Vigorous Activities for Licensing Initiatives
We continue to forge ahead with licensing activities to take in new drug candidates with the aim of introducing compounds attractive for diseases with high therapeutic need, and compounds that have high value in terms of corporate strategy and effciency, while taking into consideration the development pipeline and existing products. Our aim is to expand the development pipeline to provide a continuous stream of new market launches. In the oncology domain, we take advantage of our strength with OPDIVO in acquiring product candidate compounds in a wide range of areas such as molecular target drugs including antitumor drugs and cell therapies.
Meanwhile, we are working in anticipation of our own overseas marketing in the US and Europe. We also have departments in charge of licensing activities keenly out-licensing discovered compounds to our partners upon examining optimum measures to deliver our new in-house developed drugs to patients worldwide as quickly as possible, in light of proposed indication and market size.
Our Partners inside and outside Japan (As of October 27, 2020)
For more information about our Partnering Activities up to the present, please click the button below.
For details of alliance with the partner you want to see, click that partner's logo.
Licensing & Co-promotion
Licensing & Co-promotion
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 and is expected to be the first treatment drug for this patient population. In November 2018, Ono submitted an application for a Manufacturing and Marketing Approval for anamorelin for the improvement of body weight loss and anorexia in patients with cancer cachexia in Japan.
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 KAI Pharmaceuticals, Inc., (acquired by Amgen later), to exclusively develop and commercialize etelcalcetide hydrochloride (ONO-5163), a calcium sensing receptor agonist in Japan, which was under development for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis in the US. The product decreases serum calcium and phosphorus level and reduces risk of cardiovascular disorders including arteriosclerosis, by activating calcium sensing receptor which leads to suppressing excessive PTH secretion from the parathyroid. Amgen received an approval of etelcalcetide for the treatment of secondary hyperparathyroidism in adult hemodialysis patients with chronic kidney disease in EU in November 2016 and in the US in February 2017. In Japan, Ono received an approval of etelcalcetide for the indication of secondary hyperparathyroidism in patients on hemodialysis in December 2016 and launched it under the product name of Parsabiv® Intravenous Injection for Dialysis in February 2017.
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 in Japan with AstraZeneca K.K. (AZKK), an affiliate of AstraZeneca with regard to 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 AZKK 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, and for chronic heart failure being treated with standard care in November 2020. AZKK submitted an additional application of Forxiga® for the treatment of chronic kidney disease in December 2020.
In December 2014, Ono entered into an exclusive license agreement with Gilead Sciences, Inc. to develop and commercialize tirabrutinib hydrochloride (ONO-4059), an oral Bruton's tyrosine kinase (BTK) inhibitor, discovered and developed by Ono, world-widely except Japan, South Korea, Taiwan, China and the Association of Southeast Asian Nations (ASEAN) countries, where Ono retains development and commercialization rights. Tirabrutinib is a selective BTK inhibitor under clinical development for the treatment of patients with B-cell malignancies and auto-immune diseases in Japan. Ono received an approval for the treatment of recurrent or refractory primary central nervous system lymphoma (PCNSL) in March 2020 and launched it under the product name of Velexbru® (tirabrutinib) tablet in May 2020 in Japan. Ono also obtained an approval for additional indication of Waldenstrom macroglobulinemia (WM) and lymphoplasmacytic lymphoma (LPL) in August 2020. Tirabrutinib is currently in Phase 2 study for the treatment of pemphigus in Japan. Abroad, it is now in Phase 2 study for the treatment of B cell lymphoma.
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 5F9, their monoclonal antibody against CD47, in Japan, South Korea, Taiwan and ASEAN countries. 5F9 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. 5F9 is now under development for the treatment of patients with non-Hodgkin’s lymphoma, colorectal cancer, etc. and is expected to bring its benefit to patients suffering from various types of cancer.
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 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 conjugated sodium hyaluronate) is a formulation in which hyaluronic acid and diclofenac (anti-inflammatory drug) are chemically bound using the Seikagaku’s own proprietary technology. The product combines pain relief and anti-inflammatory effect of diclofenac designed for sustained release with the joint function improving effect of hyaluronic acid. It is expected to provide prompt and long-lasting relief of the pain and inflammation associated with osteoarthritis. Since the product is administered directly into the joint cavity as an injectable treatment, the risk of systemic adverse drug reaction is thought to be low.
Ono entered into an exclusive strategic research, development and commercialization partnership with Repare Therapeutics, Inc. (“Repare”) for development and commercialization of Repare’s small molecule Pol-theta (Polθ) inhibitor, which is now under discovery, in Japan, South Korea, Taiwan, Hong Kong, Macau and ASEAN countries. Repare is a privately-held precision oncology company pioneering synthetic lethality to develop novel therapeutics that target specific vulnerabilities of tumors in clearly defined patient populations, and is currently committed to discovering and developing a small molecule Polθ inhibitor. DNA Polymerase-theta (Polθ) is a unique, multifunctional DNA polymerase essential to repairing DNA breaks, especially in homologous recombination deficient (HRD) cells. Polθ gene expression is low in normal cells but elevated across a broad range of tumor types, including those with HRD. In this respect, a Polθ inhibitor is expected to become an effective drug across multiple tumor types.
In June 2019, Ono entered into a license agreement with Rafael Pharmaceuticals, Inc. to exclusively develop and commercialize devimistat (ONO-7912/ CPI-613), a cancer metabolism inhibitor, and other related compounds in Japan, South Korea, Taiwan and ASEAN countries. Rafael is a non-profitable 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. Ono has been conducting Phase 1 study for the treatment of pancreatic cancer in Japan and Rafael conducting Phase 3 study for the treatment of pancreatic cancer and acute myeloid leukemia in South Korea.
In October 2020, Ono entered into an exclusive license agreement with SK Biopharmaceuticals Co., Ltd. (SKBP) to exclusively develop and commercialize cenobamate, 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 (GABAA) 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. In Japan, it is in a Phase 3 clinical study by SKBP for the treatment of partial-onset seizures in adult patients. Cenobamate is expected to be a new treatment option for patients suffering from epilepsy in Japan.
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.
In November 2005, we entered into drug discovery agreement on kinases with Array Bio Pharma Inc. (became a subsidiary of Pfizer in July 2019)
Under the arrangement, the parties will seek small molecule drug candidates targeting a series of kinases selected by Ono. Ono will have the sole responsibility for clinical development and commercialization of resulting products.
In March 2008, Ono signed a collaboration agreement with Evotec AG of Germany on fragment-based drug discovery involving proteases. The collaboration applies Evotec's proprietary fragment-based drug discovery platform, EVOlution (TM) to identify novel, small molecular weight compounds active against a protease target chosen by Ono. In October 2009, an additional research collaboration agreement on ion channel drug discovery was signed. Under such agreement, Evotec is currently generating small molecule drug candidates targeting an ion channel selected by Ono by using its Evotec's proprietary fluorescence screening and ion channel drug discovery platform.
Ono has worldwide exclusive rights to develop and commercialize compounds created by Evotec.
In October 2012, Ono entered into a drug discovery collaboration agreement with Domain Therapeutics S.A. (Domain") targeting a G-Protein Coupled Receptor (GPCR). Domain applies DTect-All™, its proprietary GPCR drug discovery platform and its expertise in GPCR medicinal chemistry and pharmacology to design and optimize small molecules into drug candidates having activity against a GPCR selected by Ono.
In March 2017, 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 candidate in immuno-oncology. The collaboration has been favorably proceeding with the discovery of new drug candidates. In addition, Ono and Numab entered into another research and option agreement to discover an antibody binding to a combination of multiple discovery targets, different from the prior agreement, in the same therapeutic area of immuno-oncology in March 2020. Numab’s plug-and-play multi-specific antibody platform allows for a highly rational and reproducible process to rapidly yield promising clinical candidates with new mechanisms of action, superior efficacy and a favorable safety profile.Ono has an option to acquire intellectual property rights to, and worldwide exclusive rights to develop and commercialize, the selected lead compound to be generated through this collaboration, which will exploit one of Ono’s novel therapeutic approaches in immuno-oncology.
In November 2017, Ono entered into a research collaboration agreement with Neurimmune AG (Neurimmune) to discover and develop human monoclonal antibodies for neurodegenerative diseases.
Ono is committed to discovering and developing an innovative pharmaceutical product against neurodegenerative diseases which has high unmet medical needs by using human monoclonal antibodies efficiently generated by the Reverse Translational Medicine™ platform, Neurimmune’s proprietary high-throughput technology.
Ono will be exclusively responsible for worldwide development and marketing of selected lead antibodies to be generated based on Neurimmune's innovative drug discovery approach through this collaboration.
2In December 2017, Ono entered into a collaboration agreement with Cyclenium Pharma Inc. (Cyclenium) to exploit Cyclenium’s proprietary CMRT™ Technology and QUEST Library™ of next generation synthetic small-molecule macrocycles. In the collaboration, Ono and Cyclenium will work together to generate new drug candidates against multiple therapeutic targets selected by Ono where Cyclenium will be responsible for all medicinal chemistry efforts and Ono for the characterization of biological and pharmacological properties. Ono will have full rights and responsibility for development and commercialization of the resulting drug candidates worldwide.
In December 2017, Ono entered into a collaboration agreement with Schrödinger, Inc. to revolutionizing drug discovery through advanced computational methods.
Schrödinger is a leading provider of advanced molecular simulations and enterprise software solutions and services to accelerate and increase the efficiency of drug discovery for its clients, which include all major pharmaceutical and biotechnology companies worldwide, as well as leading materials science researchers. Schrödinger will work together with Ono to leverage Ono’s strength and Schrödinger’s computational drug discovery platform in the design of novel small molecules against therapeutic targets selected by Ono.
In September 2018, Ono entered into a collaboration agreement with Fate Therapeutics, Inc. (Fate) for the joint development and commercialization of off-the-shelf chimeric antigen receptor (CAR) -T cell product candidates for cancer.
Fate is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for cancer and immune disorders. The Company’s proprietary iPSC product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered in repeat doses.
Fate will generate two iPSC-derived CAR-T cell product candidates, one for the treatment of lymphoblastic leukemias for which Ono has an option to assume responsibilities for exclusive development and commercialization in Asia, and another for the treatment of solid tumors for which Ono has an option to assume responsibilities for worldwide development and commercialization.
In March 2019, Ono entered into a drug discovery research collaboration agreement with twoXAR, Inc. (“twoXAR”) to jointly discover and develop novel, efficacious treatments to address unmet medical needs in a specific neurological disease. twoXAR will use its proprietary artificial intelligence (AI) technology to identify a set of lead compounds which demonstrate a novel mechanism of action and will be further optimized by Ono for potential drug candidates. twoXAR will also predict a set of hypotheses which suggest the efficacy and safety of such lead compounds for the therapy. Ono and twoXAR will select several compounds with their hypotheses from this set to test in further validation study. Ono will retain exclusive rights to develop and commercialize the compounds obtained through this collaboration throughout the world.
In March 2019, Ono entered into a collaboration and license agreement with Vect-Horus S.A.S (Vect-Horus), focused on the development of novel molecules targeting neurodegenerative diseases. Ono is committed to discovering, in collaboration with Vect-Horus, an innovative pharmaceutical product which is a conjugate of a Vect-Horus’ peptide vector and Ono’s therapeutic molecule combined by using Vect-Horus’ proprietary VECTrans® technology facilitating the transport of drugs into the brain. Ono will have worldwide exclusive rights to develop and commercialize any pharmaceutical products arising out of this drug discovery 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.
From April 2014, Ono is in collaboration with Merus N.V. (“Merus”) for generation of new bi-specific antibody therapeutics. Further, Ono exercised its option under this collaboration agreement and entered into another collaboration in March 2018.
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.