Binimetinib

- Deep Cyclic Inhibitor of the MAPK pathway demonstrated strong tumor growth inhibition in preclinical studies of RAF or RAS mutant tumors, both as monotherapy and in combination - - Phase 1 portion of the Phase 1/2a trial designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of IMM-6-415 and establish a candidate recommended Phase 2 dose (RP2D) - -Initial PK, PD and safety data expected in 2024 - CAMBRIDGE, Mass., March 27, 2024 (GLOBE NEWSWIRE) -- Immuneering Corporation (Nasdaq: IMRX), a clinical-stage oncology company seeking to develop and commercialize universal-RAS/RAF medicines for broad populations of cancer patients, today announced that the first patient has been dosed in its Phase 1/2a trial of IMM-6-415 to treat advanced solid tumors with RAF or RAS mutations. IMM-6-415 is a Deep Cyclic Inhibitor (DCI) of the MAPK pathway designed with unique drug-like properties including a shorter half-life than IMM-1-104 for an accelerated cadence that will be evaluated as an oral, twice-daily treatment in humans. In animal studies, IMM-6-415 strongly inhibited the growth of tumors with RAF or RAS mutations, as both a monotherapy and in combinations. During the 2023 AACR-NCI-EORTC conference, Immuneering presented data showing that IMM-6-415 in combination with encorafenib achieved greater tumor growth inhibition and improved durability when compared head-to-head with binimetinib plus encorafenib, in animal models of RAF mutant melanoma and colorectal cancer, consistent with the thesis that DCI can outperform chronic MAPK inhibition. “We are pleased to have dosed the first patient in our Phase 1/2a trial for IMM-6-415, our second product candidate to enter the clinic,” said Ben Zeskind, Chief Executive Officer, Immuneering Corporation. “IMM-6-415 is designed to deprive malignant cells of the continuous MAPK signaling they need by strongly inhibiting the pathway twice per day, while also providing healthy cells with MAPK signaling twice per day through near-zero drug troughs. We believe the shorter half-life of IMM-6-415 could provide a potential treatment option for a broad patient population with RAS or RAF mutations. We look forward to sharing initial PK/PD and safety data from the Phase 1 portion of our Phase 1/2a trial in 2024.” The Phase 1 portion of the Phase 1/2a clinical trial is an open-label study designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of IMM-6-415 in patients with advanced RAF/RAS mutant solid tumors. The trial will include solid tumor patients with any mutation in RAF, KRAS, NRAS, or HRAS who meet the enrollment criteria. The Phase 1 portion of the trial will evaluate IMM-6-415 following a Bayesian mTPI-2 escalation design, which includes a dose escalation phase and dose evaluation phase to establish a candidate recommended phase 2 dose (RP2D), with the RP2D to be evaluated in specific tumor cohorts in the Phase 2a portion of the trial. About Immuneering Corporation Immuneering is a clinical-stage oncology company seeking to develop and commercialize universal-RAS/RAF medicines for broad populations of cancer patients with an initial aim to develop a universal-RAS therapy. The Company aims to achieve universal activity through Deep Cyclic Inhibition of the MAPK pathway, impacting cancer cells while sparing healthy cells. Immuneering’s lead product candidate, IMM-1-104, is an oral, once-daily Deep Cyclic Inhibitor currently in a Phase 1/2a trial in patients with advanced solid tumors harboring RAS mutations. IMM-6-415 is an oral, twice-daily Deep Cyclic Inhibitor currently in a Phase 1/2a trial in patients with advanced solid tumors harboring RAS or RAF mutations. The company’s development pipeline also includes several early-stage programs. For more information, please visit www.immuneering.com. Forward-Looking Statements This press release contains forward-looking statements, including within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements regarding: Immuneering’s plans to develop, manufacture and commercialize its product candidates; the treatment potential of IMM-6-415; the design, enrollment criteria and conduct of the Phase 1/2a IMM-1-104 and IMM-6-415 clinical trials; the translation of preclinical data into human clinical data; the potential advantages and effectiveness of Immuneering’s clinical and preclinical candidates; and the indications to be pursued by Immuneering including in the Phase 2a portion of the IMM-6-415 trial and timing of results. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the risks inherent in oncology drug research and development, including target discovery, target validation, lead compound identification, and lead compound optimization; we have incurred significant losses, are not currently profitable and may never become profitable; our projected cash runway; our need for additional funding; our unproven approach to therapeutic intervention; our ability to address regulatory questions and the uncertainties relating to regulatory filings, reviews and approvals; the lengthy, expensive, and uncertain process of clinical drug development, including potential delays in or failure to obtain regulatory approvals; our reliance on third parties and collaborators to conduct our clinical trials, manufacture our product candidates, and develop and commercialize our product candidates, if approved; failure to compete successfully against other drug companies; protection of our proprietary technology and the confidentiality of our trade secrets; potential lawsuits for, or claims of, infringement of third-party intellectual property or challenges to the ownership of our intellectual property; our patents being found invalid or unenforceable; costs and resources of operating as a public company; and unfavorable or no analyst research or reports. These and other important factors discussed under the caption “Risk Factors” in our Annual Report on Form 10-K for the annual period ended December 31, 2023, and our other reports filed with the U.S. Securities and Exchange Commission, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, except as required by law, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Media Contact:Gina Nugentgina@nugentcommunications.com Investor Contact:Laurence Watts619-916-7620laurence@newstreetir.com

近日，国家药品监督管理局（NMPA）官方网站公示，通过优先审评审批程序附条件批准科州制药1类新药妥拉美替尼胶囊（商品名：科露平）上市，适用于含抗PD-1/PD-L1治疗失败的NRAS突变的晚期黑色素瘤患者。该药物是全球首个且唯一获批针对NRAS突变晚期黑色素瘤适应症的MEK抑制剂，也是我国自主研发的首款MEK抑制剂。关于妥拉美替尼妥拉美替尼（tunlametinib）是一种新的针对NRAS突变的ATP非竞争性MEK抑制剂，可与RAS-RAF-MEK-ERK信号通路中的MEK1/2结合，阻断下游信号通路的传导，从而抑制肿瘤的生长。与传统MEK抑制剂相比，该产品最大的优势在于没有蓄积性。本次获批是基于一项单臂、多中心关键II期注册临床研究结果，旨在评价妥拉美替尼（HL-085）治疗NRAS突变晚期黑色素瘤患者的有效性及安全性。截至2023年02月19日，经独立评审委员会评估，有效性分析集中经确认的客观缓解率（ORR）为34.7%，中位无进展生存期（mPFS）为4.2个月，1年OS率为57.2%，既往接受过免疫治疗的ORR达到39.1%。最常见的3级及以上与治疗相关不良事件包括血肌酸激酶升高、腹泻、水肿等，整体安全性可控可管理，研究过程中无受试者因研究药物导致死亡。目前，妥拉美替尼还在开发用于治疗NRAS突变晚期黑色素、联合BRAF抑制剂治疗BRAF V600突变的转移性非小细胞肺癌，以及转移性结直肠癌，未来必将惠及更多RAS、RAF突变的实体瘤患者。关于MEK抑制剂丝裂原活化蛋白激酶（MAPK）的表达上调通常是致癌转换和癌症发展的标志。在细胞中，多种细胞信号分子与酪氨酸受体结合，控制着细胞中RAS的激活，随后根据级联信号方式磷酸化Raf、激活MEK（MEK1 和MEK2）及其唯一底物ERK（ERK1和ERK2），通过ERK作用于下游的不同底物调节细胞增殖、侵袭、血管生成及凋亡抵抗等一系列关键的细胞活动。在肿瘤细胞中，MAPK通路异常与其上游的K-ras 或B-raf 突变有关，大多数恶性黑色素瘤、乳头状甲状腺癌中都存在B-raf 突变，这种突变90% 以上是B-raf基因1796 位的胸苷酸被腺苷酸替代（T1796A），引起B-raf 蛋白第600 位的缬氨酸突变为谷氨酸（V600E），突变后的B-raf 可以不依赖于K-ras 直接激活MEK。所以单一的RAS或者RAF 抑制剂的临床疗效有限，而MEK抑制剂对于无论是K-ras 还是B-raf 突变导致的恶性肿瘤均有显著疗效。目前，全球已上市5款MEK1/2抑制剂，除了妥拉美替尼外，还包括阿斯利康的司美替尼（Selumetinib）外，还有诺华的曲美替尼(Trametinib)、罗氏/Exelixis的考比替尼（Cobimetinib）、辉瑞的比美替尼（Binimetinib）。除此以外，还有60余款MEK抑制剂在研。部分处于临床以上阶段的MEK抑制剂关于NRAS突变晚期黑色素NRAS 突变可发生于多种肿瘤，通过多途径激活细胞内信号传导通路诱导细胞周期失调，导致肿瘤细胞增殖。NRAS 突变在高加索人黑色素瘤中的发生率约15% ～ 20%，在黄种人中约10%。NRAS 突变的黑色素瘤患者原发灶Breslow 厚度深，有丝分裂率高，疾病进展快，预后差。因为RAS蛋白表面平滑，缺乏结合药物的疏水口袋，尚无特异性靶向药物，晚期治疗手段有限。研究显示，亚洲NRAS突变黑色素瘤患者接受抗PD-1治疗整体ORR约为6.1%，全球尚无靶向药物获批，临床急需开发有效的抗肿瘤治疗药物。关于科州药业科州药业致力于在肿瘤、自由基相关疾病等治疗领域开发创新药物。公司管线丰富，所有在研项目旨在瞄准中国乃至全球尚未满足的临床需求，研发具有“Best-in-Class”潜力的国际新型原创小分子药物，以填补国内外空白。参考资料1、NMPA、公司官网2、蒯梦妮,乐祥阳,李乾斌等.MEK抑制剂的研究进展[J].肿瘤药学,2017,7(05):513-522.免责声明“药渡”公众号所转载该篇文章来源于其他公众号平台，主要目的在于分享行业相关知识，传递当前最新资讯。图片、文章版权均属于原作者所有，如有侵权，请及时告知，我们会在24小时内删除相关信息。微信公众号的推送规则又双叒叕改啦，如果您不点个“在看”或者没设为"星标"，我们可能就消散在茫茫文海之中~点这里，千万不要错过药渡的最新消息哦！