In May 2005, Ono entered into a collaborative research agreement with Medarex Inc. (acquired by Bristol Myers Squibb (BMS)) a human anti-human PD-1 (programmed cell death-1) monoclonal antibody. The companies have created and developed nivolumab (ONO-4538/BMS-936558/MDX-1106) through the research collaboration. In September 2011, in order to accelerate the global development of Opdivo® (nivolumab), Ono and BMS entered into the agreement to grant BMS and expand its territorial rights to develop and commercialize Opdivo® globally, except Japan, South Korea and Taiwan. In July 2014, the companies further expanded their strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agent and combination regimens – for patients with cancer in Japan, South Korea and Taiwan. In September 2014, Ono launched Opdivo® Intravenous Infusion for the treatment of melanoma in Japan, and received additional approvals for several types of cancers,
Simultaneously, with execution of the agreement on nivolumub, Ono entered into the agreement with BMS to jointly develop and commercialize Orencia® (abatacept) for the treatment of rheumatoid arthritis in Japan with Bristol-Myers Squibb KK, a Japanese subsidiary of BMS and launched it under the product name of Orencia® for S.C. Injection in August 2013.

In December 2005, Ono signed an agreement with Novartis Pharma AG on the co-development and commercialization of rivastigmine (ONO-2540/ENA713D) in Japan for the treatment of Alzheimer's disease. It was launched in July 2011 by Ono as "Rivastach® Patch" and by Novartis Pharma KK as "Exelon® Patch" for suppression of the progression of symptoms associated with mild to moderate Alzheimer’s disease dementia. The product is the first transdermal patch developed using rivastigmine (oral drug) for the treatment of Alzheimer's disease.

In October 2006, Ono originally entered into a license agreement with Sapphire Therapeutics, Inc. (which was acquired by Helsinn Healthcare, S.A. of Switzerland) to exclusively develop and commercialize anamorelin hydrochloride (ONO-7643) in Japan, South Korea and Taiwan. Anamorelin is an orally active ghrelin receptor agonist. It has shown effects in increasing body weight and muscle mass, as well as appetite in patients with cancer cachexia. In January 2021, Ono received an approval of anamorelin in Japan for the treatment of cancer cachexia in malignant tumors of non-small cell lung cancer, gastric cancer, pancreatic cancer or colorectal cancer, and launched it under the product name of Adlumiz® tablets in April 2021.

In September 2010, Ono entered into a license agreement with Onyx Pharmaceuticals, Inc. (currently a subsidiary of Amgen) to exclusively develop and commercialize two proteasome inhibitors, carfilzomib (ONO-7057) and oprozomib (ONO-7058) for the treatment of any types of cancers in Japan. Carfilzomib has been launched in the US under the product name of Kyprolis® for the treatment of relapsed or refractory multiple myeloma since July 2012. In Japan, it was approved for the above same indication in July 2016, and launched under the product name of Kyprolis® in August 2016. In addition to the approved twice-weekly therapy in combination with dexamethasone, the additional approval of Kyprolis® once-weekly therapy in combination with dexamethasone was approved in November 2019, leading to a convenience in medication to patients.

In September 2011, Ono entered into a license agreement with Les Laboratoires Servier to exclusively develop and commercialize ivabradine hydrochloride (ONO-1162) in Japan. Ivabradine selectively inhibits an HCN channel, one of the ion channels which play the function of pacemaker of heart and to reduce heart rate without affecting systolic function of the heart or blood pressure. It was launched by Servier in the overseas for the treatment of stable angina in January 2006, and was approved for the additional indication of chronic heart failure (CHF) in EU in February 2012, and in the US in April 2015. In September 2019, Ono received an approval of ivabradine in Japan for the treatment of patients with CHF with sinus rhythm and baseline resting heart rate ≥75 beats per minute (limited to patients receiving standard treatment of CHF, including β-blocker), and launched it under the product name of Coralan® Tablets in November 2019.

In April 2013, Ono entered into a license agreement with BIAL to exclusively develop and commercialize opicapone (ONO-2370), a long acting COMT (Cathechol-O-Methyl Transferase) inhibitor in Japan, which has been discovered and developed by BIAL for the improvement of the end-of-dose motor fluctuations (wearing-off phenomenon) of Parkinson’s disease. Opicapone has shown a long-lasting effect on COMT inhibition in a once daily dosing in clinical studies, and is expected to improve a dosing convenience to patients. In June 2016, BIAL received an approval of opicapone in Europe as adjunct therapy to preparations of levodopa/DOPA decarboxylase inhibitors (DDCis) in patients with Parkinson’s disease and end-of-dose motor fluctuations who cannot be stabilized on those combinations, and has been marketing it under the product name of Ongentys®. In June 2020, Ono received an approval of opicapone in Japan for the improvement of the end-of-dose motor fluctuations (wearing-off phenomenon) of Parkinson's disease as an adjunctive therapy to levodopa preparations, and launched it under the product name of Ongentys® tablet in August 2020.

In December 2013, Ono entered into co-promotion agreement with AstraZeneca regarding dapagliflozin, sodium-glucose co-transporter 2 (SGLT-2) inhibitor. Based on this agreement, Ono is responsible for distribution and marketing of Forxiga® (dapagliflozin) Tablets and has been co-promoting it with AstraZeneca in Japan. Forxiga® is a selective and reversible SGLT-2 inhibitor which inhibits glucose reabsorption from renal uriniferous tubule, and reduces blood glucose by releasing excess glucose in blood to urine. Forxiga® is the first SGLT-2 inhibitor approved in the world for the treatment of type 2 diabetes by working independently of insulin to improve fasting blood glucose and postprandial hyperglycemia. In May 2014, both companies launched it under the product name of Forxiga® Tablets as a once-daily oral treatment of type 2 diabetes. It was also approved for the additional indications of type-1 diabetes in March 2019, chronic heart failure being treated with standard care in November 2020, and chronic kidney disease excluding patients with end-stage renal disease or undergoing dialysis in August 2021.

In July 2019, Ono entered into an exclusive license agreement with Forty Seven, Inc. (became a wholly owned subsidiary of Gilead in April 2020) for the development, manufacture and commercialization of magrolimab (ONO-7913), their monoclonal antibody against CD47, in Japan, South Korea, Taiwan and ASEAN countries. Magrolimab is a monoclonal antibody against CD47 that is designed to interfere with recognition of CD47 by the SIRPα receptor on macrophages, thus blocking the "don't eat me" signal used by cancer cells to avoid being ingested by macrophages. Ono has been conducting Phase 3 study for the treatment of TP53-mutant acute myeloid leukemia, Phase 1 study for the treatment of myelodysplastic syndromes, pancreatic cancer and colorectal cancer in Japan. Gilead has been conducting clinical studies for the treatment of myelodysplastic syndromes, acute myeloid leukemia, etc. overseas.

In May 2017, Ono entered into a license agreement with Array BioPharma Inc. (became a subsidiary of Pfizer in July 2019) to exclusively develop and commercialize encorafenib (ONO-7702), a BRAF inhibitor and binimetinib (ONO-7703), a MEK inhibitor in Japan and South Korea. Braftovi® (encorafenib) and Mektovi® (binimetinib) suppress the proliferation of tumors by targeting and selectively inhibiting the key enzymes of BRAF and MEK1/MEK2, respectively, which are different kinases of a family of serine/threonine kinases in the MAPK signaling pathway (RAS-RAF-MEK-ERK) associated with melanoma and various cancers. In Japan, Ono received an approval of both products for the indication of unresectable melanoma with a BRAF mutation in January 2019, and launched Braftovi® and Mektovi® in February 2019. In November 2020, the products were approved for the treatment of unresectable advanced or recurrent BRAF-mutant colorectal cancer that has progressed after chemotherapy, in the triplet combination therapy with cetuximab, an anti-human EGFR monoclonal antibody, and Braftovi® was also approved in the doublet combination therapy with cetuximab for the colorectal cancer indication. In May 2023, Ono submitted supplemental applications for approval of BRAFTOVI® and MEKTOVI® in Japan for the treatment of radically unresectable BRAF-mutant thyroid cancer, in doublet combination therapy with BRAFTOVI® and MEKTOVI®, for a partial change in approved items of the manufacturing and marketing approval.

In August 2017, Ono entered into a license agreement with Seikagaku Corporation (Seikagaku) to co-develop and exclusively market SI-613 in Japan under the development by Seikagaku for the treatment of osteoarthritis. Seikagaku is an R&D-based pharmaceutical company specializing in glycoscience as an area of specialization. Since its foundation in 1947, Seikagaku has continuously focused on the possibilities of glycoscience and developed original, beneficial pharmaceutical products and medical devices in the fields of orthopedic disorders and ophthalmic diseases. ONO-5704/SI-613 (diclofenac etalhyaluronate sodium) is a formulation in which hyaluronic acid and diclofenac (anti-inflammatory drug) are chemically bound using the Seikagaku’s own proprietary technology. In March 2021, Seikagaku received an approval of the product in Japan for the treatment of Osteoarthritis (knee joint and hip joint), and Ono launched it under the product name of Joyclu ® 30mg intra-articular injection in May 2021.

In June 2019, Ono entered into a license agreement with Rafael Pharmaceuticals, Inc. (the company name was changed to Cornerstone Pharmaceuticals, Inc. in May 2022) to exclusively develop and commercialize devimistat (ONO-7912), a cancer metabolism inhibitor, and other related compounds in Japan, South Korea, Taiwan and ASEAN countries. Cornerstone is a company, leading in the growing field of cancer metabolism and engaged in the development of a novel therapeutic drug for patients suffering from hard-to-treat cancers. Devimistat targets enzymes that are involved in cancer cell energy metabolism and are located in the mitochondria of cancer cells. Devimistat is designed to target the mitochondrial tricarboxylic acid (TCA) cycle, a process essential to tumor cell multiplication and survival, selectively in cancer cells. Devimistat substantially increases the sensitivity of cancer cells to a diverse range of chemotherapeutic agents. With this synergic effect, devimistat is expected to be more effective with lower side effects generally observed with chemotherapy, in potential combination with low-doses of chemotherapy.

In October 2020, Ono entered into an exclusive license agreement with SK Biopharmaceuticals Co., Ltd. (SKBP) to exclusively develop and commercialize cenobamate (ONO-2017), SKBP’s anti-seizure medication, in Japan. SKBP is a global pharmaceutical company focused on the research, development and commercialization of treatments for central nervous system (CNS) disorders, and has a pipeline of eight compounds in development for the treatment of CNS disorders, including epilepsy. Cenobamate was discovered and developed by SKBP and its U.S. subsidiary, SK life science. While the precise mechanism by which cenobamate exerts its therapeutic effect is unknown, it is believed to reduce repetitive neuronal firing by inhibiting voltage-gated sodium currents. It is also a positive allosteric modulator of the γ aminobutyric acid type A (GABA_A) ion channel. Cenobamate has been available for the treatment of partial-onset seizures in adult patients under the brand name XCOPRI® in the U.S, since May 2020. Cenobamate was also approved in EU in March 2021. In Japan, it is in Phase 3 clinical studies for the treatment of partial-onset seizures and primary generalized tonic-clonic seizures. Cenobamate is expected to be a new treatment option for patients suffering from epilepsy in Japan.

In December 2020, Ono entered into an exclusive license agreement with Chordia Therapeutics Inc. (Chordia) to develop, manufacture and commercialize the Chordia’s mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) inhibitor, CTX-177 and its related compounds world-widely. Chordia, founded in November 2017 is a bio-venture company specialized in an oncology drug discovery and development. Chordia has been aiming to create innovative anti-cancer drugs with new mode of actions. Activation of MALT1 is reported to play an important role in malignancies of lymphocytes. CTX-177 is expected to exert anti-tumor effect against these malignancies by selectively inhibiting MALT1 activity.

In February 2021, Ono entered into an exclusive license agreement with Ribon Therapeutics, Inc. (Ribon) to develop and commercialize Atamparib (ONO-7119), Ribon’s PARP7 (Poly ADP-ribose polymerase 7) inhibitor, in Japan, South Korea, Taiwan and ASEAN countries. Ribon is a biotechnology company developing first-in-class therapeutic drugs targeting novel enzyme families activated under cellular stress conditions. Ribon is exploring novel areas of biology using its BEACON⁺ platform to develop effective treatments for patients with limited therapeutic options. Atamparib has the potential to become a novel anti-cancer drug with the dual mechanisms of suppressing tumor growth and enhancing immune response to tumor cells, by inhibiting PARP7, a molecule which plays a key role in cancer survival. Ono has been conducting Phase 1 study for the treatment of solid tumor in Japan.

In March 2024, Ono entered into a license agreement with NEX-I for NXI-101. NXI-101 is a first-in-class antibody drug candidate targeting ONCOKINE-1, which is a cancer immunotherapy-resistant factor discovered by NEX-I through its proprietary target screening platform “ONCOKINE® platform”. It has a potential to be a novel antibody drug with an efficacy against multiple cancer types including cancer immunotherapy-resistant cancer.
Ono will have an exclusive right to develop and commercialize NXI-101 and its backup antibodies worldwide.

In November 2004, Ono in-licensed from Merck & Co., Inc. ("Merck"), a new class of type II diabetes oral drug sitagliptin (ONO-5435/MK-0431) and a drug for chemotherapy-induced nausea and vomiting aprepitant (ONO-7436/MK-0869).
Sitagliptin is a selective dipeptidyl-peptidase (DPP) 4 inhibitor, a drug enhancing a natural body system called the incretin system, to help regulate blood sugar, and that is a totally novel mechanism of action. In Japan, it has been co-developed with MSD K.K., Merck's Japanese subsidiary under the License Agreement between Ono and Merck and was launched in December 2009 by Ono as "GLACTIV® Tablet" and by MSD K.K. as "JANUVIA® Tablet". The drug has been commercialized by Merck as "JANUVIA® Tablet" in Europe and the US.
Aprepitant is a selective neurokinin (NK) 1 antagonist that is expected to treat chemotherapy induced nausea and vomiting not only in acute phase but in delayed phase as well. It has been developed solely by Ono in Japan and was launched as "EMEND® Capsule" in December 2009. It has been commercialized in Europe and the US by Merck & Co., Inc. as "EMEND®". In addition, in December 2011 Ono newly launched "PROEMEND® Intravenous Infusion", an injectable form of a prodrug of aprepitant (an active ingredient of EMEND® Capsule). It is expected that "PROEMEND® Intravenous Infusion" will provide a new therapeutic option to the patients and medical professionals for the treatment of chemotherapy induced nausea and vomiting because there are patients who are difficult to take "EMEND® Capsule" and majority of anticancer agents are administered intravenously.

In October 2013, Ono entered into a license agreement with Valeant Pharmaceuticals North America LLC (Its company name was changed to Baush Health Companies Inc. in July 2018) to exclusively develop and commercialize Demser® (metyrosine) in Japan. Demser® inhibits tyrosine hydroxylase related to the production of catecholamine, reduces catecholamine extremely secreted from pheochromocytoma (PC), and alleviates symptoms due to catecholamine excess secretion, such as hypertension, tachycardia and arrhythmia. In January 2019, Ono received an approval of Demser® for the improvement of status of catecholamine excess secretion in patients with PC in Japan, and launched it under the product name of Demser® Capsules in February 2019.

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 December 2016, Ono entered into worldwide OmniAb® platform license agreement with Ligand Pharmaceuticals, Inc.
OmniAb® includes three transgenic animal platforms (OmniRat®, OmniMouse® and OmniFlic®) for producing mono- and bispecific human therapeutic antibodies. The three platforms can deliver fully human antibodies with high affinity, specificity, expression, solubility and stability. Ono has rights to use the platforms to discover fully human mono- and bispecific antibodies, and is able to develop and commercialize these antibodies worldwide.

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 addition, in February 2024, Ono entered into an option and collaboration agreement with Numab to develop and commercialize a novel multi-specific macrophage engager in the oncology area that has been generated and developed by Numab. Ono has an exclusive option to develop and commercialize the multi-specific macrophage engager worldwide. Numab retains an opt-in right to develop and commercialize it jointly with Ono in the United States.

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.
In January 2022, Ono has signed an expanded drug discovery collaboration agreement with Neurimmune to discover and develop human monoclonal antibodies against Ono’s newly selected therapeutic targets for neurodegenerative diseases using the RTM™ technology platform.
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 2019, Ono entered into a strategic drug discovery alliance partnership with Cancer Research UK (CRUK) and LifeArc for cancer immunotherapy. The collaboration will identify targets for the development of both antibody and small molecule therapeutics. Boosted by investments from Ono and LifeArc, drug discovery experts will be pursuing targets within CRUK’s extensive portfolio of immuno-oncology research. And then for validated targets, LifeArc will progress antibody projects via its antibody screening and development expertise. Small molecule projects will be taken forward by CRUK Therapeutic Discovery Laboratories. Ono will have option rights to license the outputs of the alliance, and take on clinical development and commercialization of successful projects with worldwide exclusive rights.

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 research collaboration agreement with Healx Limited (Healx) to jointly discover and develop novel, efficacious treatment drugs for diseases with unmet medical needs by utilizing Healx’s unique artificial intelligence (AI) technology (Healnet). Healx, founded in Cambridge, UK in 2014, is a biopharmaceutical company, pioneering the next wave of drug discovery methods through its unique AI technology, in order to bring novel therapeutic drugs to patients with rare diseases around the world. Under this collaboration, Healx will use Healnet to identify potential indications and the mechanisms of action for Ono’s proprietary assets. Ono will conduct verification studies with our compound assets for selected diseases from their technology. Ono retains exclusive rights to develop and commercialize our compounds for the indications selected through this collaboration worldwide.

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 March 2022, Ono entered into a collaboration agreement with Iktos to discover and develop a novel small molecule compounds using Iktos’s unique artificial intelligence (AI) drug discovery technology.
Incorporated in October 2016, Iktos is a start-up company specializing in the development of AI solutions applied to chemical research, more specifically medicinal chemistry and new drug design. Under the agreement, Iktos will apply its AI technology platform and know-how, helping to bring new insights and directions into the drug discovery process based on a comprehensive data-driven chemical structure generation technology complementing Ono’s drug discovery program to expedite the identification of novel small molecules against therapeutic targets selected by Ono. Ono has exclusive worldwide rights to develop and commercialize small molecule compounds discovered in the collaboration.

In August 2022, ONO entered into an agreement to expand the research collaboration aiming to build a data-driven new drug discovery platform using Knowledge Palette’s large-scale transcriptome analysis technology. The entire picture of gene expression patterns in human cells treated with various compounds and in those given perturbations such as gene functional inhibition will be compiled into a database using Knowledge Palette's large-scale transcriptome analysis technology. Using the database leveraging with informatics approach, comprehensive cellular data will be analyzed to reveal numerous molecular mechanisms for hypothetical novel drug discovery targets, which leads to develop a platform of data driven drug discovery.

In November 2022, Ono entered a drug discovery agreement to discover and develop antibody drugs in the immuno-oncology field with Memo Therapeutics AG. Memo is an innovator in the field of antibody discovery and immune repertoire analysis. The company’s antibody discovery platform uses robust, simple, and fast microfluidic single-cell molecular cloning and screening technologies to enable antibody repertoire mining and antibody discovery at unprecedented speed, efficiency, and sensitivity.
Exploiting its technologies, Memo engages in antibody discovery for various indications for proprietary and partnered projects. The company’s current pipeline features programs in infectious diseases and immuno-oncology.

In November 2022, Ono entered a drug discovery collaboration agreement with Captor Therapeutics S.A. to develop novel small molecule degrader drugs against a currently undrugged target of interest in neurodegenerative diseases using its Targeted Protein Degradation (TPD) platform.
TPD is a revolutionary approach to developing new drugs that can target new molecular targets considered "undruggable" using classical drug modalities and provide additional treatment options for diseases where existing drugs do not provide optimal treatment.

In December 2022, Ono entered into a multi target R&D collaboration agreement with PrecisionLife Limited to identify novel therapeutic targets and patient stratification biomarkers in central nervous system (CNS) disorders for development by Ono.
PrecisionLife is a pioneering techbio company changing the way we predict, prevent, and treat chronic diseases. Its unique combinatorial analytics approach generates more insights from patient data than any other method, revealing the drivers of complex disease biology and stratifying patients at an unprecedented level of resolution.

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 February 2023, Ono entered into a collaboration and option agreement with Cue Biopharma, Inc. (Cue Biopharma) for CUE-401, a bispecific fusion protein for the treatment of autoimmune and inflammatory diseases.
CUE-401 is designed to induce and expand regulatory T cels (Tregs) through the delivery of transforming growth factor β (TGF-β) and interleukin 2 (IL-2). In pre-clinical studies conducted by Cue Biopharma, CUE-401 demonstrated induction and expansion of Tregs and has the potential to address a broad range of T-cell mediated autoimmune and inflammatory diseases.
Ono will have an exclusive option to license worldwide rights to develop and commercialize CUE -401. Cue Biopharma will also retain an option to develop and commercialize CUE-401 with Ono in the U.S.

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 March 2023, Ono entered into a worldwide drug discovery collaboration agreement with Macomics Ltd (Macomics) to develop new immuno-oncology antibody drugs against a novel macrophage target of interest in cancer.
Macomics will discover antibody candidates against a novel macrophage target identified and validated using its ENIGMAC^TM macrophage drug discovery platform. Macomics’s ENIGMAC^TM macrophage drug discovery platform integrates large volume human data sets, custom cell models, and proprietary human macrophage genome editing capability to enable identification and validation of novel macrophage therapeutic targets and is based on its deep understanding of macrophage biology. Ono will have an exclusive option to license global rights to the candidates for further development and commercialization.

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 discovery collaboration agreement with EVQLV, INC to generate novel antibodies against multiple targets selected by Ono, for the development of innovative antibody drugs.
Under the agreement, EVQLV will generate and provide therapeutic antibody designs against multiple therapeutic targets selected by Ono, using EVQLV’s proprietary Artificial Intelligence (AI)-powered Antibody Design Engine. Based on the antibody designs generated through the collaboration, Ono will generate potential antibodies to create, develop and commercialize antibody drug candidates.

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 research collaboration agreement with InveniAI® LLC, to identify novel therapeutic targets by leveraging cutting-edge InveniAI’s artificial intelligence (AI) and machine learning (ML).　InveniAI will identify novel therapeutic targets in multiple diseases specified by Ono by leveraging its AI drug discovery platforms including cutting-edge technologies, such as powerful AI and ML algorithms and Generative AI tools, and propose drug discovery hypotheses for optimization.
Ono will conduct validation studies to confirm the hypotheses for multiple therapeutic target candidates. Ono will retain exclusive rights to develop and commercialize drug candidates generated through this collaboration worldwide.

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 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.