On April 8, 2020 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Zai Lab Limited (NASDAQ: ZLAB) reported a strategic collaboration for the development and commercialization of REGN1979 (CD20xCD3 bispecific antibody) in mainland China, Hong Kong, Taiwan and Macau (Press release, Zai Laboratory, APR 8, 2020, View Source [SID1234556192]). The collaboration will support global clinical development for REGN1979, starting with the ongoing potentially registrational Phase 2 program in B-cell non-Hodgkin lymphoma (B-NHL). Additionally, if REGN1979 is approved, Zai Lab will leverage its capabilities to commercialize REGN1979 in this region. REGN1979 is the most advanced investigational bispecific monoclonal antibody from Regeneron’s bispecific platform and is designed to trigger tumor killing by linking and activating a cytotoxic T-cell (binding to CD3) to a lymphoma cell (binding to CD20).

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Under the terms of the agreement, Regeneron will receive a $30 million upfront payment and is eligible to receive up to $160 million in additional regulatory and sales milestones. Zai Lab will contribute to the global development costs for REGN1979 for certain trials and will receive the rights to develop and exclusively commercialize REGN1979 in oncology in mainland China, Hong Kong, Taiwan and Macau. Additionally, Zai Lab will make payments to Regeneron based on net sales, such that Regeneron shares in a significant portion of any potential profits. Regeneron will be responsible for the manufacture and supply of REGN1979 for development and commercialization in the region.

"Zai Lab is an ideal collaborator for us, with an established and respected track record that aligns with our mission to use the power of science to repeatedly bring new medicines to patients with serious diseases," said Israel Lowy, M.D., Ph.D., Senior Vice President and Head of Clinical and Translational Sciences for Oncology at Regeneron. "Zai’s support will not only help bolster enrollment into global REGN1979 trials, but will also enable this promising investigational medicine to reach patients faster in this key region, if approved."

"Regeneron is a global leader in the research and development of innovative medicines, and we are delighted to collaborate on the investigational bispecific antibody REGN1979 as we expand our oncology franchise into hematologic cancers," said Samantha Du, Ph.D., Founder, Chairperson and Chief Executive Officer at Zai Lab. "Zai looks forward to contributing significantly to the success of REGN1979 with our regulatory and clinical expertise, and

commercial footprint in mainland China, Hong Kong, Taiwan and Macau. We are committed to collaborating with Regeneron to expand its global effort and bring innovative medicines to patients with unmet medical needs."

REGN1979 was granted orphan drug designation by the U.S. Food and Drug Administration (FDA) for the treatment of follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). REGN1979 is currently being investigated as a treatment for late stages of FL, DLBCL and other lymphomas in a Phase 1 trial as well as a potentially registrational Phase 2 trial. Positive data for REGN1979 from the Phase 1 trial were last shared at the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

Conference Call and Webcast Information

Zai Lab will host a live conference call and webcast today, April 8, 2020 at 8:00 a.m. EST to discuss the strategic collaboration. Listeners may access the live webcast by visiting the Company’s website at View Source Participants must register in advance of the conference call. Details are as follows:

Registration Link: View Source

Conference ID: 4299594

All participants must use the link provided above to complete the online registration process in advance of the conference call. Upon registering, each participant will receive a dial-in number, Direct Event passcode, and a unique access PIN, which can be used to join the conference call.

A replay will be available shortly after the call and can be accessed by visiting the Company’s website at View Source

About the Regeneron Bispecific Antibody Platform

All of Regeneron’s bispecifics are designed to closely resemble natural human antibodies and bind to two different targets. They are derived from a next-generation version of Regeneron’s proprietary VelocImmune technology that utilizes a proprietary genetically-engineered mouse platform endowed with a genetically-humanized immune system to produce optimized fully-human antibodies and further created using the company’s Veloci-Bi platform. These allow for the creation of bispecifics with no linkers or artificial sequences. Additionally, Regeneron bispecifics are manufactured using similar approaches used for human antibody medicines, with similar pharmacokinetics.

VelocImmune has been used to create multiple antibodies including Dupixent (dupilumab), Praluent (alirocumab), Libtayo (cemiplimab-rwlc) and Kevzara (sarilumab), which are approved in multiple countries around the world. Regeneron previously used these technologies to rapidly develop a treatment for Ebola virus infection, which is currently under review by the FDA, and is now being used in efforts to create prophylactic and treatment medicines for COVID-19.

There are six Regeneron investigational bispecific antibodies currently in ongoing clinical trials for multiple blood cancers and solid tumors. These bispecifics fall into three categories:

CD3 bispecifics are designed to bridge T-cells and tumor cells. At the tumor site, they activate T-cells via their CD3 receptors and promote T-cell killing of the cancer cells. Investigational candidates include:

CD20xCD3 (REGN1979) for non-Hodgkin B-cell lymphomas;

Two distinct BCMAxCD3s (REGN5458 and REGN5459) for multiple myeloma;

MUC16xCD3 (REGN4018) for ovarian cancer.

CD28 costimulatory bispecifics are also designed to bridge T-cells and tumor cells. At the tumor site, they costimulate T-cells via their CD28 receptors and may synergize with PD-1 inhibitors and/or CD3 bispecifics. Investigational candidates include:

PSMAxCD28 (REGN5678) in combination with Libtayo for prostate cancer.

Tumor-targeted bispecifics are designed to target proteins only on the cancer cell. In this way, they may affect various signaling pathways to hamper the cancer cell’s ability to survive and proliferate. Investigational candidates include:

METxMET (REGN5093) for non-small cell lung cancer that is driven by MET mutations and/or amplifications. REGN5093 targets two different parts of the MET receptor on cancer cells to degrade the receptor and block its ability to trigger cell proliferation.

Regulatory Status of Regeneron Oncology Programs

The bispecifics mentioned in this press release are currently under clinical development, and their safety and efficacy have not been fully evaluated by any regulatory authority.

Libtayo in combination with REGN5678 is currently under clinical development for prostate cancer, and its safety and efficacy have not been evaluated by any regulatory authority for this use. Libtayo is currently approved in the U.S. for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation, and in other countries for similar indications. In the U.S., the generic name for Libtayo is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration.

As part of a global collaboration agreement, Regeneron and Sanofi are jointly developing Libtayo, as well as Regeneron’s BCMAxCD3 and MUC16xCD3 bispecific programs.

About B-cell non-Hodgkin lymphoma (B-NHL) in China

Non-Hodgkin lymphomas (NHL) represent a diverse group of cancers that originate from B-, T- or natural killer-cells, with annual incidence and death rates in China of more than 88,000 and 48,000, respectively, as of 2018. NHL originating in B-cells (B-NHL) make up 85% of all NHL cases, with the two most common subtypes being DLBCL and FL.

DLBCL is an aggressive form of B-NHL with up to 50% of patients with advanced stage disease progressing after first-line treatment (e.g., relapsing or becoming refractory to treatment). For patients with R/R DLBCL, treatment options are limited and the prognosis is poor.

FL is a slow-growing (indolent) form of B-NHL with most cases diagnosed in advanced stages. Although median survival ranges from 8 to 15 years in advanced FL, current therapeutic options are not curative, and most patients relapse within 5 years regardless of the regimen. In some cases, FL can transform into DLBCL, at which point it is often treated in the same way as DLBCL.