Chinese Biotech Puzhong Discovery Emerges as a Dark Horse in Anti-TF ADC Space with Over $1 Billion Deal

Aug 20, 2024 13:59 CST Updated 13:59

Multitude Therapeutics

Innovative Drug Developer

ADCendo

Developer of Novel Anti-Cancer Drugs

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丨Organized by the research team of the Drug Hunter Club

Today, Puzhong Discovery Pharmaceutical Technology (Shanghai) Co., Ltd. and ADCendo ApS jointly announced that they have reached an agreement on the project codenamedADCE-T02 (Puzhong Discovery's R&D code: AMT-754)A new, highly differentiated antibody-drug conjugate (ADC) targeting tissue factor (Anti-TF) has reached a licensing agreement,ADCendo will obtain the global exclusive rights for development and commercialization outside of Greater China, while Puzhong Discovery Pharmaceutical Technology (Shanghai) Co., Ltd. will retain the rights for development and commercialization in the Greater China region (including mainland China, the Hong Kong Special Administrative Region, the Macao Special Administrative Region, and Taiwan).

According to the terms of the agreement,Puzhong Discovery Pharmaceutical Technology(Shanghai) Co., Ltd. will obtainTens of Millions of Dollars in Upfront Payments, and will charge upon achieving subsequent development, regulatory, and commercial milestones.Total milestone payments exceeding 1 billion US dollars in total, as well as single-digit to low double-digit percentage royalties based on global net sales (excluding Greater China).

About ADCE-T02

ADCE-T02 is a novel, highly differentiated Anti-TF ADC. Its unique antibody design can reduce the impact on the coagulation pathway. Meanwhile, the T1000-exatecan linker-payload technology platform has been proven to amplify the "bystander effect," enhance linker stability, and possess the potential to overcome drug resistance mechanisms. These differentiated characteristics are expected to translate into higher clinical response rates, longer duration of efficacy, and better safety, offering a superior therapeutic window.ADCE-T02 has been submitted for clinical trial in Australia and is expected to file for U.S. IND in the near future.

Tissue Factor (TF) is a transmembrane glycoprotein, also known as thromboplastin, which is not expressed in the endothelial cells of the inner wall of normal tissue blood vessels. However, TF is highly expressed in various types of tumors, such as cervical cancer, breast cancer, prostate cancer, colon cancer, esophageal cancer, and pancreatic cancer.

TF promotes tumor growth by facilitating angiogenesis (the process of forming new blood vessels that supply nutrients and oxygen to the tumor). A key factor in angiogenesis is vascular endothelial growth factor (VEGF), which can be stimulated by TF. In this way, tumors are nourished and grow and metastasize due to the formation of blood vessels. Metastasis refers to the spread from the primary tumor to other parts of the body, which is caused by TF and can trigger venous thromboembolism in cancer patients.

Drugs targeting TF can be delivered specifically to tumor cells without affecting normal tissue cells, making TF an ideal target for ADC drugs. Antibody-drug conjugates (ADCs) targeting TF-overexpressing tumor cells can selectively kill TF-expressing tumor cells and inhibit tumor growth in vivo. Targeting TF can suppress tumor growth, angiogenesis, and metastasis, thereby improving patient survival rates.

Currently, TF as a drug target has not gained much attention globally.Globally, there are 11 Anti-TF ADC drug pipelines, most of which are in the preclinical stage., which have entered the clinical stage includeLepu Biotechnology'sMRG004AAndXinnuowei PharmaceuticalXNW28012, have been approved for marketing are onlyZai Lab's TIVDAK。

AboutPuzhong Discovery

Puzhong Discovery Pharmaceutical Technology (Shanghai) Co., Ltd. was founded in 2016 and is a clinical-stage company focused on ADC drug development. Puzhong Discovery has two technology platforms:MabArray—— A platform for discovering novel cell surface anti-tumor targets to construct first-in-class antibodies, andT1000 —— A novel linker-payload technology for ADC development, which enables ADCs prepared on this platform to achieve a more optimized balance in terms of bystander effect, efficacy, and safety.

MabArray The industrial-grade antibody chip platform is the core technology of Puzhong Discovery Pharmaceutical Technology (Shanghai) Co., Ltd. With a 100,000-level ultra-high-density antibody chip library, Puzhong Discovery can achieve high-resolution antigen screening that traditional methods cannot accomplish, and identify challenging antigens such as multi-transmembrane, special conformation, and glycoproteins, covering ~50% of human cell surface membrane proteins (potential drug targets) in one go, pushing cell surface antigen recognition to new heights.

T1000It is a highly hydrophilic self-cleavable linker modification technology that can be used to develop a new generation of highly efficient and stable ADC drugs. This new technology benefits from superior "hydrophobic shielding effect" and stability, significantly enhancing the therapeutic effects of ADCs compared to existing ADCs, prolonging drug 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.

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AboutAdcendo‍‍‍‍

ADCendo ApS was founded in 2017.It is the University of Copenhagen andRigshospitalet, a derivative company,Dedicated to developing breakthrough antibody-drug conjugates (ADCs) for the treatment of rare cancers.Scientific founders Niels Behrendt, Lars Engelholm, and Christoffer Nielsen from the Finsen Laboratory recently published a proof-of-concept for uPARAP-directed ADCs, in which the first-generation anti-uPARAP ADC was shown to effectively mediate curative outcomes in CDX models.

ADCendo's core pipeline is an ADC targeting the uPARAP receptor.uPARAP is a new target that is overexpressed on the surface of sarcoma and other interstitial cancer cells, including soft tissue sarcoma, osteosarcoma, gastrointestinal stromal tumors, and mesothelioma. Studies also show that uPARAP is highly expressed in stromal cells of some epithelial tumors, showing great potential in remodeling the tumor microenvironment and is expected to expand the application scope of the uPARAP target.

Currently, no uPARAP ADC has entered the clinical stage worldwide. ADCendo expects that the first indication of its uPARAP ADC—soft tissue sarcoma—will complete the first patient dosing by the end of 2024.

In 2024, the company completed an extension of its Series A financing round, raising a total of 98 million euros to advance, expand, and accelerate the development of its novel target ADC pipeline. Investors include Novo Holdings, Ysios Capital, Pontifax Venture Capital, RA Capital Management, HealthCap, Gilde Healthcare, and Dawn Biopharma, a platform company controlled by KKR.

References:

Official Websites of Various Companies

Tissue Factor TF-Targeted ADC in Development: A Promising New Therapy for Cancer!

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