FANCI x FANCL

SKY-1214, an IND-ready first-in-class FANCL/FANCI RNA splicing modulator, demonstrates tumor growth inhibition and regression to undetectable levels in NHL and difficult-to-treat MM xenograft mouse models BOSTON, MA, USA I October 24, 2024 I Skyhawk Therapeutics, Inc., a clinical-stage biotechnology company developing novel small molecule therapies designed to modulate critical RNA targets, today announced that the Company presented compelling preclinical data highlighting the therapeutic potential of its first-in-class compound, SKY-1214, at the European Organization for Research and Treatment of Cancer (EORTC)-National Cancer Institute (NCI)-American Association for Cancer Research (AACR) Molecular Targets and Cancer Therapeutics Symposium (“EORTC-NCI-AACR” or the “Triple Meeting”). SKY-1214 is a first-in-class, oral RNA splicing modulator discovered through the company’s novel RNA-splicing platform and being developed for difficult-to-treat multiple myeloma (MM) and non-Hodgkin’s lymphoma (NHL). SKY-1214 targets FANCL/FANCI, critical components of the Fanconi anemia DNA damage repair pathway, which MM and NHL cells use to maintain their genome integrity. Study authors concluded that SKY-1214 shows potent and efficacious anti-cancer activity in MM and NHL models in vitro , including in models with high-risk cytogenetic and/or genetic alterations (e.g., t(14;16), t(4;14), 1q+, and double-hit lymphoma). Additionally, in vivo treatment with SKY-1214 as a monotherapy resulted in tumor growth inhibition and regression to undetectable levels at tolerated doses in NHL and difficult-to-treat MM xenograft mouse models, including KMS-28BM. “We’re excited to present these data and to introduce SKY-1214, our most-advanced oncology program, ready for IND submission,” said Sergey Paushkin, M.D., Ph.D., Co-founder, Head of R&D at Skyhawk. “There are a number of approved treatments for both MM and NHL, but all patients with MM eventually progress and only 50% of patients with certain NHL subtypes can be cured, underscoring the urgent need for new therapies with novel mechanisms of action. SKY-1214’s profound anti-cancer activity, including in these high-risk tumor cell lines, supports further development and exploration as a single agent and in combination treatment in these difficult-to-treat cancers.” The poster is available on the Skyhawk website at www.skyhawktx.com/resources . About SKY-1214 SKY-1214 is a first-in-class, oral FANCL/FANCI targeting RNA splicing modulator being developed for difficult to treat multiple myeloma (MM) and non-Hodgkin’s lymphoma (NHL). FANCL/FANCI are critical components of the Fanconi anemia DNA damage repair pathway, which MM and NHL tumor cells use to maintain their genome integrity. Skyhawk has observed anti-tumor activity for SKY-1214 in a number of preclinical cell models, including those representing prevalent high-risk cytogenetic alterations. SKY-1214 also demonstrated anti-tumor activity in human tumor cell-derived xenograft mouse models correlating with FANCL/FANCI mRNA reduction. SKY-1214 has completed IND-enabling studies. About Skyhawk Therapeutics Skyhawk Therapeutics is a clinical-stage biotechnology company focused on the discovery and development of novel small molecule therapies designed to modulate critical RNA targets and revolutionize patient treatment for some of the world’s most intractable diseases. Skyhawk’s discovery expertise is rooted in its proprietary drug discovery platform, which assesses, identifies, and tests RNA splicing targets and small molecules across a broad range of therapeutic areas and disease states. Skyhawk has built collaborations with multiple pharma partners that leverage Skyhawk’s novel platform across disease areas including neurodegenerative disease, autoimmune disease, and oncology. For more information visit www.skyhawktx.com . SOURCE: Skyhawk Therapeutics

目前，Skyhawk全资拥有的研发管线包括神经退行性疾病、肿瘤学、神经肌肉、纤维化和其他疾病类型，大多是针对以前被认为对于传统蛋白质靶点来说的“不可成药靶点”。 Ipsen公司和Skyhawk Therapeutic宣布签署一项全球独家合作协议，以发现和开发用于治疗罕见神经系统疾病的RNA靶向的小分子药物。Ipsen将向Skyhawk支付一笔未公开金额的预付款，以获得Skyhawk开发的两款候选药物的全球权益，Skyhawk负责临床前开发，Ipsen负责后续临床开发和商业化。该合作的预付款、里程碑付款及潜在的分级特许权使用费总额高达18亿美元。 Skyhawk公司致力于通过开发改变RNA表达的小分子疗法来彻底改变疾病治疗。RNA的错误表达会导致许多疾病，从罕见病、神经系统疾病到癌症。对于这些具有挑战性的病症，可用的治疗方法很少，其中许多疾病被认为是“不可成药的”。 目前认为26%的人类蛋白质与疾病相关，但只有3%的人类蛋白质可以使用传统的蛋白质靶向方法来成药的。Skyhawk公司认为，通过小分子药物靶向并调控RNA的表达，从上游改变驱动疾病的蛋白质水平，从而解决不可成药难题。 Skyhawk公司在快速发展的机器学习模型中集成了四个不同且互补的数据集，加速了针对一系列RNA靶点的小分子候选药物的开发。 SKYSTAR®是一种靶点评估系统，集成了来自公共和专有生物信息、结构和计算生物学数据集的数据，以优先考虑高价值的RNA靶点。Skyhawk公司已通过SKYSTAR系统筛选了超过700个靶点。 SKYLIBRARYTM是Skyhawk公司特有的、定制且快速扩展中的RNA靶向化合物库。 SKYSEQTM是Skyhawk公司特有的多重筛选系统，可同时测试一系列RNA序列中的数十个高价值靶点，以识别对特定疾病靶点具有选择性的化合物。 SKYAITM是Skyhawk公司的机器学习工具，集成了来自SKYSTAR、医学化学、动物研究、毒性数据和临床项目的数据，以推动下一代新型RNA剪接调节剂的开发。 凭借其先进的药物发现平台，Skyhawk公司已经与BMS、渤健、基因泰克、默克、赛诺菲、Vertex等大型制药公司达成了合作协议。 Skyhawk开发的治疗亨廷顿症的RNA靶向的小分子药物SKY-0515正在进行1期临床试验，治疗多发性骨髓瘤和非霍奇金淋巴瘤的RNA靶向的小分子药物SKY-1214预计将在今年年底开启临床试验。 目前，Skyhawk全资拥有的研发管线包括神经退行性疾病、肿瘤学、神经肌肉、纤维化和其他疾病类型，大多是针对以前被认为对于传统蛋白质靶点来说的“不可成药靶点”。 此外，Skyhawk还与多家大型制药公司合作了十多个保密的临床前项目，涉及神经退行性疾病、肿瘤学、神经肌肉、罕见疾病和其他疾病类型。 Skyhawk研发管线