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Xencor Presents Data from Four Preclinical XmAb®2+1 Bispecific Antibody and Cytokine Programs at AACR Virtual Annual Meeting II

Xencor Presents Data from Four Preclinical XmAb®2+1 Bispecific Antibody and Cytokine Programs at AACR Virtual Annual Meeting II

Xencor在AACR虛擬年會II上展示四個臨牀前XmAb®2+1雙特異性抗體和細胞因子項目的數據
Business Wire ·  2020/06/22 13:06

Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of cancer and autoimmune diseases, today announced the presentation of new preclinical data from three XmAb®2+1 bispecific antibody programs and its IL-12-Fc cytokine program during the second session of the American Association for Cancer Research (AACR) Virtual Annual Meeting. Poster presentations and audio descriptions are available to registrants of the AACR Virtual Annual Meeting .

Xencor,Inc.。納斯達克股票代碼:XNCR)是一家臨牀階段的生物製藥公司,正在開發用於治療癌症和自身免疫性疾病的工程化單克隆抗體。該公司今天宣佈,在美國癌症研究協會(AACR)虛擬年會第二屆會議期間,公佈了三個XmAb®2+1雙特異性抗體計劃及其IL-12-FC細胞因子計劃的新的臨牀前數據。AACR虛擬年會的註冊者可以獲得海報演示文稿和音頻描述。

"Compared to many therapeutic targets for blood cancers like CD19 or CD20, which are generally restricted to specific cell populations, solid tumor targets often are expressed on a range of normal tissues, including critical organs, which can limit the therapeutic index for drug candidates," said John Desjarlais, Ph.D., senior vice president and chief scientific officer at Xencor. "The XmAb 2+1 bispecific antibody format has two domains that bind the tumor target, and this bivalent binding can preferentially bind tumor cells with high target expression, potentially sparing low-expression normal tissues. This selectivity and potency tuning of T-cell activation may provide for higher efficacy and tolerability compared to other bispecific antibody formats.

Xencor公司高級副總裁兼首席科學官John DesJarlais博士説:“與CD19或CD20等許多針對血癌的治療靶點相比,CD19或CD20通常侷限於特定的細胞羣體,而實體腫瘤靶點通常在包括關鍵器官在內的一系列正常組織中表達,這可能會限制候選藥物的治療指數,”Xencor的高級副總裁兼首席科學官約翰·德賈萊斯博士(John DesJarlais Ph.D.)説。“XmAb2+1雙特異性抗體形式有兩個結合腫瘤靶點的結構域,這種雙價結合可以優先結合靶標表達高的腫瘤細胞,潛在地避免低表達的正常組織。與其他雙特異性抗體形式相比,這種T細胞激活的選擇性和效力調節可能提供更高的療效和耐受性。

"We have also presented data from our IL-12-Fc cytokine program, which builds off of our prior work with IL-15 and IL-2. IL-12 is a potent immune signaling protein that can have a dramatic effect on shrinking tumors; however, prior clinical studies have demonstrated IL-12 to have a narrow therapeutic window, limiting potential response rates. We created an IL-12 Fc-fusion with reduced potency in order to improve tolerability, slow receptor-mediated clearance and prolong the molecule's half-life," said Dr. Desjarlais.

“我們還展示了我們的IL-12-Fc細胞因子項目的數據,該項目建立在我們之前對IL-15和IL-2的研究基礎上。IL-12是一種強大的免疫信號蛋白,可以對腫瘤縮小產生巨大影響;然而,之前的臨牀研究已經證明,IL-12的治療窗口很窄,限制了潛在的應答率。我們創造了一種效力較低的IL-12 Fc融合,以提高耐受性,減緩受體介導的清除,並延長分子的半衰期,”德賈萊博士説。

XmAb 2+1 Bispecific AntibodiesPoster: 2286, "XmAb30819, an XmAb 2+1 ENPP3 x CD3 bispecific antibody for RCC, demonstrates safety and efficacy in in-vivo preclinical studies"Poster: 5663, "Affinity tuned XmAb 2+1 PSMA x CD3 bispecific antibodies demonstrate selective activity in prostate cancer models"Poster: 5654, "Affinity tuned XmAb 2+1 anti-mesothelin x anti-CD3 bispecific antibody induces selective T cell directed cell cytotoxicity of human ovarian cancer cells"

XmAb2+1雙特異性抗體發信人:2286,“XmAb30819,一種用於腎癌的XmAb2+1ENPP3 x CD3雙特異性抗體,在體內臨牀前研究中證明了安全性和有效性”發信人:5663,“親和力調節的XmAb2+1 PSMA x CD3雙特異性抗體在前列腺癌模型中顯示選擇性活性”發信人:5654,“親和力調節的XmAb2+1抗間皮素x

ENPP3, PSMA and MSLN are tumor-associated antigens associated with renal cell carcinoma (RCC), prostate cancer and ovarian cancer, respectively, but they are not restricted to tumors and exhibit base level expression on normal tissues. Xencor has expanded its T-cell redirecting CD3 class of bispecific antibodies to create an XmAb 2+1 bispecific antibody format, utilizing an engineered heterodimeric Fc domain, two identical tumor targeting domains and one CD3 targeting domain. The affinities for antigen binding are reduced, which allows for selective engagement of high antigen-expressing tumor cells over low antigen-expressing normal cells. In preclinical models, XmAb 2+1 bispecific antibodies bound preferentially to tumor cells compared to normal cells and effectively recruited T cells to kill tumor cells selectively. Additional data presented on XmAb 2+1 PSMA x CD3 bispecific antibody candidates and XmAb30819, a first-in-class XmAb 2+1 ENPP3 x CD3 bispecific antibody, demonstrated strong reversal of tumor growth in human-cell engrafted mouse models of disease. Further data presented from preclinical studies of XmAb30819 in non-human primates demonstrated it was well-tolerated with expected pharmacodynamics and an antibody-like half-life.

ENPP3、PSMA和MSLN分別是與腎細胞癌、前列腺癌和卵巢癌相關的腫瘤相關抗原,但它們並不侷限於腫瘤,在正常組織中呈鹼基水平表達。Xencor擴展了其T細胞重定向CD3類雙特異性抗體,利用工程設計的異二聚體Fc結構域、兩個相同的腫瘤靶向域和一個CD3靶向域,創建了XmAb2+1雙特異性抗體形式。抗原結合的親和力降低,這允許高抗原表達的腫瘤細胞選擇性地與低抗原表達的正常細胞接觸。在臨牀前模型中,與正常細胞相比,XmAb2+1雙特異性抗體優先與腫瘤細胞結合,並有效地招募T細胞選擇性殺傷腫瘤細胞。關於XmAb2+1PSMA x CD3雙特異性抗體候選者和XmAb30819(一種一流的XmAb2+1ENPP3 x CD3雙特異性抗體)的更多數據表明,在人類細胞移植的小鼠疾病模型中,腫瘤生長具有很強的逆轉作用。XmAb30819在非人類靈長類動物中的臨牀前研究提供的進一步數據表明,它具有良好的耐受性,具有預期的藥效學和類似抗體的半衰期。

IL-12-Fc CytokinePoster: 5549, "Potency-reduced IL-12 heterodimeric Fc-fusions exhibit strong anti-tumor activity"

IL-12-Fc細胞運動發信人:5549,“效力降低的IL-12異二聚體Fc融合顯示出強大的抗腫瘤活性”

IL-12 is a heterodimeric proinflammatory cytokine produced by activated antigen-presenting cells, and it leads to proliferation of T cells and NK cells and increased cytotoxicity through high levels of interferon gamma signaling. IL-12-Fc fusions were engineered with potency-reduced IL-12 to improve its potential tolerability, slow receptor-mediated clearance and prolong its half-lifein vivo.In preclinical models, these potency-reduced IL-12-Fc fusions demonstrated significant anti-tumor activity concurrent with activation and proliferation of CD8+ T cells, increased PD-1 checkpoint expression and increased levels of interferon gamma in serum. Anti-tumor activity was enhanced when combined with an anti-PD-1 antibody.

IL-12是一種由活化的抗原提呈細胞產生的異源二聚體促炎細胞因子,它通過高水平的干擾素γ信號誘導T細胞和NK細胞增殖,增加細胞毒作用。IL-12-Fc融合被設計用於降低IL-12的效力,以提高其潛在的耐受性,減緩受體介導的清除,並延長其在體內的半衰期。在臨牀前模型中,這些效力降低的IL-12-Fc融合在激活和增殖CD8+T細胞的同時顯示出顯著的抗腫瘤活性,增加了PD-1檢查點的表達,並增加了血清中干擾素γ的水平。當與抗PD-1抗體聯合使用時,抗腫瘤活性增強。

The posters will be archived under "Events & Presentations" in the Investors section of the Company's website located at www.xencor.com .

這些海報將存檔在公司網站www.xencor.com投資者部分的“活動和演示”項下。

About Xencor, Inc.

關於Xencor公司

Xencor is a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of cancer and autoimmune diseases. Currently, 17 candidates engineered with Xencor's XmAb®technology are in clinical development internally and with partners. Xencor's XmAb antibody engineering technology enables small changes to the structure of monoclonal antibodies resulting in new mechanisms of therapeutic action. For more information, please visit www.xencor.com .

Xencor是一家臨牀階段的生物製藥公司,開發用於治療癌症和自身免疫性疾病的工程化單克隆抗體。目前,採用Xencor的XmAb®技術的17名候選患者正在進行內部和合作夥伴的臨牀開發。Xencor的XmAb抗體工程技術可以使單克隆抗體的結構發生微小變化,從而產生新的治療作用機制。欲瞭解更多信息,請訪問www.xencor.com。

Forward-Looking Statements

前瞻性陳述

Statements contained in this press release regarding matters that are not historical facts are forward-looking statements within the meaning of applicable securities laws, including, but not limited to, the quotations from Xencor's senior vice president and chief scientific officer and any expectations relating to future product candidates and Xencor's research and development programs. Such statements involve known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements and the timing of events to be materially different from those implied by such statements, and therefore these statements should not be read as guarantees of future performance or results. Such risks include, without limitation, the risks associated with the process of discovering, developing, manufacturing and commercializing drugs that are safe and effective for use as human therapeutics and other risks described in Xencor's public securities filings. For a discussion of these and other factors, please refer to Xencor's annual report on Form 10-K for the year ended December 31, 2019 as well as Xencor's subsequent filings with the Securities and Exchange Commission. All forward-looking statements are based on Xencor's current information and belief as well as assumptions made by Xencor. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All forward-looking statements are qualified in their entirety by this cautionary statement and Xencor undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof, except as required by law.

本新聞稿中包含的有關非歷史事實的陳述屬於適用證券法意義上的前瞻性陳述,包括但不限於Xencor高級副總裁和首席科學官的引述以及對未來候選產品和Xencor研發計劃的任何期望。這類陳述涉及已知和未知的風險、不確定性和其他因素,可能導致實際結果、業績或成就以及事件的時間與這類陳述所暗示的大不相同,因此這些陳述不應被解讀為對未來業績或結果的保證。此類風險包括但不限於與發現、開發、製造和商業化安全有效地用於人類療法的藥物的過程相關的風險,以及在Xencor的公開證券申報文件中描述的其他風險。有關這些和其他因素的討論,請參閲Xencor截至2019年12月31日的Form 10-K年度報告以及Xencor隨後提交給美國證券交易委員會(Securities And Exchange Commission)的文件。所有前瞻性陳述均基於Xencor的當前信息和信念以及Xencor所做的假設。告誡您不要過度依賴這些前瞻性陳述,這些陳述僅説明截至本文發佈之日的情況。這一警告是根據1995年“私人證券訴訟改革法案”的安全港條款作出的。所有前瞻性陳述均受本警示聲明的約束,Xencor沒有義務修改或更新本新聞稿,以反映本新聞稿發佈後的事件或情況,除非法律另有要求。

譯文內容由第三人軟體翻譯。


以上內容僅用作資訊或教育之目的,不構成與富途相關的任何投資建議。富途竭力但無法保證上述全部內容的真實性、準確性和原創性。
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