Target Disease

Primary central nervous system lymphoma (PCNSL)

Why This Disease Focus?

• Current treatment options for relapsed or refractory PCNSL are limited, and there are no medications approved in the U.S. for the treatment of PCNSL. 
• PCNSL is a serious disease with a historically poor survival rate.  
• Despite its being a rare disease, ONO PHARMA USA is dedicated to bringing effective treatment to people living with PCNSL.

Goal of Program

Bruton tyrosine kinase (BTK) inhibitor

Tirabrutinib is a highly selective irreversible BTK inhibitor, discovered and developed by ONO. In the U.S., ONO is currently carrying out the PROSPECT Study, a Phase 2 trial (NCT04947319) evaluating the safety and effectiveness of tirabrutinib for potential treatment of newly diagnosed or relapsed/refractory PCNSL. It received orphan drug designation from the FDA in March 2023.

Learn more about the PROSPECT Study

*This molecule is not approved by the FDA for any use.

Target Disease

Primary central nervous system lymphoma (PCNSL)

Why This Disease Focus?

• Current treatment options for relapsed or refractory PCNSL are limited, and there are no medications approved in the U.S. for the treatment of PCNSL. 
• PCNSL is a serious disease with a historically poor survival rate.  
• Despite its being a rare disease, ONO PHARMA USA is dedicated to bringing effective treatment to people living with PCNSL.

Goal of Program

Bruton tyrosine kinase (BTK) inhibitor

Tirabrutinib is a highly selective irreversible BTK inhibitor, discovered and developed by ONO. In the U.S., ONO is currently carrying out the PROSPECT Study, a Phase 2 trial (NCT04947319) evaluating the safety and effectiveness of tirabrutinib for potential treatment of newly diagnosed or relapsed/refractory PCNSL. It received orphan drug designation from the FDA in March 2023.

Learn more about the PROSPECT Study

*This molecule is not approved by the FDA for any use.

Target Disease

Waldenström macroglobulinemia/Lymphoplasmacytic lymphoma

Why This Disease Focus?

• Waldenstrom macroglobulinemia (WM or the name lymphoplasmacytic lymphoma), is a rare slow-growing cancer that affects your blood cells. It’s a type of non-Hodgkin’s lymphoma. It occurs when genetic mutations change certain blood cells, setting up a chain reaction of medical conditions that may be life-threatening.

Goal of Program

BTK inhibitor

Tirabrutinib is a highly selective irreversible BTK inhibitor, discovered and developed by ONO. BTK inhibition is one of the treatment standards for patients with relapsed/refractory Waldenström’s macroglobulinemia (WM) and for patients with WM who are unsuitable for immunochemotherapy (ICT).

*This molecule is not approved by the FDA for any use.

Target Disease

Gastric cancer

Why This Disease Focus?

• Approximately 1.1 million gastric cancers are diagnosed each year globally.
• Immune checkpoint inhibitors (ICIs) have been shown to be effective against various cancer types and are approved in more than 65 countries. However, not all patients respond to currently approved ICIs and certain cancer types do not respond to current ICIs.
• Tumors that don’t respond to ICIs could be using other mechanisms besides immune checkpoint pathways to evade the immune surveillance system, and gastric cancer is one cancer type that may benefit from additional immunotherapy strategies.

Goal of Program

Prostaglandin receptor (EP4) antagonist

This highly selective small‐molecule EP4 antagonist may be a target for cancer immunotherapy as it has a different mode of action from ICIs.^*

Further study of ONO‐4578 is warranted in patients with advanced or metastatic solid tumors.

*This molecule is not approved by any regulatory authority for any use.

Target Disease

Colorectal cancer

Why This Disease Focus?

• Colorectal cancer is one of the most common cancer types, with nearly 2 million new cases diagnosed globally each year.  
• Immune checkpoint inhibitors (ICIs), have been shown to be effective against various cancer types and are approved in more than 65 countries. However, not all patients respond to currently approved ICIs and certain cancer types do not respond to current ICIs.  
• Tumors that don’t respond to current ICIs could be using other mechanisms besides immune checkpoint pathways to evade the immune surveillance system, and colorectal cancer is one cancer type that may benefit from additional strategies.

Prostaglandin receptor (EP4) antagonist

ONO‐4578 is a highly selective small‐molecule EP4 antagonist.* The PGE2 receptor EP4 subtype could be a promising target for cancer immunotherapy as it has a different mode of action from ICIs.

Further study of ONO‐4578 is warranted in patients with advanced or metastatic solid tumors.

*This molecule is not approved by any regulatory authority for any use.

Target Disease

Pancreatic cancer

Why This Disease Focus?

• Pancreatic cancer affects nearly 500,000 people globally each year and has historically been difficult to treat.  
• Immune checkpoint inhibitors (ICIs), have been shown to be effective against various cancer types and are approved in more than 65 countries. However, not all patients respond to currently approved ICIs and certain cancer types do not respond to current ICIs.  
• Tumors that don’t respond to current ICIs could be using other mechanisms besides immune checkpoint pathways to evade the immune surveillance system, and pancreatic cancer is one cancer type that may benefit from additional strategies.

Goal of Program

Prostaglandin receptor (EP4) antagonist

ONO‐4578 is a highly selective small‐molecule EP4 antagonist.^* The PGE2 receptor EP4 subtype could be promising target for cancer immunotherapy as it has a different mode of action from ICIs.

Further study of ONO‐4578 is warranted in patients with advanced or metastatic solid tumors.

*This molecule is not approved by any regulatory authority for any use.

Target Disease

Non-small cell lung cancer

Why This Disease Focus?

Non-small cell lung cancer is the most common form of lung cancer. While it typically grows more slowly than small cell lung cancer, it is more likely to have spread to other parts of the body before it is diagnosed.

Goal of Program

Prostaglandin receptor (EP4) antagonist

ONO‐4578 is a highly selective small‐molecule EP4 antagonist.^* The PGE2 receptor EP4 subtype could be promising target for cancer immunotherapy as it has a different mode of action from other therapies.

Outside the U.S., ONO-4578 is being studied for a range of solid tumors, including non-small cell lung cancer.  

*This molecule is not approved by any regulatory authority for any use.

Target Disease

Hormone receptor-positive, HER2-negative breast cancer

Why This Disease Focus?

• Hormone receptor (HR)-positive, HER2-negative breast cancer is a type of breast cancer that is driven by reproductive hormones (estrogen and/or progesterone), but that lacks a protein (human epidermal growth factor receptor 2, or HER2) that makes cancers grow faster.  
• This form of breast cancer is common: Around 70-80% of breast cancers are HR-positive, and the majority of HR-positive breast cancers are HER2-negative.

Goal of Program

Prostaglandin receptor (EP4) antagonist

ONO‐4578 is a highly selective small‐molecule EP4 antagonist.^* The PGE2 receptor EP4 subtype could be promising target for cancer immunotherapy as it has a different mode of action from other immunotherapies.

Outside the U.S., it is being studied for a range of solid tumors, including hormone receptor-positive, HER2-negative breast cancer.

*This molecule is not approved by any regulatory authority for any use.

Target Disease

T-cell lymphoma

Why This Disease Focus?

• T-cell lymphomas are rare cancers, which make up 10-15% of non-Hodgkin's lymphoma (NHL). They are categorized as tumors of mature T-cell or natural killer-cell origin. 
• T-cell lymphoma can develop in lymphoid tissues and/or outside of lymphoid tissues such as liver, skin, and blood. The main subtypes of T-cell lymphoma, peripheral T-cell lymphoma and cutaneous T-cell lymphoma, have a poorer prognosis than that seen in most B-cell NHL subtypes.  
• Therefore, new treatment options are needed for patients with T-cell lymphoma.

Goal of Program

PD-1 x CD3 bispecific antibody

Our investigational PD-1 x CD3 antibody is designed to bind specifically to human PD-1 and CD3. PD-1 is an inhibitory receptor that is expressed on malignant T cells in some subtypes of T-cell lymphomas. CD3 is a component protein of the T-cell receptor. CD3-bispecific antibody therapy is a cancer immunotherapy approach designed to engage T cells with malignant cells, inducing anti-tumor activity.

ONO is currently carrying out Phase 1 clinical trial in the U.S. and Japan to investigate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ONO-4685 in patients with relapsed or refractory T-cell lymphoma.

Learn more at clinicaltrials.gov

*This molecule is not approved by any regulatory authority for any use.

Target Disease

Non-Hodgkin lymphoma, chronic lymphocytic leukemia

Why This Disease Focus?

• Non-Hodgkin lymphoma (NHL) is a group of blood cancers that begin in the white blood cells of the immune system. Chronic lymphocytic leukemia (CLL) is a subtype of NHL.  
• People whose cancers are either unresponsive to initial treatment/s or return after treatment are in need of additional therapeutic options.

Goal of Program

MALT1 Inhibitor

ONO-7018 is a selective inhibitor against a mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1). We are currently studying ONO-7018 in patients with relapsed or refractory NHL or CLL.

In the U.S., ONO is conducting an open-label, multi-center, phase 1 trial in two phases: a Dose Escalation Phase (Part 1) and a Dose Expansion Phase (Part 2). The study will help determine the maximum tolerated dose and evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of ONO-7018 in patients with relapsed or refractory NHL or CLL. 

Learn more

*This molecule is not approved by any regulatory authority for any use.

Target Disease

Pancreatic Cancer*

Why This Disease Focus?

Pancreatic cancer is the third-leading cause of cancer-related death in the US. Strategies that help enhance the efficacy of standard of care and/or immune therapy are likely the most efficient route to improve overall survival in this disease.

Goal of Program

Axl/Mer inhibitor

Three dominant characteristics of pancreatic cancer are metastasis, therapy resistance, and immunosuppression. Axl, a member of the TAM (Tyro3, Axl, MerTK) family of receptor tyrosine kinases (RTKs), is involved in cell plasticity, chemoresistance, immune suppression, and metastasis in many cancers, including pancreatic cancer.

*This molecule is not approved by any regulatory authority for any use.

Target Disease

EGFR-mutated non-small cell lung cancer

Why This Disease Focus?

• Epidermal growth factor receptor EGFR-mutated non-small cell lung cancer may occur more commonly in young adults, women, and people who have never or rarely smoked.
• EGFR is a protein expressed on the surface of cells.
• When the EGFR undergoes a mutation, it can become stuck in the “on” position, signaling cells to divide uncontrolledly (i.e., become canceous). 

Goal of Program

Axl/Mer inhibitor

Patients with EGFR-mutated non-small cell lung cancer may become resistant to commonly used EGFR tyrosine kinase inhibitors. The addition of ONO-7475 may reduce the likelihood of resistance in this type of cancer. Outside the U.S., ONO is investigating this Axl/Mer inhibitor as an addition to treatment regimens.

*This molecule is not approved by any regulatory authority for any use.

Target Disease

Solid tumor

Why This Disease Focus?

Solid tumors include cancers of the breast, bladder, colon, prostate as well as other organs or body structures.

Goal of Program

STING agonist

Stimulator of interferon genes (STING) is a cellular protein that triggers production of proinflammatory cytokines and is thought to activate the body’s antitumor immune responses. Outside the U.S., ONO is carrying out a Phase I study of ONO-7914 in combination with nivolumab in patients with solid tumors.

*This molecule is not approved by any regulatory authority for any use.

Target Disease

HER2-expressing Solid tumor

Why This Disease Focus?

ONO PHARMA and Fate Therapeutics partnered in 2018 to pioneer the manufacture of CD8 alpha-beta T cells from iPSCs, and to discover and integrate novel synthetic controls of cell function into our iPSC-derived CAR T-cell production platform for the potential treatment of solid tumors, including functional elements designed to promote cell trafficking, resist immune suppression in the tumor microenvironment, and preferentially target cancer cells.

Goal of Program

iPSC-derived HER2 CAR T-cell therapy

Preclinical data indicate a highly-differentiated therapeutic profile across a broad range of solid tumors, with the novel HER2-targeted antigen binding domain demonstrating selective targeting of cancer cells expressing HER2, including those with low expression.

*This molecule is not FDA approved for any use.

Target Disease

Autoimmune disease

Why This Disease Focus?

• Autoimmune diseases, of which there are more than 100, can be challenging to manage.  
• Antibody therapies are a promising strategy for treating a range of immune system diseases.

Goal of Program

PD-1 x CD3 bispecific antibody

PD-1 is a receptor that is expressed on activated T cells, which inhibits activation signals of the immune system. CD3 is a component of T-cell activating receptor. ONO-4685 was designed by ONO’s Research Center of Immunology, and is a bispecific antibody that targets both PD-1 and CD3. Outside the U.S., clinical trials to investigate ONO-4685 are underway.

*This molecule is not approved by any regulatory authority for any use.

Target Disease

Pemphigus

Why This Disease Focus?

• Autoimmune diseases occur when the immune system mistakenly attacks the body’s own cells.  
• Pemphigus is an autoimmune disease that causes painful or itchy blistering of the skin and the mucus membranes that line the mouth, nose, throat, eyes, and genitals.  
• While certain medications like corticosteroids can control symptoms, unmet need remains, since some patients do not respond to standard treatments.

Goal of Program

BTK inhibitor

ONO-4059 is a BTK inhibitor. In autoimmune diseases, B cell receptors, which play important roles in immunity, may be overly active. Outside the U.S., ONO-4059 is being investigated for pemphigus.

*This molecule is not approved by the FDA for any use.

Target Disease

Pain

Why This Disease Focus?

Pain is a common and potentially debilitating condition affecting around one-quarter of the global population. While some effective medicines exist, they can come with significant side effects, including risk of addiction.

Goal of Program

Endocannabinoid regulation

Outside the U.S., ONO is exploring this endocannabinoid regulator as a potential treatment for pain.

*This molecule is not approved by any regulatory authority for any use.

Target Disease

Neurodegenerative disease

Why This Disease Focus?

Neurodegenerative diseases are numerous and have limited therapeutic options, creating a growing global burden.

Goal of Program

Epigenetic regulation

ONO is carrying out a clinical Phase 1 trial in the U.S. to evaluate safety, tolerability, and pharmacokinetics of ONO-2020 in healthy adult participants.

*This molecule is not approved by any regulatory authority for any use.

Target Disease

Multiple system atrophy (MSA)

Why This Disease Focus?

Multiple system atrophy (MSA) is a rare neurological disease that can affect motor control as well as the body’s autonomic functions, including blood pressure regulation. There is currently no FDA-approved treatment for MSA. Most therapies involve managing symptoms.

Goal of Program

S1P5 receptor agonist

ONO is investigating the safety, tolerability, and pharmacokinetics of ONO-2808 in patients with MSA in a Phase 2 trial in the U.S.

*This molecule is not approved by any regulatory authority for any use.

Target Disease

Diabetic polyneuropathy

Why This Disease Focus?

• Polyneuropathy is complication of diabetes. 
• The condition affects the nerves that serve the extremities. Symptoms can include tingling or prickling; numbness or pain in the hands, legs, and feet; muscle weakness; sensitivity to touch; insensitivities to temperature changes or pain; and loss of balance or coordination.

Goal of Program

Enhancement of Schwann cell differentiation

Schwann cells, a type of support cell in the brain, wrap around axons of peripheral nerve cells to form a myelin sheath and support neural function. Research shows that Schwann cells may play a role in the pathogenesis of various polyneuropathies. Outside the U.S., ONO-2910, which may affect Schwann cell differentiation, is being investigated in diabetic polyneuropathy.

*This molecule is not approved by any regulatory authority for any use.

Target Disease

Diabetic polyneuropathy

Why This Disease Focus?

• Polyneuropathy is complication of diabetes. 
• The condition affects the nerves that serve the extremities. Symptoms can include tingling or prickling; numbness or pain in the hands, legs, and feet; muscle weakness; sensitivity to touch; insensitivities to temperature changes or pain; and loss of balance or coordination.

Goal of Program

Enhancement of Schwann cell differentiation

Schwann cells, a type of support cell in the brain, wrap around axons of peripheral nerve cells to form a myelin sheath and support neural function. Research shows that Schwann cells may play a role in the pathogenesis of various polyneuropathies. Outside the U.S., ONO-2910, which may affect Schwann cell differentiation, is being investigated in diabetic polyneuropathy.

*This molecule is not approved by any regulatory authority for any use.

Target Disease

Chemotherapy-induced peripheral neuropathy

Why This Disease Focus?

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy. It has become more prevalent as cancer treatments have become more effective over the years and people are living longer.

Goal of Program

Enhancement of Schwann cell differentiation

Schwann cells, a type of support cell in the brain, wrap around axons of peripheral nerve cells to form a myelin sheath and support neural function. Outside the U.S., ONO-2910, which may affect Schwann cell differentiation, is being investigated for CIPN.

*This molecule is not approved by any regulatory authority for any use.