Recurrent Metastatic Gastric Carcinoma

HONG KONG, China I November 7, 2023 I Akeso (9926.HK) announced positive results from an interim analysis of AK104-302 study, a randomized, double-blind, multicenter, phase III clinical study evaluating PD-1/CTLA-4 bispecific antibody, cadonilimab ( 开坦尼 ®) in combination with capecitabine plus oxaliplatin (XELOX) compared to placebo plus XELOX for first-line treatment of unresectable locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma (GC/GEJC). The trial achieved its primary endpoint by demonstrating a statistically significant overall survival (OS) improvement. The Independent Data Monitoring Committee (IDMC) recommended the early submission of a supplemental new drug application (sNDA) for cadonilimab in this indication based on the interim analysis. The interim analysis showed that cadonilimab plus chemotherapy significantly improved OS in the all-comer patients irrespective of PD-L1 status, compared to placebo plus chemotherapy, meeting the pre-defined efficacy criteria. The safety profile remained consistent with previous results, with no new safety signals identified. These data will be presented in future international academic conferences/journals. Interim Analysis Highlight: "We extend our sincere gratitude to all the investigators, participants, and patients who actively took part in the clinical trial," expressed Dr. Yu Xia, Founder, Chairman, President, and CEO of Akeso. " Thanks to your dedication and efforts, an estimated 500,000 gastric cancer patients in China may have access to a new bispecific IO drug combination therapy offering improved treatment efficiency and survival prospects. We will continue to adhere to the recommendations of IDMC, efficiently promote the study, and engage in proactive communication with China's National Medical Products Administration (NMPA) regarding the marketing application of cadonilimab for this new indication. We eagerly anticipate the early approval of this innovative therapy for the benefit of patients." ABOUT AK104-302 AK104-302 is a Phase III clinical trial evaluating the use of cadonilimab (which is the world's first approved PD-1/CTLA-4 bi-specific antibody) in combination with XELOX as first-line treatment for unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (GC/GEJC). This randomized, double-blind, multi-center study aims to assess the efficacy of cadonilimab plus XELOX compared to placebo plus XELOX in the intent-to-treat (ITT) population. The AK104-302 trial represents the first Phase III clinical study of a PD-1/CTLA-4 bispecific antibody combined with chemotherapy for first-line treatment of gastric cancer. Approximately 60% of patients in the ITT population had a PD-L1 CPS ＜ 5, a proportion comparable to real-world scenarios. About Cadonilimab Cadonilimab is a first-in-class bispecific antibody that targets both PD-1 and CTLA-4 developed by Akeso. It is a symmetric tetravalent bispecific antibody with a crystallizable fragment (Fc)-null design. In addition to demonstrating biological activity similar to that of the combination of CTLA-4 and PD-1 antibodies, cadonilimab possesses higher binding avidity in a high-density PD-1 and CTLA-4 setting than in a low-density PD-1 setting, while a mono-specific anti-PD-1 antibody does not demonstrate this differential activity. With no binding to Fc receptors, cadonilimab shows minimal antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and interleukin-6 (IL-6)/IL-8 release. These features all likely contribute to significantly lower toxicities of cadonilimab observed in the clinic. Higher binding avidity of cadonilimab in a tumor-like setting and Fc-null design may lead to better drug retention in tumors and improve safety while achieving anti-tumor efficacy. The China National Medical Products Administration has approved cadonilimab for recurrent or metastatic cervical cancer. Cadonilimab has been included and recommended in multiple clinical guidelines such as CSCO. Cadonilimab has been engaged in more than 60 ongoing clinical trials including investigator-initiated studies. Patient enrollment has been completed for the phase 3 study of cadonilimab for first-line treatment of advanced cervical cancer. A phase 3 study of cadonilimab as an adjuvant treatment for hepatocellular carcinoma is ongoing. Furthermore, a Phase 3 study comparing cadonilimab with chemotherapy to tislelizumab Injection with chemotherapy is underway for the first-line treatment of PD-L1 expression-negative non-small cell lung cancer. About Akeso, Inc. Akeso (HKEX: 09926) is a commercial-stage biopharmaceutical company committed to discovering, developing, manufacturing, and commercializing innovative medicines that address significant medical needs globally. Since our inception, we have established a distinctive and integrated R&D innovation system with the comprehensive end-to-end drug development platform (ACE Platform) and bi-specific antibody drug development technology (Tetrabody) as the fundamental components, a GMP-compliant manufacturing system and a commercialization system with an advanced operation mode. Akeso is actively developing a diverse pipeline of over 30 innovative assets in areas such as cancer, autoimmune disease, inflammation, metabolic disease, and other therapeutic fields. Among these, 19 assets have entered the clinical stage, with 3 innovative drugs already approved, NDAs for 4 drugs and 6 indications accepted, and 13 ongoing Phase III studies. Utilizing its proprietary Tetrabody technology, Akeso has successfully developed the first-in-class PD-1/CTLA-4 bispecific antibody drug to the market. Additionally, the company has five other innovative bispecific antibody drugs in the clinical stage, including ivonescimab (PD-1/VEGF), PD-1/LAG-3, TIGIT/TGF-Beta, PD-1/CD73, and claudin18.2/CD47 bispecific antibodies. In June 2022, cadonilimab was approved by the NMPA and became the first commercialized bispecific IO drug globally. Another Akeso internally discovered and developed oncology product, penpulimab (a PD-1 antibody), was granted marketing approval in China in August 2021. In December 2022, Akeso entered into a collaboration and license agreement for up to US$5 billion with Summit Therapeutics to accelerate global development and commercialization of ivonescimab. In August, the NDA submission of ivonescimab was accepted by China's NMPA and granted Priority Review. Akeso is listed on the Main Board of the Stock Exchange of Hong Kong Limited. For more information, please visit https://www.akesobio.com/en/ and follow us on X (formerly Twitter) @Akeso Inc., and Linkedin @Akeso Inc. 康方生物 SOURCE: Akeso

HONG KONG, Nov. 7, 2023 /PRNewswire/ -- Akeso (9926.HK) announced positive results from an interim analysis of AK104-302 study, a randomized, double-blind, multicenter, phase III clinical study evaluating PD-1/CTLA-4 bispecific antibody, cadonilimab (开坦尼®) in combination with capecitabine plus oxaliplatin (XELOX) compared to placebo plus XELOX in for first-line treatment of unresectable locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma (GC/GEJC). The trial achieved its primary endpoint by demonstrating a statistically significant overall survival (OS) improvement. The Independent Data Monitoring Committee (IDMC) recommended the early submission of a supplemental new drug application (sNDA) for cadonilimab in this indication based on the interim analysis. The interim analysis showed that cadonilimab plus chemotherapy significantly improved OS in the all-comer patients irrespective of PD-L1 status, compared to placebo plus chemotherapy, meeting the pre-defined efficacy criteria. The safety profile remained consistent with previous results, with no new safety signals identified. These data will be presented in future international academic conferences/journals. Interim Analysis Highlight: Cadonilimab combined with chemotherapy significantly reduces the risk of death in all-comer patients, including whose with PD-L1 CPS≥5 and PD-L1 CPS<5. The hazard ratios (HRs) for OS in patients with different PD-L1 status were superior to other disclosed PD-1 plus chemotherapy combination treatment. The combination of cadonilimab and chemotherapy also demonstrated superior OS in patients with PD-L1 CPS<5 as well as PD-L1 negative, maintaining the excellent performance seen in the phase II study. "We extend our sincere gratitude to all the investigators, participants, and patients who actively took part in the clinical trial," expressed Dr. Yu Xia, Founder, Chairman, President, and CEO of Akeso. " Thanks to your dedication and efforts, an estimated 500,000 gastric cancer patients in China may have access to a new bispecific IO drug combination therapy offering improved treatment efficiency and survival prospects. We will continue to adhere to the recommendations of IDMC, efficiently promote the study, and engage in proactive communication with China's National Medical Products Administration (NMPA) regarding the marketing application of cadonilimab for this new indication. We eagerly anticipate the early approval of this innovative therapy for the benefit of patients." ABOUT AK104-302 AK104-302 is a Phase III clinical trial evaluating the use of cadonilimab (which is the world's first approved PD-1/CTLA-4 bi-specific antibody) in combination with XELOX as first-line treatment for unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (GC/GEJC). This randomized, double-blind, multi-center study aims to assess the efficacy of cadonilimab plus XELOX compared to placebo plus XELOX in the intent-to-treat (ITT) population. The AK104-302 trial represents the first Phase III clinical study of a PD-1/CTLA-4 bispecific antibody combined with chemotherapy for first-line treatment of gastric cancer. Approximately 60% of patients in the ITT population had a PD-L1 CPS＜5, a proportion comparable to real-world scenarios. About Cadonilimab Cadonilimab is a first-in-class bispecific antibody that targets both PD-1 and CTLA-4 developed by Akeso. It is a symmetric tetravalent bispecific antibody with a crystallizable fragment (Fc)-null design. In addition to demonstrating biological activity similar to that of the combination of CTLA-4 and PD-1 antibodies, cadonilimab possesses higher binding avidity in a high-density PD-1 and CTLA-4 setting than in a low-density PD-1 setting, while a mono-specific anti-PD-1 antibody does not demonstrate this differential activity. With no binding to Fc receptors, cadonilimab shows minimal antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and interleukin-6 (IL-6)/IL-8 release. These features all likely contribute to significantly lower toxicities of cadonilimab observed in the clinic. Higher binding avidity of cadonilimab in a tumor-like setting and Fc-null design may lead to better drug retention in tumors and improve safety while achieving anti-tumor efficacy. The China National Medical Products Administration has approved cadonilimab for recurrent or metastatic cervical cancer. Cadonilimab has been included and recommended in multiple clinical guidelines such as CSCO. Cadonilimab has been engaged in more than 60 ongoing clinical trials including investigator-initiated studies. Patient enrollment has been completed for the phase 3 study of cadonilimab for first-line treatment of advanced cervical cancer. A phase 3 study of cadonilimab as an adjuvant treatment for hepatocellular carcinoma is ongoing. Furthermore, a Phase 3 study comparing cadonilimab with chemotherapy to tislelizumab Injection with chemotherapy is underway for the first-line treatment of PD-L1 expression-negative non-small cell lung cancer. About Akeso, Inc. Akeso (HKEX: 09926) is a commercial-stage biopharmaceutical company committed to discovering, developing, manufacturing, and commercializing innovative medicines that address significant medical needs globally. Since our inception, we have established a distinctive and integrated R&D innovation system with the comprehensive end-to-end drug development platform (ACE Platform) and bi-specific antibody drug development technology (Tetrabody) as the fundamental components, a GMP-compliant manufacturing system and a commercialization system with an advanced operation mode. Akeso is actively developing a diverse pipeline of over 30 innovative assets in areas such as cancer, autoimmune disease, inflammation, metabolic disease, and other therapeutic fields. Among these, 19 assets have entered the clinical stage, with 3 innovative drugs already approved, NDAs for 4 drugs and 6 indications accepted, and 13 ongoing Phase III studies. Utilizing its proprietary Tetrabody technology, Akeso has successfully developed the first-in-class PD-1/CTLA-4 bispecific antibody drug to the market. Additionally, the company has five other innovative bispecific antibody drugs in the clinical stage, including ivonescimab (PD-1/VEGF), PD-1/LAG-3, TIGIT/TGF-Beta, PD-1/CD73, and claudin18.2/CD47 bispecific antibodies. In June 2022, cadonilimab was approved by the NMPA and became the first commercialized bispecific IO drug globally. Another Akeso internally discovered and developed oncology product, penpulimab (a PD-1 antibody), was granted marketing approval in China in August 2021. In December 2022, Akeso entered into a collaboration and license agreement for up to US$5 billion with Summit Therapeutics to accelerate global development and commercialization of ivonescimab. In August, the NDA submission of ivonescimab was accepted by China's NMPA and granted Priority Review. Akeso is listed on the Main Board of the Stock Exchange of Hong Kong Limited. Contact Akeso Public Relations: [email protected] Contact Akeso Business Development: [email protected] For more information, please visit and follow us on X (formerly Twitter) @Akeso Inc., and Linkedin @Akeso Inc. 康方生物 SOURCE Akeso, Inc.

Prior data provide clinical proof-of-concept for narazaciclib’s mechanism of action in endometrial cancer Preliminary data from trial’s Phase 1 portion expected in 4Q 2023 NEWTOWN, Pa., May 11, 2023 (GLOBE NEWSWIRE) -- Onconova Therapeutics Inc. (NASDAQ: ONTX), (“Onconova”), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, today announced that the first patient has been dosed in the Company’s Phase 1/2a trial evaluating narazaciclib combined with letrozole in recurrent metastatic low-grade endometrioid endometrial cancer (LGEEC). Narazaciclib is a multi-kinase inhibitor targeting CDK 4, CDK 6, and other kinases important for cell proliferation and motility. Preliminary data from the trial’s Phase 1 portion are expected in 4Q 2023. Endometrial cancer arises in the uterine lining and is the most common cancer of the female reproductive organs. Endometrioid endometrial cancer is the most common subtype of endometrial cancer, accounting for approximately 75% of cases. Data from prior randomized and single-arm trials have demonstrated the anti-cancer activity of letrozole combined with CDK 4/6 inhibition in recurrent endometrial cancer1-3. Currently, there is no health authority-approved CDK 4/6 inhibitor for the treatment of endometrial cancer. “Improved treatment options for recurrent LGEEC are urgently needed, as the CDK 4/6 inhibitors currently used off-label for this indication are marked by limitations related to safety, tolerability, and treatment resistance,” said Bhavana Pothuri, M.D., Professor, Department of Obstetrics and Gynecology at NYU Grossman School of Medicine and Director, Gynecologic Oncology Research; Perlmutter Cancer Center and Principal Investigator of the trial. “Narazaciclib’s kinase inhibitory pro it can overcome each of these limitations thanks to reduced activity against kinases whose inhibition is associated with bone marrow toxicity and diarrhea, and increased activity against those implicated in pro-tumor immune suppression and cancer cell survival. This hypothesis is supported by data from in vitro and murine cancer models, and I look forward to its continued evaluation in the ongoing Phase 1/2a trial.” Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova, commented, “Our recurrent LGEEC program provides an opportunity to establish narazaciclib as a best-in-class therapy in an indication where clinical proof-of-concept for its mechanism of action has been demonstrated. We, therefore, view the program as a key avenue for value creation and look forward to our Phase 1/2a trial’s preliminary data readout expected later this year.” About the Phase 1/2a Trial The Phase 1/2a trial is an open-label, multicenter study evaluating narazaciclib in combination with letrozole as a second or third-line treatment for patients with recurrent metastatic LGEEC. Both narazaciclib and letrozole are administered orally with a continuous daily dosing schedule. The trial begins with a Phase 1 dose escalation phase before moving to a Phase 2 expansion cohort designed to enroll approximately 30 patients. The primary objective of the Phase 1 portion of the trial is to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics in order to determine a recommended Phase 2 dose (RP2D) of the combination. The primary objective of the Phase 2 portion will be to evaluate the efficacy of the combination at the RP2D, as measured by progression-free survival at 24 weeks. The estrogen/progesterone receptor status of participants will be recorded as part of an exploratory objective. The trial will be conducted at sites including NYU Langone Health, the site of the Principal Investigator of the study, sites affiliated with MD Anderson Cancer Center, and U.S. Oncology Research sites. References 1. Mirza MR. ESMO Virtual Congress 2020. Abstr. LBA28. 2. Konstantinopoulos PA, et al.; 2022 SGO Annual Meeting on Women’s Cancer; March 18-21, 2022. Phoenix, AZ 3. Colon-Otero G, Zanfagnin V, Hou X, et al. ESMO Open. 2020 Oct;5(5):e000926. doi: 10.1136/esmoopen-2020-000926. About Onconova Therapeutics, Inc. Onconova Therapeutics is a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer. The Company has proprietary targeted anti-cancer agents designed to disrupt specific cellular pathways that are important for cancer cell proliferation. Onconova’s novel, proprietary multi-kinase inhibitor narazaciclib (formerly ON 123300) is being evaluated in a combination trial with estrogen blockade in advanced endometrial cancer. Based on preclinical and clinical studies of CDK 4/6 inhibitors, Onconova is also evaluating opportunities for combination studies with narazaciclib in additional indications. Onconova’s product candidate rigosertib is being studied in multiple investigator-sponsored studies, including a dose-escalation and expansion Phase 1/2a study of oral rigosertib in combination with nivolumab in patients with KRAS+ non-small cell lung cancer, and a Phase 2 program evaluating rigosertib monotherapy in advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa. For more information, please visit . Forward Looking Statements Some of the statements in this release are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995, and involve risks and uncertainties. These statements relate to Onconova’s expectations regarding its clinical development and trials, its product candidates, its business and financial position. Onconova has attempted to identify forward-looking statements by terminology including "believes," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "will," "should," “preliminary,” “encouraging,” "approximately" or other words that convey uncertainty of future events or outcomes. Although Onconova believes that the expectations reflected in such forward-looking statements are reasonable as of the date made, expectations may prove to have been materially different from the results expressed or implied by such forward-looking statements. These statements are only predictions and involve known and unknown risks, uncertainties, and other factors, including the success and timing of Onconova's clinical trials, investigator-initiated trials and regulatory agency and institutional review board approvals of protocols, Onconova’s collaborations, market conditions and those discussed under the heading "Risk Factors" in Onconova's most recent Annual Report on Form 10-K and quarterly reports on Form 10-Q. Any forward-looking statements contained in this release speak only as of its date. Onconova undertakes no obligation to update any forward-looking statements contained in this release to reflect events or circumstances occurring after its date or to reflect the occurrence of unanticipated events. Company Contact: Mark Guerin Onconova Therapeutics, Inc. 267-759-3680 ir@onconova.us Investor Contact: Bruce Mackle LifeSci Advisors, LLC 646-889-1200 bmackle@lifesciadvisors.com