EphB4

HONG KONG, Sept. 30, 2024 /PRNewswire/ -- September 30, 2024, Akeso (9926. HK) announced that its internally developed PD-1/CTLA-4 bispecific antibody, cadonilimab, has received approval from the National Medical Products Administration (NMPA) for a new indication: cadonilimab in combination with fluoropyrimidine and platinum-based chemotherapy for first-line treatment of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. This is the second indication approval for cadonilimab in China, following its initial approval for marketing in June 2022. The approval of the new indication for cadonilimab combination therapy for first-line treatment of gastric/GEJ cancer is based on the COMPASSION-15/AK104-302 study. In the COMPASSION-15 study, the proportion of patients with PD-L1 CPS < 5 and PD-L1 CPS < 1 in the Intention-to-Treat (ITT) population reached 49.8% and 23%, respectively, which is significantly higher than the data disclosed in previous phase III studies of other immunotherapies for first-line treatment. In November 2023, the interim analysis of the study achieved the primary endpoint of overall survival (OS). The results showed that the cadonilimab combination therapy significantly reduced the risk of death in advanced gastric cancer patients across all PD-L1 expression levels (including those with PD-L1 CPS ≥5 and <5), extending overall survival benefits and demonstrating notable advantages in objective response and long-term survival. Previous phase III trials of PD-1 inhibitors combined with chemotherapy showed limited or no clinical benefit for patients with low or negative PD-L1 expression. The results of the COMPASSION-15 study were presented as an oral report at the 2024 AACR. In the ITT population, the median overall survival (mOS) for the cadonilimab regimen reached 15.0 months, compared to 10.8 months in the control group, extending overall survival by 4.2 months and reducing the risk of death by 38% (HR=0.62). In the PD-L1 CPS <5 group, the mOS for the cadonilimab regimen was 14.8 months, with a 30% reduction in the risk of death compared to the control group (11.1 months, HR=0.70). For the PD-L1 CPS ≥5 group, the mOS had not yet been reached, but the risk of death was reduced by 44% compared to the control group (10.6 months, HR=0.56). COMPASSION-15's principal investigator, Professor Ji Jiafu from Peking University Cancer Hospital, stated: " The prognosis for advanced gastric cancer is poor. While currently approved immunotherapy options have improved efficacy compared to traditional chemotherapy, there remains significant potential for enhancement. The cadonilimab combination therapy has substantially increased the objective response rate and overall survival in the general population while reducing disease-related mortality. Remarkably, cadonilimab shows significant overall survival benefits not only in patients with high PD-L1 CPS expression but also in those with low or negative PD-L1 CPS expression. The approval of cadonilimab as a first-line treatment effectively addresses the efficacy gap of PD-1/L1 monoclonal antibodies in patients with low or negative PD-L1 expression, providing a more comprehensive and effective immunotherapy option for advanced gastric cancer. This advancement benefits all patient populations and presents new opportunities for the global development of gastric cancer immunotherapy, carrying important clinical implications. As a clinician, I am enthusiastic about the approval of cadonilimab for advanced gastric cancer. This innovative treatment will offer a superior and more comprehensive immunotherapy option for patients, and I look forward to its impact on optimizing the current clinical landscape for advanced gastric cancer." COMPASSION-15's principal investigator, Professor Shen Lin from Peking University Cancer Hospital, stated: "We are delighted by the successful approval of cadonilimab combination therapy for the first-line treatment of advanced gastric cancer. This regimen offers significant advantages over current immunotherapy options in clinical practice, providing a superior choice not only for patients with high PD-L1 expression but also for those with low or negative PD-L1 expression, who previously lacked effective treatment options. Cadonilimab addresses the limitations of single-target immunotherapy and exemplifies the synergistic mechanism of dual immune therapy with "anti-PD-1 + anti-CTLA-4," thereby filling an important clinical gap in the treatment of advanced gastric cancer. Beyond first-line approval, the phase III clinical study (AK109-301) of cadonilimab combined with pulocimab (AK109, VEGFR-2) for treating advanced gastric cancer that has progressed after PD-1/L1 inhibitor plus chemotherapy has been initiated. There is currently a lack of effective standard treatments for patients with acquired resistance to immunotherapy, and we eagerly anticipate that this new combination regimen will yield improved results in second-line therapy for these patients, ultimately providing clinicians with more effective tools for cancer treatment." Dr. Xia Yu, Founder, Chairwoman, President, and Chief Executive Officer of Akeso Biopharma, stated: "We thank all researchers, participants, and patients involved in this clinical study. Their collective efforts have led to the approval of cadonilimab combination therapy for first-line treatment of advanced gastric cancer, introducing a novel bispecific immune therapy combined with chemotherapy. As immunotherapy evolves, global regulators and the medical community are reassessing the real-world benefits of PD-1 therapies across different PD-L1 expression levels in gastric and esophageal cancers. Cadonilimab, a novel bispecific antibody targeting both PD-1 and CTLA-4, is supported by robust evidence demonstrating significant clinical benefits for the entire gastric cancer population. Differentiating from PD-1 monoclonal antibody combinations, cadonilimab also shows substantial advantages for patients with low or negative PD-L1 expression. Akeso will continue to explore the global clinical value of cadonilimab." Gastric cancer is one of the most common malignant tumors worldwide. According to the International Agency for Research on Cancer (IARC) 2022 statistics, there are nearly one million new cases each year, making it the fifth most common cancer. China accounts for about half of these cases and deaths, with HER2-negative patients representing around 88%. For those ineligible for surgery or with metastatic gastric cancer (including gastroesophageal junction cancer), immunotherapy using PD-1/L1 monoclonal antibodies has shown success in first-line treatment, though survival benefits remain limited. Cadonilimab combination therapy is expected to provide a more effective treatment option. SOURCE Akeso, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

PARIS, Sept. 8 – Elevar Therapeutics, Inc., a fully integrated biopharmaceutical company dedicated to elevating treatment experiences and outcomes for patients who have limited or inadequate therapeutic options, today announced top-line results from the Phase 3 study of its drug candidate rivoceranib combined with camrelizumab versus sorafenib as a first-line therapy for unresectable hepatocellular carcinoma (uHCC). Camrelizumab plus rivoceranib significantly prolonged overall survival (OS) and progression-free survival (PFS), and improved overall response rate (ORR) versus sorafenib, a standard first-line treatment for uHCC. The findings will be presented Sept. 10 during the annual Congress of the European Society for Medical Oncology (ESMO) in Paris. “Camrelizumab (C) plus rivoceranib (R) vs. sorafenib (S) as first-line therapy for unresectable hepatocellular carcinoma (uHCC): a randomized, Phase 3 trial,” will be shared as a late-breaking proffered paper presentation at ESMO on Sept. 10, 8:40 a.m. – 8:50 a.m. CEST, location 7.1C – Cannes Auditorium. The session title is: Proffered Paper Session 1: GI, upper digestive. The global, randomized, open-label trial (NCT03764293) included 543 patients (ITT population). The study began in June 2019, reaching its primary endpoint in April 2022. Top-line data included: Median OS for camrelizumab+rivoceranib was 22.1 mos. [95% CI 19.1-27.2] vs. 15.2 mos. [13.0-18.5]; hazard ratio (HR) 0.62 [95% CI 0.49-0.80]; 1-sided p<0.0001, Median PFS for camrelizumab+rivoceranib was 5.6 mos. [95% CI 5.5-6.3] vs. 3.7 mos. [2.8-3.7]; HR 0.52 [95% CI 0.41-0.65]); 1-sided p<0.0001, and Confirmed ORR for camrelizumab+rivoceranib was 25.4% (95% CI 20.3-31.0), compared to 5.9% (3.4-9.4) for sorafenib. “This study marks the first positive pivotal trial to show survival benefits with an anti-angiogenic TKI plus a PD-1 inhibitor for unresectable hepatocellular carcinoma,” said Jan M. Van Tornout, M.D., MSc., chief medical officer of Elevar. “The efficacy results demonstrate that camrelizumab plus rivoceranib present as a new first-line treatment option for uHCC. We look forward to detailing additional findings, including results within Asian and non-Asian populations, shortly after our presentation at ESMO.” About Hepatocellular Carcinoma (HCC) HCC is the most common type of primary liver cancer. It most frequently occurs in people with chronic liver diseases, such as cirrhosis caused by hepatitis B or hepatitis C infection. HCC typically has a poor prognosis and a lack of treatment options and is therefore a condition with an urgent medical need. About Camrelizumab Camrelizumab (SHR-1210) is a humanized monoclonal antibody targeting the programmed death-1 (PD-1) receptor. Blockade of the PD-1/PD-L1 signaling pathway is a therapeutic strategy showing success in a wide variety of solid and hematological cancers. Camrelizumab is developed by Hengrui Pharma and has been studied in more than 5,000 patients. Currently, 50 clinical trials are underway in a broad range of tumors (including liver cancer, lung cancer, gastric cancer, and breast cancer et. all) and treatment settings. Camrelizumab, under the brand name AiRuiKa®, is currently approved for 8 indications in China, including monotherapy for the treatment of HCC (second-line), relapsed/refractory classic Hodgkin’s lymphoma (third-line), esophageal squamous cell carcinoma (second-line) and nasopharyngeal carcinoma (third-line or further) and in combination with chemotherapy for the treatment of non-small cell lung cancer (non-squamous and squamous), esophageal squamous cell carcinoma, and nasopharyngeal carcinoma in the first-line setting. The U.S. Food and Drug Administration granted Orphan Drug Designation to camrelizumab for advanced HCC in April 2021. About Rivoceranib Rivoceranib is the first small-molecule tyrosine kinase inhibitor (TKI) approved in gastric cancer in China (November 2014). Rivoceranib is a highly potent inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), a primary pathway for tumor angiogenesis. VEGFR-2 inhibition is a clinically validated approach to limit tumor growth and disease progression. Rivoceranib is co-developed by Hengrui Pharmain China and by Elevar Therapeutics, Inc. globally (excluding China). It has been studied in more than 6,000 patients worldwide and was well tolerated in clinical trials with a comparable safety profile to other TKIs and VEGF inhibitors. Rivoceranib is currently being studied as a monotherapy and in combination with chemotherapy and immunotherapy in various solid tumor indications. Clinical studies are ongoing in multiple solid tumor types including gastric cancer (as a monotherapy and in combination with paclitaxel), hepatocellular carcinoma (HCC) (in combination with camrelizumab), adenoid cystic carcinoma (as monotherapy) and colorectal cancer (in combination with Lonsurf®). Orphan drug designations have been granted in gastric cancer (U.S., EU and South Korea), in adenoid cystic carcinoma (U.S.) and in HCC (U.S.). Elevar holds the global rights (excluding China) and has partnered for the development and marketing of rivoceranib with HLB-LS in South Korea. Rivoceranib, under the name apatinib, is currently approved in China for advanced gastric cancer and in second-line advanced HCC by the Chinese-territory license-holder, Hengrui Pharma, under the brand name Aitan®. About Elevar Therapeutics Elevar Therapeutics, Inc. is a rapidly growing, fully integrated biopharmaceutical company built on the promise of elevating treatment experiences and outcomes for patients who have limited or inadequate therapeutic options. Elevar’s lead proprietary drug candidates include rivoceranib and paclitaxel micellar (Apealea®). Rivoceranib, under the name apatinib in China, was developed by Hengrui Pharma in China and approved in China as a single agent for treatment of gastric cancer in 2014 and second-line advanced HCC in 2020. It has been granted orphan drug designation in the U.S., Europe and South Korea and has been clinically tested in more than 1,000 patients worldwide in numerous cancer indications. Apealea® is a non-Cremophor EL based formulation of paclitaxel that received marketing authorization by the European Commission in November 2018, making it Europe’s first non-Cremophor EL formulation of paclitaxel approved for use in ovarian cancer. Elevar has offices in Utah, California, Ireland and South Korea. Additional information is available at ElevarTherapeutics.com. Media ContactRosemary OstmannPhone: 201-615-7751Email: rostmann@rosecomm.com

SALT LAKE CITY, USA., Nov. 17, 2020 – Elevar Therapeutics, Inc. (“Elevar”), a fully integrated biopharmaceutical company built on the promise of elevating treatment experiences and outcomes for patients who have limited or inadequate therapeutic options, today announced the Company met its initial 55 patient enrollment target for its pivotal Phase 2, open-label, multicenter, clinical trial of rivoceranib (apatinib) in patients with recurrent or metastatic adenoid cystic cancer (ACC) one year ahead of schedule. The Company also announced increasing the target size of the trial to 72 patients and expects to complete enrollment by the end of the year. The Company plans to establish an Expanded Access Program to provide rivoceranib for “compassionate use” in patients with ACC. “Today’s announcement represents an important step forward in our development and registration strategies for rivoceranib and brings us closer to providing a new potential therapeutic option to patients with recurrent or metastatic adenoid cystic cancer (ACC), a devastating disease with no therapeutic treatment options,” said Steven Norton, Ph.D., chief drug development officer at Elevar Therapeutics. “The rapid pace of enrollment underscores a strong interest by patients and physicians in the potential clinical benefit of rivoceranib in ACC which speaks to the critical unmet need for new treatment options. We are incredibly grateful to the trial participants, investigators and their staff for their commitment to completing enrollment, despite the current COVID-19 global pandemic.” The Phase 2, open-label, multicenter, single-arm clinical trial of oral rivoceranib is evaluating patients with recurrent or metastatic ACC of all anatomic sites of origin who are not eligible for curative surgery or radiotherapy. Due to an increased level of interest from physicians and patients, Elevar increased enrollment to 72 patients from the originally planned 55 patients. The primary endpoint of the study is the frequency of patients with partial or complete responses to treatment (Objective Response Rate). Secondary objectives include overall survival, progression free survival, duration of response and time to progression. “The data generated by this clinical program thus far are highly encouraging and also demonstrate the potential rivoceranib holds for recurrent and metastatic patients with adenoid cystic cancer (ACC), who have no current standard treatment options,” said Hyunseok Kang, M.D., associate professor of Clinical Medicine at University California, San Francisco. “I would like to thank my co-investigators for the speed of enrollment of this important study, especially during the ongoing pandemic. I look forward to seeing the trial results.” Rivoceranib has been granted Orphan Drug designation in the U.S., Europe and South Korea.Additional information can be found at ClinicalTrials.gov (Identifier: NCT04119453). Requests for access to rivoceranib can only be considered if the patient’s treating physician is committed to, and supportive of, the requested treatment. Physicians seeking help on behalf of their patients may contact Elevar at 801-303-7440. About Adenoid Cystic Carcinoma Adenoid cystic cancer (ACC) is a rare form of cancer with a reported 1,200 new cases diagnosed each year in the United States. Elevar is preparing to file for orphan drug designation (fewer than 200,000 patients) in the United States. ACC is considered a slow growing but relentless cancer that is characterized by nerve invasion and metastases. ACC typically occurs in salivary glands but can also occur in secretory glands located in other tissues such as the esophagus, breast and lungs. Although good local control is usually achieved by resection of the primary tumor and adjuvant radiation therapy, more than half of patients eventually have recurrent and/or metastatic disease. Currently, no curative treatments are available for these patients which underscores the need for effective new therapies. About Rivoceranib (apatinib) Rivoceranib is the first small-molecule tyrosine kinase inhibitor (TKI) to be approved in gastric cancer (China, Dec 2014). Rivoceranib acts by inhibiting angiogenesis, a critical process in cancer growth and proliferation. Specifically, rivoceranib potently and selectively inhibits VEGFR-2 which mediates the primary pathway for tumor-mediated angiogenesis. Elevar Therapeutics is developing rivoceranib for the treatment of patients with gastric cancer, colorectal cancer, hepatocellular carcinoma, and adenoid cystic carcinoma. It has been granted Orphan Drug designation in the U.S., Europe and South Korea and has been clinically tested in over 1,000 patients worldwide. As a best-in-class therapeutic known for its safety and tolerability, Elevar believes rivoceranib has the potential to significantly improve clinical outcomes in combination with chemotherapeutics and immunotherapy, as well as for maintenance therapy. About Elevar Therapeutics Elevar Therapeutics (formerly LSK BioPharma) is a rapidly growing, fully integrated biopharmaceutical company built on the promise of elevating treatment experiences and outcomes for patients who have limited or inadequate therapeutic options. Elevar’s lead proprietary drug candidates include rivoceranib (apatinib) and Apealea® (paclitaxel micellar). Rivoceranib isthe first small-molecule tyrosine kinase inhibitor (TKI) to be approved in gastric cancer (China, Dec 2014). It has been granted Orphan Drug designation in the U.S., Europe and South Korea and has been clinically tested in over 1,000 patients worldwide. Apealea® (paclitaxel micellar)is a non-Cremophor based formulation of paclitaxel that received market authorization by the European Commission in November 2018, making it Europe’s first non-Cremophor formulation of paclitaxel approved for use in ovarian cancer. Elevar Therapeutics has locations in Utah, California and South Korea, and additional information is available at www.elevartherapeutics.com. Elevar Media Contact: Elixir Health Public Relations Lindsay Rocco (862) 596-1304 lrocco@elixirhealthpr.com