Over $1.7 Billion Deal: Eternity Bio and Astellas Announce Collaboration and License Agreement for BiME® Platform and ES019 Candidate

2023Year12Month28Day, AstellasAndElpiscienceUnitedAnnouncement，TargetingBrand NewBiME(Dual-Antibody Macrophage Engager)Platform and Drug CandidatesES019Elpiscience has reached a collaboration and licensing agreement with another company. Both parties will collaborate to complete the development of two projects. Additionally, Elpiscience can grant Astellas the rights to co-develop two additional products. If Astellas exercises these rights, Elpiscience will grant it exclusive rights for further research, development, manufacturing, and commercialization of the related products.

According to the agreement, Elpiscience will receive an upfront payment and exercise fee totaling US$37 million from Astellas. In addition, Elpiscience will also receive additional research and development funding paid by Astellas to advance project development.

After Astellas exercises all rights, Elpiscience will be eligible to receive potential development, registration, and commercialization milestone payments totaling over 1.7 billion US dollars. Elpiscience will also receive royalty payments in the single-digit to double-digit percentage of global net sales of the licensed products.

Elpiscience is a clinical-stage biopharmaceutical company dedicated to leading innovation in cancer immunotherapy, aiming to benefit cancer patients worldwide. BiME (Bispecific Macrophage Engager) is a bispecific antibody platform based on tumor-associated antigens (TAA) and the inhibitory receptor (SIRPα) on macrophages. By using a blocking antibody targeting SIRPα as a macrophage engager and activator, it is linked to an anti-tumor-associated antigen (TAA) antibody, directly activating macrophages to phagocytose the specific TAA-expressing tumor.

BiME exhibits efficient phagocytosis. Fc receptors bind with TAM and tumor cells through TAA and SIRPα, specifically directing tumor-associated macrophages (TAMs) toward tumor cells. This subsequently activates the "eat-me" signal on macrophages while blocking the CD47-SIRPα "don't-eat-me" signaling pathway, thereby effectively triggering specific macrophage-mediated cytotoxicity against tumor cells.

The ES019 project is a PD-L1/SIRPα bispecific antibody molecule developed based on the BiME platform.

BiME Mechanism Diagram

Tumor-associated macrophages (TAMs) are one of the most abundant immune cells in various tumor microenvironments (TME) and are associated with poor prognosis and resistance to immune checkpoint inhibitors. BiME, as a novel technology, has the potential to alter the immunosuppressive state within the tumor microenvironment (TME) by activating macrophages and reprogramming tumor-associated macrophages (TAMs), thereby offering a new therapeutic option for cancer patients who do not respond to existing cancer immunotherapies.

The BiME platform is expected to become a novel immunotherapy in the field of diseases that currently lack effective treatment options and are rich in tumor-associated macrophages. Based on the BiME platform, Elpiscience is also continuously developing various molecules to maximize the value of this innovative platform.

Elpiscience is a clinical-stage biopharmaceutical company dedicated to leading the innovative research and development of next-generation cancer immunotherapy. Elpiscience possesses a globally innovative pipeline of cancer immunotherapy products with a broad range of targets. Relying on its outstanding R&D capabilities and innovative collaborations with international biopharmaceutical enterprises, Elpiscience adheres to the R&D goal of "one molecule per year," committing to advancing at least one globally innovative drug candidate into clinical trials each year.

Elpiscience has established three major antibody platforms. The first is the ElpiSource platform, a fully human antibody Fab library based on yeast display technology with a library capacity of up to tens of billions. It does not require animal immunization and can shorten the cycle from target to antibody screening to 2-3 months. The second is the Acebody H-L interchain disulfide bond engineered bispecific antibody platform, which addresses the challenges associated with IgG-like bispecific antibodies and simplifies the production process. The third is the BiME platform, a bispecific antibody macrophage engager that simultaneously binds to the inhibitory receptor SIRPα on macrophages and specific antigens on tumor cells, directly activating macrophages to eliminate tumor cells without triggering cytokine storms.

At the same time, based on the two major research and development strategies of eliminating immunosuppressive factors in the tumor microenvironment and reactivating exhausted T cells, Elpiscience has built an innovative product pipeline for the next generation of cancer immunotherapy, among which six candidate drugs have entered the clinical research stage.

R&D Pipeline

Among them, ES104 is a bispecific antibody that can simultaneously block the VEGF and DLL4 signaling pathways, which play important roles in angiogenesis and tumor vascularization. VEGF also plays a significant role in creating an immunosuppressive effect within the tumor immune microenvironment. Preclinical and early clinical data of ES104 indicate that blocking these two pathways simultaneously has demonstrated strong anti-tumor activity across various solid tumors, including colorectal cancer, gastric cancer, cholangiocarcinoma, pancreatic cancer, and non-small cell lung cancer. As a monotherapy, ES104 showed sustained partial responses in patients with tumors resistant to currently approved VEGF therapies who have undergone multiple lines of treatment. In May 2022, ES104 achieved positive interim results in a Phase 2 clinical study when combined with paclitaxel for the treatment of biliary tract cancer (BTC).

ES102 is a best-in-class potential OX40 agonist antibody. ES102 has demonstrated best-in-class efficacy as a monotherapy and in combination therapy in preclinical animal tumor models. ES102 is currently undergoing Phase 1 clinical trials in China, both as a monotherapy and in combination with toripalimab.

ES101 is a global first-in-class, tetravalent bispecific antibody that simultaneously targets PD-L1 and 4-1BB, featuring a unique mechanism of action with PD-L1 binding-dependent activation of 4-1BB. Currently, ES101 has entered Phase I clinical trials in both China and the United States.

This collaboration marks another significant milestone for Elpiscience. Regarding this partnership, Dr. Xiaohui Ji, Chairman of the Board and CEO of Elpiscience, stated: "Astellas is a globally leading company in developing transformative innovative drugs, and we are honored to collaborate with them. The BiME platform, independently developed by Elpiscience, breaks through the traditional cell-engaging technology dominated by T cells. For cancers that currently lack effective treatment options and are rich in tumor-associated macrophages, the bispecific antibody drug molecules generated by BiME are expected to become a new type of immunotherapy in this disease area. We look forward to working with Astellas to translate this exciting scientific achievement into groundbreaking therapeutic drugs that will benefit patients worldwide."

Astellas Chief Strategy Officer Adam Pearson stated: "Astellas is committed to developing innovative oncology treatment solutions and has made cancer immunotherapy one of its core R&D strategies. Elpiscience has demonstrated exceptional strength in the innovative R&D of next-generation cancer immunotherapies. We hope this collaboration will synergize the leading advantages of both parties in this field and ultimately create new treatment options for cancer patients."

Elpiscience is a clinical-stage biopharmaceutical company dedicated to developing transformative cancer immunotherapies with the aim of benefiting cancer patients worldwide. The company’s innovation focuses on research into the tumor microenvironment, exploring and validating more effective mechanisms for tumor killing. Based on its proprietary patented platform, Elpiscience has established a globally innovative pipeline of cancer immunotherapy products, including the novel BiME platform, which connects and activates macrophages to eliminate tumor cells without triggering inflammatory cytokine storms.

Astellas Pharma Group is a pharmaceutical company with operations in more than 70 countries and regions worldwide. Currently, we are advancing the "Focus Area Approach," a research strategy aimed at identifying continuous opportunities for new drug development by concentrating on physiological mechanisms and treatment methods to address unmet medical needs. At the same time, we are expanding our focus beyond prescription drugs by combining our expertise and knowledge with cutting-edge technologies from external partners in various fields to create Rx+® healthcare solutions. Through these efforts, Astellas is committed to staying at the forefront of the ever-evolving healthcare industry, transforming scientific advancements into value for patients.