Shanghai Yingli Pharmaceutical Co., Ltd.

Linperlisib achieved Overall Response Rate of 48% with 30% being Complete Response and manageable safety profile in the r/r PTCL phase 2 study SHANGHAI and SAN FRANCISCO, Dec. 11, 2023 /PRNewswire/ -- Shanghai Yingli Pharmaceutical Co., Ltd. (" Yingli Pharma"), a biopharmaceutical company focused on developing oral therapies for cancer and metabolic diseases, today announced the pivotal Phase 2 clinical trial results of the investigation of linperlisib in the treatment of patients with relapsed or refractory (r/r) peripheral T-cell lymphoma (PTCL). Linperlisib is a phosphoinositide 3-kinase delta (PI3Kδ) oral inhibitor, approved in China for treatment of patients with r/r follicular lymphoma after systemic therapy. "There is a vital need for new therapies to treat highly aggressive cancers such as r/r PTCL where there are very limited treatment options." said Dr. Jun Zhu, Professor, Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China, who was the leading investigator for this pivotal clinical trial. "In addition to the promising efficacy and well manageable safety of linperlisib in r/r PTCL, it is noteworthy that a high proportion of the treated patients were shown to have a complete response, and responses have been seen in all the major PTCL subtypes." "Our approach is to develop novel oral agents that will allow patients to safely administer at home," said Michael Hui, CEO of Yingli Pharma, "We are delighted that the encouraging results of this study support the use of linperlisib in this hard-to-treat disease and are excited to continue developing linperlisib in more indications. The company has applied for linperlisib marketing approval in r/r PTCL in China based on these pivotal study findings." Mr. Hui added, "We look forward to the results of an ongoing open-label multi-center Phase 2 study in the U.S. and Italy in r/r PTCL and r/r CTCL." Safe and effective treatment of r/r PTCL patients The pivotal r/r PTCL Phase 2 clinical trial enrolled 98 patients (pts) from May 2021 to October 2022 at 25 clinical sites in China. The pts had a median of two lines of prior systemic therapies. Sixty-four pts (73%) had refractory disease, 59 pts (67%) had relapsed disease, and 35 pts (40%) had both relapsed and refractory diseases. All patients received linperlisib at 80 mg QD, the RP2D for the drug, with a minimum of 6 months follow-up. The linperlisib-treated patients (Full Analysis Set N = 88) evaluated by Lugano criteria, had a 48% overall response rate, including 30% complete responses and 18% partial responses, as well as a 68% disease control rate. The median Duration of Response was not reached although the 6-month DOR rate was 75%. The median PFS was 5.5 months (95% CI, 3.5, 15.6) and the median OS was 14.2 months (95%CI, 7.9, not reached). Responses were observed across PTCL subtypes. Linperlisib was well tolerated with a differentiated and manageable safety profile, specifically having very low levels of immune-mediated toxicities. In the linperlisib-treated patient safety dataset (N=98) for the pivotal study, the most common hematologic treatment related adverse events (TRAEs) of Grade≥3 were neutropenia (32%), leukocytopenia (10%), Anemia (6%), Thrombocytopenia (5%), and Lymphocytopenia (5%). The most common nonhematologic TRAEs of Grade≥3 were pneumonia (14%) and upper respiratory tract infection (5%). Immune-mediated Grade≥3 TRAEs including elevated ALT, AST, diarrhea, colitis, rash were not reported or were <5%. Nine patients (9.2%) discontinued from the study due to various adverse events. The safety results of this study were consistent with previously reported data in other linperlisib clinical studies. About linperlisib Linperlisib, a next-generation PI3K-selective oral inhibitor, received marketing approval in China in 2022 for treatment of patients with relapsed and/or refractory follicular lymphoma after two or more systemic therapies. Linperlisib also received U.S. FDA Orphan Drug Designations for follicular lymphoma, chronic lymphocytic leukemia, and T cell lymphomas. Linperlisib is under investigation in multiple additional clinical trials as a monotherapy: frontline PTCL, r/r large granular T lymphocytic leukemia, r/r autoimmune hemolytic anemia; and in combination with other agents: in second line follicular lymphoma and marginal zone lymphoma, frontline PTCL, and r/r CTCL. In the U.S. and EU, linperlisib is being developed by 280Bio, Inc (San Francisco, CA., USA), a wholly-owned subsidiary of Yingli Pharma, in a Phase 2 clinical study in r/r T Cell Lymphomas [PTCL and CTCL]. About Yingli Pharma Shanghai Yingli Pharmaceutical Co., Ltd., founded in 2011 and located in the National Biomedical Industry Base of Shanghai Zhangjiang InnoPark, is a clinical-stage biotechnology company developing oral drugs for oncology and metabolic diseases. Yingli Pharma has partnered with Jiangsu Hengrui Pharmaceuticals Co., Ltd., for Greater China commercialization of linperlisib (Intarel®) in r/r follicular lymphoma that is conditionally approved, and other heme indications. Yingli Pharma is currently developing other oral agents in clinical stage from its oncology portfolio, including YL-13027 (TGFR1 inhibitor), YL17231 (pan-RAS inhibitor), YL-15293 (KRASG12C inhibitor), as well as a rich pipeline of additional novel oral agents in oncology. 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SOUTH SAN FRANCISCO, Calif., Dec. 1, 2023 /PRNewswire/ -- 280Bio, Inc., a clinical stage biotechnology company focused on the development of precision oncology medicines, today announced that the first patient was treated with TEB-17231 (YL-17231), a small molecule inhibitor of RAS signaling. 280Bio is a wholly owned subsidiary of Shanghai Yingli Pharmaceuticals, Inc. (Yingli Pharma) of Shanghai, China. KRAS, NRAS and HRAS genes are frequently mutated in many tumor indications causally associated with promoting tumor cell growth. TEB-17231 demonstrated potent inhibition of tumor cell proliferation in vitro and in vivo in preclinical research, exhibiting activity with different KRAS, NRAS and HRAS alterations, including tumors that have become resistant to KRAS G12C inhibitors. "We are gratified that the first patient has been dosed with our novel pan-RAS inhibitor, marking a major step in TEB-17231's clinical development, and introducing new medicines for the patients we hope to serve." said Michael Hui, Chief Executive Officer of 280Bio Inc., "This milestone highlights our commitment to addressing unmet needs in cancers through precision oncology approaches. We look forward to continued enrollment and dosing of patients in this trial." This first US patient was enrolled at The University of Texas MD Anderson Cancer Center, Houston, Texas, by David Hong, MD, Deputy Chair of Investigational Cancer Therapeutics and lead investigator on the trial. Reflecting on the high unmet need for new cancer agents, Dr. Zusheng Xu, Head of Research and Development of Yingli Pharma, said "TEB-17231 was developed to have a broader activity against the oncogenic RAS signaling pathways, than is currently demonstrated for many of the KRAS inhibitors. With its excellent pharmacologic and in vivo anti-tumor properties, we are hopeful that TEB-17231 will also be determined to be safe and efficacious by continuous oral dosing in patients." About 280Bio 280Bio, headquartered in the San Francisco Bay Area, is developing innovative precision small molecule inhibitors for the treatment of cancer. 280Bio is a wholly owned subsidiary of Shanghai Yingli Pharmaceutical Co., Ltd., Shanghai, China (Yingli Pharma), with an oncology pipeline that is leveraging the strong medicinal chemistry and pharmacology capabilities of the company. 280Bio focuses on oral agents directed against frequently mutated genetic changes and well-validated genetic instability features of many cancers. TEB-17231 is part of a strategic collaboration of 280Bio with The University of Texas MD Anderson Cancer Center, where further preclinical research of the investigational drug is continuing. The collaboration also is currently advancing clinical development in the U.S./E.U. of two other drugs, linpersilib (PI3Kδ inhibitor from Yingli Pharma, approved in China in 2022) in a T-cell lymphoma Phase 2 trial, and YL-13027 (TGFβR1 inhibitor from Yingli Pharma) in a Phase 1 dose escalation study. SOURCE 280Bio

A broadly acting KRAS Inhibitor, TEB-17231, robustly blocks tumor growth and overcomes KRASG12C inhibitor mediated resistance SHANGHAI, March 21, 2023 /PRNewswire/ -- 280Bio, Inc. a clinical stage biotechnology company, focused on the development of precision oncology medicines, today announced a presentation featuring the Company's lead development candidate TEB-17231 at the AACR Annual Meeting in Orlando, Florida to be held April 14-19, 2023. The 280Bio pipeline is focused on novel oral oncology drug candidates directed at frequently mutated genetic changes in signaling pathways and the known genetic instability features of many cancers. The presentation describes preclinical findings on a lead series of small molecule inhibitors directed against multiple KRAS-mutation-altered tumor cell lines. The lead candidate TEB-17231 showed robust tumor growth inhibition, against KRASG12V, KRASG12C, KRASG12D and other RAS mutant tumor cell lines. TEB-17231 was also shown to be active in blocking tumor growth in KRASG12C-resistant cell lines bearing different secondary mutations in KRAS. With its excellent pharmacologic properties, TEB-17231 oral dosing demonstrates strong inhibition of in vivo KRAS mutant xenograft tumor growth. The presentation details at 2023 AACR are as follows: The small molecule KRAS inhibitor, TEB-17231, blocks tumor progression and overcome KRASG12C inhibitor mediated resistance Session Category: Molecular/Cellular Biology and Genetic; Session Title: Ras-related Signaling; Monday April 17, 2023 1.30PM to 5.00PM EST Location Section 11, Poster Board 11 abstract # 2627 280Bio is advancingTEB-17231 through IND enabling studies in preparation for Phase1 studies for the treatment of KRAS-mutated cancer patients. Reflecting on the importance of the discovery and early research being presented at AACR 2023, Michael Hui, MBA, CEO & President of 280Bio, stated, "We are actively developing TEB-17231 given its demonstrated abilities to effectively inhibit different KRAS mutant tumor cells through its actions in KRAS signaling. We are excited that TEB-17231 is emerging from the company's KRAS target hub discovery platform, exemplifying the utility of our strong medicinal chemistry capabilities at 280Bio. The strategic collaboration with the MD Anderson Cancer Center (MDACC), Houston, TX, further contributes to our understanding of this interesting drug class and KRAS signaling mechanisms, and will accelerate development of TEB-17231 and other KRAS target hub agents toward the clinic." "The scientific presentation at the AACR meeting of our KRAS lead candidate TEB-17231 highlights the progress we made to move the drug candidate this year into the clinic", said Dr. Xu Zusheng, General Manager and Head of Research and Development of Yingli Pharma, "Novel agents that interfere with KRAS signaling are highly desirable, particularly in cancers where KRAS is dysregulated. Precision oncology approaches offer the advantage of identifying the KRAS mutated cancers that may be most susceptible to these novel targeted agents. The TEB-17231 drug candidate potentially brings an additional treatment option to address a high unmet need for many patients with cancer." About 280Bio 280Bio, headquartered in the San Francisco Bay Area, is developing innovative precision small molecule inhibitors for the treatment of cancer. 280Bio is a clinical-stage biotechnology company and a wholly owned subsidiary of Shanghai Yingli Pharmaceutical Co., Ltd., Shanghai, China. The company's strong medicinal chemistry and pharmacology capabilities are the foundation for 280Bio's oncology portfolio targeting KRAS, PIK3CA, P53 and PARG (genomic instability), with several drug candidates entering IND-enabling development in 2023. The company has a strategic collaboration with MD Anderson Cancer Center to advance several oncology agents into clinical development in the U.S./E.U., including the Yingli Pharma inhibitors, linpersilib (PI3Kδ inhibitor) in a T-cell lymphoma Phase 2 trial and YL-13027 (TGFβR1 inhibitor) currently in a Phase 1 dose escalation study. Media Contact: Michael Hui, MBA President & CEO 280Bio [email protected] SOURCE 280Bio