Molecular Partners Presents Positive Preclinical Data for First Switch-DARPin Candidate MP0621 at EHA 2024
Molecular Partners Presents Positive Preclinical Data for First Switch-DARPin Candidate MP0621 at EHA 2024
ZURICH-SCHLIEREN, Switzerland and CONCORD, Mass., June 14, 2024 (GLOBE NEWSWIRE) -- Proof-of-concept of Switch-DARPin platform established in vivo, enabling the use of logic-gated and reversible immune activators
Preclinical safety, efficacy, and pharmacokinetics support MP0621's potential to selectively kill cKit-positive cells and conditionally block CD47 with limited systemic side effects
MP0621 presently in IND-enabling studies with Phase 1 in AML anticipated in 2025
Switch-DARPin平台在體內建立了概念板塊，使邏輯門控和可逆免疫激活劑的使用成爲可能。
臨床前的安全性、有效性和藥代動力學支持MP0621選擇性殺死cKit陽性細胞並有條件地阻斷CD47，具有有限的全身副作用。
MP0621目前正在進行IND啓動研究，預計2025年開始AML的一期臨床試驗。
ZURICH-SCHLIEREN, Switzerland and CONCORD, Mass., June 14, 2024 (GLOBE NEWSWIRE) -- Ad hoc announcement pursuant to Art. 53 LR Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, today announced preclinical proof-of-concept data from MP0621, a multispecific cKit x CD16a x CD47 Switch-DARPin program. The data validates the Switch-DARPin concept in vivo and MP0621's potential as a next-generation therapeutic supporting hematopoietic stem cell transplantation (HSCT), initially for the treatment of acute myeloid leukemia (AML) patients. The data will be presented today in a poster session at the European Hematology Association (EHA) 2024 Hybrid Congress taking place June 13-16 in Madrid, Spain.
瑞士蘇黎世斯克利倫和美國馬薩諸塞州康科德，2024年6月14日（環球網通訊）——根據Art. 53 LR的特別公告，分子夥伴公司（Molecular Partners AG, 六合: MOLN; 納斯達克: MOLN）是一家處於臨床階段的生物技術公司，正在開發一類名爲DARPin治療的新型定製蛋白藥物，今天宣佈了MP0621的臨床前概念證明數據，該多特異性cKit x CD16a x CD47 Switch-DARPin項目驗證了概念板塊及MP0621在體內的潛力，成爲下一代治療造血幹細胞移植（HSCT）的前沿治療，最初用於急性髓系白血病（AML）患者的治療。這些數據將於今天在西班牙馬德里舉行的歐洲血液學會（EHA）2024年混合大會期間的海報展示中呈現出來。
"We designed our Switch-DARPin platform to unlock undruggable targets and enable safe use of powerful immune activators via logic-gated and reversible immune activation," said Anne Goubier, Ph.D., SVP Research & Early Development. "MP0621 is our first candidate in this series, with the aim to clear HSCs effectively and safely, by targeting cKit, engaging innate immune cells via CD16a, and blocking CD47 only on cKit+ cells. We're thrilled by these results, which validate our Switch-DARPin platform in vitro and in vivo and pave the way for a new generation of conditionally activated T cell engagers, with the potential to revolutionize therapy in areas of unmet need, such as solid tumors".
“我們設計Switch-DARPin平台是爲了解鎖無法藥物靶向的標的，通過邏輯門控和可逆的免疫激活來安全地使用強大的免疫激活劑，”研究與早期開發高級副總裁Anne Goubier博士說。“MP0621是我們系列中的第一個候選藥物，旨在通過針對cKit、通過CD16a激活先天免疫細胞，只在cKit+細胞上阻斷CD47，有效而安全地清除HSC。我們對這些結果感到非常興奮，這些結果在體內和體外驗證了Switch-DARPin平台，併爲有條件激活的T細胞誘導因子鋪平了道路，這有潛力在未滿足需求領域(如實體瘤)的革命性治療方式。
HSCT offers a potential cure for patients with AML and other malignant and non-malignant diseases. However, the toxicity of pre-HSCT conditioning often requires that it is carried out with reduced intensity, increasing the likelihood that diseased cells remain in the bone marrow and lead to relapse. Safer and more efficacious treatments are needed to improve HSCT outcomes for more patients with AML and other diseases requiring HSC transplant. MP0621 is intended to maximize the therapeutic potential of HSCT for AML patients, including those with poor cytogenetic risk profile, to extend the access to potentially curative HSCT for more patients, and to increase long term disease control post HSCT.
HSCT爲AML和其他惡性和非惡性疾病的患者提供潛在的治癒機會。然而，預HSCT條件的毒性通常需要以降低的強度進行，增加骨髓中的疾病細胞殘留，導致復發的可能性增加。需要更安全、更有效的治療來改善更多AML和其他需要HSC移植的疾病的HSCT結果。MP0621旨在最大化AML患者的HSCT治療潛力，包括那些具有不良遺傳風險患者，爲更多患者提供潛在的治癒HSCT，並在HSCT後增加長期疾病控制。
MP0621 is designed to induce eradication of HSCs while avoiding the toxicity associated with current high-intensity conditioning regimens. MP0621 engages natural killer cells and macrophages via CD16a to selectively kill targeted cKit-positive cells. cKit is critical for stem cell maintenance and renewal and thus an attractive target to select for HSCs as well as leukemic stem cells in AML. CD47 is widely expressed as "don't-eat-me" signal and prevents killing of cells, including HSCs/LSCs. Blocking CD47 can enhance damage to bound stem cells; however systemic anti-CD47 blockers cause significant toxicity, highlighting the need for conditional and targeted blockade of CD47.
MP0621的設計是在避免現有高強度檢查方案相關毒性的同時誘導根除HSC。MP0621通過CD16a與自然殺傷細胞和巨噬細胞結合以選擇性殺死靶向的cKit陽性細胞。cKit對於幹細胞維持和更新很關鍵，因此作爲HSC以及AML中的白血病幹細胞的選擇目標非常有吸引力。CD47廣泛表達於"不要吃我"信號並防止細胞(包括HSC/LSC)的殺戮。阻斷CD47可以增強綁定幹細胞的損傷；然而，全身性抗CD47阻滯劑會導致顯著的毒性，突出有條件和有針對性地阻斷CD47的必要性。
The Switch-DARPin platform provides a logic-gated "on/off" function (the "Switch") to multispecific DARPin candidates leading to target activation only in the presence of defined antigens. In MP0621, the Switch-DARPin binds to either cellular cKit or to the anti-CD47 DARPin binder. Upon MP0621 binding to cKit on cells, the Switch-DARPin will unmask the anti-CD47 DARPin, which in turn will bind CD47 and block the "don't-eat-me" signal, leveraging the power of CD47 inhibition without its associated toxicity to healthy cells. The Company is presently conducting preclinical efficacy and safety studies for MP0621 with data expected in H2 2024.
Switch-DARPin平台可提供多特異性DARPin候選治療的邏輯門控"開/關"功能(the "Switch")，只有在存在定義的抗原時才進行目標激活。在MP0621中，Switch-DARPin將綁定細胞cKit或抗CD47 DARPin結合物。當MP0621與細胞上的cKit結合時，Switch-DARPin將揭示抗CD47 DARPin，後者將結合CD47並阻斷"不要吃我"信號，利用CD47抑制的力量而不伴隨健康細胞的毒性。該公司目前正在進行MP0621的臨床前療效和安全性研究，其中數據預計在2024年下半年公佈。
In the poster presented, preclinical studies demonstrate that:
在提出的海報中，臨床前研究證明:
MP0621 selectively blocks CD47 on cells expressing cKit
Conditional blockade of CD47 enhances efficacy of cKit targeting, with phagocytosis comparable to a combo of anti-cKit and anti-CD47 monoclonal antibodies
MP0621 depleted cKit+ cells in bone marrow of humanized mice without affecting circulating immune cells
PK profile of MP0621 is suitable for HSCT therapy in humans
MP0621有選擇性地阻斷表達cKit陽性的細胞上的CD47
條件性阻斷CD47增強cKit定向治療的效果，具有可比性至抗cKit和抗CD47單克隆抗體的吞噬活性
MP0621在人類移植小鼠的骨髓中消耗了cKit陽性細胞，而不影響循環免疫細胞
MP0621的藥動學(Pharmacokinetics)適合於用於HSCT治療人類
Poster details can be found below. The full poster will be made available on Molecular Partners' website after the presentation.
該海報的詳細信息可以在下面找到。海報完整版將在公司網站上在展示後發佈。
Title: C-KIT X CD16A X CD47 Switch-DARPin with Conditional Blockade of CD47: A Next-generation Targeted Conditioning for Hematopoietic Stem Cell Transplantation
Session Title: Stem Cell Transplantation – Experimental
Abstract Number for Publication: P1294
Poster Session Timing: June 14, 2024; 6-7 pm CET
標題：C-KIT X CD16A X CD47 Switch-DARPin with Conditional Blockade of CD47: A Next-generation Targeted Conditioning for Hematopoietic Stem Cell Transplantation
會議題目：幹細胞移植 - 實驗
發表的摘要號：P1294
海報展示時間：2024年6月14日，6-7 pm CET
譯文內容由第三人軟體翻譯。