Beijing Cancer Hospital

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

HONG KONG, Sept. 30, 2024 /PRNewswire/ -- September 30, 2024, Akeso (9926. HK) announced that its internally developed PD-1/CTLA-4 bispecific antibody, cadonilimab, has received approval from the National Medical Products Administration (NMPA) for a new indication: cadonilimab in combination with fluoropyrimidine and platinum-based chemotherapy for first-line treatment of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. This is the second indication approval for cadonilimab in China, following its initial approval for marketing in June 2022. The approval of the new indication for cadonilimab combination therapy for first-line treatment of gastric/GEJ cancer is based on the COMPASSION-15/AK104-302 study. In the COMPASSION-15 study, the proportion of patients with PD-L1 CPS < 5 and PD-L1 CPS < 1 in the Intention-to-Treat (ITT) population reached 49.8% and 23%, respectively, which is significantly higher than the data disclosed in previous phase III studies of other immunotherapies for first-line treatment. In November 2023, the interim analysis of the study achieved the primary endpoint of overall survival (OS). The results showed that the cadonilimab combination therapy significantly reduced the risk of death in advanced gastric cancer patients across all PD-L1 expression levels (including those with PD-L1 CPS ≥5 and <5), extending overall survival benefits and demonstrating notable advantages in objective response and long-term survival. Previous phase III trials of PD-1 inhibitors combined with chemotherapy showed limited or no clinical benefit for patients with low or negative PD-L1 expression. The results of the COMPASSION-15 study were presented as an oral report at the 2024 AACR. In the ITT population, the median overall survival (mOS) for the cadonilimab regimen reached 15.0 months, compared to 10.8 months in the control group, extending overall survival by 4.2 months and reducing the risk of death by 38% (HR=0.62). In the PD-L1 CPS <5 group, the mOS for the cadonilimab regimen was 14.8 months, with a 30% reduction in the risk of death compared to the control group (11.1 months, HR=0.70). For the PD-L1 CPS ≥5 group, the mOS had not yet been reached, but the risk of death was reduced by 44% compared to the control group (10.6 months, HR=0.56). COMPASSION-15's principal investigator, Professor Ji Jiafu from Peking University Cancer Hospital, stated: " The prognosis for advanced gastric cancer is poor. While currently approved immunotherapy options have improved efficacy compared to traditional chemotherapy, there remains significant potential for enhancement. The cadonilimab combination therapy has substantially increased the objective response rate and overall survival in the general population while reducing disease-related mortality. Remarkably, cadonilimab shows significant overall survival benefits not only in patients with high PD-L1 CPS expression but also in those with low or negative PD-L1 CPS expression. The approval of cadonilimab as a first-line treatment effectively addresses the efficacy gap of PD-1/L1 monoclonal antibodies in patients with low or negative PD-L1 expression, providing a more comprehensive and effective immunotherapy option for advanced gastric cancer. This advancement benefits all patient populations and presents new opportunities for the global development of gastric cancer immunotherapy, carrying important clinical implications. As a clinician, I am enthusiastic about the approval of cadonilimab for advanced gastric cancer. This innovative treatment will offer a superior and more comprehensive immunotherapy option for patients, and I look forward to its impact on optimizing the current clinical landscape for advanced gastric cancer." COMPASSION-15's principal investigator, Professor Shen Lin from Peking University Cancer Hospital, stated: "We are delighted by the successful approval of cadonilimab combination therapy for the first-line treatment of advanced gastric cancer. This regimen offers significant advantages over current immunotherapy options in clinical practice, providing a superior choice not only for patients with high PD-L1 expression but also for those with low or negative PD-L1 expression, who previously lacked effective treatment options. Cadonilimab addresses the limitations of single-target immunotherapy and exemplifies the synergistic mechanism of dual immune therapy with "anti-PD-1 + anti-CTLA-4," thereby filling an important clinical gap in the treatment of advanced gastric cancer. Beyond first-line approval, the phase III clinical study (AK109-301) of cadonilimab combined with pulocimab (AK109, VEGFR-2) for treating advanced gastric cancer that has progressed after PD-1/L1 inhibitor plus chemotherapy has been initiated. There is currently a lack of effective standard treatments for patients with acquired resistance to immunotherapy, and we eagerly anticipate that this new combination regimen will yield improved results in second-line therapy for these patients, ultimately providing clinicians with more effective tools for cancer treatment." Dr. Xia Yu, Founder, Chairwoman, President, and Chief Executive Officer of Akeso Biopharma, stated: "We thank all researchers, participants, and patients involved in this clinical study. Their collective efforts have led to the approval of cadonilimab combination therapy for first-line treatment of advanced gastric cancer, introducing a novel bispecific immune therapy combined with chemotherapy. As immunotherapy evolves, global regulators and the medical community are reassessing the real-world benefits of PD-1 therapies across different PD-L1 expression levels in gastric and esophageal cancers. Cadonilimab, a novel bispecific antibody targeting both PD-1 and CTLA-4, is supported by robust evidence demonstrating significant clinical benefits for the entire gastric cancer population. Differentiating from PD-1 monoclonal antibody combinations, cadonilimab also shows substantial advantages for patients with low or negative PD-L1 expression. Akeso will continue to explore the global clinical value of cadonilimab." Gastric cancer is one of the most common malignant tumors worldwide. According to the International Agency for Research on Cancer (IARC) 2022 statistics, there are nearly one million new cases each year, making it the fifth most common cancer. China accounts for about half of these cases and deaths, with HER2-negative patients representing around 88%. For those ineligible for surgery or with metastatic gastric cancer (including gastroesophageal junction cancer), immunotherapy using PD-1/L1 monoclonal antibodies has shown success in first-line treatment, though survival benefits remain limited. Cadonilimab combination therapy is expected to provide a more effective treatment option. SOURCE Akeso, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Updated results with longer follow-up reveal confirmed ORR of 68% and median PFS of 14.2 months in patients with CLDN18.2 high or medium expression, known PD-L1 CPS (n=66). PRINCETON, N.J. and SUZHOU, China, Sept. 18, 2024 /PRNewswire/ -- Transcenta Holding Limited ("Transcenta") (HKEX: 06628), a global clinical stage biopharmaceutical company with fully-integrated capabilities in discovery, research, development and manufacturing of antibody-based therapeutics, today announced the updated results from the cohort-G data for Osemitamab (TST001) plus Nivolumab and CAPOX as the first-line treatment for the patients with advanced G/GEJ cancer (TranStar102). The updated data continues to show encouraging efficacy from previously disclosed data at ASCO 2024. The results showed that in patients with known CLDN18.2 and PD-L1 status, the median progression-free survival (mPFS) reached 14.2 months for those with H/M CLDN18.2 expression, with a confirmed objective response rate of 68%. The vast majority of these patients are PD-L1 CPS<5. Using the group of patients with very low or no CLDN18.2 expression as surrogate control, the HR for the triple combination is 0.505 (95% CI, 0.244-1.045) in favor of the CLDN18.2 H/M, any CPS expressers. The data corroborates the synergistic mechanism of action between CLDN18.2 targeting agent and checkpoint inhibitors reported by Transcenta last year at ESMO which showed that CLDN18.2 targeting antibody can induce PD-L1 expression in gastric cancer tumor cells (even in those with PD-L1 low or null expression) and T-cell infiltration. As of the cutoff date, the median OS was not reached because of the limited number of events, the 12-month survival rate for the overall population (82 patients) in this cohort was 73.8% (95% CI: 62.0- 82.4%). Previous studies have found that the combination of Zolbetuximab+CAPOX in CLDN18.2 positive patients, regardless of the PD-L1 status, leads to an improvement in PFS from 6.80 to 8.21 months (HR = 0.687 (95% CI, 0.544-0.866) (Source: Shah, Manish A et al. Nature Medicine 2023 Aug 29 (8): 2133-2141). This updated Cohort-G data shows that the efficacy from the triple combo therapy of Osemitamab (TST001) plus Nivolumab and CAPOX compares very favorably with the historical data of Nivolumab plus CAPOX combination or Zolbetuximab plus CAPOX combination. The updated data has been featured as a poster presentation (Abstract #1419p) on September 16, 2024 at the ESMO Congress 2024 in Barcelona, Spain. "The updated data from the Cohort-G trial of Osemitamab (TST001) in combination with Nivolumab and CAPOX as first-line treatment for advanced G/GEJ cancer are highly encouraging. The confirmed objective response rate and median progression-free survival in patients with high/medium CLDN18.2 expression, known PD-L1, as compared to patients with no CLDN18.2 expression, confirm the synergy between Osemitamab (TST001) and Checkpoint inhibitors and demonstrates the potential of this triple combination therapy, potentially including in low PD-L1 expressers," said Dr. Caroline Germa, Executive Vice President, Global Medicine Development and Chief Medical Officer at Transcenta, "These results highlight the promise of Osemitamab (TST001) in improving outcomes for patients with advanced G/GEJ cancer." "The Cohort-G data presented at ESMO 2024 provide compelling evidence of the clinical benefit of the triple combination therapy. The significant improvement in progression-free survival and objective response rate, particularly in patients with high/medium CLDN18.2 expression and low PD-L1 CPS, is a testament to the potential of this therapeutic approach," said Professor Lin Shen, Director, department of Gastrointestinal Oncology and Phase I Clinical Trial Center at Peking University Cancer Hospital; and Principal Investigator of the trial, "We are excited about the potential benefits this treatment could bring to our patients." A brief summary of the study is as follows: Study Design Cohort G from Transtar102 study (NCT04495296) was designed to explore the safety and efficacy of Osemitamab (TST001) plus Nivolumab and CAPOX as first-line treatment for advanced G/GEJ cancer, with a safety lead-in and expansion phase. Patients were alternately allocated to 3 or 6mg/ kg at expansion phase. Eligible patients include HER2 negative or unknown, unresectable locally advanced or metastatic G/GEJ cancer, regardless of CLDN18.2 or PD-L1 expression. CLDN18.2 and PD-L1 status were analyzed retrospectively using IHC 14G11 LDT assay and PD-L1 IHC 28-8 pharmDx at a central laboratory. The CLDN18.2 expression was divided into three subgroups: H/ M (high/medium), L (low) and R (rest: lower or negative) according to the tumor cells showing membranous CLDN18.2 staining per CLDN18.2 IHC 14G11 LDT assay. Encouraging ORR and mPFS As of the cut-off date, 82 patients had been dosed with a median follow-up of 15.2 months. The exploratory analysis of the subgroup efficacy of patients in overall, overall with/known CLDN18.2/ PD-L1, and in the subgroup with PD-L1 CPS<5 is as follows: Overall patients group: The mPFS is 12.6 months in patients with high or medium expression (H/M), 7.1 months in patients with low expression (L) and 8.5 months in the rest patients (R). Confirmed ORR was 58.1%, 52.4% and 55.6% respectively. 12 months survival rate for the overall population (n=82) is 73.8%. Overall patients with known CLDN18.2/PD-L1 (n=66): The mPFS is 14.2 months in the patients with high or medium expression (H/M), 8.5 months in patients with low expression (L) and 6.7 months in the rest patients (R). Confirmed ORR was 68.0%, 61.1% and 50.0% respectively. Subgroup with PD-L1 CPS<5 (n=56): The mPFS is 16.6 months in the patients with high or medium expression (H/M), 7.1 months in patients with low expression (L) and 5.7 months in the rest patients (R). Confirmed ORR was 71.4%, 60.0% and 47.1% respectively. Manageable Safety Profile All patients experienced treatment-related adverse events (TRAE). The most common TRAEs were hypoalbuminaemia, nausea and vomiting, most of them were of CTC AE grade 1 or 2 and manageable. The safety profile was similar to TST001 in combination with CAPOX which was presented previously (J Clin Oncol 41, 2023, suppl 16; abstr 4046). About Osemitamab (TST001) Osemitamab (TST001) is a high affinity humanized anti-CLDN18.2 monoclonal antibody with enhanced antibody-dependent cellular cytotoxicity ("ADCC"). It has shown potent anti-tumor activities in tumor xenograft models. Osemitamab (TST001) is the second most advanced CLDN18.2 targeting antibody being developed globally. Osemitamab (TST001) was generated using Transcenta's Immune Tolerance Breaking Technology (IMTB) platform. Osemitamab (TST001) kills CLDN18.2 expressing tumor cells by mechanisms of ADCC. Leveraging advanced bioprocessing technology, the fucose content of Osemitamab (TST001) was significantly reduced during the production, which further enhanced NK cells mediated ADCC activity of Osemitamab (TST001). Clinical trials for Osemitamab (TST001) are ongoing in the U.S. and China (TranStar101/NCT04396821, TranStar102/NCT04495296). Osemitamab (TST001) has been granted Orphan Drug Designation in the U.S. by FDA for the treatment of patients with gastric or gastroesophageal junction (G/GEJ) and pancreatic cancer. About Transcenta Transcenta (HKEX: 06628) is a clinical stage biopharmaceutical company with fully integrated capabilities in antibody-based biotherapeutics discovery, research, development and manufacturing. Transcenta has established global footprint, with Headquarters and Discovery, Clinical and Translational Research Center in Suzhou, Process and Product Development Center and Manufacturing Facility in Hangzhou, and Clinical Development Centers in Princeton, US and in Beijing, Shanghai and Guangzhou of China, and External Partnering Center in Boston and Los Angeles, US. Transcenta is developing 14 therapeutic antibody molecules for oncology and selected non-oncology indications including bone and kidney disorders. CONTACT: Bryan Cheng, [email protected], 15067129733 SOURCE Transcenta Holding Limited WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED