An Open-Label, Phase 1 Clinical Study to Evaluate the Safety, Tolerability, PK/PD and Preliminary Efficacy of HBM4003 in Combination With Toripalimab/ Tislelizumab in Patients With Advanced NEN and Other Solid Tumors

To select RP2D/MTD of HBM4003 in combination with Toripalimab in dose confirmation part(Part 1) and use the RP2D in dose expansion part (Part 2) to evaluate the safety, tolerability, PK/PD and preliminary efficacy of in patients with advanced NEN and other solid tumors

Start Date28 Dec 2021

Sponsor / Collaborator

Hopp Pharmaceutical (Guangzhou) Co., Ltd.

NCT05149027

/ Unknown statusPhase 1

An Open-Label, Phase 1 Clinical Study to Evaluate the Safety, Tolerability, PK/PD and Preliminary Efficacy of HBM4003 in Combination With Toripalimab in Patients With Advanced HCC and Other Solid Tumors

This is an open-label, multi-center phase 1 study. The trial, consisting of Part
1 dose confirmation and Part 2 dose expansion, is designed to evaluate the safety, tolerability, PK/PD and preliminary efficacy of HBM4003 in combination with Toripalimab in patients with advanced HCC and other solid tumors.

Start Date20 Dec 2021

Sponsor / Collaborator

Hopp Pharmaceutical (Guangzhou) Co., Ltd.

CTR20212846

/ RecruitingPhase 1

一项开放性1期研究，评估HBM4003与特瑞普利单抗联用在晚期肝细胞癌及其他实体瘤患者中的安全性、耐受性、PK/PD和初步疗效

[Translation] An open-label Phase 1 study evaluating the safety, tolerability, PK/PD, and preliminary efficacy of HBM4003 in combination with toripalimab in patients with advanced hepatocellular carcinoma and other solid tumors

第1部分：剂量递增部分，确定HBM4003与特瑞普利单抗联合用药，在晚期肝细胞癌及其他实体瘤患者中的最高耐受剂量（MTD）和/或推荐2期剂量（RP2D）第2部分：剂量扩展部分，评估HBM4003与特瑞普利单抗联合用药，在RP2D剂量下，在晚期肝细胞癌患者的初步疗效及安全性

[Translation]

Part 1: Dose escalation part, to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of HBM4003 combined with toripalimab in patients with advanced hepatocellular carcinoma and other solid tumors Part 2: Dose expansion part, to evaluate the preliminary efficacy and safety of HBM4003 combined with toripalimab at the RP2D dose in patients with advanced hepatocellular carcinoma

Start Date15 Dec 2021

Sponsor / Collaborator

Nona Biosciences Suzhou Co. Ltd.

100 Clinical Results associated with Porustobart

100 Translational Medicine associated with Porustobart

100 Patents (Medical) associated with Porustobart

Literatures (Medical) associated with Porustobart

01 Oct 2024·Journal for ImmunoTherapy of Cancer

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

Article

Author: Li, Rongqing ; Zheng, Fei ; Jiang, Yu ; Gao, Meijuan ; Tang, Bixia ; Zhao, Shuai ; Gao, Quanli ; Tao, Xiaolu ; Duan, Rong ; Huang, Gang ; Qi, Meng ; Cui, Chuanliang ; Zhang, Xiaoshi ; Guo, Jun ; Ren, Xiubao ; Yao, Li ; Lee, Michael ; Chen, Jing ; Fang, Meiyu ; Chi, Zhihong ; Luo, Ruixuan ; Chen, Yu ; Li, Feng

Background:

HBM4003 is a novel anti-CTLA-4 heavy chain-only antibody, designed to enhance Treg ablation and antibody-dependent cell-mediated cytotoxicity while ensuring a manageable safety profile. This phase I trial investigated the safety, pharmacokinetics, immunogenicity and preliminary efficacy of HBM4003 plus with anti-PD-1 antibody toripalimab in patients with advanced solid tumors, especially focusing on melanoma.

Methods:

The multicenter, open-label phase I trial was divided into two parts: dose-escalation phase (part 1) and dose-expansion phase (part 2). In part 1, HBM4003 was administered at doses of 0.03, 0.1, 0.3 mg/kg in combination with toripalimab with fixed dosage of 240 mg every 3 weeks. The recommended phase II dose (RP2D) was used in the expansion phase. Primary endpoints were safety and RP2D in part 1 and objective response rate (ORR) in part 2. Biomarkers based on cytokines and multiplex immunofluorescence staining were explored.

Results:

A total of 40 patients received study treatment, including 36 patients treated with RP2D of HBM4003 0.3 mg/kg plus toripalimab 240 mg every 3 week. 36 participants (90.0%) experienced at least one treatment-related adverse event (TRAE), of which 10 (25.0%) patients experienced grade ≥3 TRAEs and 5 (12.5%) experienced immune-mediated adverse events (irAEs) with maximum severity of grade 3. No grade 4 or 5 irAEs occurred. Efficacy analysis set included 32 melanoma patients treated with RP2D and with available post-baseline imaging data. The ORRs of anti-PD-1/PD-L1 treatment-naïve subgroup and anti-PD-1/PD-L1 treatment-failed subgroup were 33.3% and 5.9%, respectively. In mucosal melanoma, the ORR of the two subgroups were 40.0% and 10.0%, respectively. Baseline high Treg/CD4+ratio in the tumor serves as an independent predictive factor for the efficacy of immunotherapy.

Conclusions:

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.

Trial registration number:

NCT04727164.

09 Aug 2022·Proceedings of the National Academy of Sciences of the United States of AmericaQ1 · CROSS-FIELD

An anti-CTLA-4 heavy chain–only antibody with enhanced T _reg depletion shows excellent preclinical efficacy and safety profile

Q1 · CROSS-FIELD

Article

Author: Li, Jin ; Shan, Qianqian ; Gan, Xin ; Rong, Yiping ; Grosveld, Frank ; Qin, Beibei ; Jheng, Ming-Jin ; Chen, Victor ; Zhao, Jiuqiao ; Li, He ; Chen, Fei ; van Haperen, Rien ; Shen, Yuqiang ; Janssens, Rick ; Drabek, Dubravka ; He, Yun ; Wang, Jingsong ; Zhang, Yang

The value of anti-CTLA-4 antibodies in cancer therapy is well established. However, the broad application of currently available anti-CTLA-4 therapeutic antibodies is hampered by their narrow therapeutic index. It is therefore challenging and attractive to develop the next generation of anti-CTLA-4 therapeutics with improved safety and efficacy. To this end, we generated fully human heavy chain–only antibodies (HCAbs) against CTLA-4. The hIgG1 Fc domain of the top candidate, HCAb 4003-1, was further engineered to enhance its regulatory T (T reg ) cell depletion effect and to decrease its half-life, resulting in HCAb 4003-2. We tested these HCAbs in in vitro and in vivo experiments in comparison with ipilimumab and other anti-CTLA4 antibodies. The results show that human HCAb 4003-2 binds human CTLA-4 with high affinity and potently blocks the binding of B7-1 (CD80) and B7-2 (CD86) to CTLA-4. The results also show efficient tumor penetration. HCAb 4003-2 exhibits enhanced antibody-dependent cellular cytotoxicity function, lower serum exposure, and more potent anti-tumor activity than ipilimumab in murine tumor models, which is partly driven by a substantial depletion of intratumoral T reg s. Importantly, the enhanced efficacy combined with the shorter serum half-life and less systemic drug exposure in vivo potentially provides an improved therapeutic window in cynomolgus monkeys and preliminary clinical applications. With its augmented efficacy via T reg depletion and improved safety profile, HCAb 4003-2 is a promising candidate for the development of next generation anti-CTLA-4 therapy.

CLINICAL CANCER RESEARCH

Porustobart (HBM4003) plus toripalimab as second-line therapy in patients with advanced hepatocellular carcinoma: a multicenter, open-label, phase I study

Article

Author: Liu, Tian ; Hao, Jihui ; Tao, Xiaolu ; Luo, Ruixuan ; Xu, Aibing ; Shen, Jie ; Cao, Nan ; Luo, Ming ; Gao, Meijuan ; Zhang, Jingdong ; Yao, Jun ; Xu, Chongyuan ; Xin, Guijie ; Zhang, Yanqiao ; Zheng, Fei ; Yang, Di ; Yu, Ge ; Niu, Junqi ; Zhang, Ningning ; He, Yebo ; Qin, Shukui ; Chen, Yajin ; Guo, Yabing ; Wang, Gang ; Zhang, Shuwen ; Gu, Shanzhi

Abstract:

Purpose: To evaluate porustobart (HBM4003), a novel anti-CTLA-4 monoclonal antibody, combined with toripalimab as second-line therapy in advanced HCC. Patients and Methods: This phase I study included two cohorts of patients with advanced HCC: cohort 1 included patients who were anti-PD-1/PD-L1 naïve and had received first-line anti-VEGFR- tyrosine kinase inhibitor; cohort 2 included patients who had failed prior first-line anti-PD-1/PD-L1 and anti-VEGF/VEGFR therapies. Porustobart (0.45 mg/kg) and toripalimab (240 mg) were administered every 21 days. The primary endpoint was the objective response rate (ORR). Results: Totally, 16 patients were enrolled in cohort 1 and 12 in cohort 2. In the 26 patients with evaluable efficacy data, ORR was 23.1% (95% CI 9.0-43.6). Cohort 1 exhibited an ORR of 40.0%, while cohort 2 presented no objective response. The median progression-free survival was 4.2 months, with 5.7 months for cohort 1 and 3.8 for cohort 2. Biomarker exploration revealed higher abundance of intratumoral Tregs in responders before treatment, and a substantial elevation of CD4+Ki67+ and CD8+Ki67+ T cells after treatment. For safety, treatment-emergent adverse events were reported in 27 (96.4%) patients, treatment-related adverse events (TRAEs) were reported in 25 patients (89.3%), among whom 13 (46.5%) had grade ≥3 TRAEs. Serious adverse events (SAEs) were observed in 12 patients (42.9%), and treatment-related SAEs were observed in 9 (32.1%) patients. Conclusions: 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. Trial Registration: ClinicalTrials.gov identifier: NCT05149027.

News (Medical) associated with Porustobart

31 Mar 2025

·www.harbourbiomed.com

Harbour BioMed Reports Full Year 2024 Financial Results

Cambridge, MA, Rotterdam, NL, Shanghai, CN — March 31, 2025 Harbour BioMed ("HBM" or the "Company"; HKEX: 02142), a global biopharmaceutical company committed to the discovery and development of novel antibody therapeutics in immunology and oncology, today announced its financial results for the year ended December 31, 2024. Dr. Jingsong Wang, Founder, Chairman, and CEO of Harbour BioMed, commented: “The year 2024 was a pivotal period for Harbour BioMed, marked by significant progress in research and development, strategic business expansion, and operational excellence. Despite a challenging macroeconomic environment, the Company demonstrated remarkable resilience, navigating inflationary pressures, global supply chain disruptions, and geopolitical uncertainties while remaining focused on its long-term growth objectives. Throughout the year, Harbour BioMed advanced its strategic transition toward becoming a sustainably profitable global biotech engine. The Company expanded its research and development pipeline with a strong focus on immunology, autoimmune diseases, and inflammation therapeutics. Several key clinical-stage programs progressed significantly, reinforcing our vision of delivering life-changing medicines to patients worldwide. The Company also made substantial investments in its technology platforms to ensure its core antibody discovery capabilities remain at the forefront of biopharmaceutical innovation. The strategic growth of Nona Biosciences, a subsidiary of Harbour BioMed, further solidified our position as a leading partner in the global biotech ecosystem. Additionally, we strengthened our business collaborations, securing multiple licensing and co-development agreements with top-tier pharmaceutical companies to drive sustainable revenue growth. As we look ahead to 2025, we remain committed to expanding our global presence and delivering breakthrough therapies to patients.” Full Year 2024 Financial Highlights Harbour BioMed reported total revenue of US$38.1 million for the year ended December 31, 2024, with an overall profit of approximately US$2.7 million. The Company has been profitable for two consecutive years, demonstrating the uniqueness and resilience of its business model. Compared to 2023, the Company's revenue sustainability has continued to improve. Annual recurring revenue increased from US$5.7 million to US$16.9 million, reflecting a growth rate of 196.5%. Cash profit[1] reached a record high of US$30.68 million. Meanwhile, Harbour BioMed has maintained a strong financial position. As of December 31, 2024, the company's cash and cash equivalents totaled approximately US$166.8 million, providing a solid financial foundation for future growth. [1] cash profit: operating net cash inflow. Advancing a Robust and Differentiated Pipeline Harbour Therapeutics, a sub-brand parallel to Nona Biosciences, is now individually responsible for the development of the Company’s products pipeline. With a growing focus on immunology, inflammation and oncology, Harbour Therapeutics manages a highly differentiated portfolio that includes multiple innovative drug candidates in both clinical and Investigational New Drug (IND)/IND-enabling stages. In inflammation and immunology, the Company has built a robust preclinical pipeline encompassing bispecific and multi-specific antibodies generated using the HCAb-based Bispecific Immune Cell Antagonist (HBICATM) technology, as well as ultra long-acting biotherapeutics for immune-related diseases. In oncology, the Company is leveraging its HBICE® platform to develop bispecific and multi-specific antibodies with novel designs and differentiated mechanisms, such as HBM9027 (PD-L1xCD40) and HBM7004 (B7H4xCD3). In addition, the Company is utilizing its Harbour Mice® and XDC platforms to explore multiple therapeutic modalities, including HBM9033, a mesothelin-targeted ADC, and other ADC/RDC programs in early-stage development. Main products in the clinical stage include: Batoclimab (HBM9161) is the first anti-FcRn monoclonal antibody completed Phase I to pivotal trials in China. As a novel, fully human anti-FcRn monoclonal antibody, batoclimab has the potential to be a breakthrough treatment option for a wide range of autoimmune diseases. In December 2023, the Company voluntarily planned to include additional long-term safety data and re-submitted the Biologic License Application (BLA) for batoclimab to the National Medical Products Administration of China (NMPA) in June 2024. In July 2024, NMPA accepted the BLA for batoclimab for the treatment of gMG. The Phase III pivotal clinical trial results of batoclimab were published in JAMA Neurology in March 2024, demonstrating sustained efficacy and safety with long-term use of batoclimab in the treatment of gMG. HBM9378 is a fully human monoclonal antibody against thymic stromal lymphopoietin (TSLP) generated from the H2L2 Harbour Mice® platform. It is a co-development project conducted by the Company and Kelun-Biotech, with both parties equally sharing the rights. HBM9378 has fully human sequences with a lower immunogenicity risk and better bioavailability compared to other TSLP-targeting competitors. Its long half-life optimization and outstanding biophysical properties support favourable dosing and formulation advantages. The Company received IND approval of HBM9378 for moderate-to-severe asthma from the NMPA in February 2022 and completed a Phase I clinical trial in healthy subjects in China. In November 2024, the Company submitted an IND application for HBM9378 for chronic obstructive pulmonary disease (COPD) to the NMPA, which was approved in February 2025. In January 2025, the Company and Kelun-Biotech entered into an exclusive license agreement with Windward Bio, under which Windward Bio was granted an exclusive license for the research, development, manufacturing and commercialization of HBM9378 globally (excluding Greater China and several Southeast and West Asian countries). Currently, Windward Bio is preparing a global Phase II clinical trial for HBM9378. Porustobart (HBM4003) is a next-generation, fully human heavy-chain-only anti-CTLA-4 antibody discovered and developed using the HCAb Harbour Mice® platform. It is also the first fully human heavy-chain-only antibody which entered clinical development globally. Compared with conventional CTLA-4 antibodies, porustobart has unique, favourable properties, including significant Treg cell depletion and optimized pharmacokinetics for improved safety. Additionally, by enhancing antibody-dependent cellular cytotoxicity (ADCC), porustobart increases the potential to selectively deplete intratumoral Treg cells, helping to overcome the efficacy and toxicity bottleneck of current CTLA-4 therapies. The Company has implemented a global development plan for multiple types of solid tumors with an adaptive treatment design for porustobart. Positive efficacy and safety data have been observed in the monotherapy trial targeting advanced solid tumors, as well as in combination trials with PD-1 inhibitors for melanoma, CRC, NEN and HCC. HBM1020 is a first-in-class fully human monoclonal antibody generated from the H2L2 Harbour Mice® platform targeting B7H7. As a newly discovered member of the B7 family, B7H7 expression is found to be non-overlapping with PD-L1 expression in multiple tumor types, potentially playing a more significant role in tumor immune evasion. With its excellent product design and target features, HBM1020 presents great potential to address significant unmet medical needs for solid tumors. In September 2024, the Company presented the latest clinical data for patients with advanced solid tumors at the ESMO Congress 2024. The data demonstrated excellent safety and tolerability profiles for HBM1020. Of the 15 patients who received post-treatment tumor assessments, 7 patients (46.7%) achieved stable disease (SD), with two patients showing tumor shrinkage of 11% and 25%. Main products in IND and IND-enabling stages include: HBM7020 is a BCMAxCD3 bispecific antibody generated using the fully human HBICE® bispecific technology and Harbour Mice® platform. HBM7020 can crosslink targeted cells and T cells by binding to BCMA and CD3 on the cell surface, leading to potent T cell activation and cell elimination. By incorporating dual anti-BCMA binding sites for optimal cell targeting and monovalent-optimized CD3 activity to minimize CRS, HBM7020 demonstrated potent cytotoxicity with broad applications in both immunological and oncology diseases. In August 2023, HBM7020 obtained IND clearance from the NMPA to commence a Phase I trial for cancer in China. In 2024, the Company restructured its development strategy to target immunological diseases and is currently preparing an IND application. HBM9027 is a novel PD-L1xCD40 bispecific antibody developed using the HBICE® bispecific antibody technology and Harbour Mice® platform. The development of PD-L1xCD40 bispecific antibody further expands the Company’s bispecific immune cell engager into the cutting-edge DC/myeloid cell engager field, showcasing the HBICE® platform’s versatile geometry formats and plug-and-play advantages. In January 2024, HBM9027 obtained IND approval from the Food and Drug Administration (FDA) to initiate a Phase I clinical trial in the U.S. HBM7004 is a novel B7H4xCD3 bispecific antibody. Using HBICE® bispecific technology and Harbour Mice® platform, this bispecific antibody was designed to provide innovative solutions for cancer immunotherapy from both efficacy and safety perspectives. The development of B7H4xCD3 bispecific HBICE® further consolidates the Company’s bispecific immune cell engager platform, demonstrating the HBICE® platform’s versatility and plug-and-play advantages. In preclinical studies, HBM7004 demonstrated an intratumor B7H4-dependent T cell activation manner. In multiple animal models, HBM7004 showed strong anti-tumor efficacy, remarkable in vivo stability, and reduced systemic toxicity. Additionally, in preclinical models, HBM7004 exhibited a strong synergistic effect when combined with a B7H4x4-1BB bispecific antibody at a low effector-to-target cell ratio, indicating an encouraging therapeutic window. The Company is currently conducting IND-enabling studies for HBM7004. HBM9014 is a first-in-class, fully human antibody targeting leukemia inhibitory factor receptor (LIFR) for cancer treatment. It was discovered using the Harbour Mice® platform. HBM9014 blocks multiple IL-6 family cytokine pathways via LIFR to inhibit their function in promoting tumor progression, metastasis and chemoresistance. In preclinical studies, HBM9014 showed significant in vivo antitumor efficacy and enhanced efficacy in combination with cisplatin in multiple tumor models. In addition, HBM9014 exhibited strong tolerability in toxicology studies conducted on primates. In 2025, the Company will continue to actively explore drug development strategies and seek collaboration opportunities. Strategic Business Collaborations Maximizing Platform Value Harbour BioMed’s ongoing commitment to global partnerships is critical to driving both scientific and commercial success. In 2024, the Company continued expanding its business collaborations with leading academic institutions and select industrial partners, focused on driving innovation and efficiency worldwide. Leveraging its technological advantages, Harbour BioMed established Nona Biosciences to better empower industry innovators and support collaborators from Idea to IND (I to ITM). Nona Biosciences is a global biotechnology company committed to providing integrated solutions for partners worldwide, across academia, biotechnology startups, and biopharmaceutical giants. Since its launch in late 2022, Nona Biosciences has achieved remarkable success, securing numerous international collaborations across various innovative formats. The subsidiary has established four leading technology units based on HCAb, including protein engineering, conjugation technology, delivery technology, and cell therapy, to accelerate the development of next-generation therapies. Nona Biosciences signed a global out-license and option agreement with AstraZeneca in May 2024 for preclinical monoclonal antibodies to be used in developing targeted oncology therapies. In December 2024, Nona Biosciences entered a research collaboration and license agreement with Candid Therapeutics to discover next-generation T-cell engagers. Over the past year, Nona Biosciences has also formed research collaborations with multiple partners across various therapeutics areas, including Boostimmune, Alaya.bio, Umoja Biopharma, Alkyon Therapeutics, OverT Bio, and Kodiak Sciences. In January 2025, the Company announced a license agreement with Windward Bio for HBM9378, an anti-TSLP fully human antibody for immunological diseases. In February 2025, HBM Alpha Therapeutics, an innovative biotechnology company incubated by the Company, announced a strategic collaboration and license agreement with a business partner to advance novel therapies targeting corticotropin-releasing hormone (CRH) for various disorders. These collaborations further highlight the Company’s unique strengths in pushing technological boundaries and exploring new innovation pathways. With its industry-leading technology platforms and a flexible business model, the Company will continue seeking new opportunities to expand its collaboration network and maximize the value of its platforms. Incubating Breakthrough Collaborations for the Future To fully harness the potential of its unique platform technologies, Harbour BioMed continues to explore the scalability of its platform applications. The Company is incubating several joint ventures focused on next-generation therapeutics, ranging from multivalence antibodies to cell therapies. These ventures aim to broaden the application of platform technologies and create additional value for the Company. This innovative incubation model facilitates the integration of incremental resources for the diversified development of next-generation innovations, requiring minimal marginal investment while offering a high return on value growth. Representative projects include HBM Alpha Therapeutics and Shanghai NK Cell Technology Limited. 2025 Outlook: Expanding Global Presence and Driving Innovation Looking ahead to 2025, Harbour BioMed will continue driving business growth and accomplishing its mission through two key pillars, Harbour Therapeutics and Nona Biosciences. Harbour Therapeutic will advance multiple clinical trials of its internal pipeline to fully advance the global clinical development project, while Nona Biosciences will continue providing integrated discovery solutions to biotech and pharmaceutical companies, ultimately fostering an innovation ecosystem that promotes biological advancement. A range of products derived from the Company’s Harbour Mice® technology platform and T-cell engager technology will be advanced in immunology, and the ADC platform will be upgraded to the next generation. Through a combination of in-house development and business collaborations, Harbour BioMed will build a portfolio of products with differentiated competitive advantages both in immunology and immuno-oncology. Maximizing the value of its platform through strategic collaborations will continue to drive the Company’s global expansion. In 2025, as the preclinical product pipeline matures, the company expects to expand its collaboration network even further and enter into broader global partnerships, solidifying its leading position in the global market. About Harbour BioMed Harbour BioMed (HKEX: 02142) is a global biopharmaceutical company committed to the discovery and development of novel antibody therapeutics in immunology and oncology. The company is building a robust and differentiated pipeline through internal R&D capabilities, strategic global collaborations in co-discovery and co-development, and selective acquisitions. Harbour BioMed's proprietary antibody technology platform, Harbour Mice®, generates fully human monoclonal antibodies in both the conventional two heavy and two light chain (H2L2) format and the heavy chain-only (HCAb) format. Building upon HCAb antibodies, the HCAb-based immune cell engagers (HBICE®) bispecific antibody technology enables tumor-killing effects that traditional combination therapies cannot achieve. Additionally, the HCAb-based bispecific immune cell antagonist (HBICATM) technology empowers the development of innovative biologics for immunological and inflammatory diseases. By integrating Harbour Mice®, HBICE®, and HBICATM with a single B-cell cloning platform, Harbour BioMed has built a highly efficient and distinctive antibody discovery engine for developing next-generation therapeutic antibodies. For more information, please visit www.harbourbiomed.com.

Phase 1License out/inImmunotherapyPhase 3

10 Oct 2024

·www.prnewswire.com

Harbour BioMed Announces Publication of the Phase I Study Results for Porustobart in Combination with Toripalimab in Advanced Melanoma and Other Solid Tumors

CAMBRIDGE, Mass., ROTTERDAM, Netherlands and SUZHOU, China, Oct. 9, 2024 /PRNewswire/ -- Harbour BioMed (the "Company"; HKEX: 02142), a global biopharmaceutical company committed to the discovery, development, and commercialization of novel antibody therapeutics focusing on oncology and immunology, today 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. The trial evaluated porustobart in combination with the anti-PD-1 antibody toripalimab for the treatment of advanced solid tumors, with a particular focus on melanoma. These results were published in the Journal for ImmunoTherapy of Cancer (IF=10.3, 2023). This multicenter, open-label phase I trial was led by Dr. Jun Guo, Chief Physician of the Department of Melanoma and Soft Tissue Sarcoma at Beijing Cancer Hospital. The data demonstrated that the combination of porustobart and toripalimab had a manageable safety profile with no new safety signals in the treatment of solid tumors. Initial results also indicated promising antitumor activity, particularly in PD-1 treatment-naïve mucosal melanoma. Dual immunotherapy combining anti-CTLA-4 and anti-PD-1 antibodies is currently approved as a frontline treatment for several solid tumors, including melanoma, renal cell carcinoma, and non-small cell lung cancer. However, the high toxicity associated with anti-CTLA-4 antibodies has limited their broader use. Porustobart, a next-generation fully human anti-CTLA-4 antibody developed using the HCAb Harbour Mice® platform, is the first of its kind to enter clinical development globally. Its unique properties offer the potential to overcome the efficacy and toxicity challenges of conventional anti-CTLA-4 therapies, making it a promising candidate in the field of cancer immunotherapy. The phase I trial was conducted in two stages: a dose-escalation phase (Part 1) and a dose-expansion phase (Part 2). A total of 40 patients received treatment aimed at evaluating the safety, pharmacokinetics, immunogenicity, and preliminary efficacy of the combination therapy for the treatment of solid tumors, with a particular focus on melanoma. Safety Results Among the 40 patients who received study treatment, 10 (25.0%) patients reported grade ≥3 treatment-related adverse events (TRAEs). The commonly reported TRAEs were rash (30.0%), abnormal liver function (30.0%), leukopenia (25.0%), and fever (20.0%). Additionally, 5 (12.5%) patients experienced immune-related adverse events (irAEs) with maximum severity of Grade 3. No Grade 4 or 5 irAEs occurred. Efficacy Results 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%. A high baseline Treg/CD4+ ratio in the tumor was identified as an independent predictive factor for immunotherapy efficacy. In summary, the combination of porustobart 0.3 mg/kg with toripalimab 240 mg Q3W demonstrated promising antitumor activity and manageable safety in patients with advanced melanoma, including the difficult-to-treat mucosal subtypes. Further studies are needed to confirm these findings, particularly in patients with mucosal melanoma. "We are encouraged by the positive results from our phase I study of porustobart in combination with an anti-PD-1 antibody, which has shown a favorable safety profile and early signs of clinical activity," said Dr. Jingsong Wang, Founder, Chairman and CEO of Harbour BioMed. "Porustobart is the first internally developed molecule generated from our HCAb Harbour Mice® platform. We look forward to moving forward with further studies to fully explore the potential of this combination in addressing unmet medical needs and ultimately making a meaningful difference in patients' lives." About Porustobart Porustobart (HBM4003) is a fully human anti-CTLA-4 monoclonal heavy chain only antibody (HCAb) generated from Harbour Mice®. It is the first fully human heavy-chain-only monoclonal antibody entered into clinical stage globally. By enhancing antibody-dependent cell cytotoxicity (ADCC) killing activity, porustobart has demonstrated significantly improved depletion specific to high CTLA-4 expressing Treg cells in tumor tissues. The potent anti-tumor efficacy and differentiated pharmacokinetics with durable pharmacodynamic effect present a favorable product profile. This novel and differentiated mechanism of action has the potential to improve efficacy while significantly reducing the toxicity of the drug in monotherapy and combination therapy. About Harbour BioMed Harbour BioMed (HKEX: 02142) is a global biopharmaceutical company committed to the discovery, development, and commercialization of novel antibody therapeutics focusing on immunology and oncology. The Company is building its robust portfolio and differentiated pipeline through internal R&D capability, collaborations with co-discovery and co-development partners, and select acquisitions. The proprietary antibody technology platforms Harbour Mice® generates fully human monoclonal antibodies in two heavy and two light chains (H2L2) format, as well as heavy chain only (HCAb) format. Building upon the HCAb antibodies, the HCAb-based immune cell engagers (HBICE®) bispecific antibody technology is capable of delivering tumor-killing effects unachievable by traditional combination therapies. Integrating Harbour Mice®, and HBICE® with a single B cell cloning platform, our antibody discovery engine is highly unique and efficient for the development of next-generation therapeutic antibodies. For further information, please refer to . SOURCE Harbour BioMed WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultImmunotherapyPhase 1ADC

28 Aug 2024

·www.prnewswire.com

Harbour BioMed Announces 2024 Interim Results

CAMBRIDGE, Mass., ROTTERDAM, Netherlands and SUZHOU, China, Aug. 28, 2024 /PRNewswire/ -- Harbour BioMed ("HBM", or the "Company"; HKEX: 02142), a global biopharmaceutical company committed to the discovery, development, and commercialization of novel antibody therapeutics focusing on oncology and immunology, today announced its interim results for the six months ended June 30, 2024. Dr. Jingsong Wang, Founder, Chairman and CEO of Harbour BioMed, commented, "In the first half of 2024, Harbour BioMed remained profitable, demonstrating the Company's remarkable resilience and adaptability in challenging market conditions. Our global operations continue to open new avenues for future growth. Our outstanding performance has validated the feasibility of the Two-Engine strategy, driven by Harbour Therapeutics and Nona Biosciences. We are confident in our ability to enhance value creation and drive sustainable growth by fully unlocking the tremendous potential of our core innovation engine." The Company reported revenues of US$23.7 million for the first half of 2024, achieving an overall profit of approximately US$1.4 million, with a solid cash balance exceeding US$183 million. Harbour Therapeutics: Robust Portfolio and Differentiated Pipeline The Company has a robust and diversified pipeline with potentially differentiated drug candidates in immuno-oncology and inflammatory and immunology diseases. Key products include HBM9161, HBM4003, HBM9378 and HBM1020. The Company aims to deliver at least one IND submission generated from the discovery engine each year. Batoclimab (HBM9161) is a novel, fully human anti-FcRn (neonatal fragment crystallizable receptor) monoclonal antibody which has the potential to be a breakthrough treatment option for a wide range of autoimmune diseases. In June 2023, the National Medical Products Administration (NMPA) of China accepted the BLA of batoclimab for the treatment of gMG, while in December 2023, the Company voluntarily planned to include additional long-term safety data and re-submitted the BLA for batoclimab to the NMPA in June 2024, which was shortly accepted in July 2024. According to the analysis of the Open-Label extension clinical trial up to November 2023, the data demonstrated consistent efficacy and safety of batoclimab in long-term disease management. Its clinical results were published in JAMA Neurology in March 2024. Batoclimab received the "Breakthrough Therapy Certificate" from the NMPA in 2021 and achieved a positive outcome in the proof-of-concept study for treating Chinese gMG patients in July 2021. The positive topline results of its Phase III clinical trial were announced in March 2023. In October 2022, the Company entered into an agreement with NBP Pharma, a wholly owned subsidiary of the CSPC Group, to co-develop batoclimab in Greater China. The Company believes that the collaboration with CSPC Group enables the Company to optimize the market potential and advance the clinical development of batoclimab, so as to further maximize the value of batoclimab in Greater China. Porustobart (HBM4003) is a next-generation, fully human anti-CTLA-4 antibody targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). It is the first internally developed molecule generated from HCAb Harbour Mice® platform. Porustobart is the first fully human heavy chain only anti CTLA-4 antibody entered into clinical development worldwide, and has favourable properties compared with conventional anti-CTLA-4 antibodies in pre-clinical settings. Notably, porustobart exhibits unique, favourable properties including significant Treg cell depletion and optimized pharmacokinetics for improved safety. While increasing the potential to selectively deplete intratumoral Treg cells via enhanced antibody-dependent cellular cytotoxicity (ADCC) strategy, the Company believes porustobart will be able to break the significant immune-suppressive barrier of anti-cancer immunotherapies in solid tumors. Porustobart has great potential to overcome the efficacy and toxicity bottleneck of the current CTLA-4 therapies, positioning it as a key product in cancer immunotherapy. The Company has implemented a global development plan for porustobart across multiple solid tumor types, with adaptive treatment designs. Positive data on efficacy and safety have been read out from the monotherapy trial targeting advanced solid tumors, as well as the trials of combination treatment with PD-1 inhibitor for melanoma, NEN, and HCC. In January 2024, patient enrolment for combination therapy with a PD-1 inhibitor for advanced colorectal carcinoma was initiated. HBM9378 is a fully human monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), developed from H2L2 Harbour Mice® platform. It inhibits the TSLP-mediated signalling pathway by blocking the interaction between TSLP and its receptor. TSLP plays important roles in DC cell maturation, T helper 2 (Th2) cell polarization, and inflammation, particularly in both eosinophilic and non-eosinophilic inflammation asthma. HBM9378 features fully human sequences, which reduce the risk of immunogenicity and improve bioavailability compared to other TSLP-targeting competitors. Its optimized long half-life and outstanding biophysical properties provide dosing and formulation benefits. HBM9378 has entered the clinical development stage in collaboration with Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (Kelun-Biotech). In February 2022, HBM9378 received IND approval from the NMPA for the treatment of severe asthma and initiated the Phase I trial in China. In October 2023, HBM9378 completed the Phase I clinical trial, and the initiation of its Phase II clinical trial is now ongoing. The Company is also preparing the IND application for a second indication, chronic obstructive pulmonary disease (COPD), for HBM9378. HBM1020 is a first-in-class, fully human monoclonal antibody generated from Harbour Mice® platform, targeting B7H7/HHLA2. As a newly discovered member of the B7 family, B7H7/HHLA2 expression is found non-overlapping with PD-L1 expression in multiple tumor types, suggesting it may play a key role for tumor cells to escape immune surveillance beyond PD-L1 mechanisms. HBM1020 is the first product targeting B7H7/HHLA2 in clinical stage globally. With its excellent product design and target features, the Company believes that HBM1020 has significant potential to address unmet medical needs in the treatment of solid tumors, particularly in patients with low PD-L1 expression and those resistant to PD-(L)1 therapies. The Company initiated a Phase I clinical trial in the U.S. in May 2023 and has since completed multiple dose levels. The latest progress of HBM1020 will be presented at the ESMO Congress 2024. Engaged in the discovery and development of differentiated antibody therapeutics in the areas of immuno-oncology and immunology, the Company are also exploring and developing multiple programs, including novel and challenging antibody therapeutics across various disease areas. In oncology field, alongside monoclonal antibodies (mAbs) such as HBM1022 (CCR8) and HBM9014 (a LIFR-targeting mAb), the Company is also generating bispecific antibodies from the HBICE® platform, featuring innovative designs and differentiated mechanisms such as HBM7020 (BCMAxCD3), HBM9027 (PD-L1xCD40), and HBM7004 (B7H4xCD3). In addition, leveraging the advantages of the Harbour Mice® platform and utilizing the XDC platform, the Company is exploring more therapeutic modalities in oncology, including HBM9033 (a MSLN-targeted ADC) and other ADC/RDC programs in early stages. In the inflammatory and immunology field, the Company has built a robust preclinical pipeline, encompassing bispecific and multi-specific antibody programs in targeting Type 2 pathways and for other inflammatory and immunology conditions. Nona Biosciences: An Efficient Value Creation Engine As a pioneer in innovative antibody platform technology, the Company continues to empower the innovators in the industry and support its collaborators from I to ITM (Idea to IND) through Nona Biosciences. By leveraging flexible business models and robust internal discovery capabilities, Nona Biosciences is maximizing platform value by combining the strengths of the Company with those of its collaborators. To fully utilize the unique platform technologies, Nona Biosciences continues to explore the expansion of platform technology applications, generating impactful values for the Company. The Company has established partnerships with over 25 industry pioneers and academic researchers, further expanding its collaboration network both in China and globally. In February 2024, Nona Biosciences entered into a collaboration agreement with Boostimmune, a biotech company dedicated to developing next-generation anti-cancer therapies via modulating immune systems. The collaboration aims to leverage Nona Biosciences' proprietary H2L2 Harbour Mice® to accelerate the development of ADCs against novel targets. In May 2024, Nona Biosciences entered into a license agreement with Astra Zeneca for preclinical monoclonal antibodies that will be used to create targeted therapies in oncology. Under the terms of the agreement, Nona Biosciences shall receive US$19 million upon completion of the transaction, is eligible to receive an additional US$10 million in potential near-term milestone payments and up to US$575 million upon achieving specified development, regulatory, and commercial milestones, as well as tiered royalty payments on net sales. In addition, Nona Biosciences is eligible to receive payments for the option programs should Astra Zeneca exercise these options. In July 2024, Nona Biosciences entered into a collaboration agreement with Alaya.bio, a biotechnology company developing a novel polymeric delivery platform, to precisely target and reprogram cells in situ and thus to significantly simplify the way CAR-T cell therapies are being developed, manufactured and administered. Nona Biosciences continuous to optimize, upgrade and further develop its technology, establishing a robust antibody discovery platform, protein engineering platform, conjugation technology platform, HCAb-CAR screening platform and delivery technology platform to use mRNA-encoding target gene as immunogen to tackle difficult targets. These platforms enable the Company to address more novel and challenging drug targets globally. About Harbour BioMed Harbour BioMed (HKEX: 02142) is a global biopharmaceutical company committed to the discovery, development, and commercialization of novel antibody therapeutics focusing on immunology and oncology. The Company is building its robust portfolio and differentiated pipeline through internal R&D capability, collaborations with co-discovery and co-development partners, and select acquisitions. The proprietary antibody technology platforms Harbour Mice® generates fully human monoclonal antibodies in two heavy and two light chains (H2L2) format, as well as heavy chain only (HCAb) format. Building upon the HCAb antibodies, the HCAb-based immune cell engagers (HBICE®) bispecific antibody technology is capable of delivering tumor-killing effects unachievable by traditional combination therapies. Integrating Harbour Mice®, and HBICE® with a single B cell cloning platform, our antibody discovery engine is highly unique and efficient for the development of next-generation therapeutic antibodies. For further information, please visit SOURCE Harbour BioMed

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatocellular Carcinoma	Phase 2	-	Harbour BioMed (Shanghai) Co., Ltd.	-
Melanoma	Phase 2	-	Harbour BioMed (Shanghai) Co., Ltd.	-
Renal Cell Carcinoma	Phase 2	-	Harbour BioMed (Shanghai) Co., Ltd.	-
Metastatic Colorectal Carcinoma	Phase 1	China	Hopp Pharmaceutical (Guangzhou) Co., Ltd.	28 Dec 2021
Neuroendocrine tumor of pancreas	Phase 1	China	Hopp Pharmaceutical (Guangzhou) Co., Ltd.	28 Dec 2021
Non Functioning Pancreatic Endocrine Tumor	Phase 1	China	Hopp Pharmaceutical (Guangzhou) Co., Ltd.	28 Dec 2021
Advanced Hepatocellular Carcinoma	Phase 1	China	Nona Biosciences Suzhou Co. Ltd.	15 Dec 2021
Advanced Neuroendocrine Neoplasm	Phase 1	China	Nona Biosciences Suzhou Co. Ltd.	14 Oct 2021
Neuroendocrine Carcinoma	Phase 1	China	Nona Biosciences Suzhou Co. Ltd.	14 Oct 2021
Advanced Lung Non-Small Cell Carcinoma	Phase 1	China	Nona Biosciences Suzhou Co. Ltd.	28 Apr 2021

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04727164 (Pubmed) Manual	Phase 1	Solid tumor \| Melanoma	40	Toripalimab + HBM4003	mecylfxmab(nkbsevvjes) = dvnmdmkcdy rsvoxnsium (dgdonovnxu ) View more	Positive	04 Oct 2024
				Toripalimab + HBM4003 (anti-PD-1/PD-L1 treatment-naïve)	znvvwlgpaq(wpkcztdtvl) = rngapzqlwz nkmkkuyghr (xgcfircujn ) View more
NCT05149027 (ASCO 12023 \| ASCO 22023) Manual	Phase 1	Hepatocellular Carcinoma	28	Toripalimab+Porustobart (pts who failed previous anti-VEGFR multikinase inhibitor(s) treatment while have not received anti-PD-(L)1 treatment + Cohort 1)	juosxcsrvd(stpuwmikip) = nwrsoocjuq nvkhfvimuw (dlrneharxi, 21.3 - 73.4) View more	Positive	26 May 2023
				Toripalimab+Porustobart (pts who failed previous anti-PD-(L)1 and anti-VEGF(R) treatments + Cohort 2)	juosxcsrvd(stpuwmikip) = gvgrflamkx nvkhfvimuw (dlrneharxi, 0.2 - 41.3) View more
NCT05167071 (AACR2023) Manual	Phase 1	Advanced Neuroendocrine Neoplasm Microsatellite Stable (MSS)	16	porustobart+toripalimab	jyftvobkuf(houuhcipat) = ptdusyugba fzrqtvozax (wcmlpghnyb ) View more	Positive	14 Apr 2023
				porustobart+toripalimab (neuroendocrine carcinoma)	jyftvobkuf(houuhcipat) = bxokxwkqzs fzrqtvozax (wcmlpghnyb ) View more
NCT04727164 (ESMO_IO2022) Manual	Phase 1	Locally Advanced Melanoma First line	40	HBM4003 0.03-0.3 mg/kg+Toripalimab 240 mg (Cohort A)	uchuiuiwap(htmehysltc) = zzlhtzhvyd jlndbfwdpa (uehfwwxhbf, 44.9 - 92.2) View more	Positive	08 Dec 2022
				HBM4003 0.03-0.3 mg/kg+Toripalimab 240 mg (Cohort B)	uchuiuiwap(htmehysltc) = atyqctqpox jlndbfwdpa (uehfwwxhbf, 14.2 - 61.7) View more

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