SHANGHAI, April 16, 2024 /PRNewswire/ — Mabwell (688062.SH), an innovation-driven biopharmaceutical company with entire industry chain, presented the preclinical research findings of three potential novel drug candidates in poster format at the American Association for Cancer Research (AACR) Annual Meeting, held from April 5 to 10, 2024.
Poster Presentation
1. Disrupting IL-11/IL-11R signaling by an efficacious anti-IL-11 antibody 9MW3811 enhances T cell tumor infiltration and synergizes with anti-PD-1 therapies in vivo
Synopsis No.: 2365
The reported 9MW3811 is a high-affinity humanized neutralizing antibody against IL-11 independently developed by Mabwell, and has IND applications approved in China, the United States, and Australia, and its phase I clinical trials are ongoing in Australia and China.
As an important inflammation factor, IL-11 plays a significant role in the development and progression of fibrosis and tumor. Studies have shown that high expression of IL-11 is associated with the prognosis of various tumors such as lung cancer, hepatic cancer, and colorectal cancer. IL-11 not only promotes the growth of tumor cells through the STAT3 pathway but also has a significant impact on immune cells in the tumor microenvironment. 9MW3811 effectively blocks the formation of the IL-11/IL-11Ra/gp130 ternary complex by binding to IL-11, thereby inhibiting the activation of downstream signaling pathways. 9MW3811 has shown good anti-tumor therapeutic effects in multiple preclinical pharmacodynamic models, especially when used in combination with anti-PD-1 antibodies, it significantly promotes lymphocytic infiltration of CD8+ T cells, improves the T cell exhaustion caused by anti-PD-1 antibodies, upregulates the secretion of cytotoxic cytokines, thus exhibiting better combined anti-tumor effects.
2. 2MW4991, a novel ADCC-enhanced integrin αvβ8 blocker, exhibits high anti-tumor potency and was well tolerated in cynomolgus monkeys
Synopsis No.: 6349
The reported 2MW4991 is a high-specificity and high-affinity ADCC-enhanced antibody targeting integrin αvβ8. Integrin αvβ8 is an important activator of TGF-β, and specifically regulates the activity of TGF-β in immune cells. Studies have found that integrin αvβ8 is highly expressed in various tumors, and blocking αvβ8 can completely inhibit the release of TGF-β. 2MW4991 can completely block the release of TGF-β mediated by αvβ8, showing strong anti-tumor activity in various pharmacodynamic models such as CT26 and EMT6, and significantly promotes immune cell infiltration in tumors, greatly increasing the sensitivity of immune-excluded tumors to PD1 inhibitors. 2MW4991 has a significant synergistic effect when used in combination with PD1. The studies conducted in non-primate models have shown that 2MW4991 has good safety and metabolic profiles.
3. 2MW4691, a novel CCR8/CTLA-4 bispecific antibody, displays potent anti-tumor efficacy by specifically depleting tumor-infiltrating Tregs and blocking CTLA-4 signaling on CD8+ T cells
Synopsis No.: 6350
The reported 2MW4691 is an ADCC-enhanced bispecific antibody targeting CCR8/CTLA-4. Targeting CTLA-4 has a strong anti-tumor effect, but its clinical application is limited due to strong side effects. CCR8 is a specific marker of tumor-infiltrating Tregs, and is almost not expressed in other immune cells and peripheral Tregs. Single-cell sequencing analysis of Treg cells infiltrating various tumors found that CCR8 is expressed in a small subset of Treg cells infiltrating tumors, and CTLA-4 is widely expressed in Treg cells and CD8+ T cells. 2MW4691 retains high affinity targeting CCR8 and attenuated CTLA-4-binding and -blocking activity, specifically eliminating Treg cells infiltrating tumors. Due to the lower CTLA-4 expression in the peripheral tissues, 2MW4691 only blocks the immunosuppression mediated by CTLA-4 signaling on peripheral CD8+ T cells. 2MW4691 demonstrates strong anti-tumor activity in preclinical CCR8 single transgenic animal models, CTLA-4 single transgenic animal models, and double transgenic animal models, and has shown good metabolic activity and safety in primate animals.
About Mabwell
Mabwell (688062.SH) is an innovation-driven biopharmaceutical company with the entire value chain of the pharmaceutical industry. We provide more effective and accessible therapy and innovative medicines to fulfill global medical needs. Since 2017, an advanced R&D system which covers target discovery, early discovery, druggability, preclinical, clinical research and manufacturing transformation was established. Mabwell has 14 pipeline products in different stages based on a world-class and state-of-the-art R&D engine, including 10 novel drug candidates and 4 biosimilars. We focus on the therapeutic areas of oncology, auto-immune diseases, metabolic disorders, ophthalmologic diseases and infectious diseases, etc. Of these, 3 products have been approved and commercialized, 1 product has been filed for MA approval, 3 products are in pivotal trials. We have also undertaken 1 national major scientific and technological special project for "Significant New Drugs Development", 2 projects for National Key R&D Programmes, and multiple provincial and municipal science and technological innovation projects. Mabwell’s Taizhou factory possesses robust in-house manufacturing capability compliant with international GMP standards regulated by the NMPA, FDA and EMA, and has passed the EU QP Audit. The large-scale manufacturing base located in Shanghai is under construction. Our mission is "Explore Life, Benefit Health" and our vision is "Innovation, from ideas to reality". For more information, please visit www.mabwell.com/en.
Forward-Looking Statements
This press release contains forward-looking statements including, but not limited to, the potential safety, efficacy, regulatory review or approval and commercial success of our product candidates and those relating to the Company’s product development, clinical studies, clinical and regulatory milestones and timelines, market opportunity, competitive position, possible or assumed future results of operations, business strategies, potential growth opportunities and other statements that are predictive in nature. "Forward-looking statements" are statements that are not historical facts and involve a number of risks and uncertainties, which may cause actual results to be materially different from any future results expressed or implied in the forward-looking statements. These statements may be identified by the use of forward-looking expressions, including, but not limited to, "expect," "anticipate," "intend," "plan," "believe," "estimate," "potential," "predict," "project," "should," "would," and similar expressions and the negatives of those terms.
Forward-looking statements are based on the Company’s current expectations and assumptions. Forward-looking statements are subject to a number of risks, uncertainties, and other factors, many of which are beyond the Company’s control, including, but not limited to: environment; politic; economy; society; legislation; our dependence on our product candidates, most of which are still in preclinical or various stages of clinical development; our reliance on third-party vendors, such as contract research organizations and contract manufacturing organizations; the uncertainties inherent in clinical testing; our ability to complete required clinical trials for our product candidates and obtain approval from regulatory authorities for our product candidates; our ability to protect our intellectual property; the potential impact of COVID-19; the loss of any executive officers or key personnel. In case one or more of these risks or uncertainties deteriorate, or any assumptions are incorrect, the actual results may be seriously inconsistent with the stated results.
The Company cautions all the persons not to place undue reliance on any such forward-looking statements, which speaks only as of the date of this press release. The Company disclaims any obligation, except as specifically required by law and the rules of the applicable Stock authority to publicly update or revise any such statements to reflect any change in expectations or in events, conditions, or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. All forward-looking descriptions, figures and assumptions in this press release are applicable to this statement.
>
This content was prepared by our news partner, Cision PR Newswire. The opinions and the content published on this page are the author’s own and do not necessarily reflect the views of Siam News Network
