CDIPT

NANJING, China, July 31, 2023 /PRNewswire/ -- Nanjing Leads Biolabs Co., Ltd. (hereinafter referred to as "Leads Biolabs" or "Company") announced today that the National Medical Products Administration (NMPA) and the U.S. Food and Drug Administration (FDA) have approved its first-in-human Investigational New Drug (IND) applications for LBL-034, an anti-GPRC5D/CD3 bispecific antibody invented by Leads Biolabs with global intellectual property rights, for the treatment of relapsed/refractory multiple myeloma. Currently, no GPRC5D-targeting antibody has been approved for marketing. This is a first-in-human, single-arm, multicenter, open-label, dose-escalation and expansion clinical study, and plans to enroll patients with relapsed/refractory multiple myeloma who have failed prior therapies including but not limited to at least one proteasome inhibitor (PI), one immunomodulator (IMiD) as well as other standard treatments. This study aims to evaluate the safety and tolerability of LBL-034, determine the recommended Phase II dose and assess its efficacy in patients with multiple myeloma. "Despite recent progress and continuous advancements in multiple myeloma, the time between recurrences has been steadily decreasing, particularly as the number of treatment lines increases. This ultimately leads to emergence of relapsed or refractory multiple myeloma, reaffirming its status as an incurable malignant tumor that poses a serious threat to human life. In light of this challenging reality, the urgent need for more effective and innovative treatment options has never been more evident." said Dr. Charles Cai, Chief Medical Officer of Leads Biolabs, "LBL-034 adopts a unique molecular design, which enables the drug to specifically bind to GPRC5D-expressing tumor cells with high affinity, and reduces the risk of non-specific activation of T-cells, thereby enhancing anti-tumor efficacy and reducing potential risk of immunotoxicity. LBL-034 demonstrated robust anti-tumor activities and good safety profile in pre-clinical studies. We adhere to our tradition of innovation and aim to deliver an important, novel and effective treatment option for patients with poor prognosis of relapsed/refractory multiple myeloma." About GPRC5D: G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D) is a C-type 7-channel transmembrane receptor protein. GPRC5D is low expressed in normal human tissues but specifically overexpressed in multiple myeloma. The intensity of GPRC5D expression is an independent prognostic factor in multiple myeloma, and its overexpression is significantly associated with reduced overall survival. Therefore, GPRC5D may be an important potential target for the treatment of plasma cell diseases such as multiple myeloma. About multiple myeloma: Multiple myeloma is a malignant plasma cell disease caused by abnormal proliferation of clonal plasma cells, accounting for 10-15% of hematologic malignancies and about 1.4% of all malignancies. It is the second most common hematological malignancy in adults after non-Hodgkin's lymphoma and mostly occurs in the elderly. According to the data released by the World Health Organization (WHO), the number of new cases and deaths of multiple myeloma worldwide in 2020 were 176,000 and 117,000 respectively, and the number of new cases and deaths of multiple myeloma in China were 21,000 and 16,000 respectively. Currently, multiple myeloma is still an incurable malignant tumor, and the five-year survival rate of patients is approximately 24.8% in China, 33.3% in Japan, and 46.7% in the United States. In recent years, with the successful development of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), selective nuclear output inhibitors, CD38-targeted antibodies, bispecific antibodies, and CAR-T cell therapies, the tumor response rate and survival prognosis have been significantly improved. However, multiple myeloma remains an unmet clinical need for more effective treatments. About LBL-034: LBL-034 is a humanized IgG1 subtype asymmetric bispecific antibody targeting both GPRC5D and CD3 and Leads Biolabs fully owns the worldwide intellectual property rights. LBL-034 induces T-cell-mediated killing of myeloma cells by redirecting CD3+ T-cells to myeloma cells expressing GPRC5D. LBL-034 has the potential to be a transformative best-in-class GPRC5D-targeted immunotherapy for multiple myeloma. Clinical studies are planned to evaluate the safety and efficacy of LBL-034 in patients with relapsed/refractory multiple myeloma. Nanjing Leads Biolabs Co., Ltd. is a clinical-stage biotechnology company founded in Nanjing by a team of senior U.S.-trained antibody drug developers. Since 2014, Leads Biolabs has been dedicated to the discovery and development of novel antibody drugs with independent intellectual property rights for the treatment of oncology and other major diseases of high unmet medical needs, particularly the challenges in cancer immunotherapy. Our extensive R&D pipeline consist of more than twenty novel tumor immunotherapy molecules based on monoclonal and bispecific antibody technology platforms. Leads Biolabs is committed to providing safe, effective, accessible and affordable new drugs to address the unmet needs of patients around the world. For more information, please visit: Business contact: [email protected] SOURCE LEADS BIOLABS

SAN DIEGO, CA, USA I LONDON, UK, and HOUSTON, TX, USA I July 24, 2023 I Replay, a genome writing company reprogramming biology by writing and delivering big DNA, and The University of Texas MD Anderson Cancer Center (“MD Anderson”), today announced that the U.S. Food & Drug Administration (FDA) has issued a ‘safe to proceed’ for the Investigational New Drug (IND) application for NY-ESO-1 TCR/IL-15 NK, a first-in-class engineered T-Cell Receptor Natural Killer (TCR-NK) cell therapy for relapsed or refractory multiple myeloma. MD Anderson is the IND sponsor. NY-ESO-1 TCR/IL-15 NK is being developed by Syena, an oncology-focused product company launched by Replay and MD Anderson based upon the scientific discoveries of Katy Rezvani , M.D., Ph.D. , professor of Stem Cell Transplantation & Cellular Therapy at MD Anderson. Syena has an exclusive licensing agreement for MD Anderson’s TCR-NK platform. A study in patients with synovial sarcoma and myxoid/round cell liposarcoma received IND clearance from the FDA in June 2023 . "This IND clearance of Syena’s engineered TCR-NK cell technology in hematological malignancies swiftly follows the FDA’s clearance of our solid tumor study in sarcoma, signalling the rapid advancement of our TCR-NK program into the clinic and the breadth of our engineered TCR-NK cell therapy’s potential," said Adrian Woolfson, Executive Chairman, President, and Co-Founder of Replay. Lachlan MacKinnon, CEO and Co-Founder of Replay, commented: “With clinical studies in two indications, spanning solid tumors and hematological malignancies, we are excited for the potential of Syena's first-in-class 'off-the-shelf' engineered TCR-NK platform to address multiple unmet clinical needs.” “NY-ESO-1 is highly expressed in certain patients with multiple myeloma and associated with a poor prognosis, so this clinical study will be key to further understanding the potential of our TCR-NK platform in hematological malignancies,” said Dr Katy Rezvani. “I look forward to the study beginning later this year.” Ends Disclosure MD Anderson has an institutional conflict of interest with Replay and Syena, and MD Anderson will implement an Institutional Conflict of Interest Management and Monitoring Plan to manage these relationships. About Replay Replay is a genome writing company, which aims to define the future of genomic medicine through reprogramming biology by writing and delivering big DNA. The Company has assembled a toolkit of disruptive platform technologies — including a high payload capacity HSV platform, a hypoimmunogenic cell therapy platform, and a genome writing platform — to address the challenges currently limiting clinical progress and preventing genomic medicine from realizing its potential. The Company’s hub-and-spoke business model separates technology development within Replay from therapeutic development in a portfolio of product companies that leverage its technology platforms. For example, the Company recently incorporated a first-in-class engineered TCR-NK cell therapy product company using technology developed by Katy Rezvani, MD, PhD, at The University of Texas MD Anderson Cancer Center in Houston, Texas. Replay’s synHSV™ technology, a high payload capacity HSV vector capable of delivering up to 30 times the payload of AAV, is utilized by Replay’s four gene therapy product companies, bringing big DNA treatments to diseases affecting the skin, eye, brain, and muscle. Replay is led by a distinguished team of academics, entrepreneurs, and industry experts. The Company raised $55 million in seed financing in July 2022 and is supported by an international syndicate of investors including: KKR, OMX Ventures, ARTIS Ventures, and Lansdowne Partners. Replay is headquartered in San Diego, California. For further information please visit www.replay.bio and follow us on LinkedIn and Twitter . About MD Anderson The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. The institution’s sole mission is to end cancer for patients and their families around the world. MD Anderson is one of only 53 comprehensive cancer centers designated by the National Cancer Institute (NCI). MD Anderson is No. 1 for cancer in U.S. News & World Report’s “Best Hospitals” rankings and has been named one of the nation’s top two hospitals for cancer since the rankings began in 1990. MD Anderson receives a cancer center support grant from the NCI of the National Institutes of Health (P30 CA016672). About NY-ESO-1 TCR/IL-15 NK NY-ESO-1 TCR/IL-15 NKs are adoptive Natural Killer (NK) cells expressing an affinity-enhanced T-cell receptor (TCR) reactive directed against the NY-ESO-1-specific cord blood-derived NK cells. The cells are engineered to express the CD3 and TCR signalling complex and IL-15, and use the same manufacturing method as that used for the engineered CAR-NKs, which have demonstrated safety and efficacy in lymphoma ( Liu et al, NEJM 2020 ). NY-ESO-1 (New York Esophageal Squamous cell carcinoma 1) is an established cancer-testis antigen with re-expression in multiple cancer types, and restricted expression in healthy tissues. This expression pattern and its ability to elicit humoral and cellular immune responses makes it a compelling target for TCR-T cell therapy. TCR-engineered NK cells retain their intrinsic capacity to target tumor cells through their native receptors. The fact that NK cells kill tumor cells that down-regulate or lack MHC through the ‘missing self’ mechanism, may make disease escape through the most common primary mechanism of acquired resistance, less likely. IND-enabling studies have confirmed that NY-ESO-1 TCR/IL-15 NK cells do not kill healthy human cell lines derived from organs including the heart, lungs, liver, and kidneys. About multiple myeloma Multiple myeloma is a common hematological malignancy, with an estimated 34,920 new cases diagnosed in the United States in 2021, accounting for 1.8% of all new cases of cancer in the country. There has been a steady increase in the available treatment options for these patients, including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and monoclonal antibodies. More recently, two separate autologous chimeric antigen receptor T (CAR-T) cells, and bispecific targeting BCMA have also been approved for the treatment of multiple myeloma. They have shown impressive response rates and duration of response but are associated with serious toxicity, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, pancytopenia, prolonged hypogammaglobulinemia, immunodeficiency and delayed-onset progressive movement disorders. There are no approved therapies for patients who have failed the BCMA targeting therapies and the outcome of relapsed/refractory multiple myeloma, especially the triple-class refractory multiple myeloma patients, who are refractory to a PI, an IMiD, and an anti-CD38 monoclonal antibody has been poor. SOURCE: Replay

Replay and MD Anderson announce FDAclearance of IND applicationforfirst-in-classT-Cell ReceptorNatural Killer (TCR-NK)cell therapy for multiple myeloma Phase 1 study of NY-ESO-1 TCR/IL-15 NK for relapsed or refractory multiple myeloma,first TCR-NK clinical study in hematological malignancies, anticipated to commence Q3 2023 Follows earlier IND clearance for solid tumor study in synovial sarcoma and myxoid/ round cell liposarcoma received in June 2023 San Diego, California, London, UK, and Houston, Texas, July24,2023– Replay, a genome writing company reprogramming biology by writing and delivering big DNA, and The University of Texas MD Anderson Cancer Center (“MD Anderson”), today announced that the U.S. Food & Drug Administration (FDA) has issued a ‘safe to proceed’ for the Investigational New Drug (IND) application for NY-ESO-1 TCR/IL-15 NK, a first-in-class engineered T-Cell Receptor Natural Killer (TCR-NK) cell therapy for relapsed or refractory multiple myeloma. MD Anderson is the IND sponsor. NY-ESO-1 TCR/IL-15 NK is being developed by Syena, an oncology-focused product company launched by Replay and MD Anderson based upon the scientific discoveries of Katy Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation & Cellular Therapy at MD Anderson. Syena has an exclusive licensing agreement for MD Anderson’s TCR-NK platform. A study in patients with synovial sarcoma and myxoid/round cell liposarcoma received IND clearance from the FDA in June 2023. "This IND clearance of Syena’s engineered TCR-NK cell technology in hematological malignancies swiftly follows the FDA’s clearance of our solid tumor study in sarcoma, signalling the rapid advancement of our TCR-NK program into the clinic and the breadth of our engineered TCR-NK cell therapy’s potential," said Adrian Woolfson, Executive Chairman, President, and Co-Founder of Replay. Lachlan MacKinnon, CEO and Co-Founder of Replay, commented: “With clinical studies in two indications, spanning solid tumors and hematological malignancies, we are excited for the potential of Syena's first-in-class 'off-the-shelf' engineered TCR-NK platform to address multiple unmet clinical needs.” “NY-ESO-1 is highly expressed in certain patients with multiple myeloma and associated with a poor prognosis, so this clinical study will be key to further understanding the potential of our TCR-NK platform in hematological malignancies,” said Dr Katy Rezvani. “I look forward to the study beginning later this year.” Ends Disclosure MD Anderson has an institutional conflict of interest with Replay and Syena, and MD Anderson will implement an Institutional Conflict of Interest Management and Monitoring Plan to manage these relationships. About Replay Replay is a genome writing company, which aims to define the future of genomic medicine through reprogramming biology by writing and delivering big DNA. The Company has assembled a toolkit of disruptive platform technologies — including a high payload capacity HSV platform, a hypoimmunogenic cell therapy platform, and a genome writing platform — to address the challenges currently limiting clinical progress and preventing genomic medicine from realizing its potential. The Company’s hub-and-spoke business model separates technology development within Replay from therapeutic development in a portfolio of product companies that leverage its technology platforms. For example, the Company recently incorporated a first-in-class engineered TCR-NK cell therapy product company using technology developed by Katy Rezvani, MD, PhD, at The University of Texas MD Anderson Cancer Center in Houston, Texas. Replay’s synHSV™ technology, a high payload capacity HSV vector capable of delivering up to 30 times the payload of AAV, is utilized by Replay’s four gene therapy product companies, bringing big DNA treatments to diseases affecting the skin, eye, brain, and muscle. Replay is led by a distinguished team of academics, entrepreneurs, and industry experts. The Company raised $55 million in seed financing in July 2022 and is supported by an international syndicate of investors including: KKR, OMX Ventures, ARTIS Ventures, and Lansdowne Partners. Replay is headquartered in San Diego, California. For further information please visit and follow us on LinkedIn and Twitter. About MD Anderson The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. The institution’s sole mission is to end cancer for patients and their families around the world. MD Anderson is one of only 53 comprehensive cancer centers designated by the National Cancer Institute (NCI). MD Anderson is No. 1 for cancer in U.S. News & World Report’s “Best Hospitals” rankings and has been named one of the nation’s top two hospitals for cancer since the rankings began in 1990. MD Anderson receives a cancer center support grant from the NCI of the National Institutes of Health (P30 CA016672). About NY-ESO-1 TCR/IL-15 NK NY-ESO-1 TCR/IL-15 NKs are adoptive Natural Killer (NK) cells expressing an affinity-enhanced T-cell receptor (TCR) reactive directed against the NY-ESO-1-specific cord blood-derived NK cells. The cells are engineered to express the CD3 and TCR signalling complex and IL-15, and use the same manufacturing method as that used for the engineered CAR-NKs, which have demonstrated safety and efficacy in lymphoma (Liu et al, NEJM 2020). NY-ESO-1 (New York Esophageal Squamous cell carcinoma 1) is an established cancer-testis antigen with re-expression in multiple cancer types, and restricted expression in healthy tissues. This expression pattern and its ability to elicit humoral and cellular immune responses makes it a compelling target for TCR-T cell therapy. TCR-engineered NK cells retain their intrinsic capacity to target tumor cells through their native receptors. The fact that NK cells kill tumor cells that down-regulate or lack MHC through the ‘missing self’ mechanism, may make disease escape through the most common primary mechanism of acquired resistance, less likely. IND-enabling studies have confirmed that NY-ESO-1 TCR/IL-15 NK cells do not kill healthy human cell lines derived from organs including the heart, lungs, liver, and kidneys. About multiple myeloma Multiple myeloma is a common hematological malignancy, with an estimated 34,920 new cases diagnosed in the United States in 2021, accounting for 1.8% of all new cases of cancer in the country. There has been a steady increase in the available treatment options for these patients, including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and monoclonal antibodies. More recently, two separate autologous chimeric antigen receptor T (CAR-T) cells, and bispecific targeting BCMA have also been approved for the treatment of multiple myeloma. They have shown impressive response rates and duration of response but are associated with serious toxicity, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, pancytopenia, prolonged hypogammaglobulinemia, immunodeficiency and delayed-onset progressive movement disorders. There are no approved therapies for patients who have failed the BCMA targeting therapies and the outcome of relapsed/refractory multiple myeloma, especially the triple-class refractory multiple myeloma patients, who are refractory to a PI, an IMiD, and an anti-CD38 monoclonal antibody has been poor. Contacts: Replay Dr Adrian Woolfson/Lachlan MacKinnon info@replay.bio Consilium Strategic Communications – Media relations Amber Fennell/David Daley /Isabelle Abdou replay@consilium-comms.com