本期看點(diǎn)：

1. 突破性RAS抑制劑 daraxonrasib用于治療既往接受過(guò)治療的轉(zhuǎn)移性RAS突變胰腺導(dǎo)管腺癌（PDAC）患者，其1/2期臨床試驗(yàn)的 積極結(jié)果發(fā)表在《新英格蘭醫(yī)學(xué)雜志》 。

2. 創(chuàng)新BTK降解劑bexobrutideg（NX-5948）用于治療慢性自發(fā)性蕁麻疹（CSU）的臨床前和1期臨床試驗(yàn)數(shù)據(jù)積極，接受治療的健康受試者的血液和皮膚中均實(shí)現(xiàn)了快速且強(qiáng)力的BTK降解。

Daraxonrasib（RMC-6236）：公布1/2期臨床試驗(yàn)數(shù)據(jù)

Revolution Medicines公司日前宣布，著名醫(yī)學(xué)期刊《新英格蘭醫(yī)學(xué)雜志》已發(fā)表一份，介紹了在研RAS抑制劑daraxonrasib針對(duì)既往接受過(guò)治療的轉(zhuǎn)移性RAS突變胰腺導(dǎo)管腺癌患者的1/2期臨床試驗(yàn)數(shù)據(jù)。Daraxonrasib是一種在研口服、可與激活狀態(tài)的RAS結(jié)合的多選擇性、非共價(jià)抑制劑。美國(guó)FDA已授予daraxonrasib突破性療法認(rèn)定和孤兒藥資格，用于治療既往接受過(guò)治療、攜帶G12突變的轉(zhuǎn)移性PDAC患者。Daraxonrasib通過(guò)抑制野生型和突變型處于激活狀態(tài)下的RAS蛋白與其下游效應(yīng)因子之間的相互作用，抑制RAS信號(hào)傳導(dǎo)。

此次在《新英格蘭醫(yī)學(xué)雜志》上發(fā)表的試驗(yàn)數(shù)據(jù)顯示，在26例攜帶RAS G12突變、接受300 mg劑量daraxonrasib二線治療的患者亞組中，客觀緩解率達(dá)到35%（95% CI：17%~56%）。中位緩解持續(xù)時(shí)間為8.2個(gè)月（95% CI：3.8個(gè)月至無(wú)法評(píng)估），中位無(wú)進(jìn)展生存期為8.5個(gè)月，中位總生存期為13.1個(gè)月。在38例攜帶RAS G12、G13或Q61突變的患者中，29%的患者達(dá)到客觀緩解（95% CI：15%~46%）。中位緩解持續(xù)時(shí)間為8.2個(gè)月（95% CI：3.8個(gè)月至8.8個(gè)月），中位無(wú)進(jìn)展生存期為8.1個(gè)月，中位總生存期為15.6個(gè)月。

安全性方面，在接受300 mg或更低劑量daraxonrasib治療的168例PDAC患者中，96%的患者報(bào)告了任意級(jí)別的治療相關(guān)不良事件；30%的患者報(bào)告了3級(jí)或更高級(jí)別的此類事件。發(fā)生率至少為10%的治療相關(guān)不良事件包括皮疹、腹瀉、惡心、口腔炎或黏膜炎、嘔吐和疲乏。

Bexobrutideg（NX-5948）：公布1期臨床試驗(yàn)數(shù)據(jù)

Nurix Therapeutics公司公布了其開(kāi)發(fā)的創(chuàng)新BTK降解劑bexobrutideg用于治療慢性自發(fā)性蕁麻疹的臨床前和1期臨床試驗(yàn)數(shù)據(jù)。Bexobrutideg是一種具有口服生物利用度的BTK降解劑，旨在通過(guò)招募cereblon E3連接酶復(fù)合物來(lái)消除BTK蛋白。該機(jī)制能高效標(biāo)記BTK蛋白以進(jìn)行蛋白酶體降解，從而同時(shí)消除BTK的激酶依賴性和支架功能。

研究結(jié)果表明，靶向降解BTK可能比單純的BTK抑制能更廣泛、更深入地抑制致病性免疫信號(hào)，這為bexobrutideg未來(lái)在炎癥和免疫學(xué)適應(yīng)癥中的臨床開(kāi)發(fā)提供了支持。在臨床前研究中，bexobrutideg不僅在關(guān)鍵的免疫細(xì)胞類型中展現(xiàn)出強(qiáng)效的BTK降解能力，還在抑制FcεRI驅(qū)動(dòng)的蕁麻疹病理反應(yīng)方面表現(xiàn)出優(yōu)于已上市BTK抑制劑的效果。在健康受試者中，無(wú)論是單次還是多次遞增劑量的口服給藥，bexobrutideg在血液和皮膚中均實(shí)現(xiàn)了快速且強(qiáng)力的BTK降解。這些數(shù)據(jù)共同支持了bexobrutideg在CSU中實(shí)現(xiàn)深層組織層面的致病性免疫信號(hào)抑制的潛力。

Soquelitinib：公布1期臨床試驗(yàn)數(shù)據(jù)

Corvus Pharmaceuticals公司公布了其小分子白細(xì)胞介素-2誘導(dǎo)的T細(xì)胞激酶（ITK）抑制劑soquelitinib用于治療中度至重度特應(yīng)性皮炎的1期臨床試驗(yàn)數(shù)據(jù)。ITK是一種主要表達(dá)于T細(xì)胞中的酶，在T細(xì)胞和自然殺傷（NK）細(xì)胞的免疫功能中起重要作用。通過(guò)抑制ITK，soquelitinib有望抑制自身免疫和炎癥反應(yīng)。

此次公布的結(jié)果顯示，soquelitinib在所有4個(gè)隊(duì)列中均展現(xiàn)出良好的安全性與積極的療效，且隊(duì)列1-3存在劑量依賴性療效趨勢(shì)。在安全性方面，所有隊(duì)列均未發(fā)現(xiàn)重大安全問(wèn)題，不良事件發(fā)生率（41.7%）與安慰劑組持平，均為1-2級(jí)，且未導(dǎo)致劑量調(diào)整或中斷，也未出現(xiàn)嚴(yán)重不良事件及顯著實(shí)驗(yàn)室指標(biāo)異常。在療效方面，隊(duì)列3（200 mg每日兩次，持續(xù)4周）和隊(duì)列4（200 mg每日兩次，持續(xù)8周）分別有50%和75%的患者達(dá)到了濕疹面積和嚴(yán)重度指數(shù)較基線減少75%（EASI 75）；兩隊(duì)列中分別有8%和25%的患者達(dá)到EASI 90；兩隊(duì)列中分別有25%和33%患者的研究者整體評(píng)估（IGA）評(píng)分為0/1（皮膚癥狀清除或幾乎清除）。在隊(duì)列3和隊(duì)列4中，疾病控制效果在整個(gè)治療后隨訪期（分別為90天和30天）內(nèi)得以持續(xù)維持。相比之下，已獲批系統(tǒng)性療法的公開(kāi)數(shù)據(jù)顯示，患者通常在停藥后四周內(nèi)即出現(xiàn)病情惡化或反彈，部分病例甚至需要接受救援治療。

▲接受soquelitinib治療4周和8周后患者實(shí)現(xiàn)持久緩解且無(wú)反彈（圖片來(lái)源：參考資料[7]）

參考資料：

[1] Positive Results from PulseSight’s Phase I Clinical Trial of PST-611 in Dry AMD/Geographic Atrophy Presented at ARVO 2026. Retrieved May 15, 2026, from https://www.globenewswire.com/news-release/2026/05/11/3291570/0/en/positive-results-from-pulsesight-s-phase-i-clinical-trial-of-pst-611-in-dry-amd-geographic-atrophy-presented-at-arvo-2026.html

[2] MBX Biosciences Provides Obesity Portfolio Update Including Initial Phase 1 Data for MBX 4291 Supporting Potential for Once-Monthly Dosing. Retrieved May 15, 2026, from https://www.globenewswire.com/news-release/2026/05/11/3291731/0/en/mbx-biosciences-provides-obesity-portfolio-update-including-initial-phase-1-data-for-mbx-4291-supporting-potential-for-once-monthly-dosing.html

[3] NexThera Unveils U.S. Phase 1 Data for Eye-drop wAMD Candidate ‘NT-101’. Retrieved May 15, 2026, from https://www.biospectator.com/news/view/28691

[4] Enliven Therapeutics Announces Oral Presentation at the EHA 2026 Congress Featuring Additional Positive Phase 1 Clinical Trial Data for ELVN-001 in CML. Retrieved May 15, 2026, from https://www.prnewswire.com/news-releases/enliven-therapeutics-announces-oral-presentation-at-the-eha-2026-congress-featuring-additional-positive-phase-1-clinical-trial-data-for-elvn-001-in-cml-302769668.html

[5] Imviva Biotech Presents Data Demonstrating Durable Clinical Responses from Ongoing Phase 1/2 Study of CTA313 in Systemic Lupus Erythematosus at ASGCT 2026. Retrieved May 15, 2026, from https://www.globenewswire.com/news-release/2026/05/14/3295203/0/en/imviva-biotech-presents-data-demonstrating-durable-clinical-responses-from-ongoing-phase-1-2-study-of-cta313-in-systemic-lupus-erythematosus-at-asgct-2026.html

[6] Nurix Therapeutics Presents New Preclinical and Phase 1 Translational Data Supporting Bexobrutideg (NX-5948) in Chronic Spontaneous Urticaria at the 2026 Society for Investigative Dermatology Annual Meeting. Retrieved May 15, 2026, from https://www.globenewswire.com/news-release/2026/05/14/3295365/0/en/nurix-therapeutics-presents-new-preclinical-and-phase-1-translational-data-supporting-bexobrutideg-nx-5948-in-chronic-spontaneous-urticaria-at-the-2026-society-for-investigative-de.html

[7] Corvus Pharmaceuticals Presents Soquelitinib Phase 1 Atopic Dermatitis Data at the Society for Investigative Dermatology (SID) Annual Meeting. Retrieved May 15, 2026, from https://www.globenewswire.com/news-release/2026/05/14/3294761/0/en/corvus-pharmaceuticals-presents-soquelitinib-phase-1-atopic-dermatitis-data-at-the-society-for-investigative-dermatology-sid-annual-meeting.html

[8] ????, ‘??? ???’ ???? 美1? “IND ??”. Retrieved May 15, 2026, from https://www.biospectator.com/news/view/28727

[9] First Participant Dosed in AskBio Phase 1/Phase 2 Gene Therapy Trial of AB-1009 for Late-Onset Pompe Disease (LOPD). Retrieved May 15, 2026, from https://www.globenewswire.com/news-release/2026/05/11/3291834/0/en/first-participant-dosed-in-askbio-phase-1-phase-2-gene-therapy-trial-of-ab-1009-for-late-onset-pompe-disease-lopd.html

[10] Actuate Therapeutics Announces FDA Clearance of IND for Oral Elraglusib and Strategic Initiatives to Advance the Elraglusib Development Program. Retrieved May 15, 2026, from https://www.globenewswire.com/news-release/2026/05/11/3291744/0/en/actuate-therapeutics-announces-fda-clearance-of-ind-for-oral-elraglusib-and-strategic-initiatives-to-advance-the-elraglusib-development-program.html

[11] Ukko Announces First Participant Dosed in Phase 1/2a Clinical Study Evaluating UKK-0018 for Peanut Allergy Treatment. Retrieved May 15, 2026, from https://secure.businesswire.com/news/home/20260507797257/en/Ukko-Announces-First-Participant-Dosed-in-Phase-12a-Clinical-Study-Evaluating-UKK-0018-for-Peanut-Allergy-Treatment

[12] AbCellera Reports Q1 2026 Business Results & Announces Positive Interim Phase 1 Clinical Data for ABCL635. Retrieved May 15, 2026, from https://secure.businesswire.com/news/home/20260511135503/en/AbCellera-Reports-Q1-2026-Business-Results-Announces-Positive-Interim-Phase-1-Clinical-Data-for-ABCL635

[13] First-in-Class Oral PKM2 Modulator SYX-5219 Phase 1a Trial Data to be Presented at SID 2026. Retrieved May 15, 2026, from https://www.sitryx.com/news/first-in-class-oral-pkm2-modulator-syx-5219-phase-1a-trial-data-to-be-presented-at-sid-2026

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