MENLO PARK, Calif.--(BUSINESS WIRE)--Synthekine Inc., an engineered cytokine therapeutics company, today presented positive translational results from the Phase 1a dose escalation portion of a Phase 1a/1b clinical trial of its first-in-class α/β-IL-2R biased partial agonist, STK-012, at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting in Houston.

加利福尼亚州门洛帕克市（商业新闻短讯）--工程细胞因子治疗公司Synthekine Inc.今天在休斯顿举行的癌症免疫治疗学会（SITC）第39届年会上，首次对α/β-IL-2R偏向部分激动剂STK-012进行了1a/1b期临床试验，该试验的1a期剂量递增部分取得了积极的转化结果。

STK-012 is engineered to selectively stimulate CD25+ antigen-activated T cells, which are associated with potent anti-tumor activity, and avoid broad stimulation of other lymphocytes, such as natural killer (NK) cells, which are associated with IL-2 toxicity. The Phase 1b dose expansion portion of the study in adults with advanced solid tumors remains ongoing (NCT05098132) and will include treating patients with STK-012 in combination with standard of care therapy in first line PD-L1 negative non-small cell lung cancer (NSCLC)..

STK-012被设计为选择性刺激CD25+抗原激活的T细胞，其与有效的抗肿瘤活性相关，并且避免广泛刺激其他淋巴细胞，例如与IL-2毒性相关的自然杀伤（NK）细胞。。。

Initial clinical findings for STK-012 monotherapy from the Phase 1a dose escalation portion of the study were presented at AACR earlier this year, showing a favorable safety profile without Capillary Leak Syndrome (CLS) and with single agent efficacy, including multiple objective responses, in IO-refractory solid tumors.

今年早些时候，在AACR上介绍了该研究1a期剂量递增部分STK-012单药治疗的初步临床发现，显示出良好的安全性，无毛细血管渗漏综合征（CLS），单药疗效，包括多目标反应，IO难治性实体瘤。

The findings shared at SITC build on these monotherapy results from the same study population, further demonstrating the mechanism of action of STK-012 and its ability to selectively induce T cell activation and expansion..

SITC共享的发现建立在同一研究人群的这些单一疗法结果的基础上，进一步证明了STK-012的作用机制及其选择性诱导T细胞活化和扩增的能力。。

Results presented in the STK-012 poster at SITC include an analysis of key biomarkers, such as cytokine induction and memory CD8 T cell activation and expansion, both of which were found to correlate with best overall response (BOR). The poster also includes analysis of the TCR clonal expansion observed upon treatment with STK-012 monotherapy, which led to an 80-fold median increase in expanding TCR clones.

SITC STK-012海报中的结果包括对关键生物标志物的分析，例如细胞因子诱导和记忆CD8 T细胞活化和扩增，这两者均与最佳总体反应（BOR）相关。海报还包括对STK-012单药治疗后观察到的TCR克隆扩增的分析，这导致扩增的TCR克隆中位数增加了80倍。

TCR clonal expansion was found to correlate with both progression-free survival (PFS) and BOR in these patients..

发现TCR克隆扩增与这些患者的无进展生存期（PFS）和BOR相关。。

“We are very encouraged by the translational data for STK-012 monotherapy as it represents a powerful advancement in cancer therapy, designed to realize the full efficacy potential of IL-2 while eliminating severe toxicities typically associated with IL-2 treatment,” said Martin Oft, M.D., chief scientific officer of Synthekine.

Synthekine首席科学官Martin Oft医学博士说：“STK-012单一疗法的转化数据让我们非常鼓舞，因为它代表了癌症治疗的一个强大进步，旨在实现IL-2的全部疗效潜力，同时消除通常与IL-2治疗相关的严重毒性。”。

“Our data reinforces STK-012’s unique mechanism of action, as demonstrated by selective expansion of antigen activated T cells without broad expansion of other lymphocytes including NK cells. In addition, we see strong and sustained induction of interferon gamma (IFNγ) coupled with minimal increase of interleukin-6 (IL-6), supporting the efficacy and tolerability profile of STK-012.

“我们的数据强化了STK-012独特的作用机制，如抗原激活T细胞的选择性扩增所证明的，而没有包括NK细胞在内的其他淋巴细胞的广泛扩增。此外，我们看到干扰素γ（IFNγ）的强烈持续诱导，加上白细胞介素-6（IL-6）的最小增加，支持STK-012的功效和耐受性特征。

We look forward to advancing this promising candidate to the next stage of clinical development.”.

我们期待着将这个有希望的候选人推进到临床发展的下一阶段。”。

The company will also present two posters for STK-026, a biased IL-12 cytokine partial agonist. The preclinical data to be presented demonstrates STK-026 is engineered to retain the potent antitumor activity of IL-12 while avoiding its systemic toxicities. In addition, results of a GLP toxicology study in cynomolgus monkeys showed excellent tolerability of STK-026 and confirmed its preferential activity toward CD8 T cells.

该公司还将为STK-026（一种有偏见的IL-12细胞因子部分激动剂）提供两张海报。将要提供的临床前数据表明STK-026被设计为保留IL-12的有效抗肿瘤活性，同时避免其全身毒性。此外，食蟹猴GLP毒理学研究的结果显示STK-026具有良好的耐受性，并证实了其对CD8 T细胞的优先活性。

Relative to therapies based on unmodified IL-12, STK-026 is tuned to bias immune activation toward the adaptive and away from the innate immune systems, thus avoiding NK cell mediated dose-limiting toxicities that are the hallmark of IL-12 therapy, including cytokine release syndrome (CRS), hepatoxicity, and lymphopenia..

相对于基于未修饰的IL-12的疗法，STK-026被调整为将免疫激活偏向适应性并远离先天免疫系统，从而避免NK细胞介导的剂量限制性毒性，这是IL-12疗法的标志，包括细胞因子释放综合征（CRS），肝毒性和淋巴细胞减少症。。

Details are as follows and available on the SITC website:

详情如下，请访问SITC网站：

Title: T cell and Immune Activation from a Phase 1 Study of STK -012, a First-in-class IL-2R α/ß Selective Partial Agonist in Advanced Solid Tumors

Session Name: Novel Single-Agent Immunotherapies

课程名称：新型单药免疫疗法

Session Date & Time: Friday, November 8, 2024, 9:00 AM – 7:00 PM CT

会议日期、时间：美国中部时间2024年11月8日星期五上午9:00至下午7:00

Format: Poster Presentation

Abstract Number: 1325

摘要编号：1325

Title: STK -026, a detoxified IL-12 partial agonist is well-tolerated and sustains CD8+ T cell activity with repeat doses in cynomolgus macaques

标题：STK-026，一种解毒的IL-12部分激动剂，在食蟹猴中具有良好的耐受性，并通过重复剂量维持CD8+T细胞活性

Session Name: Immune-Stimulants and Immune Modulators

课程名称：免疫兴奋剂和免疫调节剂

Session Date & Time: Friday, November 8, 2024, 9:00 AM – 7:00 PM CT

会议日期、时间：美国中部时间2024年11月8日星期五上午9:00至下午7:00

Format: Poster Presentation

格式：海报展示

Abstract Number: 941

摘要编号：941

Title: Gradual lymphocyte activation with IL-12 partial agonist STK-026 maintains anti-tumor efficacy but escapes acute NK-mediated cytokine release and toxicities associated with WT IL-12

标题：用IL-12部分激动剂STK-026逐渐激活淋巴细胞可维持抗肿瘤功效，但可逃避急性NK介导的细胞因子释放和与WT IL-12相关的毒性

Session Name: Immune-Stimulants and Immune Modulators

课程名称：免疫兴奋剂和免疫调节剂

Session Date & Time: Saturday, November 9, 2024, 9:00 AM – 8:30 PM CT

会议日期和时间：美国中部时间2024年11月9日星期六上午9:00至晚上8:30

Format: Poster Presentation

格式：海报展示

Abstract Number: 964

Copies of the posters will be available on Synthekine’s website following presentation at the meeting.

在会议上介绍后，海报的副本将在Synthekine的网站上提供。

About Synthekine

关于Synthekine

Synthekine is harnessing the potential of cytokine therapeutics to develop selective immunotherapies designed to improve the treatment paradigm of cancer and inflammatory disease. Using insights on cytokine structure and function, the company engineers therapeutics designed to unlock the full efficacy potential of cytokines while avoiding their associated toxicities.

Synthekine正在利用细胞因子疗法的潜力开发选择性免疫疗法，旨在改善癌症和炎症性疾病的治疗范例。利用对细胞因子结构和功能的见解，该公司设计了治疗方法，旨在释放细胞因子的全部功效潜力，同时避免其相关毒性。

Synthekine is applying principles of cytokine partial agonism and immunological specificity across multiple protein engineering platforms to create a broad and deep pipeline of product candidates. These novel immunotherapies include modified cytokines, cytokine-enhanced cell therapies and surrogate cytokine agonists.

Synthekine正在跨多个蛋白质工程平台应用细胞因子部分激动和免疫特异性的原理，以创建广泛而深入的候选产品管道。这些新型免疫疗法包括修饰的细胞因子，细胞因子增强的细胞疗法和替代细胞因子激动剂。

For more information, visit www.synthekine.com, and follow us on X @synthekine and LinkedIn..

有关更多信息，请访问www.synthekine.com，并在X@synthekine和LinkedIn上关注我们。。