VelaVigo Licenses Nectin4/TROP2 Bispecific ADC to Avenzo in $800M Global Deal

On November 18, VelaVigo Cayman Limited announced that it had entered into a global strategic collaboration agreement with Avenzo Therapeutics, Inc. (“Avenzo”). Under the agreement, VelaVigo will grant AvenzoDevelop, manufacture, and commercialize Nectin4/TROP2 bispecific antibody-drug conjugates globally (excluding Greater China), while retaining relevant rights in Greater China.

The two parties will jointly advance the global development and clinical application of the project. The project plans to submit Investigational New Drug (IND) applications to the U.S. Food and Drug Administration (FDA) and China’s National Medical Products Administration (NMPA) in 2025.

Under the terms of the agreement, Orange Sail Pharma will receive an upfront payment and near-term milestone payments totaling up to $50 million. Upon achieving key milestones in development, regulatory approval, and commercialization, the company is eligible for additional milestone payments of up to $750 million, as well as tiered royalties based on sales of Avenzo products in its designated territory.(Note: The total transaction amount was $800 million, equivalent to approximately RMB 5.792 billion.)

This marks Avenzo’s second acquisition of innovative Chinese drug assets this year in its development of next-generation oncology therapies, with a total transaction value exceeding $1.8 billion.On January 5, Avenzo Therapeutics acquired the global (excluding Greater China) development and commercialization rights to two projects from Anrui Biopharma for potential total payments exceeding $1 billion. One of these is ARTS-021, a potential best-in-class selective inhibitor of cyclin-dependent kinase 2 (CDK2).

Orange Sail Medicine focuses on the development of multispecific antibodies and antibody-drug conjugates (ADCs). Since its establishment in 2021, it has built an extensive R&D pipeline comprising more than ten first-in-class/best-in-class (FIC/BIC) multispecific antibody and ADC candidates, with a focus on oncology and autoimmune diseases. Meanwhile, Orange Sail Medicine has established VelaVigo Bio in the United States to advance global clinical development and collaborations.

According to the company’s official website, OrangeSail Bio focuses on four major disease areas addressing global health challenges: oncology, autoimmunity and inflammation, neurodegenerative diseases, and ophthalmology. Its pipeline includes bispecific/multispecific antibodies, antibody-drug conjugates (ADCs), and novel therapeutic modalities. The company is also committed to building a robust internal discovery engine and establishing a “closed loop” between discovery and clinical development through translational medicine. Furthermore, by combining internal discovery and development with win-win partnerships, OrangeSail Bio continuously builds and advances its product portfolio with the highest quality and efficiency.

Since its inception, OrangeSail Pharma has carried a “star-studded” aura—founded by Dr. Li Jing, former Senior Vice President of WuXi Biologics. In 2021, the company secured $50 million in angel-round funding, established its global R&D headquarters in Shanghai, and set up a clinical center in Boston, USA.

Dr. Li Jing, the founder, has previously worked at Wyeth Pharmaceuticals (now Pfizer), the Oncology Research Department and Biologics New Drug Center of Novartis Pharmaceuticals, and the Biologics New Drug R&D Department of WuXi Biologics. He possesses over 20 years of experience in innovative biologic drug development at international pharmaceutical companies. The Biologics New Drug R&D Department at WuXi Biologics, established by Dr. Li in 2013, built a drug discovery team of more than 300 members, ranking first in China’s biologics industry at that time. It developed a pipeline of over 300 projects and completed the transfer of more than 40 projects, successfully supporting the biologic drug product pipelines of numerous domestic and international companies.

Certainly, the key to sustaining the “star enterprise” halo lies in its exceptionally strong talent team and pipeline R&D capabilities.Within just three years, OrangeSail Biopharma has advanced multiple molecules to the IND-enabling study stage. At the 2024 AACR Annual Meeting, OrangeSail Biopharma publicly disclosed preclinical data for two of its pipelines: VBC101-F11, an EGFR/cMet bispecific antibody-drug conjugate (ADC), and VBC103, a TROP2/Nectin-4 bispecific ADC.

OrangeSail Pharma’s core pipeline focuses on the highly sought-after lung cancer targets EGFR and c-MET, which have attracted significant investment from multinational corporations (MNCs) such as AstraZeneca. VBC101-F11 is a bispecific antibody-drug conjugate (ADC) developed by OrangeSail Pharma that targets EGFR and c-Met, featuring a low-affinity EGFR arm and a high-affinity c-Met arm. In vivo CDX models using various lung cancer cell lines demonstrated that VBC101-F11 exhibited a clear advantage over AbbVie’s ABBV-399 in inhibiting tumor growth at a single dose of 3 mg/kg, with tumor growth inhibition (TGI) rates of 60% versus 17%.

VBC103 focuses on the Trop2 and Nectin4 targets, which are highly co-expressed in urothelial carcinoma, triple-negative breast cancer, and other tumors.VBC103 delivers a TOPOi payload with a potent bystander effect to tumor cells, maximizing efficacy while minimizing safety concerns.Data show that VBC103 exhibits enhanced binding affinity, internalization, and cytotoxicity compared with the Nectin-4 monoclonal antibody or the approved Nectin-4 ADC, Padcev.

Notably, the acquirer, Avenzo Therapeutics, is a clinical-stage biotechnology company founded just three years ago. Co-established in 2022 by Dr. Athena Countouriotis and Dr. Mohammad Hirmand, the company also boasts a strong “star enterprise” profile.

Dr. Athena Countouriotis serves as President, Chief Executive Officer, and Chairman of Avenzo Therapeutics. Previously, as President and CEO, she led Turning Point Therapeutics through its initial public offering (IPO) in 2019 and its eventual acquisition by Bristol Myers Squibb for $4.1 billion in August 2022. During this period, she and her team raised more than $1.2 billion through multiple equity financings.

Dr. Mohammad Hirmand has over 20 years of experience in clinical development within the biotechnology industry. He previously served as Executive Vice President and Chief Commercial Officer at Turning Point Therapeutics, and as Chief Commercial Officer at Peloton Therapeutics (which was 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 2022, Avenzo secured approximately $200 million in seed and Series A financing from five prominent investors, including SR One, OrbiMed, Foresite Capital, Surveyor Capital, and Lilly Asia Ventures. In March 2024, Avenzo announced the closing of an oversubscribed $150 million Series A-1 financing round.On November 18, the day of the transaction, Avenzo also announced that it had secured an additional $39 million in the third tranche of its Series A financing.

Avenzo is developing and advancing a portfolio of potential best-in-class oncology therapies that target cell cycle control to prevent the abnormal cell proliferation that drives many cancers.Currently, the only public pipeline asset displayed on its official website is ARTS-021 (AVZO-021), a selective CDK2 inhibitor acquired from Anrui Biologics in January this year. ARTS-021 is undergoing a multicenter Phase I clinical trial in the United States for the treatment of HR+/HER2- metastatic breast cancer and other advanced solid tumors.Furthermore, in the January transaction this year, Avenzo also secured an exclusive option for a preclinical project from Anrui Biologics, with an IND submission scheduled for early 2025.

In previous reports, Avenzo expressed its intention to acquire early-stage oncology small molecules, including antibody-drug conjugates (ADCs), and stated that it would seek ADC opportunities in China with the assistance of Lilly Asia Ventures. Behind a series of swift financing rounds and license-in deals lies Dr. Countouriotis’s ambition to rapidly pursue an initial public offering (IPO) on the Nasdaq, potentially as early as 2024 or 2025.

According to foreign media reports, Dr. Countouriotis, founder of Avenzo Therapeutics, has been seeking ADC assets for some time. Earlier this year, Avenzo submitted higher bids in other transactions within this hot sector, as multinational corporations (MNCs) “offered quite high prices,” and she believed that the market for single-target ADC drugs might already be saturated.

Regarding the Nectin-4/TROP2 targets, Dr. Countouriotis stated that these two targets have never been combined before, so this could be the first Nectin-4/TROP2 bispecific antibody-drug conjugate (ADC). Currently, Gilead has a TROP2 ADC, Trodelvy, while Pfizer and Astellas have a Nectin-4 ADC, Padcev.

References:

VCBeat: "Avenzo Therapeutics Announces Completion of $50 Million Angel Round to Accelerate the Development of Its Innovative Drug Discovery Platform and Pipeline Progress"

Medaverse “$1.04 Billion! Avenzo Therapeutics’ CDK2 Inhibitor Secures Overseas Licensing Deal”