BioAtla, LLC, a global biotechnology company focused on the development of Conditionally Active Biologic (CAB) protein therapeutics, and F1 Oncology, Inc., a biotechnology company discovering and developing a new class of adoptive cellular therapies (ACTs), today announced a global license agreement to combine BioAtla's CAB technology with F1 Oncology's proprietary technologies to develop and commercialize chimeric antigen receptor T-cell (CAR-T) therapies and other ACTs for the treatment of cancer.
F1 Oncology recently completed a $37M Series A financing led by F1 BioVentures LLC, Sinobioway Group, and SunTerra Capital. Through its international affiliates, F1 Oncology also entered into a development and commercialization agreement with Shanghai SunTerra Biotechnology Ltd. and its network of academic investigators to enable clinical investigation of CAB CAR-T candidates in China. F1 Oncology's partners intend to begin clinical trials in China in 2017 targeting a solid tumor indication using F1's first CAB CAR-T therapy candidate. The financial terms of this agreement include technical and regulatory milestone-based equity investments of up to $50 million through 2018, as well as supply-related payments by target and indication. F1 Oncology retains rights to all products outside China, Hong Kong, Macau and Taiwan.
BioAtla has granted F1 Oncology an exclusive worldwide license under patents and know-how controlled by BioAtla to discover, develop, manufacture and commercialize ACT preparations and treatments for cancer. The financial terms of this license to F1 Oncology include a mid-single digit royalty outside of China, Hong Kong, Macau and Taiwan (the Territory). Within the Territory, the license is royalty-free and fully paid, and BioAtla shares in the product revenue. In exchange for the license rights, as well as BioAtla's agreement not to compete in ACTs, BioAtla received a majority, non-controlling interest of the outstanding capital stock of F1 Oncology and has no funding or financial obligation. BioAtla also has a conditional and time-limited option to acquire at a fixed valuation all of the outstanding equity securities of F1 Oncology held by all other investors.
BioAtla and F1 Oncology have identified CAR-T and other ACT therapies as potential opportunities for the application of CAB technology. BioAtla has demonstrated in preclinical studies that CAB antibodies can be constructed in the same single chain format used by CAR-Ts and can retain their selectivity for binding under conditions representative of the tumor microenvironment (TME) and with minimal to no detectable binding in normal cell conditions. CARs are constructs that contain an antigen–binding domain of an antibody fused to a strong T-cell activator domain. T-cells modified with the CAR construct can bind to the antigen and be stimulated to attack the bound cells. On-target, off-tumor toxicity has largely limited current CAR-T therapies to target blood cancers such as leukemia and some lymphomas. While CAR-T related toxicities are multifactorial and complex, CAR-T cells containing CAB CAR domains targeting solid tumor antigens would be intended to reduce on-target, off-tumor toxicity and potentially increase patient safety.
"We are pleased and excited to collaborate with Dr. Frost and his experienced team at F1 Oncology to combine our CAB technology with F1 Oncology's proprietary technology and manufacturing expertise to develop new CAR-T therapies. Through our combined efforts, F1 Oncology will focus on developing effective and safer therapy to patients and especially to those afflicted with solid tumor cancers representing the great majority of cancer cases," stated Jay M. Short, Ph.D., Chairman, President and Chief Executive Officer of BioAtla. "The structure of our agreements provides for the advancement of CAB opportunities in the important field of ACTs while allowing BioAtla to focus its research, development and management capabilities and financial resources on its primary objectives of creating and commercializing CAB antibodies for cancer therapy and for treatment of other diseases."
"Dr. Short and I have a successful history of early research collaborations in protein evolution that we look forward to applying to this key challenge of adoptive cellular therapy for solid tumors" noted Gregory I. Frost, Ph.D., Chairman and CEO of F1 Oncology, Inc. "While patient safety, CAR-T cell engraftment, and definitive radiologic response are the key milestones from which these first programs must be judged, we are encouraged by the successful generation and pre-clinical testing by F1 Oncology of conditionally active CAR-T cells in primary human lymphocytes with a number of BioAtla's CAB domains in F1 Oncology's CAR-T platform."
About Conditionally Active Biologics (CABs)
Conditionally Active Biologic proteins are generated using BioAtla's proprietary protein discovery, evolution and expression technologies. These proteins can be mAbs, enzymes and other proteins designed with functions dependent on changes in microphysiological conditions (e.g., pH level, oxidation, temperature, pressure, presence of certain ions, hydrophobicity and combinations thereof) both outside and inside cells.
Studies have shown that cancerous tumors create highly specific conditions at their site that are not present in normal tissue. These cancerous microenvironments are primarily a result of the well understood unique glycolytic metabolism associated with cancer cells, referred to as the Warburg Effect. CAB-designed mAbs can be programmed to deliver their therapeutic payload and/or recruit the immune response in specific and selected locations and conditions within the body. CABs have the potential to increase safety because they are designed to be active only in the presence of a particular cellular microenvironment thereby preferentially binding to their intended target protein in the area of disease. In addition, the activation is reversible and can repeatedly switch 'on and off' should the CAB move from a diseased to a normal cellular microenvironment and vice versa, thereby further reducing chances the CAB would bind to the same protein located in healthy tissue or in other parts of the body and cause undesirable toxicity.
About F1 Oncology, Inc.
F1 Oncology, Inc. is a private Delaware C corporation formed in November 2015 with operations in West Palm Beach, Florida, San Diego, California and international affiliates in George Town, Cayman Islands, Hong Kong, and Shanghai, China. F1 Oncology was founded by Gregory Frost, Ph.D., co-founder and former CEO of Halozyme Therapeutics Inc., Health Sector Chief at Intrexon Corporation, and current managing director of F1 BioVentures, LLC, a biotechnology-focused investment vehicle. F1 Oncology leverages its globally integrated science, development and informatics teams located across multiple time zones to accelerate the design, high-throughput screening, discovery and development of adoptive cellular therapy candidates. The company is developing two CAB-based ACT platforms to develop TME restricted CAR-T therapies for solid tumors, as well as developing highly scalable systems for global deployment, beginning in Asia. Learn more at www.f1oncology.com.
About BioAtla, LLC
BioAtla is a global biotechnology company with operations in San Diego, California, and Beijing, China. BioAtla develops novel monoclonal antibody and other protein therapeutic product candidates designed to have more selective targeting, greater efficacy, and more cost-efficient and predictable manufacturing than traditional antibodies. By utilizing its proprietary technologies in product design and development, from target discovery to manufacturing and preclinical studies, BioAtla seeks to develop differentiated, patentable therapeutic proteins for its partners, including Pfizer, Inc., Sinobioway and F1 Oncology, and for its internal programs. BioAtla has over 170 patents issued and pending that cover its platform technologies representing a full complement of therapeutic protein development capabilities.
About Beijing Sinobioway Group Company, Limited
Sinobioway was founded in 1992 and is one of the three main industrial groups affiliated with Peking University. Sinobioway is mainly engaged in bioeconomy system establishment and bio-industry development. It primarily invests in biomedicine, bioagriculture, bioenergy, bioenvironment, bioservices, biomanufacturing and biointelligence. Biologic therapeutics is a particular focus of Sinobioway in its plans to develop and commercialize new medicines. Sinobioway is constructing a large biologics production facility, with a long-term capability goal of 100 production lines, in the planned 20 billion RMB bio-economic zone under construction in Hefei.