WT1

BEIJING & SHANGHAI--( BUSINESS WIRE )--Biocytogen Pharmaceuticals (Beijing) Co., Ltd. (“Biocytogen”, HKEX: 02315) and CtM Biotech (Shanghai) Co., Ltd ("CtM Bio") today jointly announce that the development of a tri-specific T cell engager for an intracellular target achieved milestone progress. In just one year since the start of the collaboration, the companies have identified a WT1/HLA-A02-specific T cell engager (WT1xCD3x4-1BB tri-specific antibody) with outstanding preclinical anti-tumor activities for both hematological malignancies and solid tumors. The incorporation of the T co-stimulatory signal for WT1-targeting T cell engager further gives it the best-in-class properties and first-in-class potential. Its preclinical data has been accepted for presentation at the upcoming 2024 AACR annual meeting. WT1 (Wilms’ tumor gene 1) is an intracellular protein highly enriched in certain cancer cells compared to normal tissues, making it an attractive tumor target for cancer immunotherapy. To identify novel WT1-targeting antibody-based therapeutics, Biocytogen harnessed its RenTCR-mimic TM mice and high-throughput in vivo and in vitro screening platforms to successfully generate WT1 antibodies with superior specificity and high affinity to the HLA/peptide complex. These antibodies were further engineered using CtM’s state-of-the-art T cell engager technology, which is specifically designed to overcome T cell over-activation toxicity and prevent T cell exhaustion, leading to highly effective, safe and controllable multi-specific engagers. Dr. Yuelei Shen, President and CEO of Biocytogen, said, “ Our collaborative efforts with CtM Bio have progressed rapidly, resulting in the identification of novel immunotherapies targeting WT1. This rapid and effective development of multi-specific T cell engagers undoubtedly validates CtM Bio’s advanced T-cell engager technology, along with our expertise in discovering fully human TCR-mimic antibodies against intracellular targets. We anticipate advancing this preclinical candidate into clinical trials soon, providing treatment options for patients with acute myeloid leukemia, ovarian cancer, and various solid tumors.” Dr. Lei Fang, Vice President of Lepu Biopharma and CEO of CtM Bio, said, “ The combination of Biocytogen’s streamlined fully human antibody discovery capabilities and CtM Bio’s deep understanding of immune cell engagers have greatly accelerated our development of differentiated T cell engagers targeting WT1. We look forward to continued collaborations to further develop this candidate and initiate clinical trials. Together, we aim to usher in a new era of therapies targeting intracellular tumor antigens and broaden the applications of T cell engagers for the treatment of solid tumors, which will ultimately offer new opportunities for cancer patients.” About the TCR-Mimic Antibody Discovery Platform Biocytogen’s TCR-Mimic platform focuses on the discovery of fully human antibodies to intracellular targets that are presented on the cell surface by MHC class I molecules. Leveraging proprietary RenTCR-mimic TM (HLA/RenMab) mice and specialized immunization protocols, Biocytogen’s platform is designed to generate TCR-mimic (TCRm) antibodies that are highly specific for peptide/HLA complexes and not HLA itself. Subsequently, Biocytogen’s high-throughput antibody screening platform aims to swiftly identify TCR-mimic antibodies with higher specificity and affinity than endogenous TCRs derived from patients to overcome tumor immune escape. Currently, antibody hits for multiple intracellular targets, including TAAs, cancer-testis antigens, mutated protein antigens, and viral protein antigens, are being evaluated in vivo and in vitro . Fully human antibody sequences obtained from the TCR-mimic platform can empower the development of T cell engagers, bispecific/multispecific antibodies, and CAR-T therapies. About the T-cell Engager Platform T-cell engagers are typically bispecific antibodies with one targeting tumor-associated antigens (TAAs) and the other activating CD3 signal on T cells. The mechanisms involve promoting the formation of an immune synapse between T cells and cancer cells, activating T cells to induce the lysis of cancer cells. To overcome the limitations of existing T cell engagers, CtM Bio has developed a unique T cell engager platform called TOPAbody. By introducing T-cell co-stimulatory signal 4-1BB and finely tuning the affinity and activity of each module in the engager, TOPAbody allows for the effective enhancement of T cell cytotoxicity with minimal side effects. TOPAbody prolongs T cell lifespan and promotes T cell infiltration into tumors. Currently, several products from this platform have demonstrated outstanding anti-tumor activity, particularly showing significant promise for immunologically "cold" tumors that do not respond to PD-1 treatment. About Biocytogen Biocytogen (HKEX: 02315) is a global biotechnology company that drives the research and development of novel antibody-based drugs with innovative technologies. Founded on gene editing technology, Biocytogen leverages genetically engineered proprietary RenMice ® (RenMab TM /RenLite ® /RenNano ® /RenTCR-mimic TM ) platforms for fully human monoclonal/bispecific/multispecific antibody discovery, bispecific antibody-drug conjugate discovery, nanobody discovery and TCR-mimic antibody discovery, and has established an off-the-shelf library of >400,000 fully human antibody sequences against approximately 1000 targets for worldwide collaboration. As of June 30, 2023, 50 therapeutic antibody and multiple clinical asset co-development/out-licensing/transfer agreements and 42 target-nominated RenMice ® licensing projects have been established around the globe, including several partnerships with multinational pharmaceutical companies (MNCs). Biocytogen pioneered the generation of drug target knock-in humanized models for preclinical research, and currently provides a few thousand off-the-shelf animal and cell models under the company’s sub-brand, BioMice TM , along with preclinical pharmacology and gene-editing services for clients worldwide. Headquartered in Beijing, Biocytogen has branches in China (Haimen Jiangsu, Shanghai), USA (Boston, San Francisco), and Germany (Heidelberg). For more information, please visit http://en.biocytogen.com.cn . About CtM Bio CtM Bio, a subsidiary of Lepu Biopharma (2157.HK), is a science-driven biotech company committed to the development of innovative antibody-based therapies that could ultimately address the un-met medical needs. The company’s focus is to integrate its knowledge in immunology and disease biology with the most cutting-edge technology and platforms, aiming to design novel antibodies that could fully unlock the potential of immunotherapy. Lepu Biopharma is China-based global-oriented innovation-driven biopharmaceutical company. The company is committed to innovation, focusing on the discovery, development and commercialization of drug candidates with the first and optimal potential of the same kind in anti-tumor targeted therapy and immunotherapy drugs. The company's mission is to develop safe, effective, and accessible drugs to improve cancer patients’ quality of life and to address huge gaps in medical needs. The company attaches great importance to the continuous construction of commercialization capacity and strives to realize the strong transformation and industrialization capacity from core technology to finished drugs.

Marker Therapeutics, Inc. (Nasdaq: MRKR), a clinical-stage immuno-oncology company focusing on developing next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, today reported a clinical update on the APOLLO study. The Phase 1 APOLLO study is investigating MT-601, a multi-tumor associated antigen (multiTAA)-specific T cell product, for the treatment of patients with lymphoma who have failed or are ineligible to receive anti-CD19 CAR T cell therapy. The Company previously reported first enrollment in the dose escalation stage of the Phase 1 trial (Press Release, June 12, 2023). The patient had diffuse large B cell lymphoma (DLBCL) and failed four prior lines of therapy, including anti-CD19 CAR T cell therapy. Marker reported in September that the study participant tolerated the treatment well without treatment-related adverse events and achieved a complete metabolic response eight weeks after the second infusion of MT-601 (Press Release, September 11, 2023). Marker reports today that six months following the initial treatment with MT-601 the study participant has maintained complete response to treatment. These clinical results are reinforced by non-clinical proof-of-concept data demonstrating that MT-601 has the potential to eradicate lymphoma cells resistant to anti-CD19 CAR T cells, highlighting the therapeutic potential of MT-601 in vitro (Press Release, May 31, 2023). Although CD19-targeting CAR T cell therapies have gained acceptance as treatment for patients with lymphoma, up to 60% of patients treated with CAR T therapies relapse within one year (Chong EA et al, N Engl J Med, 2021). This APOLLO study participant relapsed within 90 days after CAR T cell therapy, yet maintained a complete response for at least six months after treatment with MT-601, suggesting that MT-601 is more durable compared to CAR T cells in this study participant. CAR T cell therapies, which have known severe side effects such as neurotoxicity, are also currently being investigated by the FDA for the risk of potential induction of secondary cancers (U.S. Food and Drug Administration, November 28, 2023), adding another layer of concern for patients and clinicians. Notably, multiTAA-specific T cell therapies have been well-tolerated in clinical trials, and Marker believes that multiTAA-specific T cells are a safe alternative to CAR T cells due to their non-genetically engineered approach that selectively expands tumor-specific T cells from a patient’s/donor’s blood without the risk of mutagenesis. “Witnessing the sustained complete response in our first patient treated with MT-601 over six months has been an encouraging and rewarding experience,” commented Dr. Geoffrey Shouse, the Principal Investigator at City of Hope National Medical Center in Duarte California. "This is a remarkable achievement, demonstrating the potential impact of MT-601 in patients with lymphoma who have relapsed after anti-CD19 CAR T cell therapy. We are encouraged by the benefit this therapy has provided for one our patient’s life, the newfound hope it brings, and the potential impact MT-601 could have as a novel treatment option for patients with lymphoma." “Relapse rates following CAR T cell therapy are high,” said Juan F. Vera, M.D., President and Chief Executive Officer of Marker Therapeutics. “The ongoing complete response observed after MT-601 infusion in a CAR relapsed patient with lymphoma suggests superior durability of our therapy over CAR T cells in this patient. To further validate these observations, we have already enrolled additional patients in this study to replicate and reinforce these promising results." Dr. Vera continued: “The sustained complete response is a significant milestone in our Phase 1 study and highlights the potential benefit of MT-601 in patients who relapse after anti-CD19 CAR T cell therapy. We will continue to monitor long-term treatment effects and durability of response and look forward to treating additional participants in this Phase 1 study.” MT-601 utilizes a novel non-genetically modified approach that specifically targets six different tumor antigens upregulated in lymphoma cells (Survivin, PRAME, WT-1, NY-ESO-1, SSX-2, MAGEA-4). Marker is currently investigating MT-601 in the Company-sponsored Phase 1 APOLLO trial (clinicaltrials.gov identifier: NCT05798897) for the treatment of lymphoma patients who are relapsed/refractory after or ineligible to anti-CD19 CAR T cell therapies. The APOLLO trial (clinicaltrials.gov Identifier: NCT05798897) is a Phase 1, multicenter, open-label study designed to evaluate the safety and efficacy of MT-601 in participants with relapsed or refractory lymphoma who either failed anti-CD19 chimeric antigen receptor (CAR) T cell therapy or are ineligible for anti-CD19 CAR T cell therapy. The primary objective of this exploratory Phase 1 clinical trial is to evaluate the optimum dose, safety, and preliminary efficacy of MT-601 in participants with various lymphoma subtypes. Under the APOLLO trial, nine clinical sites across the United States will cumulatively enroll up to approximately 30 participants during the dose escalation phase. The multi-tumor associated antigen (multiTAA)-specific T cell platform is a novel, non-genetically modified cell therapy approach that selectively expands tumor-specific T cells from a patient's/donor’s blood capable of recognizing a broad range of tumor antigens. Clinical trials that enrolled more than 200 patients with various hematological malignancies and solid tumors showed that autologous and allogeneic multiTAA-specific T cell products were well tolerated and demonstrated durable clinical responses, and consistent epitope spreading. The latter is typically not observed with other T cell therapies and enables the potential contribution to a lasting anti-tumor effect. Marker Therapeutics, Inc. is a clinical-stage immuno-oncology company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications. The T cell therapy technology developed by Marker is based on the selective expansion of non-engineered, tumor-specific T cells that recognize tumor associated antigens (i.e., tumor targets) and kill tumor cells expressing those targets. This population of T cells is designed to attack multiple tumor targets following infusion into patients and to activate the patient’s immune system to produce broad spectrum anti-tumor activity. Because Marker does not genetically engineer the T cells, Marker believes that its product candidates will be easier and less expensive to manufacture, with reduced toxicities, compared to current engineered CAR-T and TCR-based approaches, and may provide patients with meaningful clinical benefit. As a result, Marker believes its portfolio of T cell therapies has a compelling product profile, as compared to current gene-modified CAR-T and TCR-based therapies. The content above comes from the network. if any infringement, please contact us to modify.

- Independent Data Monitoring Committee (IDMC) Recommended Continuation of Phase 3 REGAL Trial Without Any Modifications - - IDMC Expressed Satisfaction with Speed of Enrollment and High Study Integrity - - IDMC Will Review Most Current Survival Data at Next Scheduled IDMC Meeting in Q1 2024 - SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) (“SELLAS” or the “Company”), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, today announced a positive review of the ongoing Phase 3 REGAL clinical trial of galinpepimut-S (GPS) in acute myeloid leukemia (AML) by the Independent Data Monitoring Committee (IDMC). The IDMC performed a routine, prespecified risk-benefit assessment of unblinded data from the study and has recommended that the trial continue without modifications. The IDMC also requested that the survival database be updated immediately prior to the next IDMC meeting, which will take place in Q1 2024, and be provided to the IDMC for its review at the meeting. “We are very encouraged by the IDMC’s recommendations to continue the Phase 3 trial without any modifications as well as positive commentary on the high level of study integrity and conduct and their request of an ad hoc database update that could potentially expedite their review and analyses of all current survival and safety data,” said Angelos Stergiou, MD, ScD hc, President and Chief Executive Officer at SELLAS. “This review comes on the heels of reaching our patient enrollment target, ex-China, and we very much look forward to the IDMC’s next meeting in the first quarter of 2024. We believe that, based on its unique mechanism of action, GPS may offer a promising new treatment option to patients with AML.” REGAL is a Phase 3 open-label registrational clinical trial for GPS in AML patients who have achieved complete remission following second-line salvage therapy (CR2 patients). The primary endpoint is overall survival. The IDMC is an independent group of medical, scientific, and biostatistics experts who are responsible for reviewing and evaluating patient safety and efficacy data for REGAL, and for monitoring quality and overall conduct to ensure the validity, scientific and clinical merits of the study. The IDMC charter provides for periodic reviews for safety, efficacy, and futility in addition to the interim and final analyses. SELLAS is a late-stage clinical biopharmaceutical company focused on the development of novel therapeutics for a broad range of cancer indications. SELLAS’ lead product candidate, GPS, is licensed from Memorial Sloan Kettering Cancer Center and targets the WT1 protein, which is present in an array of tumor types. GPS has the potential as a monotherapy and combination with other therapies to address a broad spectrum of hematologic malignancies and solid tumor indications. The Company is also developing SLS009 (formerly GFH009), a small molecule, highly selective CDK9 inhibitor, which is licensed from GenFleet Therapeutics (Shanghai), Inc., for all therapeutic and diagnostic uses in the world outside of Greater China. For more information on SELLAS, please visit www.sellaslifesciences.com. The content above comes from the network. if any infringement, please contact us to modify.