On November 18th, VelaVigo Cayman Limited announced a global strategic partnership agreement with Avenzo Therapeutics, Inc. (Avenzo). According to the agreement, Orange Sail Pharmaceuticals will grant Avenzo the development, production, and commercialization of Nectin4/TROP2 bispecific antibody conjugates worldwide (excluding Greater China), while retaining relevant rights in Greater China.

Both parties will jointly promote the development and clinical application of the project on a global scale. The project plans to submit an IND to the US Food and Drug Administration (FDA) and the National Medical Products Administration (NMPA) of China by 2025.

According to the terms of the agreement, Orange Sail Pharmaceuticals will receive a down payment of up to $50 million and recent milestone payments. After achieving key milestones in development, regulatory approval, and sales, the company is expected to receive up to $750 million in follow-up milestone payments and tiered royalty payments based on sales in the Avenzo region. (Note: The total transaction amount is 800 million US dollars, equivalent to approximately 5.792 billion Chinese yuan)

This is the second time Avenzo, which is developing next-generation cancer therapies, has invested in Chinese innovative drug assets this year. On January 5th, Avenzo purchased the global (excluding Greater China) development and commercialization rights of two projects of Anrui Biotechnology for a potential total payment of over $1 billion. One of them is the potential best in class cyclin dependent kinase 2 (CDK2) selective inhibitor ARTS-021.

Two dual antibody ADCs with excellent preclinical data

Chengfan Pharmaceutical focuses on the development of multispecific antibodies and antibody conjugated drugs (ADCs). Since its establishment in 2021, it has established a wide research and development pipeline covering more than ten first/best (FIC/BIC) multispecific antibodies and ADC molecules, focusing on fields such as oncology and autoimmune diseases. Meanwhile, Orange Sail Pharmaceuticals has established VelaVigo Bio in the United States to promote clinical development and collaboration worldwide.

According to the company's official website, Orange Sail Pharmaceuticals focuses on four major disease areas of global health challenges: cancer, autoimmune and inflammatory diseases, neurodegenerative diseases, and ophthalmology, including bispecific/multispecific antibodies, ADCs, and new treatment modalities. Simultaneously committed to building a powerful internal discovery engine and establishing a "closed loop" between discovery and clinical development through translational medicine. In addition, combining internal discovery/development with win-win partnerships to continuously build and advance its product portfolio with the highest quality and efficiency.

Since its establishment, Orange Sail Pharmaceutical has carried a "star halo" - founded by Dr. Li Jing, Senior Vice President of Original Medicine Mingbio. In 2021, it received a $50 million angel round investment and established a global research and development headquarters in Shanghai, as well as a clinical center in Boston, USA.

Founder Dr. Li Jing has worked in the oncology research department and biopharmaceutical center of Wyeth Pharmaceuticals (now Pfizer), Novartis, and the drug development department of WuXi Biologics, with over 20 years of experience in innovative biopharmaceutical research and development for international pharmaceutical companies. Founded by Dr. Li Jing in 2013, the new drug research and development department of WuXi Biologics has established a drug discovery team of over 300 people, which was a pioneer in the Chinese biopharmaceutical industry at that time. Established pipelines for over 300 projects and completed the transfer of over 40 projects, successfully assisting multiple domestic and foreign companies in their biopharmaceutical product pipelines.

Of course, the key to maintaining the halo of a "star enterprise" lies in its strong talent team and pipeline research and development capabilities. In just three years, Orange Sail Pharmaceuticals has advanced multiple molecules to the IND application research stage. At the AACR in 2024, Orange Sail Pharmaceuticals released preclinical study data for its EGFR/cMet dual antibody ADC VBC101-F11 and TROP2/Antin-4 dual antibody ADC VBC103 pipelines for the first time

The core pipeline of Orange Sail Pharmaceuticals focuses on the highly popular lung cancer target of AstraZeneca and other MNCs: EGFR/c-MET. VBC101-F11 is a dual antibody ADC developed by Orange Sail Pharmaceuticals that targets EGFR/cMet. It has a low affinity EGFR arm and a high affinity cMet arm. In in vivo CDX models using various lung cancer cell lines, VBC101-F11 showed significant advantages in tumor growth inhibition at a single dose of 3mg/kg compared to ABBV-399 (AbbVie) (TGI of 60% vs. 17%).

VBC103 focuses on Trop2 and Nectin4 targets highly co expressed in urothelial carcinoma, triple negative breast cancer and other tumors. VBC103 provides tumor cells with TOPOi payloads with strong bystander effects, maximizing efficacy while minimizing safety concerns. Data shows that VBC103 has enhanced binding affinity, internalization, and cytotoxicity compared to Nectin4 monoclonal antibody or approved Nectin4 ADC Padcev.

Over 1.8 billion US dollars, purchase of Chinese innovative drug assets

It is worth mentioning that Avenzo Therapeutics, the acquiring company, is a clinical stage biotechnology company that has only been established for 3 years. It was co founded by Dr. Athena Countouriotis and Dr. Mohammad Hirmand in 2022, and has a strong "star enterprise" temperament.

Dr. Athena Countouriotis serves as the President, CEO, and Chairman of Avenzo. Previously, as President and CEO, she led Turning Point Therapeutics to complete its IPO in 2019 and was ultimately acquired by Bristol Myers Squibb for $4.1 billion in August 2022. During this period, she and her team raised over $1.2 billion through multiple equity financing.

Dr. Mohammad Hirmand has over 20 years of clinical development experience in biotechnology, having served as Executive Vice President and Chief Marketing Officer of Turning Point Therapeutics and Chief Marketing Officer of Peloton Therapeutics (acquired by Merck for $2.2 billion in July 2019).

Since its establishment in August 2022, Avenzo has raised a total of $386 million in funding. In 2022, Avenzo has secured approximately $200 million in seed and Series A funding from five well-known investors, including SR One, OrbiMed, Foresite Capital, Surveyor Capital, and Eli Lilly Asia Fund. In March 2024, Avenzo announced the completion of an oversubscribed $150 million Series A1 funding round. On the trading day of November 18th, Avenzo also announced that it had secured an additional $39 million in the third round of Series A financing.

Avenzo is building and advancing a range of potential best in class tumor therapies that target cell cycle control to prevent abnormal cell proliferation that leads to many cancers. At present, the only publicly available pipeline on its official website is ARTS-021 (AVZO-021), a CDK2 selective inhibitor acquired from Anrui Biotechnology in January of this year. ARTS-021 has carried out a multicenter phase I clinical trial in the United States for the treatment of HR+/HER2 metastatic breast cancer and other advanced solid tumors. In addition, in the transaction in January this year, Avenzo also obtained the exclusive option to submit a preclinical project to IND by Anrui Biotechnology in early 2025.

In previous reports, Avenzo expressed interest in acquiring early-stage oncology small molecules, including ADC, and will seek ADC opportunities in China with the help of Lilly Asia Fund. Behind a series of swift financing and license in transactions, Dr. Countouriotis hopes to quickly go public on NASDAQ through an IPO, possibly as early as 2024 or 2025.

According to foreign media reports, Dr. Countouriotis, the founder of Avenzo, has been searching for ADCs for some time now. Earlier this year, Avenzo offered higher prices in other transactions in this hot field because MNCs were "quite expensive" and she believed that single target ADC drugs may have been oversaturated.

For the Nectin4/TROP2 targets, Dr. Countouriotis stated that these two targets have never been combined before, so this may be the first Nectin4/TROP2 dual antibody ADC. Currently, Gilead has a TROP2 ADC Trodelvy, while Pfizer and Astellas have a Nectin-4ADC Padcev.