Since April 2014, Ono has been in collaboration with Merus N.V. (“Merus”) for generation of new bi-specific antibody therapeutics, and ONO-4685, a bi-specific antibody obtained through this collaboration is now in clinical development. Additionally Ono entered into another collaboration with Merus in March 2018 to generate a new bi-specific antibody binding different combination of therapeutic targets from that of the 2014 agreement.
A bi-specific antibody has an ability to bind to two different targets simultaneously. Merus will generate bi-specific antibodies called Biclonics® that bind certain target molecules selected by Ono using Merus’ proprietary Biclonics® technology platform. Ono will further evaluate biological activities and safety profiles of selected antibodies with the goal of generating new drug candidates in the area of autoimmune disease. Ono will have worldwide exclusive rights to develop, manufacture, and commercialize the resulting products developed through the collaboration.

In March 2017, Ono entered into a research and option agreement with Numab Therapeutics AG (Numab) to discover and develop a multi-specific antibody drug candidate in immuno-oncology. In March 2022, Ono exercised its option to enter into a development and license agreement with Numab. Under the Agreement, Ono has exclusive global development and commercialization rights for the multi-specific antibody.
Separately from the above agreement, in March 2020, Ono expanded the alliance with Numab by entering into a second research and option agreement to discover and develop a distinct multi-specific antibody drug candidate in immuno-oncology, binding to a distinct combination of therapeutic targets from that covered by the 2017 Agreement.

In November 2017, Ono entered into a first drug discovery collaboration agreement with Neurimmune AG (Neurimmune) to discover and develop human monoclonal antibodies against Ono’s selected therapeutic target in the field of neurodegenerative diseases. The companies are committed to creating innovative human-derived monoclonal antibodies against neurodegenerative diseases which have high medical needs, by using Neurimmune’s proprietary Reverse Translational Medicine™ (RTM™) technology platform, a unique antibody drug creation approach.
Under the collaborations with Neurimmune, Ono retains exclusive rights for worldwide development and commercialization of antibody products resulting from the collaboration.

In September 2018, Ono entered into a drug discovery collaboration agreement with Fate Therapeutics, Inc (Fate) with the aim of developing drugs to treat iPS cell-derivedchimeric antigen receptor (CAR)-T cells for cancer.
Fate is a clinical stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for cancer and immune disorders. Fate's iPS cell product platform enables the mass production of off-the-shelf, engineered, homogeneous cell products that can be administered repeatedly. In June 2022, Ono executed an amendment agreement to expand its collaboration with Fate by adding a new CAR-NK cell therapy option in addition to CAR-T cells, as well as a second target for solid tumors. ONO will provide Fate with antibodies that bind to the target. Fate creates cell therapy candidates for two solid tumor targets, and Ono has rights to develop and commercialize them worldwide with Fate’s retaining the option to develop and commercialize them in the U.S. and Europe. In November 2022, Ono exercised the option to develop and commercialize ONO-8250/FT825, iPS cell-derived chimeric antigen receptor (CAR)-T cell product candidate targeting human epidermal growth factor receptor 2 (HER2)-expressing solid tumors, created under the collaboration agreement with Fate. By exercising the option, Ono and Fate will jointly develop and commercialize ONO-8250/FT825 in the U.S. and Europe, and Ono will acquire the exclusive rights to develop and commercialize ONO-8250/FT825 in the rest of the world. Fate retains manufacturing responsibilities for the products created from the collaboration.

In March 2021, Ono entered into a non-exclusive license agreement with PeptiDream Inc. (PeptiDream) to introduce PeptiDream’s proprietary automated Peptide Discovery Platform System (PDPS) technology platform. By using this PDPS (automated platform), High-affinity peptides will be identified through the use of the PDPS technology platform for new drug discovery targets, and Ono thereby aim to discover and develop innovative new drugs in a short period of time with a high probability of success. In March 2023, Ono also entered into a drug discovery collaboration agreement with PeptiDream to discover and develop novel macrocyclic constrained peptide drugs against multiple targets of Ono’s interest. Under the new agreement, Ono will obtain the exclusive worldwide rights to develop and commercialize such drug candidates.

In August 2021, Ono entered into a drug discovery collaboration agreement with MiraBiologics Inc. to discover and create the next generation of biopharmaceuticals. MiraBiologics, founded in July 2017, is a bio-venture company dedicated to creating next-generation multifunctional biopharmaceuticals. In this collaboration, Ono and MiraBiologics will use Mirabiorogics’ own proprietary LassoGraft Technology®, a new technology that combines cyclic peptide searching method and protein engineering and be committed to jointly generating biopharmaceutical candidates aiming for regulation of multiple therapeutic targets selected by Ono. Ono obtains exclusive rights to develop and commercialize biopharmaceutical drug candidates worldwide generated using their technology through the collaboration.

In January 2023, Ono entered an option and research collaboration agreement with Monash University to discover and develop antibodies targeting G protein-coupled receptors (GPCRs), in order to create novel therapeutics for the treatment of autoimmune and inflammatory diseases.
In August 2024, Ono entered into a new option and research collaboration agreement.
The Agreement executed this time is to discover and create antibodies binding to a therapeutic target of GPCRs different from the existing agreement. Similar to the earlier collaboration, under the terms of the Agreement, Monash University’s Biomedicine Discovery Institute will lead another antibody discovery campaign to target GPCR traditionally hard to target. Ono will obtain exclusive worldwide rights to develop and commercialize a therapeutic product based on an antibody that Ono will select from the multiple anti-GPCR antibodies created by Monash University. Ono will make an upfront payment to Monash University with the research funding during the option period.
Monash University spin-outs are developing sustainable solutions to global challenges like climate change and advancing the human species through scientific breakthroughs in IVF, cardiovascular disease, mental health and more.

In January 2023, Ono entered into an agreement with KSQ Therapeutics (KSQ) to acquire multiple research-stage DNA damage response programs identified using KSQ’s proprietary, integrated discovery CRISPRomics® platform technology.
KSQ's proprietary CRISPRomics® platform technology enables genome-scale, in vivo validated, unbiased drug discovery across broad therapeutic areas. Ono will retain worldwide exclusive development and commercialization rights to any drug candidates to be discovered by Ono.

In March 2023, Ono entered into a drug discovery collaboration agreement with MOLCURE Inc. (MOLCURE) to discover and develop innovative antibody drugs for multiple targets utilizing MOLCURE’s AI-driven platform technology.
MOLCURE's AI drug discovery platform technology integrates with evolutionary molecular engineering, next-generation sequencing, laboratory automation technologies, and a proprietary database containing more than one billion molecular entries. These capabilities enable the delivery of diverse, high affinity, specific and functional antibodies and peptides for researchers. Ono will obtain option rights to exclusively and globally develop and commercialize therapeutic antibody drug candidates generated through the collaboration.

In August 2023, Ono entered into a drug discovery collaboration agreement with Twist Bioscience Corporation, (Twist), to discover and develop innovative antibodies for autoimmune diseases. Under the terms of the agreement, Twist will utilize the Twist Biopharma Solutions Library of Libraries to conduct research activities to discover novel antibodies against therapeutic target(s) identified by Ono. Twist’s Library of Libraries is an expansive collection of synthesized antibody libraries based on naturally occurring sequences that harness innovative structural and developability features to cover a wide range of drug targets.
Ono will retain exclusive rights to globally develop, manufacture and commercialize therapeutic antibody drugs generated through the collaboration.

In September 2023, Ono entered into a drug discovery collaboration agreement with Adimab, LLC (Adimab), the global leader in the discovery and optimization of fully human monoclonal and bispecific antibodies, to discover and develop innovative antibody drugs in the oncology field.
Under the terms of the agreement, Adimab will discover novel therapeutic antibodies against multiple targets selected by Ono and generate bispecific antibody product candidates. Ono will evaluate and develop such candidates at the pre-clinical and clinical stages.
Ono will have an option to obtain exclusive rights to globally develop, manufacture and commercialize the candidates to be generated through this collaboration.

In October 2023, Ono entered into a research collaboration agreement with Turbine to identify and validate novel therapeutic targets in the field of oncology using Simulated Cell^TM, its in silico cell simulation technology that leverages machine learning to build an end-to-end, interpretable cell simulation platform based on protein interactome and additional omics layers. Informing biopharma R&D through in silico experiments improves the likelihood of success for truly novel therapies and allows existing assets to be optimally targeted at responder patients. Ono will exclusively develop and commercialize drug candidates to the targets identified by Turbine worldwide.

In December 2023, Ono entered into a research collaboration agreement with UK Dementia Research Institute (“UK DRI”), a national institute that dedicates research on dementia, to identify the novel therapeutic targets in the research field of dementia.
In this collaboration, as part of the promotion of our ongoing open innovation, Ono will initiate a multi-year collaborative research with UK DRI to identify novel therapeutic targets related to the diagnosis, prevention, and treatment of dementia. Ono will call for research themes from affiliated with UK DRI, focusing on our research areas of interest, such as diseases involving glial cells and neuroinflammation, etc. Ono will provide funding for selected joint research themes to identify new therapeutic target molecules for the treatment of dementia. During the research collaboration period, Ono will utilize its expertise and knowledge in the field of neuroscience to drive the joint research. Through the research collaboration, Ono will also identify new therapeutic target molecules for various types of dementia and conduct exploratory research to elucidate the mechanisms involved.
As for such molecules identified through the collaboration, Ono will generate drug candidates against those target molecules and work towards the development and commercialization of new drugs for the treatment of dementia.

In February 2024, Ono entered into a drug discovery collaboration agreement with Epsilon Molecular Engineering, Inc. (EME) to generate novel VHH antibodies, aiming at the creation of innovative VHH antibody drugs. EME will obtain novel humanized VHH antibodies against multiple targets selected by Ono, by leveraging EME’s proprietary humanized VHH screening platform, “The Month”. Ono will hold option rights to exclusively develop and commercialize the antibody drug candidates generated through the collaboration worldwide.

In March 2024, Ono entered into a five-year, university-wide strategic research alliance agreement with Harvard University aiming at validating novel therapeutic targets.
In this alliance, as part of our ongoing open innovation initiative to collaborate with external partners, the request for proposals will be for research projects focused on the validation of novel therapeutic targets from labs across Harvard University in Ono’s priority research areas of oncology, immunology, neurology, and specialty with high unmet medical needs. Working together with Harvard’s Office of Technology Development (OTD), Ono will support research projects that are jointly selected, and with the combined expertise and resources of both Ono and Harvard, this strategic alliance will promote our innovative drug discovery efforts.

In March 2024, Ono entered into a collaboration agreement with Sibylla Biotech to generate novel drug candidates for neurological disorders. Sibylla utilizes its proprietary protein degradation technology platform, PPI-FIT* technology to identify and generate small molecule Folding Interfering Degraders (FIDs) that induce the degradation of a target protein against therapeutic targets selected by Ono. Ono will generate drug candidates based on FIDs obtained from Sibylla and have an exclusive right to develop and commercialize these compounds worldwide.

In March 2024, Ono entered into a comprehensive drug discovery collaboration agreement with the University of Oxford to verify drug discovery seeds and obtain screening compounds for the creation of innovative medicines.
In this comprehensive collaboration, Ono will meticulously select drug discovery seeds from the Oxford’s portfolio that align with our research priority themes, and Oxford will conduct validation tests and compound screening for the drug discovery seeds at Oxford. First, Ono has selected the research theme relating to neuroscience, which is one of our four priority research areas and is also an expertise area at Oxford.

In April 2024, ONO entered into a drug discovery collaboration agreement with PRISM BioLab to generate novel drug candidates in the oncology area. PRISM BioLab is a discovery and development biotechnology company utilizing proprietary PepMetics® technology to discover orally available small molecule inhibitors of protein-protein interaction (PPI) targets and transform lives of patients suffering from cancer, autoimmune, fibrosis and other diseases.
Ono and PRISM will collaborate to identify and generate development drug candidates of a protein-protein interaction (PPI) target selected by Ono utilizing PRISM’s proprietary PepMetics® technology. Ono will acquire exclusive worldwide rights to develop and commercialize small molecule compounds generated through the collaboration.

In October 2024, we entered into a license agreement with LigaChem Biosciences, Inc. for LCB97, a pre-clinical stage antibody-drug conjugate (ADC) in the field of solid tumors, as well as a research collaboration and license agreement to generate novel ADC candidates using LCB’s proprietary ConjuAll™ ADC platform. LCB97 targets the L1 cell adhesion molecule (L1CAM) and has demonstrated strong anti-tumor effects in various mouse cancer models. Additionally, we have entered into a separate research collaboration and license agreement to generate novel ADC candidates using LCB’s ConjuAll™ ADC platform, obtaining global rights to ADCs against multiple targets.

In December 2024, Ono Entered into Drug Discovery Collaboration Agreement with Congruence Therapeutics (Congruence) to generate novel small molecule correctors against multiple protein targets in the oncology area by leveraging Congruence’s proprietary drug discovery platform, Revenir™.
Under the terms of the agreement, Congruence will generate small molecule correctors by leveraging the Revenir™. Ono will obtain exclusive option rights to develop, manufacture and commercialize the identified small molecule correctors worldwide.

In March 2025, Ono entered into a drug discovery collaboration agreement with Reborna Biosciences, Inc. (“Reborna”) to generate new small molecule compounds that target ribonucleic acid (RNA) in the central nervous system. We will jointly conduct drug discovery research with the aim of identifying small molecule compounds using Reborna’s proprietary RNA-targeting drug discovery platform. Ono will obtain an exclusive option right to develop, manufacture and commercialize the small molecule compounds worldwide.

In April 2025, Ono entered into a drug discovery collaboration agreement with Jorna Therapeutics. (“Jorna”) to use AI-based drug discovery platform. Under the agreement, Jorna will design RNA editing drug sequences using its proprietary protein and RNA generative AI model, which is based on the quantum mechanics-based AI called SkyEngine. Ono will have an exclusive option right to discover, develop, and commercialize drug candidates generated by the sequences designed by Jorna worldwide.

In November 2015, Ono entered into a drug discovery collaboration agreement with Vanderbilt University to discover novel, efficacious therapeutic drugs for diseases with unmet medical needs. Under the agreement, Ono and Vanderbilt University have been engaged in jointly identifying compounds to validate if an under-explored family of ion channels or transporters has a potential for a therapeutic target, and based on the validation, will discover clinical candidates for the treatment of CNS disorders.