IMP-9064

SHANGHAI, China, Aug. 19, 2022 (GLOBE NEWSWIRE) -- IMPACT Therapeutics, a biopharmaceutical company dedicated to the discovery and development of targeted anti-cancer therapeutics based on synthetic lethality, announced today that the US Food and Drug Administration (FDA) has granted Orphan-Drug Designation (ODD) to our fixed-dose combination capsule of Senaparib (PARP inhibitor) and temozolomide (TMZ) for the treatment of adult patients with small cell lung cancer (SCLC). Dr. Jun Bao, CEO of IMPACT Therapeutics, said “This is the first ODD IMPACT received from US FDA, which is a major development milestone for our company. This reflects efforts of our colleagues and collaborators. We shall take this as a further encouragement to our mission 'Make IMPACT on Cancer Treatment'.” IMPACT Therapeutics is conducting a global Phase Ⅰb/Ⅱ open-label, multi-center, dose escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor efficiency of Senaparib in combination with temozolomide in patients with advanced solid tumors and small cell lung cancer (NCT04434482). The study has been approved for clinical trials in the United States, Australia, South Korea and other countries and regions. The preliminary clinical results for a phase I b/II study investigating the PARP inhibitor Senaparib in combination with temozolomide (TMZ) for the treatment of advanced solid tumors have been presented as a poster at the 2022 ASCO Annual Meeting. A total of 14 patients were enrolled for dose escalation and the dose escalation has been completed in all planned dose levels. The MTD and RP2D were determined as senaparib 80 mg once daily plus temozolomide 20 mg once daily. The ORR was observed in 4 of 12 (33.3%) evaluable patients, including 3 confirmed PR. The DCR was 83.3%. Median DOR was 3.6 months. Two patients remain on treatment for more than 1 year. A total of 14 patients with extensive stage small cell lung cancer post first-line treatment were enrolled as of the date. The ORR was observed in 3 of 7 (42.9%) evaluable patients, including 2 confirmed PR who were still on treatment. All AEs reported were manageable. The recruitment for part 2 is still ongoing. About Senaparib Senaparib is a PARP inhibitor developed by IMPACT. The compound is currently in a Phase III study for ovarian cancer, and Phase II studies for small cell lung cancer and other indications worldwide, including China. Senaparib’s preliminary clinical data demonstrated superior tolerability and wider therapeutic window compared to other marketed PARP inhibitors, showing the best-in-class potential. At present, clinical trials conduction and commercialization preparations of Senaparib for various indications in mainland China, Hong Kong and Macau are being performed by a joint venture company established by IMPACT Therapeutics and Junshi Biosciences. About Temozolomide Temozolomide (TMZ) is an orally available alkylating anti-tumor agent. In preclinical animal models, the combination of Senaparib and TMZ showed potential to mimic synthetic lethality, demonstrating significant synergistic anti-tumor activity, while not producing additive toxicity. About IMPACT Therapeutics IMPACT Therapeutics is a biopharmaceutical company dedicated to the discovery and development of targeted anti-cancer therapeutics based on synthetic lethality. IMPACT Therapeutics has assembled one of the most comprehensive DNA damage responses (DDR) global pipeline of novel drug candidates generated by in-house discovery efforts and is expanding to other novel synthetic lethality targets to broaden its pipeline. IMPACT pipeline products include PARP inhibitor (Senaparib/ IMP4297), Wee1 inhibitor (IMP7068), ATR inhibitor (IMP9064) and other novel DDR pathway inhibitors. The lead clinical program, PARP inhibitor (Senaparib/ IMP4297), is in Phase II/III studies for ovarian cancer, small cell lung cancer and other indications worldwide, including China. Senaparib’s preliminary clinical data demonstrated superior tolerability and wider therapeutic window compared with other PARPi. Phase I study of Wee1 inhibitor (IMP7068) is conducted globally. ATR Inhibitor IMP9064 has received US IND Clearance from FDA and China IND application from NMPA and Phase I dose escalation is ongoing. Hedgehog pathway inhibitor (IMP5471) has received IND approval from NMPA.

2022年6月17日，CDE受理了Merck旗下子公司Merck Serono在研ATR抑制剂M1774的进口1类新药临床申请。来源：CDE网站  关于”合成致死“ “合成致死”是指两个基因同时发生突变导致细胞死亡的现象，其中单个基因发生突变都不会造成细胞死亡。 PARP抑制剂是第一个利用“合成致死”概念在临床上取得成功的药物。BRAC突变或HRD（同源重组修复缺陷）某些突变的肿瘤对PAPR抑制剂敏感，因此，BRAC和PARP就成为合成致死的一对靶点，这在临床上已被完全验证。 PARP靶点现状来源：药渡数据库 其中，PARP赛道的First-in-Class药物--阿斯利康的Olaparib自2014年12月16日上市以来，全球销售额一路向上，值得一提的是，Olaparib于2018年8月22日获NMPA批准在国内上市后，2019年销售总额相较于2018接近翻番。Olaparib全球销量情况来源：药渡数据库PARP抑制剂的研发虽然获得了巨大的成功，但是，肿瘤患者的需求依然存在，各个药企依然在自身发展和治愈他人的双重愿景中寻求新的发展方向。  关于ATR ATR是科学家们发现的另外一个“合成致死”靶点。 ATR和ATM是DNA损伤反应信号通路中的两种重要蛋白，它们被DNA损伤激活。ATR抑制剂通过阻断ATR介导的信号通路，可以扰乱DNA的损伤修复。研究显示，在ATM缺失的肿瘤细胞中，ATR抑制剂可以产生“合成致死”效应，在导致ATM缺失肿瘤细胞死亡的同时，并不影响正常细胞。 关于M1774 AACR年会的最新数据显示，ATR通路是DDRi领域最有前途的路径之一，Merck正在全力推进口服共济失调毛细血管扩张突变基因Rad-3相关激酶（ATR）抑制剂M1774的开发。M1774是建立在之前静脉注射ATR抑制剂Berzosertib的研究基础上新开发的ATR抑制剂。M1774研发情况来源：药渡数据库 在一项名为NCT04170153（DDRiver Solid Tumors 301）临床研究中，M1774单一疗法剂量递增部分的研究已经完成，后续Ib期的单药剂量研究将对M1774的安全性、耐受性以及PK/PD做进一步的评估，研究结果未来将对外公布。此项研究目前仍在进行患者招募。 NCT04170153临床研究来源：药渡数据库 目前正在进行的研究是M1774联用PARP抑制剂niraparib用于特定DDR基因突变（在ARIDIA, ATRX 和/或 DAXX, 以及ATM中存在明确的功能丧失基因突变）的肿瘤患者的有效性。 NCT05396833临床研究来源：药渡数据库 这是一项开放标签的、多中心的临床Ib临床研究，旨在评估ATR抑制剂M1774联用DDR抑制剂/免疫检查点抑制剂在转移癌或局部晚期不可切除肿瘤患者中的安全性、耐受性和PK/PD。该项研究尚未开始招募。  ATR竞争格局 来源：药渡数据库 Ceralasertib最早布局ATR抑制剂的药企阿斯利康，其在研药物Ceralasertib已于2022年6月10日获批国内I期临床试验。 来源：CDE官网 来源：药渡数据库 Schisandrin B五味子乙素原研公司为浙江鼎辉医药科技有限公司，Schisandrin B已于2020年1月19日获CDE临床默示许可，批准适应症：本品可减少阿霉素引起的心脏毒性的发生率和严重程度，适用于接受阿霉素治疗的患者。 来源：药渡数据库 Berzosertib原研公司为Vertex Pharmaceuticals，Berzosertib注射液已于2021年5月17日获CDE临床默示许可，批准适应症：广泛期小细胞肺癌。来源：药渡数据库IMP-9064原研公司为香港英派药业有限公司，IMP-9064片已于2022-03-01获CDE临床默示许可，批准适应症：晚期实体瘤。2022年05月31日，由上海瑛派药业有限公司在中国大陆开展临床一期试验，用于治疗实体瘤。（CTR20221315）2022年02月11日，由南京英派药业有限公司在美国开展临床一期试验，用于治疗实体瘤。（NCT05269316）2021年12月22日，由上海瑛派药业有限公司向中国国家药品监督管理局NMPA提交IND申请，用于治疗实体瘤，为中国化药一类。（CXHL2101779;CXHL2101780）2021年10月29日，由香港英派药业有限公司开展临床二期试验，用于治疗实体瘤。（https://mp.weixin.qq.com/s/O0pF7ZxrJbRTEKGcF6iIxg）来源：药渡数据库 ART-0380原研公司为Artios Pharma，目前正在英国和美国开展临床二期试验，用于治疗肿瘤，腹膜癌，卵巢癌，输卵管癌和转移癌。（NCT04657068）来源：药渡数据库ATRN-119原研公司为Aprea Therapeutics，目前正在美国开展临床二期试验，用于治疗实体瘤。（NCT04905914）来源：药渡数据库 Camonsertib原研公司为Repare Therapeutics。2022年05月31日，由Repare Therapeutics在美国开展临床二期试验，用于治疗慢性淋巴细胞白血病。（NCT05405309）2020年07月22日，由Repare Therapeutics在加拿大，丹麦和英国等国家和地区开展临床二期试验，用于治疗实体瘤。（NCT04497116） 来源：药渡数据库更多关于ATR抑制剂的相关信息，关注药渡数据。请欢迎下面二维码联系数据库试用。