--First-in-human trial evaluating safety, tolerability, and clinical activity of FX-909 in patients with advanced solid malignancies including advanced urothelial carcinoma--

--首次人体试验评估FX-909在晚期实体恶性肿瘤（包括晚期尿路上皮癌）患者中的安全性，耐受性和临床活性--

CAMBRIDGE, Mass., Jan. 26, 2024 /PRNewswire/ -- Flare Therapeutics Inc., a biotechnology company targeting transcription factors (TF) to discover precision medicines for cancer and other diseases, today announced a poster presentation outlining the Phase 1 clinical trial design of FX-909, a highly potent and selective inhibitor of PPARG, at the 2024 ASCO Genitourinary Cancers Symposium taking place from January 25-27, 2024 in San Francisco, CA..

马萨诸塞州剑桥市，2024年1月26日，一家针对转录因子（TF）的生物技术公司Flare Therapeutics Inc.今天宣布了一份海报展示，概述了FX-909（一种高效选择性PPARG抑制剂）的第一阶段临床试验设计，在2024年1月25日至27日于加利福尼亚州旧金山举行的2024年ASCO泌尿生殖系统癌症研讨会上。。

'FlareTx has built a robust body of preclinical evidence that supports investigation of FX-909 in clinical trials in patients,' said Michael L. Meyers, M.D., Ph.D., Chief Medical Officer of Flare Therapeutics. 'Results shown to date reveal that FX-909 eradicates tumors in urothelial cancer (UC) animal models at low oral doses.

Flare Therapeutics首席医疗官迈克尔·梅耶斯（MichaelL.Meyers）医学博士说，FlareTx已经建立了一套强有力的临床前证据，支持在患者临床试验中对FX-909进行调查迄今为止显示的结果显示FX-909在低口服剂量下根除尿路上皮癌（UC）动物模型中的肿瘤。

Our scientists have also leveraged high PPARG expression as a defining feature of luminal muscle-invasive UC (MIUC) to identify genetically defined populations and select the patients that may be more likely to benefit from a treatment like FX-909. In addition, we recently shared novel translational data correlating increased PPARG expression with an immunosuppressive tumor microenvironment (TME) and shorter real-world progression-free survival to anti-PD1 treatment.'.

我们的科学家还利用高PPARG表达作为管腔肌肉浸润性UC（MIUC）的定义特征，以鉴定遗传定义的人群，并选择可能更可能受益于FX-909等治疗的患者。此外，我们最近共享了新的翻译数据，这些数据将PPARG表达增加与免疫抑制性肿瘤微环境（TME）以及抗PD1治疗的较短的现实无进展生存期相关联。

PPARG drives luminal cell identity and accounts for two-thirds of all advanced cases of UC. Targeting PPARG offers a novel approach to treating advanced UC that could pave the way to improved clinical outcomes in patients with a luminal subtype. Treatment of genetically defined UC xenografts with FX-909 has shown an 84% tumor growth inhibition at a dose expected to be equivalent to a 50 mg dose in humans – the starting dose in the Phase 1 clinical study..

PPARG驱动腔细胞身份，占UC所有晚期病例的三分之二。靶向PPARG提供了一种治疗晚期UC的新方法，可以为改善管腔亚型患者的临床结果铺平道路。用FX-909治疗基因定义的UC异种移植物显示出84%的肿瘤生长抑制作用，其剂量预计相当于人类50毫克的剂量-这是第一阶段临床研究的起始剂量。。

FX-909-CLINPRO-1 (NCT05929235) is a first-in-human, multicenter, open-label Phase 1 study designed to assess the safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of FX-909 given orally to patients with advanced solid malignancies. Exploratory objectives include the evaluation of patient selection biomarkers from tissue and blood samples and association with clinical outcomes.

FX-909-CLINPRO-1（NCT05929235）是第一项人体多中心开放标签1期研究，旨在评估FX-909口服给晚期实体恶性肿瘤患者的安全性和耐受性，药代动力学（PK），药效学（PD）和初步临床活性。探索性目标包括评估组织和血液样本中患者选择的生物标志物以及与临床结果的关联。

In the US, approximately 10 sites are planned for Phase 1A and 12-15 sites for Phase 1B..

在美国，计划在1A期建设10个场地，在1B期建设12-15个场地。。

'While advanced bladder cancer and MIUC remain lethal diseases, we are starting to see a real renaissance in providing new treatment options, thanks to increasing knowledge of the underlying molecular pathways involved,' said Gopa Iyer, Genitourinary Oncologist & Early Drug Development Specialist, Memorial Sloane Kettering Cancer Center.

纪念斯隆·凯特琳癌症中心泌尿生殖系统肿瘤学家兼早期药物开发专家戈帕·艾耶（Gopa Iyer）说：“虽然晚期膀胱癌和MIUC仍然是致命疾病，但由于对所涉及的潜在分子途径的了解不断增加，我们开始看到在提供新的治疗选择方面真正的复兴。”。

'FlareTx's novel mechanism of action offers the possibility of a much needed second line option for patients who demonstrate disease progression following standard-of-care platinum chemotherapy, immune checkpoint inhibition, and/or ADC-based therapies.'.

“FlareTx的新型作用机制为在标准治疗铂类化疗，免疫检查点抑制和/或基于ADC的治疗后表现出疾病进展的患者提供了急需的二线选择的可能性。”。

Details for the presentation are as follows:

演示的详细信息如下：

Poster Title: A Phase 1, First-in-Human, Dose-Escalation and Expansion Study of FX-909 in Patients with Advanced Solid Malignancies, Including Advanced Urothelial CarcinomaAbstract Number: TPS709Presenter: Gopa Iyer MD, Memorial Sloane Kettering Cancer CenterDate, Time: Session B: Urothelial Carcinoma – Friday, January 26, 2024, 11:30 AM-1:00 PM PT; 5:45 PM-6:45 PM PTLocation: Moscone West Conference Center, San Francisco, California Posters, Exhibits, and Food Room.

海报标题：FX-909在晚期实体恶性肿瘤（包括晚期尿路上皮癌）患者中的第一阶段，首次人体剂量递增和扩展研究摘要编号：TPS709主持人：Gopa Iyer MD，Memorial Sloane Kettering Cancer CenterDate，时间：会议B：尿路上皮癌-2024年1月26日，星期五，上午11:30-下午1:00 PT；5： 下午45:00-6:45 p地点：加利福尼亚州旧金山莫斯科内西会议中心海报、展品和食品室。

About FX-909Flare Therapeutics' lead investigational compound, FX-909, is a first-in-class, highly potent and selective small molecule that inhibits the transcription factor peroxisome proliferator-activated receptor gamma (PPARG) to treat patients with the luminal subtype of advanced urothelial carcinoma (UC) and potentially other solid tumors.

关于FX-909Flare Therapeutics的主要研究化合物FX-909是一种一流的高效选择性小分子，可抑制转录因子过氧化物酶体增殖物激活受体γ（PPARG）治疗晚期尿路上皮癌（UC）和潜在的其他实体瘤的管腔亚型患者。

Preclinical data for FX-909 has demonstrated robust anti-tumor activity, excellent PK/PD correlation, durable efficacy, and a favorable safety profile in mouse models of UC (PPARG-amp and RXRA-mut) at very low oral doses..

FX-909的临床前数据表明，在非常低的口服剂量下，UC小鼠模型（PPARG-amp和RXRA-mut）具有强大的抗肿瘤活性，优异的PK/PD相关性，持久的功效和良好的安全性。。

About the FX-909 Phase 1 StudyThe ongoing Phase 1 study is a first-in-human, dose-escalation and -expansion study of FX-909 in patients with advanced solid malignancies, including advanced urothelial carcinoma. The study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical activity of FX-909.

关于FX-909 1期研究正在进行的1期研究是FX-909在晚期实体恶性肿瘤（包括晚期尿路上皮癌）患者中的首次人体剂量递增和扩展研究。该研究将评估FX-909的安全性，耐受性，药代动力学，药效学和临床活性。

FX-909 will be given initially in a dose-escalation phase (Part A) to determine the recommended Phase 2 dose. FX-909 will be given initially orally once daily in 28-day cycles. Part B will be a monotherapy expansion phase to further evaluate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of FX-909 in patients with locally advanced (unresectable) or metastatic urothelial carcinoma.

FX-909最初将在剂量递增阶段（a部分）给予，以确定推荐的2期剂量。FX-909最初将在28天的周期内每天口服一次。B部分将是单一疗法扩展阶段，以进一步评估FX-909在局部晚期（不可切除）或转移性尿路上皮癌患者中的疗效，安全性，耐受性，药代动力学和药效学。

Additional information on this clinical trial can be found on www.clinicaltrials.gov (NCT05929235). About Advanced Urothelial Carcinoma (UC)There are an estimated 725,549 people living with bladder cancer in the United States alone, making it the sixth most common cancer overall, and fourth most common among men (SEER – 2020).

有关该临床试验的其他信息，请访问www.clinicaltrials.gov（NCT05929235）。关于晚期尿路上皮癌（UC），仅在美国，估计就有725549人患有膀胱癌，使其成为第六大最常见的癌症，在男性中排名第四（SEER-2020）。

Each year, there are more than 83,000 new cases diagnosed among men and women, and about 25% of those cases are classified as muscle-invasive UC (DRG 2020). Treatment outcomes have remained poor with typical five-year survival rates of 8% in advanced metastatic disease (SEER – 2020). The transcription factor peroxisome proliferator-activated receptor gamma (PPARG) is associated with the luminal lineage subtype which represents approximately 65% of all advanced UC cases (Robertson, Cell 2017).

每年，在男性和女性中诊断出超过83000例新病例，其中约25%被归类为肌肉浸润性UC（DRG 2020）。治疗结果仍然很差，晚期转移性疾病的典型五年生存率为8%（SEER-2020）。转录因子过氧化物酶体增殖物激活受体γ（PPARG）与管腔谱系亚型相关，约占所有晚期UC病例的65%（Robertson，Cell 2017）。

Recurrent genetic alterations in PPARG are characteristic of this molecular subtype..

PPARG的反复遗传改变是这种分子亚型的特征。。

About Flare Therapeutics Inc.Flare Therapeutics is a biotechnology company exclusively focused on drugging transcription factors (TFs) to fully unlock the therapeutic potential of this previously elusive target class. Flare Therapeutics' integrated discovery engine converges rich genetic, biochemical, and chemical insights to reveal druggable pockets and identify small molecule ligands capable of modulating TFs of high therapeutic potential.

关于Flare Therapeutics Inc.Flare Therapeutics是一家生物技术公司，专门专注于药物转录因子（TFs），以充分发挥这一以前难以捉摸的目标类别的治疗潜力。Flare Therapeutics的集成发现引擎汇集了丰富的遗传，生化和化学见解，以揭示可药用的口袋，并鉴定能够调节具有高治疗潜力的TF的小分子配体。

Our proteomic and mass spectrometry platform is powered by a proprietary library of electrophilic compounds unique to Flare Therapeutics. The team has rapidly established an emerging pipeline of programs, highlighted by FX-909, a first-in-class investigational orally bioavailable small molecule inhibitor of PPARG, a master regulator of the luminal lineage in advanced urothelial cancer that has entered the clinic.

我们的蛋白质组学和质谱平台由Flare Therapeutics独有的亲电化合物专有文库提供支持。该团队迅速建立了一系列新兴项目，FX-909是一种一流的口服生物可利用小分子PPARG抑制剂，是晚期尿路上皮癌管腔谱系的主要调节因子，已进入临床。

For more information, please visit www.flaretx.com and follow us on LinkedIn..

有关更多信息，请访问www.flaretx.com并在LinkedIn上关注我们。。

SOURCE Flare Therapeutics

源耀斑疗法