Mabwell Publishes the Preclinical Study Results on Its Nectin-4 Targeting ADC in A Well-known AACR Journal
SHANGHAI,June 15,2023 -- Recently,the preclinical study results of 9MW2821,the first domestically developed Nectin-4-targetingADC by Mabwell,were published in the renowned journal "Molecular Cancer Therapeutics" under the American Association for Cancer Research (AACR). The paper comprehensively elaborated on the development and preclinical study results of 9MW2821 as a new generation Nectin-4-targeting ADC,and systematically compared it with the only approved Nectin-4-targeting ADC on the market (PADCEV,EV).
Nectin-4 is closely related to the progression and poor prognosis of malignant tumors. Enfortumab Vedotin (EV) is the first Nectin-4-targeting ADC approved by the US Food and Drug Administration (FDA) for the treatment of advanced urothelial carcinoma. However,inadequate efficacy has limited progress in the treatment of other solid tumors with EV. Ocular,pulmonary,and hematological toxic side effects are common in nectin-4-targeting therapy,which frequently results in dose reduction and/or treatment termination. These reasons may limit the wider use of Nectin-4-targeting therapy.
9MW2821 is a novel Nectin-4-targeting ADC based on inter-chain site specific conjugate technology,composed of specially designed linker,novel antibody molecule,and the cytotoxic drug MMAE. It not only has good tumor binding ability and target specificity,but also differs from existing Nectin-4-targeting ADC therapy (PADCEV,EV). It has more homogeneous composition,more stable structure,and superior tumor delivery ability.
In vitro cell experiments and animal studies have found that the unique structure of 9MW2821 brings the following significant characteristics:
9MW2821 enhances the antibody's internalization activity,exhibiting similar tumor internalization activity asEV in Nectin-4 high-expressing tumors and superior tumor internalization activity compared to EV in low-abundance tumors.
9MW2821 improves the plasma stability of the drug and significantly improves itspharmacokinetic (PK) characteristics. In PK studies,it had a higher intra-tumoral concentration of MMAE (9MW2821,Cmax: 106 pmol/ml; EV,Cmax: 76 pmol/ml; p＜0.01) and intra-tumoral exposure (9MW2821,AUC0-t: 2452 pmol/mL*h; EV,AUC0-t: 2116 pmol/mL*h; p＜0.05).
In theCDX models,9MW2821 exhibit comparable activity as EV in urothelial carcinoma,and has superior tumor suppression effects in non-small cell lung cancer and breast cancer. In addition,the PDX models show that it has excellent tumor suppression effects in different tumors,including cervical cancer and lung cancer models,and also has certain tumor therapeutic effects in low- to medium-abundance solid tumors and large volume solid tumors.
9MW2821 has good drug safety,and toxicology studies have shown that it has milder skin toxicity,eye toxicity and gastrointestinal toxicity at equivalent doses.
9MW2821 is an ideal ADC with homogeneous drug-to-antibody ratio,tumor-specific properties,bystander killing effect,ideal efficacy in multiple solid tumors,and an acceptable therapeutic window. Based on the above study results,the company is conducting phase I/II clinical studies for 9MW2821 in multiple solid tumors and validating the related study results.
About 9MW2821
The novel Nectin-4-targetingADC,developed independently based on the Mabwell ADC Platform and High-throughput Screening Platform,has applied for multiple patents for its antibody molecule,linker,drug molecule,and platform-related site-specific conjugation technology.
Currently,multiple clinical studies covering more than 10 types of tumors are being conducted. Preliminary data shows that at the recommended phase 2 dose (RP2D),among 12 evaluable subjects with urothelial carcinoma,the objective response rate (ORR) reached 50%,and the disease control rate (DCR) reached 100%; among 6 evaluable subjects with cervical cancer,the ORR reached 50%,and the DCR reached 100%. The expansion of multiple cohorts,including urothelial carcinoma,cervical cancer,prostate cancer,HER-2 negative breast cancer,and non-small cell lung cancer,is actively being pursued.
About Molecular Cancer Therapeutics
Molecule Cancer Therapeutics (anAACR journal,Print ISSN: 1535-7163,Online ISSN: 1538-8514) publishes translational research studies focused on the discovery and preclinical development of therapeutic agents for oncology. It is an authoritative journal in the ADC field.
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 R&D 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 auto-immune diseases,oncology,metabolic disorders,ophthalmologic diseases and infectious diseases,etc. Of these,2 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 several 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.
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,"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,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.
