IL-11RA

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 . 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. SOURCE Mabwell

Innovent plans to release detailed results from the study at future medical conferences or in journals. Innovent Biologics is hoping that a phase 3 win for its thyroid eye disease (TED) treatment will provide a first shot at the Chinese equivalent of a market that has already been conquered by Amgen’s Tepezza in the U.S. Like Tepezza, Innovent’s candidate IBI311 targets the insulin-like growth factor 1 receptor (IGF-1R). The candidate hit the primary endpoint of the phase 3 Restore-1 trial by showing a greater reduction in eyeball protrusion—known as proptosis—than placebo. The percentage of subjects with a reduction in proptosis of 2 mm or more in one eye without the equivalent increase in proptosis in the other eye was 85.8% among the IBI311 group, compared with just 3.8% among those who received placebo. The candidate also showed “significant” improvement on key secondary endpoints for the trial, including overall response rate, percentage of subjects with a clinical activity score of 0 or 1, and mean change in proptosis from baseline, Innovent said in a Feb. 20 release. No serious adverse events occurred, added the biotech, which plans to release detailed results from the study at future medical conferences or in journals. Lei Qian, vice president of clinical development at Innovent, said the company plans to submit a new drug application to Chinese regulators “as soon as possible” based on the results. TED occurs in 16 out of every 100,000 women and 2.9 in every 100,000 men, according to Innovent. The condition is clearly a tempting target, with Horizon Pharma’s Tepezza quickly securing blockbuster sales. Horizon noticed a drop off in uptake in the drug’s third year on the market, with Amgen making this a top priority when it acquired the biotech in October 2023. Still, as the only approved treatment for TED in the U.S., Tepezza garnered sales of $1.66 billion in its first full year on the market and $1.97 billion in 2022 before stalling out. Amgen also sees an international opportunity for Tepezza. The drug is under review in Japan and the company will file this year for approval in Europe. A subcutaneous version of the treatment is also in development. "There are no targeted drugs approved in the field of TED in China so far, while the treatment costs of overseas targeted drugs are beyond many patients' reach,” Qian explained in Innovent’s release this morning. The clinical success of IBI311’s comes a month after mazdutide, a GLP-1/glucagon receptor agonist that Innovent licensed from Eli Lilly, demonstrated weight loss abilities in a phase 3 trial. Qian aligned these recent wins with the Chinese approval of its hypercholesterolemia injection Sintbilo in August 2023 as proof of the strength of Innovent’s late-stage strategy. “With the approval of Sintbilo, the NDA acceptance of mazdutide and the endpoints met in phase 3 study of IBI311, Innovent is strategically establishing its innovative commercial and late-stage portfolio in the fields of cardiovascular and metabolic diseases, endocrinology and ophthalmology,” Qian added. Innovent isn’t the only biotech looking to stake out a piece of TED territory. Last month, Kriya Therapeutics announced plans to get a gene therapy into the clinic for the condition next year, while Lassen Therapeutics has already dosed the first patient in a phase 1 trial of an interleukin-11 receptor targeted at TED.

Proceeds will fund Phase 2 study in thyroid eye disease (TED) with LASN01 and continue development of LASN500 in Investigational New Drug (IND) enabling studies The Phase 1 study for LASN01 in healthy volunteers has been completed and patient cohorts in idiopathic pulmonary fibrosis (IPF) and TED are enrolling The IND for LASN01 Phase 2 program in the US has received Food and Drug Administration (FDA) clearance and one site is currently active SAN DIEGO--(BUSINESS WIRE)-- Lassen Therapeutics, a clinical stage biotech company developing first-in-class antibody therapeutics, LASN01, targeting interleukin-11 receptor (IL-11R) as a potential treatment for fibro-inflammatory diseases such as TED and IPF, and a highly potent, first-in-class monoclonal antibody, LASN500, targeting the interleukin-18 binding protein (IL-18BP) as a potential treatment for cancer, today announced the closing of an oversubscribed Series B financing which raised $85 million. Frazier Life Sciences co-led the financing along with new investor Longitude Capital. The syndicate also included new investors BVF Partners and Catalio Capital Management as well as existing investors, Alta Partners and Longwood Capital. Concurrent with this financing, Brian Liu, M.D. from Longitude Capital and Matthew Hobson, Ph.D. from Catalio Capital Management have joined the Board of Directors. Proceeds from this financing will support the LASN01 clinical program and advance IND-enabling activities for LASN500. The clinical program for LASN01 is focused primarily in TED with a cohort in IPF in the Phase 1 program. Lassen recently presented data using orbital fibroblast cells from TED patients demonstrating that LASN01 suppresses multiple markers associated with TED disease progression including hyaluronan production, cell proliferation, and other markers such as procollagen. Recent accomplishments and future activities with use of proceeds in the LASN01 program include: Expansion of the Phase 1 study in IPF and TED: The Phase 1 study in healthy volunteers has been completed and demonstrated a favorable safety profile, pharmacokinetics, and target engagement, leading to expansion of the program to patient cohorts in IPF and TED; both cohorts are currently enrolling patients with the first patient dosed in TED. Initiation and expansion of the Phase 2 program in TED in the US and ex-US: Lassen has received US IND clearance from the FDA as well as Clinical Trial Authorisation (CTA) from the Medicine and Healthcare Products Regulatory Agency (MHRA). One site is active with additional sites being activated in the US and ex-US. Development of subcutaneous formulation: Process development work to create a subcutaneous presentation of LASN01 has been initiated. “I am very pleased with the recent advancements at Lassen, particularly in successfully concluding the Series B financing round which will facilitate the continued development of our two pipeline products,” said Maria Fardis, Ph.D., Chief Executive Officer of Lassen. “The proceeds allow us to advance LASN01 Phase 1 and 2 clinical programs and develop a subcutaneous formulation for LASN01. This antibody has significant potential as a treatment for fibro-inflammatory disorders including TED. Our data in orbital fibroblasts have been highly encouraging and paired with our Phase 1 single and multiple ascending dose safety data, support advancement of LASN01 in Phase 2 for TED.” “We are very excited about Lassen and the opportunity to develop two first-in-class programs, one in fibro-inflammatory disorders and the other in cancer, along with the management team’s ability to expeditiously execute these programs in pursuit of new therapeutic options for patients,” said Brian Liu, M.D. Managing Director at Longitude Capital. “We are encouraged by the progress of LASN01, the lead program at Lassen which is entering Phase 2 and is a first-in-class antibody that binds to a novel target, an important differentiator in a broad set of fibro-inflammatory indications addressing serious unmet medical needs.” About LASN01 LASN01 is a first-in-class monoclonal antibody targeting the receptor for IL-11 (IL-11R). IL-11 is a central mediator of fibro-inflammatory disorders and blocking its activity has the potential to offer a novel modality for treatment of thyroid eye disease (TED) and other fibro-inflammatory diseases. In preclinical studies, LASN01 led to the suppression of cell proliferation, hyaluronan secretion, and procollagen from primary TED orbital fibroblasts. These results indicate that LASN01 has the potential to be a new therapeutic agent for the treatment of TED. Please refer to (NCT 05331300) for additional details related to this clinical trial. About LASN500 LASN500 is a highly potent, first-in-class monoclonal antibody targeting the IL-18 binding protein (IL-18BP). IL-18BP is elevated at the tumor site in multiple cancer indications and blockade of this protein allows for elevation of IL-18 at the tumor site, which is expected to provide a better safety profile. About Lassen Therapeutics Lassen Therapeutics is a clinical-stage biotech company developing first-in-class antibodies as potential treatments for fibro-inflammatory disorders, such as thyroid eye disease (TED), and cancer. The company’s lead candidate, LASN01, is a first-in-class monoclonal antibody targeting IL-11 receptor (IL-11R) and is currently being evaluated for the treatment of TED and idiopathic pulmonary fibrosis (IPF). Lassen is also developing LASN500, a highly potent, first-in-class monoclonal antibody targeting the IL-18 binding protein (IL-18BP) for cancer. For more information, please visit and follow us on LinkedIn. About Frazier Life Sciences Frazier Life Sciences invests globally in private and publicly-traded companies that discover, develop and commercialize innovative biopharmaceuticals. Frazier Life Sciences' funds comprise over $3.3 billion in capital raised, including venture funds focusing on company creation and private companies, and public funds focused on small and mid-cap public companies. Since 2005, over 60 Frazier Life Sciences portfolio companies, many of which were created or seeded by Frazier, have completed IPOs or M&As. The Frazier Life Sciences team consists of over 40 professionals with deep experience in biopharmaceuticals, primarily located in Palo Alto, CA (headquarters), San Diego, Seattle, Boston, New York, and London. About Longitude Capital Longitude Capital is a leading healthcare venture capital firm that invests in transformative biotechnology, medical technology, and health solutions companies seeking to improve clinical outcomes, enhance patient quality of life, and drive efficiency of healthcare delivery. Founded in 2006, Longitude Capital invests in both privately held and publicly traded companies through a variety of investment approaches. Longitude Capital has offices in Menlo Park, CA, Greenwich, CT, and Boston. For more information, please visit or LinkedIn.