Multitude Therapeutics: A Clinical-Stage ADC Innovator Leveraging Proprietary MabArray and T1000 Platforms

May 15, 2024 10:53 CST Updated 10:53

Multitude Therapeutics

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Two exclusive major technological patent platforms,For the development of a new generation of ADC drugs.Follow me to learn every dayAn ADC pharmaceutical company, so today the editor will focus on introducing this "the more low-key, the more successful" ADC pharmaceutical company to all of you — Puzhong Discovery Pharmaceutical Technology (Shanghai) Co., Ltd.

AboutPuzhong Discovery

Puzhong Discovery Pharmaceutical Technology (Shanghai) Co., Ltd. is a clinical-stage company focused on the development of ADC drugs, and its founders have a track record of continuous successful entrepreneurial experience. Puzhong Discovery has the capability to develop industry-leading ADC products, with its competitive edge lying in two technological platforms: MabArray (Sci Adv. 2020 6(11): EAAX2271) — an antibody platform for discovering novel cell surface anti-tumor targets to construct First-in-Class targets, and T1000 — a novel linker/payload technology used for ADC development. ADCs prepared using this platform achieve a more optimized balance in terms of bystander effect, efficacy, and safety. The combination of MabArray and T1000 generates significant synergistic effects, enabling Puzhong Discovery to build an ADC "catalog" that holds promise for treating malignant tumors with high unmet medical needs, such as small cell lung cancer, colorectal cancer, pancreatic cancer, and renal cancer, while achieving higher and more durable responses.

Puzhong Discovery Pharmaceutical Technology (Shanghai) Co., Ltd. has received honors such as "High-tech Enterprise," "Top 50 Most Investment-worthy Startups in Shanghai 2020," and "Top 50 Most Innovative Pharmaceutical Enterprises in China." Its investors include well-known institutions such as Genesis Capital, Northern Light Venture Capital, Cowin Venture Capital, Loyal Valley Capital, and M Ventures (Merck Corporate Strategic Investment Fund).

"Out of Necessity"Transformation

From the new drug research and development team under Abmart Pharmaceutical Technology (Shanghai) Co., Ltd., to today's Puzhong Discovery Pharmaceutical Technology (Shanghai) Co., Ltd. (hereinafter referred to as "Puzhong Discovery"), the emergence of Puzhong Discovery is a natural outcome of the transformation from scientific research to industrial application.

At the beginning, Puzhong Discovery did not intend to engage in the research and development of innovative drugs. A review of the experience of the founding team of Puzhong Discovery reveals that most of the founding members, represented by Tang Yanfang, the Chief Operating Officer of Puzhong Discovery, come from drug discovery platforms. Relying on their previous in-depth work in the technical platform field, before 2019, they had consistently been involved in the construction of drug discovery platforms.

However, heroes are made by the times. Between 2016 and 2018, China-produced innovative drugs entered an early stage of vigorous development. Compared with the then widely pursued hot targets such as "PD-1" and "PD-L1", Puzhong Discovery Pharmaceutical Technology (Shanghai) Co., Ltd. found that using an innovative target screening technology platform to "find targets" was still an emerging model. In this regard, Tang Yanfang said that there were many partners at that time, but among them, there were many onlookers, and very few who were truly willing to invest.

Against the backdrop of significant achievements of ADC drugs in the solid tumor field at that time, they chose to embark on the ADC niche track to carry out innovative drug research and development. With the support of their own technology platform, Puzhong Discovery Pharmaceutical Technology (Shanghai) Co., Ltd.'s R&D process advanced rapidly.

All Roads Lead to Rome. In Tang Yanfang's view, the rapid progress of Puzhong Discovery in ADC drugs is certainly encouraging, but what they are more concerned about is: the success of ADC drugs proves the importance of technology platforms in drug development. As they initially envisioned, Puzhong Discovery focuses on longer-term drug innovation and development.

Introduction to the Core Team:

Tang Yanfang

Co-founder, Chief Operating Officer

After years of dedication to drug research and development, Puzhong Discovery Pharmaceutical Technology (Shanghai) Co., Ltd. was established in 2019.

R&D Progress

Introduction to Core Technology Platform:

Puzhong Discovery Pharmaceutical Technology (Shanghai) Co., Ltd. is a platform-based company with a global perspective in target innovation, driven by the dual technologies of MabArray (target discovery) and T moiety (ADC). Relying on its technical platform and unique cyclic and open ecosystem model, the company currently has over 10 pharmaceutical projects based on novel targets.

MabArray Industrial-Grade Antibody Chip Platform

Puzhong Discovery Pharmaceutical Technology (Shanghai) Co., Ltd.'s core technology, supported by a 100,000-level ultra-high-density antibody chip library, enables the completion of high-resolution antigen screening that traditional methods cannot achieve. It can identify challenging antigens such as multi-transmembrane, special conformation, and glycoproteins, covering approximately 50% of human cell surface membrane proteins (potential drug targets) in one go, pushing cell surface antigen recognition to new heights.

T Moiety ADC Technology Platform

It is a highly hydrophilic self-cleaving linker modification technology that can be used to develop a new generation of highly efficient and stable ADC drugs. This new technology benefits from an enhanced "hydrophobic shielding effect" and stability, significantly improving the therapeutic efficacy of ADCs compared to existing ADCs, prolonging the drug's action time, and overcoming multidrug tumor resistance. More importantly, the toxic side effects have not increased, further expanding the therapeutic window of existing ADC drugs.

Introduction to the R&D PipelineIntroduction:

Through public channels, it is understood that the current ADC pipelines discovered by Puzhong Discovery Pharmaceutical Technology(Shanghai) Co., Ltd. are the above five, among which AMT-151, AMT-253, and AMT-562 have entered the clinical stage. CUSP06, in collaboration with Oncologie, has also entered the clinical stage.

AMT-151Jointly developed by Puzhong Discovery and Lianning Bio, targeting FRα. The antibody is a recombinant humanized antibody independently developed by Puzhong Discovery, the payload is the novel toxin molecule DUO-5, and the linker adopts Lianning's K-lock site-specific conjugation technology.

AMT-151 has been approved for clinical trials in China and Australia.

AMT-253It is an ADC targeting MUC18 developed based on the T1000 platform, with exatecan as the payload. It has currently been approved for clinical trials in China and Australia for the treatment of solid tumors.

Preclinical results show that AMT-253 has demonstrated significant anti-tumor activity in various CDX or PDX models, including melanoma, cervical squamous cell carcinoma, head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, lung squamous cell carcinoma, small cell lung cancer, ovarian cancer, and liver cancer.

Currently, AMT-253 is the only ADC under research targeting MUC18, showing significant differentiation.

AMT-562It is an ADC drug targeting HER3 developed based on the T-Moiety technology platform, with the antibody mAb562. Both as a single agent and in combination, it has demonstrated significant anti-tumor activity in in vitro models.

Financing Progress

External Cooperation

On October 21, 2021, Linking Bio and Puzhong Discovery reached a strategic cooperation.

Lian NingBiology andThe Strategic Cooperation Agreement Signing Ceremony of Puzhong Discovery Pharmaceutical Technology (Shanghai) Co., Ltd. was Successfully Held in Suzhou; Lian Ning Bio CEO Ye Zhengyi, Puzhong Discovery COO Tang Yanfang, and Other Relevant Personnel Attended the Signing Ceremony.

This signing marks that both parties will fully cooperate in the development of novel antibody-drug conjugates primarily targeting solid tumors such as ovarian cancer, based on the principles of equal cooperation, mutual benefit, and win-win outcomes. The collaboration aims to leverage the strengths of both parties to support each other, achieving high-quality, robust, and sustainable development for both sides.

On June 8, 2022, Oncologie reached an overseas licensing agreement with Puzhong Discovery Pharmaceutical Technology(Shanghai) Co., Ltd. for a potentially highly differentiated CDH6-targeted antibody-drug conjugate (ADC).

OncoC4 Announces Licensing Agreement with Puzhong Discovery Pharmaceutical Technology(Shanghai) Co., Ltd. for the Development and Commercialization of AMT-707 (Now Referred to as CUSP06). AMT-707 is a potentially highly differentiated, Second-in-Class antibody-drug conjugate (ADC) targeting CDH6.

According to the terms of the license agreement, OncoMed has obtained the exclusive rights to develop and commercialize CUSP06 globally outside of Greater China. Puzhong Discovery Pharmaceutical Technology (Shanghai) Co., Ltd. will receive an upfront payment, development, regulatory, and sales milestone payments, as well as tiered royalties.

On January 31, 2024, WuXi XDC Collaborated with Puzhong Discovery Pharmaceutical Technology (Shanghai) Co., Ltd. and HuiLian to Empower ADC Drug Development

WuXi XDC and Puzhong Discovery (Multitude Therapeutics) announced a collaboration and signed a Memorandum of Understanding (MOU) with ADC drug research company Shanghai HuiLian Biopharmaceutical Co., Ltd. ("HuiLian") for comprehensive cooperation on novel toxin-linker technologies and Contract Research, Development, and Manufacturing Organization (CRDMO) services for ADCs.

END

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