Molecular Partners Presents Preclinical Proof-of-Concept for CD3 Switch-DARPin T Cell Engager, Clinical Biomarker Analyses for MP0317 at SITC 2024
Molecular Partners Presents Preclinical Proof-of-Concept for CD3 Switch-DARPin T Cell Engager, Clinical Biomarker Analyses for MP0317 at SITC 2024
Preclinical proof-of-concept data supports the potential of CD3 Switch-DARPin platform to activate and boost T cells in the presence of tumor targets only
通過體外概念驗證數據支持CD3交換雲計算-DARPin平台在腫瘤靶標存在的情況下激活和增強T細胞的潛力
MP0317's ability to activate CD40 in a variety of tumor types further evidenced by comprehensive clinical biomarker analyses
MP0317在各種腫瘤類型中激活CD40的能力得到了全面的臨床生物標誌物分析進一步證實
ZURICH-SCHLIEREN, Switzerland and CONCORD, Mass., Nov. 07, 2024 (GLOBE NEWSWIRE) -- 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 ("Molecular Partners" or the "Company"), today announced the presentation of data pertaining to two programs, including preclinical proof-of-concept for a novel T cell engager Switch-DARPin in solid tumors, and comprehensive biomarker analyses from the completed Phase 1 clinical trial of MP0317. Posters will be presented at the 2024 Annual Meeting of the Society for Immunotherapy of Cancer (SITC), being held November 8–10 in Houston, TX, with the following details:
瑞士蘇黎世和美國馬薩諸塞州康科德,2024年11月07日(GLOBE NEWSWIRE) -- Molecular Partners AG (SIX: MOLN; 納斯達克: MOLN),一家處於臨床階段的生物科技公司,正在開發一類新型定製蛋白藥物,名爲DARPin治療藥物(「Molecular Partners」或「公司」),今日宣佈了與兩個項目相關的數據介紹,包括針對固體腫瘤中一種新型T細胞接合物Switch-DARPin的體外概念驗證,以及MP0317完成的一期臨床試驗中全面生物標誌物分析的數據。 海報將在2024年國際癌症免疫治療學協會(SITC)年會上展示,該會議定於11月8日至10日在得克薩斯州休斯敦舉行,具體內容如下:
Title: Unlocking precision: a next generation multi-specific CD3 Switch-DARPin with enhanced function to tackle the current limitations of T cell engagers in ovarian cancer
Abstract & Poster Number: 842
標題: 解鎖精準:下一代多特異性CD3開關-DARPin,功能增強,以克服目前T細胞結合劑在卵巢癌中的侷限性
摘要 & 海報編號: 842
Title: Comprehensive biomarker analyses from a Phase 1 study reveals marked tumor microenvironment modulation in patients with advanced solid tumors treated with MP0317, a FAP-localized CD40 agonistic DARPin
Abstract & Poster Number: 612
標題: 從一項階段1研究中進行的全面生物標誌物分析揭示,使用MP0317治療的晚期實體腫瘤患者表現出顯著的腫瘤微環境調節,MP0317是一種FAP定位的CD40激動型DARPin
摘要 & 海報編號: 612
Timing & Location: November 9, 2024 at 9 am – 8:30 pm CT; Exhibit Halls AB
時間 & 地點: 2024年11月9日,上午9點至晚上8:30,中部時間; 展覽廳AB
Both posters will be made available on Molecular Partner's website in the Scientific Documents section.
兩份海報將在Molecular Partner的網站上的科學文檔部分提供。
"Our Switch-DARPin platform provides a novel approach to tumor-localized T-cell engagement and costimulation through its logic-gated on/off Switch mechanism. We are excited to have the opportunity to add this MoA to our validated CD3 T cell engager approach," said Patrick Amstutz, Ph.D., CEO of Molecular Partners. "We hope to open therapeutic avenues for co-stimulating T-cell engagers, by rendering them silent in the circulation and activating them at the tumor site."
我們的交換機-DARPin平台通過其邏輯門控制的開關機制,爲腫瘤定位t細胞參與和共刺激提供了一種新穎的方法。我們很高興有機會將這種作用機制添加到我們經過驗證的CD3萬億細胞參與者方法中,"Molecular Partners首席執行官Patrick Amstutz博士表示。"我們希望爲共刺激t細胞參與者開闢治療途徑,使其在循環中保持沉默,並在腫瘤部位激活它們。"
CD3 Switch-DARPin: Preclinical proof-of-concept for T cell engager with enhanced function in solid tumors
CD3交換機-DARPin:對固體腫瘤中功能增強的t細胞參與者的臨床前概念驗證
The Switch-DARPin platform provides a logic-gated "on/off" function (the "Switch") to multispecific DARPin candidates leading to immune activation only in the presence of defined antigens. This allows targeting the immune activation to tumors, increasing both efficacy and safety and opening up new opportunities for cancer treatment. T cell engagers (TCE) are a powerful class of immuno-oncology therapies but have faced a range of challenges such as high toxicity and limited specificity, particularly against solid tumors. By employing a multi-specific Switch-DARPin, Molecular Partners aims to bring additional dimensions of safety and potency to the fundamental TCE mechanism.
Switch-DARPin平台爲多特異性DARPin候選藥物提供了邏輯門控制的「開關」功能,只有在存在定義的抗原時才導致免疫活化。這允許將免疫激活定位到腫瘤,提高療效和安全性,爲癌症治療開闢新機會。t細胞參與者(TCE)是一類強大的免疫腫瘤學療法,但面臨着一系列挑戰,如高毒性和有限的特異性,特別是對抗固體腫瘤。Molecular Partners通過使用多特異性Switch-DARPin,旨在爲基本的TCE機制增加額外的安全性和效力。
The data to be presented at SITC provide further validation of the Company's Switch-DARPin platform and preclinical proof-of concept that conditional T cell activation in solid tumors is feasible, as exemplified in preclinical ovarian cancer models. The presented multi-specific Switch-DARPin molecule comprises DARPins targeting:
在SITC上呈現的數據進一步驗證了公司的Switch-DARPin平台以及在固體腫瘤中有條件地激活t細胞的臨床前概念的可行性,如在臨床前卵巢癌模型中展示的。呈現的多特異性Switch-DARPin分子包括定位DARPins:
- CD3, to engage and activate T cells
- CD2, a co-stimulator of CD3 on T cells
- Mesothelin, a notable tumor antigen overexpressed across several cancer types, including ovarian cancer, and used as anchoring target for the Switch-DARPin
- And the Switch-DARPin, which binds either to the tumor antigen EpCAM or to the CD3 DARPin mentioned above. In a default state, the whole molecule is in closed state (or Switched off), masking the CD3 DARPin and preventing immune activation. When tumor antigens mesothelin and EpCAM are present, the Switch-DARPin "switches" to bind EpCAM instead of the CD3 DARPin, thereby freeing the CD3 DARPin and allowing it to bind and activate T cells. T cell activation is further enhanced through co-stimulation by the CD2 DARPin.
- CD3是參與和激活T細胞的
- CD2是T細胞上CD3的共刺激因子
- Mesothelin是一種顯著的腫瘤抗原,在多種癌症類型中過度表達,包括卵巢癌,並用作Switch-DARPin的錨定靶點
- Switch-DARPin可以結合腫瘤抗原EpCAm或上述CD3 DARPin。在默認狀態下,整個分子處於關閉狀態(或關斷狀態),掩蓋了CD3 DARPin並阻止免疫激活。當腫瘤抗原Mesothelin和EpCAm同時存在時,Switch-DARPin會"轉變"以結合EpCAm,而不是CD3 DARPin,從而釋放CD3 DARPin並允許其結合並激活T細胞。通過CD2 DARPin的共刺激,T細胞的激活進一步增強。
This CD3 Switch-DARPin molecule effectively induces potent tumor regression in vivo, with reduced cytokine release, a significant toxicity event for TCEs in the clinic, compared to an unmasked CD3 with CD2 co-stimulation. In addition, co-engagement of CD2 leads to sustained T cell activation and cytotoxic capacity. Finally, masking of CD3 prevents T cell activation in the absence of tumor antigens, hence potentially allowing for "silent" TCEs outside of tumors. Taken together, masking CD3 may reduce the risk of CRS and provide a better safety profile to TCEs.
這種CD3 Switch-DARPin分子在體內有效誘導強效的腫瘤消退,與在臨床中未掩蓋的CD3和CD2共刺激相比,細胞因子釋放減少,這是TCEs的一個重大毒性事件。此外,CD2的共同參與導致T細胞的持續激活和細胞毒能力。最後,CD3的掩蓋防止了在缺乏腫瘤抗原的情況下T細胞的激活,因此可能允許腫瘤之外的"隱形"TCEs。總的來說,掩蓋CD3可能降低CRS的風險,併爲TCEs提供更好的安全性特點。
MP0317: Comprehensive biomarker data further support CD40 activation locally in tumor microenvironment
MP0317:全面的生物標誌物數據進一步支持CD40在腫瘤微環境中的局部激活
MP0317 is a CD40 agonist designed to activate immune cells specifically within the tumor microenvironment (TME) by anchoring to fibroblast activation protein (FAP) which is expressed in high amounts in the stroma of various solid tumors. This tumor-localized approach has the potential to deliver greater efficacy with fewer side effects compared to systemic CD40-targeting therapies.
MP0317是一種CD40激動劑,旨在通過與各種實體瘤基質中高濃度表達的成纖維細胞激活蛋白(FAP)結合,特異性地激活腫瘤微環境(TME)內的免疫細胞。這種腫瘤局部化治療方法有潛力在與全身性CD40靶向療法相比,提供更高的療效並減少副作用。
The poster presents the results of a comprehensive biomarker analyses from the completed Phase 1 multi-center, open label, dose-escalation trial of MP0317 monotherapy in patients with advanced solid tumors. The research further demonstrates the ability of MP0317 to induce a targeted, tumor-localized CD40 activation and its suitability for Q3W (every three weeks) and Q1W (weekly) dosing. The CD40 pathway is activated in a broad-spectrum of cancer types and various tumor locations. Evidence of TME remodeling in patients treated with pharmacologically active doses is exemplified by increases in dendritic cells, M1 macrophages, plasma cells, and T follicular helper cells, as well as IFNγ downstream activation and an increased dendritic cell maturation gene signature score. Peripheral pharmacodynamic effects aligned with the MP0317 mode of action are also seen, including increases in CXCL10 chemoattractant, transient B-cell reduction, and activation in blood.
該海報展示了在已完成的Phase 1多中心、開放標籤、劑量遞增試驗中,對MP0317單藥治療晚期實體瘤患者的全面生物標誌物分析結果。研究進一步證明了MP0317誘導靶向腫瘤局部化CD40激活的能力,以及其適用於Q3W(每三週一次)和Q1W(每週一次)的劑量。CD40途徑在廣譜的癌症類型和各種腫瘤部位中被激活。與藥理活性劑量治療的患者中TME重塑的證據體現在樹突狀細胞、M1巨噬細胞、漿細胞和T輔助細胞的增加,以及IFNγ下游激活和樹突狀細胞成熟基因特徵得分增加。與MP0317作用模式一致的外周藥效效應也可見,包括CXCL10趨化因子的增加、短暫的B細胞減少以及在血液中的激活。
Molecular Partners is in discussion with leading academic centers regarding potential investigator-initiated combination trials of MP0317.
Molecular Partners正在與領先的學術中心討論關於MP0317潛在的調查者發起的聯合試驗。
About DARPin Therapeutics
DARPin (Designed Ankyrin Repeat Protein) therapeutics are a new class of custom-built protein drugs based on natural binding proteins that open new dimensions of multi-functionality and multi-target specificity in drug design. The flexible architecture, intrinsic potential for high affinity and specificity, small size and high stability of DARPins offer benefits to drug design over other currently available protein-based therapeutics. DARPin candidates can be radically simple, with a single DARPin unit acting as the delivery vector to a specific target; or multispecific, with the possibility of engaging more than five targets, and combining multiple and conditional functionalities in a unique DARPin drug candidate. The DARPin platform is designed to be a rapid and cost-effective drug discovery engine, producing drug candidates with optimized properties and high production yields. DARPin therapeutics have been clinically validated across several therapeutic areas and developed through to the registrational stage.
關於DARPin治療
DARPin(設計的蛋白質螺旋重複體)治療是一種基於自然結合蛋白的新型定製蛋白藥物,打開了藥物設計中多功能性和多靶點特異性的新維度。 DARPin的靈活結構、內在的高親和力和特異性、小尺寸和高穩定性帶來了與其他當前可用的基於蛋白質的治療藥物相比的優勢。 DARPin候選藥物可以是根本簡單的,一個DARPin單位作爲傳遞載體到特定靶點;或者是多特異性的,可能涉及超過五個靶點,並結合多個和條件功能在一個獨特的DARPin藥物候選體中。 DARPin平台旨在成爲快速、經濟高效的藥物發現引擎,生產具有優化性能和高產量的候選藥物。 DARPin治療已經在幾個治療領域得到臨床驗證,並發展到註冊階段。
About Molecular Partners AG
Molecular Partners AG is a clinical-stage biotech company pioneering the design and development of DARPin therapeutics for medical challenges other drug modalities cannot readily address. The Company has programs in various stages of pre-clinical and clinical development, with oncology as its main focus. Molecular Partners leverages the advantages of DARPins to provide unique solutions to patients through its proprietary programs as well as through partnerships with leading pharmaceutical companies. Molecular Partners was founded in 2004 and has offices in both Zurich, Switzerland and Concord, MA, USA. For more information, visit and find us on LinkedIn and Twitter/X @MolecularPrtnrs
關於Molecular Partners AG
Molecular Partners AG是一家臨床階段的生物技術公司,致力於設計和開發DARPin治療藥物,以解決其他藥物療法難以解決的醫學挑戰。 該公司在各個臨床前和臨床開發階段都有項目,以腫瘤學爲主要研究方向。 Molecular Partners利用DARPins的優勢,通過其專有項目以及與領先製藥公司的合作,爲患者提供獨特解決方案。 Molecular Partners成立於2004年,並在瑞士蘇黎世和美國馬薩諸塞州康科德都設有辦公室。有關更多信息,請訪問 並在LinkedIn和Twitter/X @MolecularPrtnrs上找到我們
For further details, please contact:
Molecular Partners:
Seth Lewis, SVP Investor Relations & Strategy
Concord, Massachusetts, U.S.
seth.lewis@molecularpartners.com
Tel: +1 781 420 2361
Concord, Massachusetts, U.S.
分子合作伙伴:
Seth Lewis,投資者關係和策略高級副總裁
Concord, Massachusetts, 美國
seth.lewis@molecularpartners.com
電話:+1 781 420 2361
Laura Jeanbart, PhD, Head of Portfolio Management & Communications
Zurich-Schlieren, Switzerland
laura.jeanbart@molecularpartners.com
Tel: +41 44 575 19 35
Laura Jeanbart,博士,投資組合管理和通信負責人
瑞士蘇黎世-施利根
laura.jeanbart@molecularpartners.com
電話:+41 44 575 19 35
Cautionary Note Regarding Forward-Looking Statements
Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation: implied and express statements regarding the clinical development of Molecular Partners' current or future product candidates; expectations regarding timing for reporting data from ongoing clinical trials or the initiation of future clinical trials; the potential therapeutic and clinical benefits of Molecular Partners' product candidates and its RDT and Switch-DARPin platforms; the selection and development of future programs; Molecular Partners' collaboration with Orano Med including the benefits and results that may be achieved through the collaboration; and Molecular Partners' expected business and financial outlook, including anticipated expenses and cash utilization for 2024 and its expectation of its current cash runway. These statements may be identified by words such as "aim", "expect", "guidance", "intend", "outlook", "plan", "potential", "will" and similar expressions, and are based on Molecular Partners' current beliefs and expectations. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements. Some of the key factors that could cause actual results to differ from Molecular Partners' expectations include its plans to develop and potentially commercialize its product candidates; Molecular Partners' reliance on third party partners and collaborators over which it may not always have full control; Molecular Partners' ongoing and planned clinical trials and preclinical studies for its product candidates, including the timing of such trials and studies; the risk that the results of preclinical studies and clinical trials may not be predictive of future results in connection with future clinical trials; the timing of and Molecular Partners' ability to obtain and maintain regulatory approvals for its product candidates; the extent of clinical trials potentially required for Molecular Partners' product candidates; the clinical utility and ability to achieve market acceptance of Molecular Partners' product candidates; the potential that Molecular Partners' product candidates may exhibit serious adverse, undesirable or unacceptable side effects; the impact of any health pandemic, macroeconomic factors and other global events on Molecular Partners' preclinical studies, clinical trials or operations, or the operations of third parties on which it relies; Molecular Partners' plans and development of any new indications for its product candidates; Molecular Partners' commercialization, marketing and manufacturing capabilities and strategy; Molecular Partners' intellectual property position; Molecular Partners' ability to identify and in-license additional product candidates; unanticipated factors in addition to the foregoing that may impact Molecular Partners' financial and business projections and guidance; and other risks and uncertainties that are described in the Risk Factors section of Molecular Partners' Annual Report on Form 20-F for the fiscal year ended December 31, 2023, filed with Securities and Exchange Commission (SEC) on March 14, 2024 and other filings Molecular Partners makes with the SEC. These documents are available on the Investors page of Molecular Partners' website at . In addition, this press release contains information relating to interim data as of the relevant data cutoff date, results of which may differ from topline results that may be obtained in the future. Any forward-looking statements speak only as of the date of this press release and are based on information available to Molecular Partners as of the date of this release, and Molecular Partners assumes no obligation to, and does not intend to, update any forward-looking statements, whether as a result of new information, future events or otherwise.
關於前瞻性聲明的警示
本新聞稿中包含的任何不屬於歷史事實描述的聲明可能構成《1995年修訂的《私人證券訴訟改革法》》中定義的前瞻性聲明,包括但不限於:暗示和明示關於Molecular Partners當前或將來產品候選品的臨床發展的聲明;關於報告進行中臨床試驗數據的時間或未來臨床試驗的啓動的預期;Molecular Partners產品候選品及其RDt和Switch-DARPin平台的潛在治療和臨床益處的聲明;未來項目的選擇和開發;Molecular Partners與Orano Med的合作,包括通過合作可能實現的益處和成果;Molecular Partners對其2024年預期業務和財務展望,包括預期的支出和現金使用情況以及對目前現金透支的預期。這些聲明可能通過諸如「目標」、「期望」、「指導」、「打算」、「展望」、「計劃」、「潛在」、「將」等類似表述進行識別,並基於Molecular Partners目前的信仰和期望。這些聲明涉及可能導致實際結果與此類聲明中所反映結果有明顯區別的風險和不確定性。導致Molecular Partners預期結果與預期結果不一致的一些關鍵因素包括其開發和潛在商業化產品候選品的計劃;Molecular Partners在某些情況下可能無法完全控制的第三方合作伙伴和合作方;Molecular Partners用於其產品候選品的持續和計劃臨床試驗和臨床前研究,包括此類試驗和研究的時間安排;臨床前研究和臨床試驗結果可能無法預測未來臨床試驗結果的風險;Molecular Partners獲得和維持其產品候選品的監管批准的時間及其能力;Molecular Partners產品候選品可能需要的臨床試驗的範圍;Molecular Partners產品候選品的臨床效用和市場接受能力;Molecular Partners產品候選品可能出現嚴重有害、不良或不可接受的副作用的潛在性;任何健康大流行、宏觀經濟因素和全球事件對Molecular Partners臨床前試驗、臨床試驗或運營或其依賴的第三方運營的影響;Molecular Partners發展其產品候選品的任何新適應症的計劃;Molecular Partners的商業化、營銷和製造能力和策略;Molecular Partners的知識產權地位;Molecular Partners識別和許可其他產品候選品的能力;可能影響Molecular Partners財務和業務預測和指引的上述以外的意外因素;及Molecular Partners年度報告「Risk Factors」部分中描述的其他風險和不確定性,該報告於2023年12月31日結束財政年度已提交給證券交易委員會(SEC),並於2024年3月14日向SEC提交。這些文件可在Molecular Partners網站的投資者頁面找到。此外,本新聞稿包含截至相關數據截止日期的臨時數據,其結果可能與未來可能獲得的頭條結果有所不同。任何前瞻性聲明僅截至本新聞稿日期有效,並基於Molecular Partners在本新聞稿發佈日期獲得的信息,Molecular Partners不承擔更新任何前瞻性聲明的義務,也無意更新任何前瞻性聲明,無論是由於新信息、將來事件還是其他原因。
譯文內容由第三人軟體翻譯。