porustobart (HBM4003) / Harbour BioMed, Solstice Oncology - LARVOL DELTA

A phase Ib dose-expansion study of porustobart, an anti-CTLA-4 heavy chain only monoclonal antibody, in combination with toripalimab in patients with advanced high-grade neuroendocrine neoplasms (NENs) (AACR 2023) - P1 | "Porustobart 0.3 mg/kg or 0.45 mg/kg plus toripalimab 240mg Q3W showed promising anti-tumor activity and an acceptable safety profile in pts with advanced high-grade NENs."

Clinical • Combination therapy • Metastases • P1 data • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor

Harbour BioMed Partner, Solstice Oncology, announces $225 Million Series A Financing to Advance Porustobart, a Neoadjuvant Immuno-Oncology Therapy (PRNewswire) - "Solstice is advancing its lead candidate porustobart, a differentiated, second-generation, Fc-enhanced cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, across two clinical indications, one in microsatellite-stable (MSS) colon cancer and a second, undisclosed indication....In a Phase 2 clinical study conducted by Harbour BioMed, porustobart in combination with tislelizumab, a PD-1 inhibitor, demonstrated a 30% objective response rate (7 of 23 patients) in late-line patients with MSS metastatic colorectal cancer without liver metastases, with responses showing encouraging durability. The median duration of response was 8.4 months....Phase 2 trial of porustobart for colon cancer will be open for enrollment early in the fourth quarter of 2026...for which we anticipate data in the second half of 2027."

Enrollment status • Financing • P2 data • Colorectal Cancer

Neoadjuvant Pembrolizumab and Porustobart in Resectable pMMR/MSS Colon Cancer (clinicaltrials.gov) - P2 | N=100 | Not yet recruiting | Sponsor: Solstice Oncology, Inc.

New P2 trial • pMMR • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

HBM Holdings Limited…is pleased to announce that the Company has entered into an exclusive license agreement and equity partnership agreement (the 'Agreements') with Solstice Oncology…under which, the Company has agreed, among other things, to grant Solstice Oncology an exclusive license to develop and otherwise commercialize a clinical stage portfolio asset HBM4003 outside Greater China (HKEXnews) - "Pursuant to the terms of the Agreements, the Company is eligible to receive upfront consideration valued at over US$105 million, comprising (a) an upfront cash payment of US$50 million, (b) a near-term cash payment of US$5 million, and (c) over US$50 million of equity interest in Solstice Oncology to be issued and allotted to the Company. The Company is also eligible to receive additional development, regulatory and commercial milestone payments of up to approximately US$1.1 billion, contingent on the achievement of certain future events, and tiered royalties on net sales of HBM4003 outside Greater China."

Licensing / partnership • Solid Tumor

Harbour BioMed Announces Positive Phase II Results for HBM4003 and Tislelizumab Combination in MSS mCRC (PRNewswire) - "The multicenter, open-label Phase II study (NCT05167071) enrolled 24 heavily pretreated patients with non-liver-metastatic (NLM) MSS mCRC....Among the 23 evaluable patients, the combination therapy achieved: Objective Response Rate (ORR): 34.8% (8 partial responses). Disease Control Rate (DCR): 60.9% (8 partial responses + 6 stable diseases). Median Progression-Free Survival (mPFS): 4.2 months."

P2 data • Colorectal Cancer

Efficacy and Safety of HBM4003, an anti-CTLA-4 Antibody, Combined with Tislelizumab in MSS Metastatic Colorectal Cancer: A Multicenter, Phase II Study [WITHDRAWN] (ESMO 2025) - No abstract available

Clinical • Metastases • P2 data • Colorectal Cancer • Oncology • Solid Tumor

Harbour BioMed to Present Phase II Data of HBM4003 and Tislelizumab Combination in MSS Metastatic Colorectal Cancer at ESMO 2025 (PRNewswire) - "Harbour BioMed...announced that it will present Phase II clinical data on its next-generation, fully human heavy-chain-only anti-CTLA-4 antibody, porustobart (HBM4003), in combination with tislelizumab, for the treatment of microsatellite stable (MSS) metastatic colorectal cancer (mCRC), at the ESMO Congress 2025...In this multicenter, open-label, Phase II study (NCT05167071), heavily pretreated non-liver metastatic MSS mCRC patients were enrolled. Preliminary efficacy and safety data will be presented in a poster session during the ESMO Congress 2025."

P2 data • Colorectal Cancer

Efficacy and safety of HBM4003 combined with toripalimab in refractory neuroendocrine neoplasms: a multicenter, phase II study. (PubMed, EClinicalMedicine) - P1 | "This study was funded by Harbour BioMed (Shanghai) Co. Ltd."

Journal • P2 data • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor

Porustobart (HBM4003) plus toripalimab as second-line therapy in patients with advanced hepatocellular carcinoma: a multicenter, open-label, phase I study. (PubMed, Clin Cancer Res) - P1 | "The combination of porustobart and toripalimab shows promising efficacy as a second-line therapy in anti-PD-1/PD-L1 naïve patients with advanced HCC and a manageable safety profile."

IO biomarker • Journal • P1 data • Hepatocellular Cancer • Oncology • Solid Tumor • CD4 • CD8

HBM4003 Combine With Toripalimab in Patients With Advanced NEN and Other Solid Tumors Study (clinicaltrials.gov) - P1 | N=53 | Active, not recruiting | Sponsor: Harbour BioMed (Guangzhou) Co. Ltd. | Not yet recruiting ➔ Active, not recruiting | Trial completion date: Jun 2024 ➔ Jun 2026 | Trial primary completion date: Oct 2023 ➔ Sep 2025

Enrollment closed • Trial completion date • Trial primary completion date • Endocrine Cancer • Neuroendocrine Tumor • Solid Tumor

Toripalimab in combination with HBM4003, an anti-CTLA-4 heavy chain-only antibody, in advanced melanoma and other solid tumors: an open-label phase I trial. (PubMed, J Immunother Cancer) - P1 | "HBM4003 0.3 mg/kg plus toripalimab 240 mg every 3 week demonstrated manageable safety in solid tumors and no new safety signal. Limited data demonstrated promising antitumor activity, especially in PD-1 treatment-naïve mucosal melanoma."

Combination therapy • IO biomarker • Journal • Metastases • P1 data • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • CD4

Harbour BioMed Announces Publication of the Phase I Study Results for Porustobart in Combination with Toripalimab in Advanced Melanoma and Other Solid Tumors (PRNewswire) - P1 | N=61 | NCT04727164 | Sponsor: Harbour BioMed (Guangzhou) Co. Ltd. | "Harbour BioMed...announced the online publication of the results from its phase I clinical trial of porustobart (HBM4003), the Company's first-in-class fully human heavy chain antibody targeting CTLA-4....These results were published in the Journal for ImmunoTherapy of Cancer....Among the 40 patients who received study treatment, 10 (25.0%) patients reported grade ≥3 treatment-related adverse events (TRAEs)....Efficacy was evaluated in 32 melanoma patients treated with the recommended phase II dose (RP2D) of porustobart 0.3 mg/kg combined with toripalimab 240 mg every three weeks (Q3W), and who had available post-baseline imaging data. The objective response rate (ORR) was 33.3% in the anti-PD-1/PD-L1 treatment-naïve subgroup. For patients with mucosal melanoma, the ORR in this anti-PD-1/PD-L1 treatment-naïve subgroup was 40.0%."

P1 data • Melanoma

A phase Ib study of porustobart (HBM4003), an anti-CTLA-4 heavy chain only monoclonal antibody, in combination with toripalimab in patients with hepatocellular carcinoma. (ASCO 2023) - P1 | "Porustobart 0.45 mg/kg in combination with toripalimab 240mg Q3W showed promising anti-tumor activity in patients with advanced HCC, as well as an acceptable safety profile. Clinical trial information: NCT05149027."

Clinical • Combination therapy • P1 data • Anemia • Gastrointestinal Cancer • Hematological Disorders • Hepatocellular Cancer • Leukopenia • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia • CD4 • CD8

Harbour BioMed Reports Results of Phase Ib Clinical Trial of Porustobart in Combination of Toripalimab in Patients with Hepatocellular Carcinoma at ASCO 2023 (PRNewswire) - "Harbour BioMed...announced the results of phase Ib clinical trial of porustobart (HBM4003), in combination of toripalimab in patients with hepatocellular carcinoma (HCC) (trial code: NCT05149027) were released at the American Society of Clinical Oncology (ASCO) Annual Meeting 2023."

P1 data • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

LUNCHEON PRESENTATION II: Clinically-Validated Fully Human HCAbs Empower Next-Gen Therapeutics (PEGS 2023) - "VHs from this platform do not have the hallmark residues present in camelid VHHs, predicting a low immunogenicity in human and evidenced by anti-CTLA4 HCAb Porustobart in phase 2 clinical trials. Fully human VH domains have great potential to generate a multitude of modalities for therapeutic and diagnostic uses."

Clinical

A Study Evaluating the Safety, Tolerance and Anti-tumor Activity of a Study Drug in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=65 | Completed | Sponsor: Harbour BioMed US, Inc. | Active, not recruiting ➔ Completed | Trial primary completion date: Sep 2022 ➔ Jan 2023

Metastases • Trial completion • Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • BRAF

Harbour BioMed Reports Full Year 2022 Financial Results (PRNewswire) - "Porustobart, the next-generation anti-CTLA-4 antibody, is the first fully human heavy chain only antibody in the world that has entered into clinical development....Further clinical data of this combination therapy with PD-1 for patients with Neuroendocrine Neoplasms (NEN) will be released in 2023..."

P1 data • Neuroendocrine Tumor • Oncology • Solid Tumor

Harbour BioMed Announces Results of Phase Ib Clinical Trial of Porustobart in Combination with Toripalimab in Advanced High-Grade Neuroendocrine Neoplasms at AACR Annual Meeting (Businesswire) - P1b | N=61 | NCT05167071 | Sponsor: Harbour BioMed (Guangzhou) Co. Ltd. | "Harbour BioMed...announced that the results of its phase Ib clinical trial of porustobart (HBM4003) in combination of toripalimab in patients with advanced high-grade neuroendocrine neoplasms (NENs) (trial code: NCT05167071) had been scheduled for presentation in a poster session at the American Association for Cancer Research (AACR) Annual Meeting 2023 and published in the online proceedings of the AACR.....Porustobart in combination with toripalimab showed promising anti-tumor activity in advanced high-grade neuroendocrine neoplasms (NENs). The ORR and DCR were 38.5% and 69.2% in neuroendocrine carcinoma (NEC) patients. The results showed great potential to develop porustobart as a cornerstone therapy for immuno-oncology."

P1 data • Neuroendocrine Tumor • Oncology • Solid Tumor

A phase I dose-escalation and expansion study of HBM4003, an anti-CTLA-4 heavy chain only monoclonal antibody, in patients with advanced solid tumors. (ASCO 2022) - P1 | "HBM4003 showed a favorable safety profile, promising antitumor activity and intratumoral Treg depletion in pts with advanced solid tumors at the 0.45 mg/kg Q3W DL."

Clinical • P1 data • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • CTLA4

A Phase I Study of HBM4003, an anti-CTLA-4 Heavy Chain Only Monoclonal Antibody, in Combination with Toripalimab in Advanced Melanoma (ESMO-IO 2022) - P1 | "Both of the PR cases were mucosal subtype. Conclusions HBM4003 0.3 mg/kg plus toripalimab 240mg Q3W showed promising anti-tumor activity in anti-PD-(L)1 naive patients with advanced melanoma including acral and mucosal subtypes, as well as an acceptable safety profile."

Combination therapy • P1 data • Melanoma • Oncology • Solid Tumor

A Phase I Dose-Escalation Study of HBM4003, an anti-CTLA-4 Heavy Chain Only Monoclonal Antibody, in Combination with Pembrolizumab (IASLC-WCLC 2022) - P1 | "Introduction: Combination therapy with ipilimumab plus PD-1 inhibitors has shown promising efficacy in various tumor types, demonstrating higher rates of response than either agent alone...The pt had partial response (PR) at cycle 3 of tislelizumab treatment... HBM4003 0.3 mg/kg Q3W+ pembrolizumab showed preliminary antitumor activity and a tolerable safety profile in advanced NSCLC."

Combination therapy • P1 data • Anemia • Hematological Disorders • Immunology • Interstitial Lung Disease • Lung Cancer • Musculoskeletal Pain • Non Small Cell Lung Cancer • Oncology • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • CD4 • CD8

A phase I dose-escalation study of HBM4003, an anti-CTLA-4 heavy chain only monoclonal antibody, in combination with toripalimab in advanced melanoma and other solid tumors. (ASCO 2022) - P1 | "Background: Combination therapy of ipilimumab plus PD-1 inhibitors has shown promising efficacy in various tumor types, demonstrating higher rates of response than either agent alone. HBM4003 0.3 mg/kg Q3W+ toripalimab showed promising antitumor activity and a tolerable safety profile in advanced melanoma. Hence, 0.3 mg/kg Q3W was selected as the recommended dose for dose-expansion in advanced melanoma."

Combination therapy • P1 data • Gastroenterology • Gastrointestinal Disorder • Genito-urinary Cancer • Hematological Disorders • Immunology • Leukopenia • Melanoma • Mucosal Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer • CD4 • CD8 • CTLA4

[VIRTUAL] A phase I dose-escalation study of HBM4003: An anti-CTLA-4 heavy-chain-only mAb (ESMO 2021) - P1 | "Preliminary for HBM4003 are encouraging. At 0.45mg/kg Q3W, there was no DLT and no cases of grade 3 diarrhea. There was one confirmed PR."

P1 data • Oncology • Solid Tumor • CTLA4 • PD-1

Harbour BioMed Announces 2022 Interim Results (PRNewswire) - "Recent product highlights - Porustobart (HBM4003): Completed the patients enrollment in phase Ib trial for combination therapy in NET/NEC in August 2022. The preclinical results were published in the Proceedings of the National Academy of Sciences (PNAS) in August 2022, with its mechanism of action and characteristics having been further recognized by industry experts."

Enrollment status • Preclinical • Neuroendocrine Tumor • Oncology • Solid Tumor

A Study Evaluating the Safety, Tolerance and Anti-tumor Activity of a Study Drug in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=65 | Active, not recruiting | Sponsor: Harbour BioMed US, Inc. | Trial primary completion date: Jun 2022 ➔ Sep 2022

Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • BRAF