BOSTON--(BUSINESS WIRE)--Scorpion Therapeutics, Inc. (“Scorpion”), a pioneering clinical-stage oncology company dedicated to transforming the lives of cancer patients by redefining the frontier of precision oncology, today presented initial, first-in-human clinical results from its Phase 1/2 study of STX-478 in advanced solid tumor patients in a Proffered Paper late-breaking session at the European Society for Medical Oncology (“ESMO”) Congress 2024 in Barcelona, Spain.

波士顿--（商业新闻短讯）--Scorpion Therapeutics，Inc.（“Scorpion”）是一家开创性的临床阶段肿瘤学公司，致力于通过重新定义精确肿瘤学的前沿来改变癌症患者的生活，今天在西班牙巴塞罗纳举行的2024年欧洲医学肿瘤学会（“ESMO”）大会上，在提交的论文后期突破性会议上，首次展示了STX-478在晚期实体瘤患者中的1/2期临床研究结果。

Initial Phase 1 monotherapy data for STX-478, an oral, once-daily, mutant-selective, allosteric PI3Kα inhibitor, demonstrated potentially best-in-class PI3Kα inhibition, with anti-tumor activity observed in multiple cancer types, including HR+/HER2- breast cancer (BC), gynecological tumors, and other solid tumors.

STX-478是一种口服，每日一次，突变选择性的变构PI3Kα抑制剂，其初始1期单药治疗数据显示出潜在的最佳PI3Kα抑制作用，在多种癌症类型中观察到抗肿瘤活性，包括HR+/HER2-乳腺癌（BC），妇科肿瘤和其他实体瘤。

STX-478 was well-tolerated, including in pre-diabetic, diabetic and heavily pre-treated patients and showed no significant wild-type-mediated toxicities..

STX-478耐受性良好，包括糖尿病前期，糖尿病和严重预处理的患者，并且没有显示出明显的野生型介导的毒性。。

“We are pleased to report the initial Phase 1/2 trial results of STX-478, which was designed as the first PI3Kα inhibitor to fully maximize the potential of pathway inhibition in patients with solid tumors and is the first program emerging from our next-generation precision oncology discovery engine,” said Adam Friedman, M.D., Ph.D., Chief Executive Officer of Scorpion.

Scorpion首席执行官Adam Friedman医学博士说：“我们很高兴报告STX-478的初步1/2期试验结果，STX-478被设计为第一种PI3Kα抑制剂，可充分发挥实体瘤患者通路抑制的潜力，是我们下一代精准肿瘤学发现引擎中出现的第一个项目。”。

“STX-478 demonstrates potent and potentially best-in-class PI3Kα pathway inhibition as established by our early, differentiated signals of monotherapy efficacy, which exceed benchmarks of other pathway inhibitors. We also are encouraged by early safety data that demonstrates minimal evidence of wild-type PI3Kα-mediated toxicities, with no patients discontinuing STX-478 due to treatment-related adverse events.

“STX-478显示出有效且潜在的最佳PI3Kα途径抑制作用，这是由我们早期的单药治疗疗效分化信号所建立的，超过了其他途径抑制剂的基准。我们也受到早期安全性数据的鼓舞，这些数据显示野生型PI3Kα介导的毒性证据很少，没有患者因治疗相关的不良事件而停用STX-478。

Together, these results suggest that our highly-selective mutant PI3Kα inhibitor could overcome the limitations of currently available pathway inhibitors and, consequently, meaningfully improve clinical outcomes for patients with PI3Kα kinase or helical domain-mutated solid tumors. We look forward to continuing to progress our clinical-stage and discovery pipeline as we work to broaden the reach and impact of precision oncology for patients with high unmet medical need.”.

总之，这些结果表明，我们的高选择性突变PI3Kα抑制剂可以克服目前可用的途径抑制剂的局限性，从而有意义地改善PI3Kα激酶或螺旋结构域突变实体瘤患者的临床结果。随着我们努力扩大精准肿瘤学对高度未满足医疗需求的患者的影响和影响，我们期待着继续推进我们的临床阶段和发现流程。”。

“Approved and investigational non-selective PI3Kα inhibitors, as well as approved AKT inhibitors, have shown clinical benefit in HR+/HER2- breast cancer in Phase 3 studies. However, their therapeutic benefit is limited by PI3Kα pathway inhibition in normal tissues, resulting in dose-limiting toxicities, including hyperglycemia, rash and diarrhea,” said Alberto J.

Alberto J。

Montero, M.D., affiliated with University Hospitals Cleveland, and trial investigator. “By selectively targeting mutant PI3Kα, one of the most prevalent oncogenes in cancer, STX-478 has the potential to improve clinical outcomes and quality of life for patients during treatment. In the trial, STX-478 achieves exposures capable of driving several-fold deeper target inhibition than other PI3Kα inhibitors, while avoiding their toxicities, even with the majority of patients having prediabetes or diabetes.

。“通过选择性靶向突变型PI3Kα（癌症中最常见的癌基因之一），STX-478有可能在治疗过程中改善患者的临床结果和生活质量。在试验中，STX-478实现了能够比其他PI3Kα抑制剂更深几倍的靶向抑制作用，同时避免了它们的毒性，即使大多数患者患有糖尿病前期或糖尿病。

I am excited about the early results in patients with breast cancer and other solid tumors and look forward to further clinical development.”.

我对乳腺癌和其他实体瘤患者的早期结果感到兴奋，并期待着进一步的临床发展。”。

Initial Data from the Phase 1/2 Study of STX-478 in Advanced Solid Tumors

STX-478在晚期实体瘤中的1/2期研究的初步数据

In the Proffered Paper presented at ESMO, 61 patients with both kinase and helical domain PIK3CA mutations were treated with STX-478 at doses ranging from 20mg to 160mg daily, as of the data cutoff on June 21, 2024. Of the enrolled patients, 29 patients had HR+/HER2- BC and 32 patients had other solid tumors.

在ESMO提交的论文中，截至2024年6月21日的数据截止日期，61名同时具有激酶和螺旋结构域PIK3CA突变的患者接受了STX-478治疗，剂量范围为每天20mg至160mg。在登记的患者中，29名患者患有HR+/HER2-BC，32名患者患有其他实体瘤。

Additionally, 54% of patients were pre-diabetic or diabetic, and 41% of BC patients had a prior PI3Kα pathway inhibitor. 97% of BC patients had previously received a CDK4/6 inhibitor. Enrolled patients were heavily pre-treated with a median of three prior lines of therapy (ranging from 1-7)..

。97%的BC患者以前曾接受过CDK4/6抑制剂。登记的患者接受了严重的预处理，中位数为三种治疗方案（范围从1-7）。。

Pharmacokinetic and Selectivity Profile

药代动力学和选择性概况

Preliminary pharmacokinetic analysis supports once-daily dosing of STX-478, with dose proportional and linear STX-478 plasma exposure and an estimated half-life of approximately 60 hours. At doses ≥ 40mg QD, STX-478 exceeded the average exposures needed for in vivo efficacy in mouse models and achieved target coverage several fold higher than other approved or investigational PI3Kα inhibitors.

初步药代动力学分析支持每日一次给药STX-478，剂量比例和线性STX-478血浆暴露，估计半衰期约为60小时。在剂量≥40mg QD时，STX-478超过了小鼠模型体内功效所需的平均暴露量，并且达到的目标覆盖率比其他批准或研究的PI3Kα抑制剂高几倍。

STX-478 reached a maximum tolerated dose (MTD) of 100mg daily..

STX-478达到每日100mg的最大耐受剂量（MTD）。。

Preliminary Safety Data

初步安全数据

STX-478 was well-tolerated in a high-risk population, which included diabetics, pre-diabetics and patients intolerant to other PI3Kα pathway inhibitors, populations excluded from other PI3Kα studies. Most treatment-related adverse events (TRAEs) were mild-to-moderate and transient; TRAEs of ≥ 15% included: fatigue (30%), hyperglycemia (23%), nausea (20%) and diarrhea (15%).

STX-478在高危人群中耐受性良好，其中包括糖尿病患者，糖尿病前期患者和对其他PI3Kα途径抑制剂不耐受的患者，这些人群被排除在其他PI3Kα研究之外。大多数治疗相关不良事件（TRAEs）是轻度至中度和短暂的；≥15%的TRAE包括：疲劳（30%），高血糖（23%），恶心（20%）和腹泻（15%）。

No Grade ≥ 3 PI3Kα WT toxicity adverse events (hyperglycemia, diarrhea and rash) were observed, and minimal changes in fasting glucose were observed at any STX-478 dose level..

没有观察到≥3级PI3KαWT毒性不良事件（高血糖，腹泻和皮疹），并且在任何STX-478剂量水平下观察到空腹血糖的最小变化。。

No patients discontinued STX-478 due to a TRAE, and two dose-limiting toxicities observed at 160mg rapidly resolved after a brief dose interruption.

由于TRAE，没有患者停用STX-478，在短暂的剂量中断后，在160mg时观察到的两种剂量限制性毒性迅速消退。

Initial Clinical Activity Data

初始临床活动数据

As of the data cutoff in 43 evaluable patients, the confirmed/unconfirmed overall response rate (ORR) was 23% (5/22) in HR+/HER2- metastatic breast cancer; 21% (9/43) in all tumor types; and 44% (4/9) in gynecologic cancers, which compares favorably to approved PI3Kα pathway inhibitors (monotherapy ORR 4 – 6%).

截至43名可评估患者的数据截止，HR+/HER2转移性乳腺癌的确诊/未确诊总有效率（ORR）为23%（5/22）；所有肿瘤类型中有21%（9/43）；在妇科癌症中占44%（4/9），与已批准的PI3Kα途径抑制剂（单药治疗或4-6%）相比更为有利。

All responses were confirmed following the data cutoff. The disease control rate across tumors was 67%. Tumor reductions were seen in 72% of all patients as a monotherapy agent across all dose levels. Multiple responses were seen in both PI3Kα kinase and helical domain mutant tumors at multiple dose levels, and many responses were sustained and deepened over several months of therapy..

数据截止后，所有回复均得到确认。肿瘤的疾病控制率为67%。在所有剂量水平上，72%的患者作为单一治疗剂观察到肿瘤减少。在多剂量水平下，PI3Kα激酶和螺旋结构域突变肿瘤均出现多种反应，并且在几个月的治疗中，许多反应得以持续并加深。。

Mutant PIK3CA circulating tumor DNA levels markedly decreased on therapy in 86% of patients (19/22 evaluable patients).

突变型PIK3CA循环肿瘤DNA水平在86%的患者（19/22可评估患者）中治疗后显着降低。

The presentation will be available here on Scorpion’s website following the conclusion of the session.

会议结束后，将在Scorpion的网站上进行演示。

“Scorpion is dedicated to bringing highly-selective small molecules to cancer patients as quickly as possible, and the presentation of these data is a testament to the team’s exceptional execution and the productivity of our fully-integrated discovery organization,” said Mark Chao, M.D., Ph.D., Chief Medical Officer of Scorpion.

Scorpion首席医疗官马克·曹（Mark Chao）医学博士说：“Scorpion致力于尽快为癌症患者带来高选择性的小分子，这些数据的呈现证明了该团队的出色执行力和我们全面整合的发现组织的生产力。”。

“These exciting data bolster our confidence in the profile of STX-478 and in the continued advancement of the trial as we actively enroll patients into ongoing multiple expansion cohorts across a range of solid tumors and in combinations with active standard of care agents including fulvestrant and CDK4/6 inhibitors in HR+/HER2- breast cancer and lay the groundwork for the rapid advancement of this novel treatment.

“这些令人兴奋的数据增强了我们对STX-478概况和试验持续进展的信心，因为我们积极将患者纳入一系列实体瘤的正在进行的多重扩增队列，并与包括氟维司群和CDK4/6抑制剂在内的活性标准护理剂联合用于HR+/HER2乳腺癌，并为这种新型治疗的快速发展奠定了基础。

We would like to thank the patients, caregivers and investigators for sharing our commitment to advancing next-generation cancer treatments, and we look forward to providing updates from this study at future medical meetings.”.

我们要感谢患者，护理人员和研究人员分享我们对推进下一代癌症治疗的承诺，我们期待着在未来的医学会议上提供这项研究的最新信息。”。

About STX-478

关于STX-478

STX-478 was designed to improve outcomes in patients harboring PI3Kα mutations, one of the most prevalent drivers of cancer, occurring in over 166,000 patients per year with breast, gynecological and other solid tumors in the United States alone. In preclinical models, STX-478 demonstrated robust activity across a range of both kinase and helical domain PI3Kα mutations while sparing wild-type PI3Kα activity in normal tissues; previous generations of non-selective PI3Kα inhibitors have limited patient benefit due to these on-target toxicities.

STX-478旨在改善PI3Kα突变患者的预后，PI3Kα突变是最常见的癌症驱动因素之一，仅在美国，每年就有166000多名乳腺癌，妇科和其他实体瘤患者发生。在临床前模型中，STX-478在一系列激酶和螺旋结构域PI3Kα突变中均表现出强大的活性，同时在正常组织中保留了野生型PI3Kα活性；由于这些靶向毒性，前几代非选择性PI3Kα抑制剂对患者的益处有限。

Scorpion’s Phase 1/2 clinical trial is a multi-center, global, open-label study designed to evaluate the safety and tolerability of STX-478 in multiple ascending doses for patients with locally advanced or metastatic HR+/HER2- breast cancer and other solid tumors driven by PI3Kα mutations. The program has rapidly advanced into multiple expansion cohorts across a range of solid tumors and in breast cancer as monotherapy and in combinations with fulvestrant and CDK4/6 inhibitors.

Scorpion的1/2期临床试验是一项多中心，全球，开放标签研究，旨在评估STX-478在多次递增剂量下对局部晚期或转移性HR+/HER2-乳腺癌和其他实体瘤患者的安全性和耐受性。由PI3Kα突变驱动。该计划作为单一疗法以及与氟维司群和CDK4/6抑制剂的组合，已迅速发展为一系列实体瘤和乳腺癌的多个扩展队列。

To learn more about the first-in-human trial of STX-478, please visit this page..

要了解有关STX-478首次人体试验的更多信息，请访问此页面。。

About Scorpion Therapeutics

关于蝎子疗法

Scorpion is a pioneering clinical-stage oncology company redefining the frontier of precision medicine to deliver optimized and transformational therapies for larger populations of patients with cancer. Scorpion has built a proprietary and fully-integrated platform of the most advanced technologies across cancer biology, medicinal chemistry, and data sciences, with the goal of consistently and rapidly creating exquisitely selective small molecule compounds against an unprecedented spectrum of targets.

Scorpion是一家开创性的临床阶段肿瘤公司，它重新定义了精准医学的前沿，为更多的癌症患者提供优化和转化的治疗方法。Scorpion在癌症生物学、药物化学和数据科学领域建立了一个拥有最先进技术的专有和完全集成的平台，目标是始终如一地快速创建针对前所未有的靶标谱的精细选择性小分子化合物。

Scorpion aims to leverage its platform to advance a broad pipeline of wholly-owned, optimized compounds across three target categories: best-in-class molecules targeting validated oncogene targets; first-in-class molecules for previously undruggable targets; and first-in-class molecules for novel cancer targets.

Scorpion旨在利用其平台，在三个目标类别中推进广泛的全资优化化合物渠道：针对经过验证的癌基因靶标的同类最佳分子；用于先前不可药用靶标的一流分子；以及用于新型癌症靶标的一流分子。

For more information, visit www.scorpiontx.com..

For more information, visit www.scorpiontx.com..