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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. 19, 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, bryan.cheng@transcenta.com, 15067129733
ISM001-055 is a novel drug designed in-house using generative AI to target TNIK (Traf2- and NCK- interacting kinase) and has progressed through Phase IIa clinical testing. Preliminary results from this 12-week study demonstrated that ISM001-055 possesses a favorable safety profile and dose-dependent response in lung function in patients with IPF. ISM001-055's positive Phase IIa results represent a proof-of-concept success for AI-driven drug discovery. CAMBRIDGE, Mass., Sept. 18, 2024 /PRNewswire/ -- Insilico Medicine, a clinical-stage generative AI-driven drug discovery company, announced positive preliminary results from its Phase IIa clinical trial evaluating ISM001-055. ISM001-055 is a first-in-class small molecule targeting TNIK (Traf2- and Nck-interacting kinase) and was designed utilizing generative AI to treat idiopathic pulmonary fibrosis (IPF). The study met both its primary endpoint of safety and its secondary efficacy endpoints, demonstrating dose-dependent response in forced vital capacity (FVC), a critical measure of lung function in IPF patients. Insilico's proprietary AI platform facilitated ISM001-055's target identification and molecular design. Its development was recently described in a March 2024 Nature Biotechnology paper, which detailed TNIK's identification as a novel therapeutic target in IPF and ISM001-055 subsequent design. This comprehensive paper showcased ISM001-055's preclinical evaluation and positive Phase 0 & Phase I clinical studies justifying this intervention's potential as a disease-modifying agent for IPF. ISM001-055's Phase IIa study(NCT05938920) was a randomized, double-blind, placebo-controlled trial that enrolled 71 patients with IPF across 21 sites in China. Patients were randomized to receive either placebo, 30mg once daily (QD), 30mg twice daily (BID), or 60mg QD for 12 weeks. Patient enrollment was initiated in April 2023, and the last subject's follow-up visit was completed in August 2024. A parallel Phase IIa(NCT05975983) clinical trial in the U.S. is ongoing and actively enrolling patients. In this 12-week Phase IIa study, ISM001-055 met its primary endpoint of safety and tolerability across all dose levels. Positive results were also reported for the secondary efficacy endpoint, wherein a dose-dependent FVC improvement was observed. Patients receiving 60mg QD of ISM001-055 demonstrated the largest improvement in FVC. Complete topline data will be released at the upcoming medical conference and clinical trial results will be submitted for publication in a peer-reviewed journal. "These results are very encouraging, particularly the dose-dependent response in FVC. IPF is a devastating disease, and seeing improvements in lung function over just 12 weeks of treatment is a promising indication that ISM001-055 may provide a new therapeutic option for patients. Our Phase IIa in the U.S. is actively recruiting patients," said Toby M. Maher, MD, PhD, a leading expert in interstitial lung disease and an investigator in the trial. "Last year, I presented a lecture on how generative AI can help with end-to-end drug discovery from disease modeling and target identification to generation of novel drugs with the desired properties and purposing it to a specific disease. I used Insilico's TRAF2 and NCK-interacting kinase (TNIK) inhibitor as a case study going from 0 to Phase I. The fact that this same drug demonstrated efficacy in addition to safety in a Phase IIa study is extraordinary and represents a true first in this new era of AI-powered drug discovery," said Michael Levitt, PhD, 2013 Nobel Laureate in Chemistry. "With all the hype that surrounds the potential of generative AI in drug discovery and many other potential applications, it is thrilling see to the dose dependence of ISM001-055 in Insilico Medicine's phase IIa IPF clinical trial. This is strong evidence that the drug is truly effective and that favorable results will continue to be seen in future trials," said Charles Cantor, PhD, a renowned geneticist and advisor to the company since 2014. "This is great news for the field of AI for drug discovery. The fact that this molecule is safe and has a dose-dependent response means that there is a green light for further studies. I am hopeful it continues its path to making a difference," said Alan Aspuru-Guzik, PhD, Professor of Chemistry and Computer Science at the University of Toronto and CIFAR AI Chair at the Vector Institute. "This study result represents a critical milestone in AI-powered drug discovery and in my life to date," said Alex Zhavoronkov, PhD, co-CEO of Insilico Medicine. "While we expected the drug to be safe, we did not expect to see such a clear dose-dependent efficacy signal after such a short dosing period. IPF is a very diverse disease and it is very rare to see improvement in FVC. With our novel TNIK inhibitor, we attempted to go after what we think is a common mechanism in fibrotic diseases and in aging to maximize indication expansion potential." "I am excited to see that ISM001-055 demonstrated obvious clinical efficacy in IPF patients in only 3-months treatment. While preliminary, this clinical data is certainly encouraging, and provides the clinical validation of AI-powered drug R&D for both novel target and novel molecule," said Feng Ren, PhD, co-CEO and CSO of Insilico Medicine. " This is a significant milestone for Insilico Medicine and the AI driven drug discovery Industry. The milestone is achieved due to the contribution of both the capabilities of our proprietary generative AI platform and the efforts of our multidisciplinary R&D team. We will continue to fully commit to provide breakthrough solutions for the benefit of the patients globally." Following the positive results from this Phase IIa trial, Insilico Medicine will engage regulatory authorities to discuss the design of a Phase IIb study. The company aims to explore extended treatment durations and larger patient cohorts to further investigate ISM001-055's therapeutic potential in IPF. About ISM001-055 and TNIK ISM001-055 is a potentially first-in-class small molecule targeting TNIK utilizing generative AI. In IPF, the activation of TNIK drives pathological fibrosis in the lungs, contributing to the progressive decline in lung function. By inhibiting TNIK, ISM001-055 aims to halt or reverse fibrotic processes, offering a disease-modifying treatment for patients with IPF. In February 2023, ISM001-055 received Orphan Drug Designation from the FDA for treating Idiopathic Pulmonary Fibrosis. About the Phase IIa Study The double-blind, placebo-controlled Phase IIa clinical trial (NCT05938920) evaluated the safety, tolerability, pharmacokinetics, and preliminary efficacy of 12-week oral ISM001-055 dosage in 71 subjects with IPF. Patients from 21 sites were randomized into four parallel cohorts: 30mg QD, 30mg BID, 60mg QD, and placebo. Preliminary results from the study show ISM001-055 demonstrated a good safety profile and dose-response trend in lung function in IPF patients. About Idiopathic Pulmonary Fibrosis (IPF) Idiopathic Pulmonary Fibrosis (IPF) is a chronic, scarring lung disease characterized by a progressive and irreversible decline in lung function. Affecting approximately 5 million people worldwide, IPF carries a poor prognosis, with a median survival of 3 to 4 years. Current treatments, including antifibrotic drugs, can slow disease progression but do not stop or reverse it, leaving a significant unmet need for more effective, disease-modifying therapies. IPF is an age-related disease, with the average age of onset typically between 60 and 70 years, and it is most commonly diagnosed in older adults. The disease is rare in individuals under the age of 50. About Insilico Medicine Insilico Medicine, a global clinical-stage biotechnology company powered by generative AI, connects biology, chemistry, and clinical trial analysis using next-generation AI systems. The company has developed AI platforms that utilize deep generative models, reinforcement learning, transformers, and other modern machine learning techniques to assist novel target discovery and the generation of novel molecular structures. Insilico Medicine is developing breakthrough solutions to discover and develop innovative drugs for cancer, fibrosis, immunity, central nervous system diseases, infectious diseases, autoimmune diseases, and aging-related diseases. www.insilico.com
SYDNEY, Sept. 18, 2024 /PRNewswire/ -- The Australian Clear Aligner Society (ACAS) recently brought together top orthodontic experts worldwide. Among the distinguished speakers was Smartee Chief Scientist, Prof. Gang Shen, who delivered an insightful presentation titled "The Clear S8 Orthopedic Therapy: Fundamental Mechanisms, Therapeutic Procedures, and Clinical Efficiency." His talk focused on cutting-edge advancements in mandibular repositioning technology. Prof. Gang Shen at ACAS 2024 Tackling Complex Challenges within Global Orthodontics At the conference, Prof. Shen introduced clear S8 technology, developed in collaboration with Smartee. Building on the Diagnostic classification of malocclusion with facial convexity, Prof. Shen delivered an in-depth analysis of the mechanisms behind mandibular retrusion and the S8-SGTB treatment protocols for both physiological and pathological mandibular retrusion. Prof. Shen highlighted that facial convexity, influenced by regional and genetic factors, presents a complex challenge worldwide. The intricate manifestations and overlapping causes make diagnosis and treatment difficult. The S8 mandibular advancement technology provides an alternative solution that not only corrects dental alignment but also improves facial aesthetics, enhancing treatment efficiency and patient outcomes significantly. Prof. Gang Shen Sharing Smartee GS Case Study Case Spotlight: Innovative Solutions in Action In the case showcase session, Prof. Shen was the first expert to present a case involving a 28-year-old adult with Class II malocclusion. Using S8-SGTB, Prof. Shen demonstrated the rapid correction of a deep overbite, large overjet, and an excessive curve of Spee. He pinpointed the factors contributing to the stability of adult mandibular repositioning, making it clear that with accurate classification, appropriate treatment protocols, and advanced devices, adult mandibular repositioning is not only possible but highly effective and stable over time. Advancing Orthodontic Innovation Prof. Shen's presentation reinforced Smartee's position at the forefront of orthodontic innovation. The clear S8 mandibular repositioning technology drew significant attention from the global orthodontic community, reflecting the growing demand for solutions pushing conventional treatments' boundaries. As Smartee deepens its strategic partnership with Prof. Shen, the collaboration promises to unlock new possibilities in clear aligner orthodontics, addressing unmet clinical needs and driving the industry forward.
TAIPEI and SAN DIEGO, Sept. 18, 2024 /PRNewswire/ -- Senhwa Biosciences, Inc. (TPEx: 6492), , a drug development company focusing on first-in-class therapeutics for oncology, rare diseases, and infectious diseases, today announced that an Investigational New Drug (IND) application for Pidnarulex has been submitted to the U.S. FDA by the NCI. Senhwa' investigational drug, Pidnarulex (CX-5461), has been selected as an experimental drug in the NExT (NCI Experimental Therapeutics) cancer program, sponsored by the Division of Cancer Treatment and Diagnosis (DCTD), National Cancer Institute (NCI), part of the U.S. National Institutes of Health (NIH), for a five-year period. This drug will be used in a pharmacodynamic (PD) pilot study involving patients with advanced solid tumors. In addition to this monotherapy trial, NCI is considering to plan future clinical trials for Pidnarulex (CX-5461) in combination with other therapies, including immunotherapy, antibody-drug conjugates (ADC), and PARP inhibitors (Poly ADP-ribose Polymerase inhibitors, PARPi). Should these trials be realized, they will be led by the NCI, leveraging its medical team, scientific talent network, and regulatory resources—capabilities that most biotech companies would struggle to accomplish independently. This support from the NCI is hoped to significantly accelerate the development and expansion of indications for Pidnarulex (CX-5461), ultimately benefiting patients with an earlier market launch. This clinical trial, for which the IND application has been submitted by NCI's Division of Cancer Treatment and Diagnosis (DCTD), aims to explore the response of various biomarkers to Pidnarulex (CX-5461) in patients with or without homologous recombination deficiency (HRD). Pidnarulex (CX-5461), developed by Senhwa, is a first-in-class small-molecule designed to stabilize G-quadruplex (G4) structures, which are frequently observed in promoters of oncogenes. By stalling replication fork progression, Pidnarulex induces DNA damage and promotes cancer cell death. Through this mechanism, Pidnarulex holds great potential as a therapeutic agent for various cancers. In recent years, immunotherapy has become the fastest-growing category in the cancer drug market, while the development of antibody-drug conjugates (ADC) is undoubtedly an important trend in biopharmaceuticals. Major pharmaceutical companies, including Pfizer, AbbVie, AstraZeneca, and Merck, have invested billions of dollars in acquiring or licensing related technologies. According to a recent report from market research firm Evaluate, the ADC market is expected to reach $30 billion by 2028, while the global cancer immunotherapy market will surpass a staggering $224 billion by 2030. Given that only about 20% to 25% of patients are effectively treated with immunotherapy, combining immunotherapy with targeted drugs is becoming increasingly important in cancer treatment. Combination therapies can address multiple treatment pathways within the complex tumor microenvironment and may enhance the efficacy of immunotherapy, making it a hot research area for major pharmaceutical companies. Therefore, Senhwa is confident and optimistic about the NCI's plans to advance clinical trials of Pidnarulex (CX-5461) in combination with immunotherapy and ADCs.
SAN DIEGO, Sept. 18, 2024 /PRNewswire/ -- Hyundai Bioscience USA announced that it has signed an MOU with the University of California San Diego (UCSD) to conduct an investigator-initiated trial to evaluate the efficacy of Xafty®, a niclosamide-based antiviral developed by its Korean headquarters, in treating "Long-COVID". The trial will be led by UCSD Professor Ajay Bharti, an infectious disease specialist and clinical trialist. Dr. Bharti's particular expertise in the neurocognitive effects of viral illnesses make him perfectly suited to run the investigator initiated trial. "This is an outstanding opportunity for UC San Diego and Hyundai Bioscience to partner together to tackle Long-COVID," Professor. Davey Smith, Director of the UCSD Altman Clinical and Translational Research Institute (ACTRI) of UCSD and an authority on viral illnesses, especially COVID, said about the collaboration. "There is no therapy currently available for the condition, which affects millions of people around the world." Xafty, an oral antiviral agent, is a new drug that improved the bioavailability of niclosamide, which is known to have antiviral efficacy against more than 30 viruses. It is currently in a phase 3 clinical trial in Korea targeting high-risk groups for COVID-19 and is expected to apply for phase 3 to the U.S. FDA soon. In a previous phase 2 clinical trial, Xafty successfully met the FDA's primary endpoints, demonstrating a faster symptom improvement rate than other existing treatments, especially in high-risk groups. "Being able to reduce symptoms during acute COVID-19 is an impressive accomplishment," Dr. Smith, who has helped run numerous antiviral trials in COVID-19, HIV, and Mpox, said. "Many large recent trials testing antivirals have not had such success. This may point to Xafty's effectiveness in Long-COVID as well." Long-COVID is a complex disease that is suggested to be caused by residual virus, excessive inflammation, and consequent nerve damage. Patients suffer from various symptoms such as chronic fatigue, inflammation, and cognitive decline, but existing treatments rely on a single mechanism and fail to resolve these complex symptoms. This is one of the reasons why a clear treatment for Long-COVID has not yet been developed. Xafty is expected to resolve the complex symptoms of Long-COVID through inflammation inhibition and neuro-protection mechanisms, rather than simply suppressing the virus. It is because niclosamide, Xafty's main pharmaceutical ingredient, is anticipated to provide practical therapeutic effects to patients through multiple mechanisms such as virus removal, suppression of immune hypersensitivity, and recovery of nerve damage. In a recent Parkinson's disease preclinical study conducted by Hyundai Bioscience, Xafty demonstrated to promote dopamine production and nerve cell recovery. When Xafty was administered to a Parkinson's animal model with suppressed dopamine production, a higher dopamine level was confirmed than in the group administered with the existing Parkinson's disease treatment, dopamine precursor (Madopar®), suggesting that it can make a significant contribution to improving symptoms such as brain fog and cognitive impairment due to nerve damage in people with Long-COVID. Dr. Ajay Bharti, the PI of this study, said, "We already knew about the broad-spectrum antiviral efficacy of niclosamide, but after seeing data showing that Xafty, having improved the long-standing problem of bioavailability, showed excellent symptom improvement in a COVID-19 clinical trial, especially in the high-risk group, we came up with the idea of using the drug to treat Long COVID." He added, "In particular, the fact that Xafty recovered neurons in a preclinical study of Parkinson's disease and promoted dopamine production, resulting in higher dopamine levels than the control group that took Madopar®, was an important trigger for this clinical study." Dr. Smith added, "The goal of this study is to confirm that niclosamide can solve the complex symptoms of Long COVID through multiple mechanisms such as virus suppression, inflammation suppression, and neuroprotection. We hope that the clinical trial will be successful and provide a practical treatment option for Long COVID patients, which will be historic." About Hyundai Bioscience Hyundai Bioscience is a biotechnology company that develops drugs based on its novel drug delivery system technologies to deliver active ingredients safely and efficiently to targeted areas of the human body. Founded in 2000, Hyundai Bioscience focuses on repurposing or expanding indications of existing drugs using its proprietary organic-inorganic hybrid technologies. Hyundai Bioscience is a public company listed on KOSDAQ (symbol: 048410) in South Korea. For more information, please contact Ms. Joobin Jung, Global PR Manager (joobin@hyundaibio.com).
SAN FRANCISCO and SUZHOU, China, Sept. 18, 2024 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, cardiovascular and metabolic, ophthalmology and other major diseases, announces that clinical data of IBI363 (first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein) combined with bevacizumab in advanced colorectal cancer is presented at the 2024 ESMO Congress. Currently, Innovent is conducting Phase 1/2 clinical trials in China, the United States, and Australia to evaluate the safety, tolerability and efficacy of IBI363 in subjects with advanced solid tumors. First-in-class PD-1/IL-2α-bias bispecific antibody fusion protein IBI363 combined with bevacizumab in patients with advanced colorectal cancer: Results from Phase 1 study This Phase 1 study was conducted to evaluate the safety, tolerability and preliminary efficacy of IBI363 combined with bevacizumab in subjects with advanced colorectal cancer. A total of 35 subjects received treatment of IBI363 combined with bevacizumab, demonstrating promising anti-tumor efficacy with good tolerability and safety As of the data cutoff date (Aug 30, 2024), a total of 35 subjects with advanced colorectal cancer received combination treatment at 3 different dose levels (0.6 mg/kg IBI363 combined with 5 mg/kg bevacizumab Q2W, 1 mg/kg IBI363 combined with 5 mg/kg bevacizumab Q2W, and 1.5 mg/kg IBI363 combined with 7.5 mg/kg bevacizumab Q3W). Among them, 91.4% of the subjects had advanced colorectal cancer with microsatellite stable (MSS) or proficient mismatch repair (pMMR), and the MSI/MMR status was unknown in 8.6% subjects. 91.4% of the subjects had previously received 2 or more lines of systemic anti-tumor treatment. 51.4% of the subjects had liver metastases. 25.7% of the subjects had received prior immunotherapy. 40% of the subjects had KRAS/NRAS exon 2/3/4 mutations. The most common treatment related adverse events (TRAEs) were arthralgia, thyroid disorders, and rash. The total incidence of TRAEs ≥ grade 3 was 22.9%. Immune related adverse events (irAEs) ≥ grade 3 occurred in 5.7% of subjects. The safety profile of the combination regimen was similar to that of IBI363 monotherapy, and no new safety signals were identified. Promising anti-tumor activity in subjects with MSS/pMMR colorectal cancer; durable responses with a trend towards long-term benefit As of the cutoff date, 32 subjects were efficacy evaluable having underwent at least one post-baseline tumor assessment. The ORR was 21.9% (confirmed ORR was 15.6%), and DCR was 65.6%. The median DoR was 8.1 months (95% CI: 1.5~8.2). The median PFS follow-up time was 7.6 months (95% CI: 4.0~9.4), and the median PFS was 4.1 months (95% CI: 1.7~8.1). The median OS was not reached. Promising efficacy signals in colorectal cancer with and without baseline liver metastases Among the 17 subjects with baseline liver metastases who underwent at least one post-baseline tumor assessment, ORR was 11.8% and DCR was 58.8%. Among the 15 subjects without baseline liver metastases who underwent at least one post-baseline tumor assessment, ORR was 33.3% and DCR was 73.3%. Promising efficacy signals in both IO-treated and IO-naïve colorectal cancer Among the 8 subjects who had received prior immunotherapy and underwent at least one post-baseline tumor assessment, ORR was 25.0% and DCR was 62.5%. Among the 24 IO-naïve subjects who underwent at least one post-baseline tumor assessment, ORR was 20.8% and DCR was 66.7%. Promising efficacy signals in colorectal cancer with and without KRAS/NRAS exon 2/3/4 mutations Among the 14 subjects with RAS exon 2/3/4 mutations and who had undergone at least one post-baseline tumor assessment, ORR was 21.4% and DCR was 57.1%. Among the 10 subjects without RAS exon 2/3/4 mutations who had undergone at least one post-baseline tumor assessment, ORR was 30.0% and DCR was 90.0%. In addition, data from a Phase 1 clinical study of IBI363 monotherapy in a colorectal cancer cohort, presented at ASCO 2024, showed promising efficacy and good tolerability. Ongoing studies are now exploring IBI363 in other malignancies, including NSCLC, melanoma and other solid tumors, as well as in combination regimens for MSS/pMMR advanced colorectal cancer. Updates on relevant data and analysis will be shared at upcoming academic conferences and in journals. Professor Tao Zhang, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, stated: "Colorectal cancer is the third most common cancer type globally and ranks fourth in cancer-related mortality[1]. Despite recent advancements in colorectal cancer treatment, challenges such as chemotherapy toxicity and resistance continue to affect patients and clinicians. While immunotherapy offers new hope for advanced colorectal cancer patients, it is currently only approved for those with MSI-H/dMMR tumors. Research indicates that immunotherapy has limited efficacy in non-MSI-H/dMMR advanced colorectal cancer[2]. As an important cytokine activating tumor-specific CD8+T cells, IL-2 is complementary to immune checkpoint inhibitors in MOA. The combination of PD-1 and IL-2 may reverse the exhaustion of tumor-specific CD8+ T cells thereby overcoming immune resistance. The PD-1/IL-2α-bias bispecific molecule IBI363, when combined with bevacizumab, has shown promising anti-tumor activity in patients with non-MSI-H/dMMR advanced colorectal cancer. This combination has shown clinical benefits in both ORR and PFS, and maintains a manageable safety profile. Additionally, the combination regimen has proven effective in colorectal cancer patients with or without liver metastasis, prior immunotherapy, and RAS exon 2/3/4 mutations. IBI363 combined with bevacizumab elicited encouraging objective response rates and disease control rates, with durable responses and a trend towards long-term benefits, without introducing new safety risks in a colorectal cancer population that has previously shown very little response to immunotherapy. Overall, current clinical data suggest that IBI363 combined with bevacizumab holds significant promise for colorectal cancer and deserves further exploration." Dr. Hui Zhou, Senior Vice President of Innovent, stated: "On top of the preliminary data reported at ASCO, we are presenting more updated data at the ESMO Congress. In non-MSI-H/dMMR advanced colorectal cancer, the combination of IBI363 with bevacizumab has demonstrated strong anti-tumor effects, with durable responses and a trend towards long-term benefits. These promising results in a relatively 'cold' tumor suggest significant potential for IBI363 in this disease area. We are confident in the broad development prospects of IBI363 and look forward to seeing more mature data from higher doses and extended follow-up, which will help us advance to the next stage of clinical development." About IBI363 (First-in-class PD-1/IL-2α-bias bispecific antibody fusion protein) IBI363 is a first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein independently developed by Innovent Biologics. It functions by both blocking the PD-1/PD-L1 pathway and activating the IL-2 pathway. The IL-2 arm of IBI363 is designed to maintain its affinity for IL-2Rα while reducing binding to IL-2Rβ and IL-2Rγ, thereby minimizing toxicity. The PD-1 binding arm not only blocks PD-1 but also selectively delivers IL-2. This approach targets and activates tumor-specific T cells that express both PD-1 and IL-2α, leading to more precise and effective activation of this T cell subpopulation. IBI363 has demonstrated robust antitumor activity in various tumor-bearing pharmacological models, but also showed outstanding efficacy in PD-1 resistance and metastasis models. In response to urgent clinical needs, Innovent is conducting clinical studies in China, the United States and Australia to further explore the efficacy and safety of IBI363 in advanced tumors. About Innovent Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 11 products in the market. It has 3 new drug applications under regulatory review, 4 assets in Phase III or pivotal clinical trials and 18 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, Adimab, LG Chem and MD Anderson Cancer Center. Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn. Forward-Looking Statements This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly. These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions. Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect. References 1. https://publications.iarc.fr/Databases/Iarc-Cancerbases/GLOBOCAN-2012-Estimated-Cancer-Incidence-Mortality-And-Prevalence-Worldwide-In-2012-V1.0-2012. 2. Baraibar I, Mirallas O, Saoudi N et al. Combined Treatment with Immunotherapy-Based Strategies for MSS Metastatic Colorectal Cancer. Cancers (Basel). 2021 Dec 16;13(24):6311.
Clinical Trials/Medical Discoveries
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