Berzosertib

战略合作中国上海，2025年5月30日——中国领先的生物制药企业上海爱科百发生物医药技术股份有限公司（简称"爱科百发"）今日宣布，与人工智能制药创新领军企业Partex达成战略合作及后续协议，将共同开发并对外授权具有同类最佳潜力的临床前阶段ATR抑制剂AK0658。此次合作是继自分泌运动因子抑制剂AK0707项目合作后双方的再度携手。根据此次协议，爱科百发将主导AK0658的临床前开发及早期临床策略，Partex则将运用自主研发的Asset42人工智能平台，深度挖掘该药物在多个新适应症领域的全生命周期管理潜力，同时主导战略合作伙伴遴选并推进全球对外授权工作。AK0658作为新一代临床前阶段ATR抑制剂，相较于目前研发进度领先的Berzosertib，展现出更佳的选择性、优化的药代动力学特性及卓越的体内疗效。该化合物针对DNA损伤修复（DDR）通路异常的多项癌症适应症具有显著治疗潜力。爱科百发首席运营官袁海卿博士表示：AK0658有望通过合成致死疗法为DDR缺陷型癌症患者带来突破。Partex在运用人工智能开拓管线价值方面的能力已获充分验证，我们相信此次深度合作将加速AK0658的全球化进程，为亟需治疗的患者提供变革性疗法。Partex首席商务官Frank Grams博士表示：基于AK0707合作奠定的基础，我们期待与爱科百发共同推进这一重要项目。AK0658的早期数据极具说服力，我们的人工智能策略将显著加速其最佳适应症筛选与理想合作伙伴的匹配进程。此次战略合作的深化标志着双方在AI赋能药物开发领域进入全新阶段。根据协议，双方将建立AI驱动的全周期协同机制，这种"AI+全球化"双轮驱动模式，旨在将AK0658的研发周期压缩，并通过智能匹配机制快速锁定战略合作伙伴，最终加速创新疗法的全球化开发与商业化进程。关于爱科百发上海爱科百发生物医药技术股份有限公司专注于儿科及呼吸系统疾病等未满足医疗需求的创新疗法开发，同时积极寻求AK0658等创新抗肿瘤管线的对外授权机会，最大化其全球治疗价值。关于PartexPartex是人工智能制药领域的全球创新者，其自主研发的Asset42平台通过先进机器学习技术，实现新治疗用途发现、临床潜力优化及全球化授权交易的全流程赋能。如需了解本公司更多信息，请访问我们的网站：www.arkbiosciences.com投资者垂询：IR@arkbiosciences.com扫码关注我们微信公众号 | 爱科百发

Artios Pharma, a startup developing drugs that weaken a tumor’s ability to maintain its DNA, announced positive results in a subset of patients with advanced cancer. It’s the first big data reveal for the Cambridge, UK-based startup, which has been relatively quiet since 2021, when it struck a drug discovery partnership with Novartis and raised $153 million in Series C financing. The company’s drug, called ART0380, inhibits a DNA repair enzyme called ATR. When administered with a low dose of the chemotherapy irinotecan, the drug shrank tumors in 37% of patients whose cancer was considered “deficient” in another DNA damage response protein dubbed ATM, according to data from a Phase 1/2 study. In patients whose tumors lacked the ATM protein entirely, the response rate was 50%, with a median duration of response of 5.7 months so far. The response rate was 22% in patients with low levels of ATM. Patients with the ATM protein, however, did not respond to the therapy. “All those patients unfortunately progress quickly and unfortunately die very quickly,” Artios Chief Medical Officer Ian Smith told Endpoints News in an interview. The new data, presented Tuesday at the American Association for Cancer Research meeting, comes from 58 patients with advanced-stage and metastatic solid tumors who were treated at the dose the company plans to use in a Phase 2 study. Artios CEO Niall Martin told Endpoints that the company has funds “through 2026.” He said the startup is looking to raise another round of private funding to test its ATR inhibitor in pancreatic and colorectal cancers before pursuing bigger and broader tissue-agnostic studies. Martin said the company’s partnership with Novartis, which wasn’t focused on its ATR inhibitor, identified several targets that could potentially be paired with Novartis’ radioligand therapies, including its prostate cancer drug Pluvicto, and discussions are underway on next steps. Artios had struck a partnership with Merck KGaA in 2020 to search for drugs that target other DNA repair proteins, but Martin told Endpoints that partnership has ended. Artios was founded in 2016 to discover a new wave of drugs that target complex networks of proteins dedicated to the faithful replication and preservation of our genomes. While cancer can survive, and even thrive, with some DNA repair enzymes missing, too many missing pieces can cause the cancer to self-destruct. A class of drugs called PARP inhibitors exploit this vulnerability by blocking the eponymous DNA repair protein in tumors that have mutations in genes called BRCA1 and BRCA2, which are also important for DNA repair. Several companies have been searching for the next combination of targets that can deliver a similar double whammy to tumors, but progress has been slow. “The field hasn’t really evolved much since PARP inhibitors,” Martin said. “So we’ve been really thinking about what are the layers of DNA damage that are created in tumors that could be used as their sort of Achilles heel.” One of those layers, according to Artios, is a phenomenon called replication stress, which can occur when DNA replication, a key step for dividing cells, is blocked. ATR and ATM are two proteins that detect and clear up these blockages. Many forms of chemotherapy obstruct DNA replication. By first inducing a bit more of that stress with a low dose of chemo — but not enough to kill the cancer itself — and then blocking ATR in tumors with little to no ATM, Artios hoped to deliver a triple whammy to tumors. “There’s always been a push to get rid of chemotherapy and have targeted drugs,” Smith said.“But if you can’t get rid of chemotherapy, what you can do is really minimize it. And that’s what we’ve done here.” Smith said the company saw two complete responses, including one in a 62-year-old female who had pancreatic cancer but has been off treatment and cancer-free since August 2023. Neutropenia, a decline in white blood cells, was the most common side effect seen in 53% of patients, with grade 3 neutropenia in 45% of patients. Anemia occurred in 41% of patients. Fatigue, diarrhea, nausea and vomiting were also common side effects. Several other drugmakers have developed their own ATR inhibitors, but lackluster results have caused some pharma companies, including Bayer and Roche, to discontinue or pare back these efforts. “ATR inhibitors have been languishing,” Smith said. “The response rates are low relative to the toxicity that you tend to get.” Roche cut its partnership with Repare Therapeutics in 2024, which paused its ATR inhibitor program earlier this year after modest responses in only 19% and 17% of endometrial and ovarian cancer patients, respectively. Merck KGaA dropped its first ATR inhibitor, berzosertib, but is still testing a second one, called tuvusertib. And AstraZeneca is testing its ATR inhibitor ceralasertib in a Phase 3 study in lung cancer with its immunotherapy Imfinzi, which is expected to complete in August. Artios executives told Endpoints that other ATR inhibitors have faltered for three reasons: the drug’s half-life was too long, leading to intolerable toxicity; the drug was tested as a monotherapy, leading to low efficacy; or the drug was paired with the wrong therapies or tested in the wrong genetic subtypes of cancer. Martin said the company plans to develop a companion diagnostic to identify patients that are most likely to respond to its drug, with an initial focus on ATM. But Artios is looking for other biomarkers that may make tumors vulnerable to ATM inhibitors too. “This whole process of replication stress can be in up to 30% to 40% of tumors,” Martin said. “So there’s a huge area of biology which no one really has tapped into.”