Apatinib Mesylate

Phase 3 CARES-310 study found combination of camrelizumab and rivoceranib continued to show sustained long-term survival compared with sorafenib as a first-line treatment for uHCC Final analysis reported the longest median overall survival for any treatment in a global Phase 3 trial in uHCC Combination is the only uHCC therapy to increase median overall survival to approximately two years with greater than one in three patients alive at three years FORT LEE, N.J., May 30, 2024 (GLOBE NEWSWIRE) -- Elevar Therapeutics, Inc., a majority-owned subsidiary of HLB Co., Ltd., today announced the landmark overall survival (OS) analysis of camrelizumab and rivoceranib as a first-line treatment for unresectable hepatocellular carcinoma (uHCC) will be presented at an in-person poster presentation during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting on June 1. The abstract can be viewed at asco.org/abstracts. “The CARES-310 final OS analysis confirmed statistically superior and clinically meaningful survival improvement with a manageable safety pro the combination of camrelizumab and rivoceranib as a first-line treatment for patients suffering from unresectable hepatocellular carcinoma,” said Saeho Chong, Elevar chief executive officer. “These data confirm that the novel combination therapy represents a clinically differentiated improvement to the standard of care in first-line treatments for uHCC.” “The CARES-310 landmark analysis reported the longest median overall survival for any treatment in a global Phase 3 trial in the uHCC setting,” said Ahmed Omar Kaseb, M.D., professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. “The combination of camrelizumab and rivoceranib shows distinct promise to advance the standard of care for patients suffering with unresectable hepatocellular carcinoma.” The interim analysis of CARES-310 OS was completed after data cut-off on Feb. 8, 2022. For the final analysis, 16 months later, camrelizumab + rivoceranib continued to show clinically meaningful survival improvement compared with sorafenib, with manageable safety profile. The extended follow-up further confirmed the favorable benefit-to-risk pro camrelizumab + rivoceranib, supporting it as a potential new first-line treatment option for uHCC. In the final analysis, median OS was significantly prolonged with camrelizumab + rivoceranib vs. sorafenib (23.8 mo [95% CI 20.6-27.2] vs. 15.2 mo [95% CI 13.2-18.5]; hazard ratio 0.64 [95% CI 0.52-0.79]; 1-sided p < 0.0001). OS rate with camrelizumab + rivoceranib vs. sorafenib was 49.0% vs. 36.2% at 24 mo, and 37.7% vs. 24.8% at 36 mo. OS benefits with camrelizumab + rivoceranib were generally consistent across subgroups, regardless of geographical region, race and etiology. CARES-310 was the first trial to demonstrate significant progression-free survival (PFS) and overall survival benefits with immunotherapy plus an anti-angiogenic tyrosine kinase inhibitor (TKI) over standard TKI as first-line treatment for uHCC. ASCO 2024 CARES-310 Landmark Overall Survival In-Person Presentation The in-person poster presentation (abstract number 4110), titled “Camrelizumab plus rivoceranib vs sorafenib as first-line therapy for unresectable hepatocellular carcinoma (uHCC): Final overall survival analysis of the Phase 3 CARES-310 study,” will be presented June 1 from 1:30 p.m. to 4:30 p.m. CT during the poster session: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary. The abstract can be viewed at: asco.org/abstracts. Additional ASCO 2024 CARES-310 Online Publication Additional data from CARES-310 will be available as an online publication. Abstract number e16197 is titled: “Role of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte-ratio (PLR) in unresectable hepatocellular carcinoma (uHCC): Subgroup analysis of patients treated with camrelizumab (cam) + rivoceranib (rivo) in the CARES-310 trial.” The abstract can be viewed at: asco.org/abstracts. 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 CARES-310 CARES-310 (NCT03764293) was a randomized, open-label, international Phase 3 study, which included 543 patients with unresectable or metastatic HCC who had not received prior systemic therapy. Patients were randomized 1:1 to receive the combination of camrelizumab + rivoceranib or sorafenib (400 mg orally twice daily), a standard-of-care first-line multi-kinase inhibitor treatment for uHCC. Camrelizumab was administered intravenously (190 mg) every two weeks and rivoceranib was administered orally (250 mg) once daily. The study was conducted at 95 study sites across 13 countries/regions, in which systemic treatment for uHCC independent of etiology, rivoceranib plus camrelizumab demonstrated statistically significant and clinically meaningful prolonged overall survival and progression-free survival, and improved overall response rate versus sorafenib. The co-primary endpoints were overall survival and progression-free survival. Secondary endpoints included objective response rate and duration of response. About Camrelizumab Camrelizumab (SHR-1210) is a humanized monoclonal antibody that binds to 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, etc.) and treatment settings. Camrelizumab, under the brand name AiRuiKa®, is currently approved for eight indications in China, including monotherapy for the treatment of HCC (second-line), in combination with rivoceranib as a treatment for uHCC (first-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, a small-molecule tyrosine kinase inhibitor (TKI), 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 currently being studied as a monotherapy and in combination with chemotherapy and immunotherapy in various solid tumor indications. Ongoing clinical studies include uHCC (in combination with camrelizumab), gastric cancer (as a monotherapy and in combination with paclitaxel), adenoid cystic carcinoma (as a monotherapy) and colorectal cancer (in combination with Lonsurf®). Rivoceranib was the first TKI approved in gastric cancer in China (November 2014). It is also approved in China in combination with camrelizumab as a first-line treatment for uHCC (January 2023). The drug has been studied in more than 6,000 patients worldwide and was well tolerated in clinical trials with a comparable safety pro other TKIs and VEGF inhibitors. Orphan drug designations have been granted in gastric cancer (U.S., EU and South Korea), in adenoid cystic carcinoma (U.S.) and in uHCC (U.S.). Elevar Therapeutics, Inc. holds the global rights (excluding China) to rivoceranib and has partnered for its development and marketing with HLB-LS in South Korea. Rivoceranib, under the name apatinib, is also approved in China for advanced gastric cancer and in second-line advanced HCC by the Chinese-territory license-holder, Jiangsu Hengrui Pharmaceuticals Company Ltd., (Hengrui Pharma), under the brand name Aitan®. About Elevar Therapeutics Elevar Therapeutics, Inc. is a fully integrated biopharmaceutical company built on the promise of elevating treatment experiences and outcomes for patients who have limited or inadequate therapeutic options. With expertise rooted in oncology, Elevar is focused on identifying and developing promising medicines for complex yet under-treated health conditions across a range of therapeutic areas. Elevar’s lead proprietary drug candidate is rivoceranib. Elevar is headquartered in New Jersey, with offices in South Korea. Additional information is available at ElevarTherapeutics.com. Media Contact: Jeanette Bressi Head, Corporate Communications, Elevar Therapeutics jbressi@elevartherapeutics.com 609-439-3997 Investor Relations Contact: Ashley R. Robinson, LifeSci Advisors, LLC arr@lifesciadvisors.com

AstraZeneca made multiple headlines related to Asia this week. In addition, the FDA's rejection of Hengrui's PD-1 inhibitor made our news roundup. AstraZeneca's CEO wants to tap into China's innovation explosion. The company inked an oncology antibody deal with Harbour BioMed, and it plans to build a $1.5 billion ADC plant in Singapore. Hengrui and Elevar's proposed PD-1/VEGFR liver cancer combination has been rejected by the FDA. Plus more. 1. AstraZeneca to harness China's explosion of innovation to boost cell therapy R&D Innovation in China has “exploded,” and AstraZeneca plans to utilize its growing presence in the country to boost its R&D ambitions in cell therapy, CEO Pascal Soriot said during an investor event. Clinical development of cell therapy in China can “move much faster than anywhere else in the world,” he said. The British pharma has made several deals with Chinese companies over the past two years, including its $1 billion acquisition of Gracell Biotechnologies. 2. AstraZeneca pays $19M to Harbour BioMed's Nona for preclinical cancer antibodies Speaking of tapping into China’s innovation, AstraZeneca paid Harbour BioMed’s U.S. subsidiary Nona Biosceicnes $19 million upfront for preclinical monoclonal antibodies as potential targeted cancer therapies. Nona’s mice-based technology can produce heavy chain-only antibodies. The deal also includes $10 million in near-term payments and another $575 million in biobucks. 3. AstraZeneca places $1.5B bet on end-to-end ADC manufacturing in Singapore Meanwhile, AZ has unveiled plans to build a $1.5 billion antibody-drug conjugate manufacturing facility in Singapore. The site, expected to be operational by 2029, will become the company’s first end-to-end ADC production site. The move comes shortly after CEO Soriot said AZ is building separate drug supply chains for China and Western countries amid geopolitical risks. In recent years, Singapore has become a hot destination for biopharma manufacturing expansions. 4. FDA snubs another China-made PD-1 with rejection of Elevar, Hengrui's liver cancer combo The FDA has rejected Jiangsu Hengrui Pharma and Elevar Therapeutics’ respective applications for PD-1 inhibitor camrelizumab and the VEGFR inhibitor rivoceranib for use as a combination in first-line liver cancer. The FDA cited unresolved issues from the inspection of Hengrui’s manufacturing facility for camrelizumab as well as unfinished clinical trial site inspections. The partners aim to refile as soon as possible. 5. Takeda gets crafty with $1.2B biobucks deal to create molecular glues with Degron Takeda has signed a $1.2 billion biobucks deal with Shanghai’s Degron Therapeutics to work on molecular glue degraders for multiple targets in oncology, neuroscience and inflammation. Degron will use its GlueXplorer platform to find the new glues for therapeutic targets selected by Takeda. Degron has an in-house pipeline, including five early-stage molecular glue candidates in oncology. 6. Otsuka pulls plug on Alzheimer's agitation drug after 2nd failed trial Otsuka has officially ended development of AVP-786 after the NMDA receptor antagonist failed to move the needle in agitation associated with Alzheimer’s disease in a phase 3 trial. Otsuka obtained the drug from its $3.5 billion acquisition of Avanir Pharmaceuticals in 2015, which also gave the Japanese pharma Nuedexta for the rare disorder pseudobulbar affect. 7. Merck KGaA unit avoids DOJ prosecution after exposing scheme to divert drugs to China Two Florida residents pleaded guilty to conspiring to “fraudulently procure deeply discounted products” from Merck’s KGaA’s Sigma-Aldrich and ship them to China using faked export documents. The Department of Justice decided not to prosecute the German firm’s life science division, MilliporeSigma, because the company quickly disclosed the scheme and cooperated with the government’s investigation. 8. Chinese CDMO Asymchem expands footprint with deal to take over former Pfizer UK site China’s Asymchem Laboratories inked a deal to purchase a former Pfizer small molecule API pilot plant and part of its development labs in Sandwich, England. As part of a bigger cost-cutting scheme, Pfizer last year laid off 500 staffers at the plant. The purchase marks Asymchem’s first foray into Europe, and the firm expects to hire 100 workers by the end of the year, including many former Pfizer employees. Other News of Note: 9. Bristol Myers lines up Opdivo treatment in Pakistan, Rwanda and beyond as part of 10-year access campaign 10. Astellas, Yaskawa Electric Corporation ink pact to explore automated cell therapy production 11. Serum Institute deploys first doses of Oxford, Novavax-partnered malaria shot to Africa 12. No treachery here: Celltrion signs 'The Traitors' star Mollie Pearce for bowel disease campaign