Our Pipeline

We think differently and innovate relentlessly in pursuit of elegant solutions to the most difficult challenges facing patients. Our next-generation therapeutics are transforming patient care today.

Our cutting-edge science serves as the foundation for a deep and diverse pipeline of small-molecule and protein therapeutics focused on significant unmet medical needs – a pipeline of first-in-class drugs with new mechanisms of action that target previously untapped receptors and enzymes.

Omeros

Pipeline

Omeros has retained exclusive control of worldwide commercial rights for all products, product candidates, and programs.

Antibody
Small Molecule
Antibody and
Small Molecule
Download full PDF
Print
Reset

Complement Franchise (iCAB)

Narsoplimab

(MASP-2 inhibitor, lectin pathway)
Stem Cell Transplant-Associated TMA (TA-TMA)
Phase 3
Stem Cell Transplant-Associated TMA (TA-TMA)

Narsoplimab: Our first-in-class monoclonal antibody complement inhibitor

Narsoplimab, also known as OMS721, is an investigational fully human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway of the complement system. The lectin pathway is activated primarily by tissue damage or microbial infection. Importantly, unlike other complement-targeting drugs on the market or in development, inhibition of MASP-2 by narsoplimab does not interfere with the classical complement pathway, a critical component of the acquired immune response to infection. Narsoplimab is designed to prevent complement-mediated inflammation and endothelial damage without affecting other pathways of innate immunity.

The 61% response rate and 68% 100-day survival seen with narsoplimab-treated TA-TMA patients in the pivotal clinical trial represent an approximately three-fold improvement when compared to an untreated age- and disease status-matched cohort from a systematic literature review.1,2

1Khaled SK, Claes K, Goh YT, et al. Narsoplimab, a mannan-binding lectin-associated protease-2 inhibitor, for the treatment of adult hematopoietic stem-cell transplantation–associated thrombotic microangiopathy. J Clin Oncol. 2022; 40(22):2447-2457.

2Whitaker S, Nangia N, Ng E, Sotolongo S, Pullman W. Systematic literature review of the natural history of hematopoietic stem cell transplant-associated thrombotic microangiopathy in adults. Presented at: 48th Annual Meeting of the European Society for Blood and Marrow Transplantation; March 19-23, 2022.

Breakthrough Therapy and Orphan status

In the US, the FDA has granted narsoplimab the following designations: (1) Breakthrough Therapy designation in patients who have persistent TMA despite modification of immunosuppressive therapy, (2) Orphan Drug designation for the prevention (inhibition) of complement-mediated TMAs and (3) Orphan Drug designation for the treatment of TA-TMA.

The European Commission also granted narsoplimab a designation as an Orphan Medicinal Product for treatment in hematopoietic stem cell transplantation.

Learn more about narsoplimab

Find clinical trials for NARSOPLIMAB in TA-TMA here

Explore our research programs in complement-mediated disease

Stem Cell Transplant-Associated TMA (TA-TMA)
IgA Nephropathy (IgAN)
Phase 3
IgA Nephropathy (IgAN)

Narsoplimab: Our first-in-class monoclonal antibody complement inhibitor

Narsoplimab, also known as OMS721, is an investigational fully human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway of the complement system. The lectin pathway is activated primarily by tissue damage or microbial infection. Importantly, unlike other complement-targeting drugs on the market or in development, inhibition of MASP-2 does not interfere with the classical complement pathway, a critical component of the acquired immune response to infection. Narsoplimab is designed to prevent complement-mediated inflammation and endothelial damage without affecting other pathways of innate immunity.

In a Phase 2 clinical trial of patients with severe IgA nephropathy, narsoplimab-treated patients received a median of one course of 12 weekly doses per year and showed a median proteinuria reduction of 64.4% and a sustained proteinuria reduction of 38% from baseline after an unprecedented nearly 3-year follow-up period.

Breakthrough Therapy and Orphan status

In the US, the FDA has granted narsoplimab the following designations: (1) Breakthrough Therapy designation for the treatment of IgA nephropathy and (2) Orphan Drug designation in IgA nephropathy.

In Europe, narsoplimab has received from the European Commission designation as an Orphan Medicinal Product for the treatment of primary IgA nephropathy.

Learn more about narsoplimab

Find clinical trials for NARSOPLIMAB in IgA nephropathy here

Explore our research programs in complement-mediated disease

IgA Nephropathy (IgAN)
Atypical Hemolytic Uremic Syndrome (aHUS)
Phase 3
Atypical Hemolytic Uremic Syndrome (aHUS)

Narsoplimab: Our first-in-class monoclonal antibody complement inhibitor

Narsoplimab, also known as OMS721, is an investigational fully human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway of the complement system. The lectin pathway is activated primarily by tissue damage or microbial infection. Importantly, unlike other complement-targeting drugs on the market or in development, inhibition of MASP-2 does not interfere with the classical complement pathway, a critical component of the acquired immune response to infection. Narsoplimab is designed to prevent complement-mediated inflammation and endothelial damage without affecting other pathways of innate immunity.

Phase 2 clinical results are positive and a Phase 3 clinical program is underway.

Fast Track and Orphan status

In the US, the FDA has granted narsoplimab the following designations: (1) Fast Track designation for the treatment of patients with aHUS and (2) Orphan Drug designation for the prevention (inhibition) of complement-mediated TMAs, which includes aHUS.

Learn more about narsoplimab

Find clinical trials for NARSOPLIMAB in aHUS here

Explore our research programs in complement-mediated disease

Atypical Hemolytic Uremic Syndrome (aHUS)
COVID-19
Phase 2
COVID-19

Narsoplimab: Our first-in-class monoclonal antibody complement inhibitor

Narsoplimab, also known as OMS721, is an investigational fully human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway of the complement system. The lectin pathway is activated primarily by tissue damage or microbial infection. Importantly, unlike other complement-targeting drugs on the market or in development, inhibition of MASP-2 does not interfere with the classical complement pathway, a critical component of the acquired immune response to infection. Narsoplimab is designed to prevent complement-mediated inflammation and endothelial damage without affecting other pathways of innate immunity.

Narsoplimab was the only complement inhibitor included in the I-SPY COVID Trial, an adaptive platform clinical trial sponsored by Quantum Leap Healthcare Collaborative. The platform trial was designed to screen and identify rapidly agents effective in treating critically ill COVID-19 patients. Narsoplimab showed the largest reduction in mortality risk across all agents reported from the I-SPY COVID Trial. No new safety signals were identified for narsoplimab in the setting of critically ill COVID-19 patients.

Narsoplimab has been used internationally under an expanded access program, successfully treating patients with severe acute COVID-19. In addition, recent publications demonstrate the primary role of lectin pathway hyperactivation in consumptive hypocomplementemia and secondary infection risk in patients with severe COVID-19 and narsoplimab’s ability to restore complement function and the adaptive immune response in those patients. This same lectin pathway hyperactivation and resultant hypocomplementemia/increased infection risk has been identified in a substantial percentage of studied patients with long COVID or post-acute sequelae of COVID-19 infection (PASC). Omeros is advancing a diagnostic kit to identify both acute and long COVID patients who, we believe, would benefit from treatment with narsoplimab.

COVID-19
Lupus Nephritis & Other Renal Diseases
Phase 2
Lupus Nephritis & Other Renal Diseases

Narsoplimab: Our first-in-class monoclonal antibody complement inhibitor

Narsoplimab, also known as OMS721, is an investigational fully human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway of the complement system. The lectin pathway is activated primarily by tissue damage or microbial infection. Importantly, unlike other complement-targeting drugs on the market or in development, inhibition of MASP-2 does not interfere with the classical complement pathway, a critical component of the acquired immune response to infection. Narsoplimab is designed to prevent complement-mediated inflammation and endothelial damage without affecting other pathways of innate immunity.

In a Phase 2 clincial trial, narsoplimab reduced proteinuria by an unprecedented 70% in patients with lupus nephritis. We plan to initiate a Phase 3 program for narsoplimab in lupus nephritis.

Learn more about narsoplimab

Explore our research programs in complement-mediated disease

Lupus Nephritis & Other Renal Diseases

OMS906

(MASP-3 inhibitor, alternative pathway)
PNH and a Wide Range of Other Alternative Pathway Disorders
Phase 1
PNH and a Wide Range of Other Alternative Pathway Disorders

OMS906: Monoclonal antibody complement inhibitor

OMS906 is a humanized monoclonal antibody targeting mannan-binding lectin-associated serine protease-3 (MASP-3), the key activator of the alternative pathway of complement. The alternative pathway is involved in a wide range of diseases and disorders, including those targeted by marketed alternative pathway inhibitors or those in development. Unlike these drugs, MASP-3 inhibition does not interfere with the classical complement pathway, a critical component of the acquired immune response to infection.

PNH and a Wide Range of Other Alternative Pathway Disorders

OMS1029

(MASP-2)
Long-Acting 2nd Generation Antibody Targeting Lectin Pathway Disorders
Phase 1
Long-Acting 2nd Generation Antibody Targeting Lectin Pathway Disorders

OMS1029: Long-acting second-generation antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2)

OMS1029 is a long-acting second-generation antibody targeting MASP-2, the effector enzyme of the lectin pathway of the complement system. Based on pharmacokinetic/pharmacodynamic data to date, dosing in humans is expected to be once-monthly to once-quarterly by subcutaneous or intravenous administration.

Omeros has initiated a Phase 1 clinical trial to evaluate the safety and tolerability of OMS1029 in healthy subjects.

Long-Acting 2nd Generation Antibody Targeting Lectin Pathway Disorders

MASP-2, MASP-3, MASP-2/-3

Disorders of the Lectin and Alternative Pathways of Complement
Phase 1
Disorders of the Lectin and Alternative Pathways of Complement

Small-molecule inhibitors of MASP-2, MASP-3, MASP-2/-3

As part of lifecycle planning for narsoplimab, we are developing orally available small-molecule inhibitors of MASP-2 as well as small-molecule inhibitors of MASP-3 and bispecific inhibitors of MASP-2/-3.

Disorders of the Lectin and Alternative Pathways of Complement

Addiction

OMS527

(PDE7 inhibitor)
Addictions and Compulsive Disorders; Movement Disorders
Phase 1
Addictions and Compulsive Disorders; Movement Disorders

OMS527: Small-molecule phosphodiesterase 7 (PDE7) inhibitor

OMS527 is a small-molecule PDE7 inhibitor that modulates dopamine levels in the areas of the brain responsible for addiction. OMS527 reduces craving and relapse across multiple drugs of abuse, including nicotine, opioids, and alcohol, and also blocks binge eating in animal models. Omeros’ PDE7 inhibitors do not appear to be addictive or to depress pleasure from normal activities (e.g., social interactions, sex, sports, etc.), both of which are shortcomings of currently marketed addiction therapies.

We reported positive results from our Phase 1 single-ascending- and multiple-ascending-dose clinical trial designed to assess safety, tolerability and pharmacokinetics of our lead compound in healthy subjects. The double-blind, randomized, placebo-controlled trial evaluated six cohorts of eight volunteers in the single-ascending-dose portion of the trial, including a cohort to assess whether pharmacokinetics is affected by food, and three cohorts of 12 volunteers in the multiple-ascending-dose portion. The compound was generally well tolerated with no significant adverse events being reported. The pharmacokinetic data support once-daily dosing, with or without food. Our focus is nicotine addiction and we are planning our Phase 2 development.

Explore our research programs in central nervous system disorders

Addictions and Compulsive Disorders; Movement Disorders

OMS405

(PPARγ)
Addictive Disorders
Phase 2
Addictive Disorders

OMS405: Small-molecule peroxisome proliferator-activated receptor gamma (PPARγ) agonist

In our peroxisome proliferator-activated receptor gamma program, we are advancing PPARγ agonists for the treatment and prevention of addiction to substances of abuse, which may include opioids, nicotine and alcohol. Omeros is the first to demonstrate a link between PPARγ and addiction disorders and has a broad intellectual property estate directed to this target. Data from clinical studies and from animal models of addiction demonstrate that PPARγ agonists could be efficacious in the treatment of a wide range of addictions.

Our collaborators at The New York State Psychiatric Institute have completed two Phase 2 clinical trials related to our PPARγ program. These studies evaluated a PPARγ agonist, alone or in combination with other agents, for treatment of addiction to heroin and to nicotine. Recently published results of the heroin study demonstrated that, although not altering the reinforcing or positive subjective effects of heroin, the PPARγ agonist significantly reduced heroin craving and overall anxiety. The National Institute on Drug Abuse provided substantially all of the funding for these clinical trials and solely oversaw the conduct of these trials. We can use these data for future FDA submissions and retain all rights to the PPARγ program. We have also reported positive results from a Phase 2 clinical trial conducted by an independent investigator evaluating the effects of a PPARγ agonist in patients with cocaine use disorder, which showed decreased cravings and protection of brain white matter.

Addictive Disorders

Immuno-oncology

GPR174

Cancer
Phase 1
Cancer

GPR174: Small-molecule inhibitor of GPR174

GPR174 is well positioned to be a unique target for cancer immunotherapy.

  • As a Gαs-coupled GPCR, it activates the immunosuppressive cAMP/PKA signaling pathway, an actively pursued immuno-oncology target.
  • Unlike other GPCRs, GPR174 expression is restricted to immune cells and is primarily found on T cells, NK cells, B cells and, at lower levels, on myeloid cell subsets such as non-classical monocytes. For these reasons, on-target, dose-limiting toxicities unrelated to immune activation should not be a liability.
  • We have found that membranes presenting phosphatidylserine are capable of activating GPR174, resulting in T cell suppression that is reversible by our GPR174 inhibitors. The combination of inhibitors of GPR174, adenosine 2A, and potentially other targets could prevent relapse associated with a lack of memory T cells, a major limitation of CAR T and adoptive T cell therapies that focus on cell surface checkpoints.

Based on our data, we believe that GPR174 controls a major pathway in cancer and that modulation of the receptor could provide a seminal advance in immunotherapies that harness the body's own immune system to fight cancer.

Cancer

Adoptive T Cell Therapies/CAR T

Cancer
Phase 1
Cancer

CAR T and Adoptive T Cell Therapies: Small-molecule inhibitors for cancer

Our proprietary technology combines inhibitors of GPR174, adenosine A2, and potentially other targets to limit the negative impact of immunosuppressive signaling on the function of T cells. This greatly enhances interleukin-2 production and skews the cells toward a central memory phenotype, preventing relapse associated with a lack of memory T cells, a significant shortcoming of many currently marketed immunotherapies.

Beyond GPR174, we have initiated innovative programs to target more globally immunosuppressive signaling in T cells, which could yield another wholly new class of immuno-oncology therapeutics with significant advantages over existing therapies (e.g., PD-1/PD-L1 checkpoint inhibitors).

Cancer

Discovery Platform Technologies

GPCR Platform

Immunologic, immuno-oncologic, CNS, Metabolic, CV, Musculoskeletal & Other Disorders
Phase 1
Immunologic, immuno-oncologic, CNS, Metabolic, CV, Musculoskeletal & Other Disorders

GPCR Platform

We developed the first – and we believe the only – high-throughput system to identify synthetic ligands, including antagonists, agonists, and inverse agonists, that bind to and affect the function of orphan G protein-coupled receptors.

Immunologic, immuno-oncologic, CNS, Metabolic, CV, Musculoskeletal & Other Disorders