Biliary Cancer

Study on the Tolerability and Pharmacokinetics of HX009 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=80 | Active, not recruiting | Sponsor: Hangzhou Hanx Biopharmaceuticals, Ltd. | N=25 ➔ 80 | Trial primary completion date: Nov 2023 ➔ Dec 2024

Enrollment change • Metastases • Trial primary completion date • Oncology • Solid Tumor • PD-L1

Cis-binding/blockade of CD47 by CD47xPD1 BsAb HX009 enhanced PD1 blockade induced T-cell activation (SITC 2023) - "1 We thus hypothesized that PD1xCD47-dual targeting BsAb (HX009)could potentially enhance T-cell activation over PD1-mAb, seemingly consistent with our earlier observation that HX009 consistently showed higher T-cell activation (~3x per EC50 value) in a reporter assay over PD1-mAb (HX008),2 even with low affinity SIRPa/CD47 binding. This was also further confirmed with the observatiions that HX009 can compete with high-affinity CD47 mAb binding to PD1+CD47+ double positive T-cells, but not to the CD47+ single positive cells (no enhanced avidity). Conclusions HX009 CD47xPD1-BsAb T-cell could have potential superior T-cell activation than PD1-mAb, which could be potentially translated into stronger immunotherapy efficacy."

IO biomarker • Melanoma • Oncology • Solid Tumor • CD47 • CD8 • IL2 • SIRPA

Crown Bioscience Enables HanX Biopharmaceutical to Progress HX009 to Clinical Trials (Businesswire) - "Crown Bioscience...announced that its collaborative work with HanX Biopharmaceutical Co., Ltd. ('HanX'), employing a unique and broad portfolio of preclinical modeling in support of HanX’s successful FDA Investigational New Drug (IND) application, has been published in Scientific Reports, a journal within the Nature portfolio....Specifically, this new study showed that HX009 exerted robust anti-lymphoma activity in two cell-derived xenograft (CDX) models (Raji B-lymphoma and Karpas-299 T-lymphoma) with high CD47 expression. Additionally, custom patient-derived xenograft (PDX) models established by Crown Bioscience, further confirmed the efficacy of CD47 targeting by HX009. In addition, an A20-hCD47 mouse B-lymphoma model developed in hSIRPα/hCD47/PD-1/PD-L1 quadruple knock-in genetically engineered mouse models (HuGEMMTM) mice, HX009 exhibited superior anti-lymphoma efficacy compared to CD47 or PD-1 targeting alone."

Preclinical • Hematological Malignancies • Lymphoma • Oncology

HanX Biopharmaceuticals announces HX009 IND approval from FDA (PRNewswire) - "Hanx Biopharmaceuticals...announced that the company has received Investigational New Drug (IND) approval to start clinical trial of the potentially first-in-class recombinant anti-CD47/PD-1 bispecific antibody (BsAb), HX009, in Patients with relapsed/refractory Lymphoma. This is a Phase IB/II clinical study to be conducted in the United States to evaluate HX009 in the treatment of lymphoma patients who have failed standard therapy....The approval by FDA to start clinical trial in US strengthens the development of HX009 globally, and enhances the company's position in the field of bispecific antibody research."

IND • New P1/2 trial • Hematological Malignancies • Lymphoma • Oncology

Non-clinical pharmacology of HX009, a novel FIC PD1xCD47 BsAb (AACR 2023) - P1/2 | "In summary, the desired PK and safety profiles of HX009, along with anti-tumor activity, supporting further clinical development. Currently, HX009 is under clinical investigation (ClinicalTrials.gov Identifier: NCT05189093)."

Clinical • Oncology • SIRPA

HX009, a first-in-class PD1xCD47 BsAb, demonstrated anti-AML activity in PDX models (AACR 2023) - "AM7577 model responded significantly better than AM8096, likely due to the significantly higher expression of CD47 and also better than Ara-C standard of care (SOC) treatment at 3mg/kg. In contrast, in the subcutaneous transplanted AML cell line-derived model, MV4-11, there is little anti-tumor activity observed, although there is significant expression of CD47 on the tumor cells. In conclusion, our data seems to suggest that HX009 could be a candidate immunotherapy for CD47hi AML, with CD47 expression being a positive predictive biomarker, warranting further evaluation."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • CD47 • SIRPA

HX009, a novel BsAb dual targeting PD1 x CD47, demonstrates potent anti-lymphoma activity in preclinical models. (PubMed, Sci Rep) - "In the humanized mouse syngeneic A20 B-lymphoma (huCD47-A20) HuGEMM model, which has quadruple knocked-in hPD1xhPD-L1xhCD47xhSIRPα genes and an intact autologous immune-system, a contribution of effect is demonstrated for each targeted biologic (HX008 targeting PD1 and SIRPα-Fc targeting CD47), which is clearly augmented by the dual targeting with HX009. Lastly, the expression of the immune-checkpoints PD-L1/L2 and CD47 seemed co-regulated among a panel of lymphoma-derived-xenografts, where HX009 maybe more effective in those with upregulated CD47. Our data warrants HX009's further clinical development for treating NHLs."

IO biomarker • Journal • Preclinical • Hematological Malignancies • Immune Modulation • Infectious Disease • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • PD-1 • SIRPA

Preclinical pharmacology modeling of HX009, a clinical stage first-in-class PD-1xCD47 BsAb, for anti-lymphoma applications (SITC 2022) - P1/2 | "Methods HX009, a 2x2 symmetric BsAb molecule targeting PD1/CD47, was designed and constructed by grafting a low affinity SIRP α to the 3’ of Fc HX008 (anti-PD1 IgG1-Mab) frame with weakened CD47 binding. Conclusions HX009 demonstrated strong preclinical anti-lymphoma activity of HX009, confirming the contributions from both targeting MOAs (CD47/PD1), as well the superior activity of dual targeting as designed, validating our hypothesis. A Phase I/II study for this first-in-class BsAb is ongoing in patients with relapsed/refractory lymphoma, including both B and T cell subtypes (ClinicalTrials.gov Identifier: NCT05189093 )."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • T Cell Non-Hodgkin Lymphoma • SIRPA

Study on the Tolerability and Pharmacokinetics of HX009 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=25 | Active, not recruiting | Sponsor: Hangzhou Hanx Biopharmaceuticals, Ltd.

Metastases • New P1 trial • Oncology • Solid Tumor • PD-L1

The Safety, Tolerability, and Initial Efficacy of HX009 in Patients With Advanced Malignancies (clinicaltrials.gov) - P1 | N=21 | Completed | Sponsor: Waterstone Hanxbio Pty Ltd | Active, not recruiting ➔ Completed | Trial completion date: Sep 2021 ➔ Sep 2022

Trial completion • Trial completion date • Oncology • Solid Tumor

Development of RO assay for anti-PD-1 mAb and anti-PD-1×CD47 BsAb utilizing hPD-1/hCD47 dual humanized mice, at preclinical setting to facilitate clinical validation (SITC 2022) - "Surface expressing CD47 and PD-1 receptors are recognized two most important checkpoints for both innate and adaptive immunity suppressing tumor immunity, and have been explored for immunotherapies, in the cases of investigational drugs, HX008 (PD-1 mAb) and HX009 (CD47 × PD1 BsAb). Further detailed to be analyzed, including HX009 RO values for PD-1 receptor only, CD47 receptor only and total for combining both receptors. Conclusions Supposing further data from HX-009 RO modelling proven valid, RO assay using humanized mice could become a standard method of choice for RO assay development at the preclinical stage, enabling simpler/efficient clinical development."

Preclinical • Oncology • CD47

Recombinant Humanized Anti-CD47 / PD-1 Bifunctional Antibody HX009 Injection in the Treatment of Advanced Solid Tumors (clinicaltrials.gov) - P2 | N=210 | Active, not recruiting | Sponsor: Waterstone Hanxbio Pty Ltd | Recruiting ➔ Active, not recruiting

Enrollment closed • Gastrointestinal Cancer • Oncology • Solid Tumor • PD-L1

Recombinant Humanized Anti-CD47/PD-1 Bifunctional Antibody HX009 in Patients With Relapsed/Refractory Lymphoma (clinicaltrials.gov) - P1/2; N=99; Recruiting; Sponsor: Waterstone Hanxbio Pty Ltd

Clinical • New P1/2 trial • Follicular Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma

[VIRTUAL] First-in-human phase 1 dose escalation study of HX009, a novel recombinant humanized anti-PD-1 and CD47 bispecific antibody, in patients with advanced malignancies. (ASCO 2021) - P1 | "HX009, on an every 2 weeks dosing schedule, up to 7.5 mg/kg, is well-tolerated, without any DLT to date . Antitumor activity was seen at 1 mg/kg and 5 mg/kg cohorts with objective responses in multiple tumor types; Further investigation in phase Ib/II studies is warranted."

Clinical • P1 data • Anemia • Brain Cancer • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gallbladder Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Hematological Disorders • Hepatology • Lung Cancer • Mesothelioma • Oncology • Ovarian Cancer • Pancreatic Cancer • Pneumonia • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thrombocytopenia • Triple Negative Breast Cancer • CD47

The Safety, Tolerability, and Initial Efficacy of HX009 in Patients With Advanced Malignancies (clinicaltrials.gov) - P1; N=21; Active, not recruiting; Sponsor: Waterstone Hanxbio Pty Ltd; Recruiting ➔ Active, not recruiting; N=37 ➔ 21

Clinical • Enrollment change • Enrollment closed • Oncology • Solid Tumor

Recombinant Humanized Anti-CD47 / PD-1 Bifunctional Antibody HX009 Injection in the Treatment of Advanced Solid Tumors (clinicaltrials.gov) - P2; N=210; Recruiting; Sponsor: Waterstone Hanxbio Pty Ltd; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Gastrointestinal Cancer • Oncology • Solid Tumor