1

Next-Generation TherapeuticsTransforming Patient Care Today

Gregory A. Demopulos, M.D.Chairman & CEOJanuary 8, 2018

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Safe Harbor

This presentation contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are based on the current intent and expectations of the management of Omeros Corporation. These statements are not guarantees of future performance and involve risks and uncertainties that are difficult to predict. Omeros’actual results and the timing and outcome of events may differ materially from those expressed in or implied by the forward-looking statements because of risks associated with Omeros’unproven preclinical and clinical development activities, regulatory oversight, product commercialization, intellectual property claims, competitive developments, litigation and other factors. For additional information about the factors that affect the company's business, please see the company's latest Forms 10-K and 10-Q filed with the Securities and Exchange Commission. Except as required by law, Omeros undertakes no obligation to update any forward-looking statements in this presentation, whether as a result of new information, future events or otherwise.

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Pipeline behindMarketed OMIDRIA®

Program (Product) Molecule Targeted Disease / Procedure Pre-clinical Phase 1 Phase 2 Phase 3 FDA

ApprovalEconomic

Rights

Clinical Programs

MASP-2 / Lectin Pathway (OMS721) Ab Atypical Hemolytic Uremic Syndrome

MASP-2 / Lectin Pathway (OMS721) Ab IgA Nephropathy

MASP-2 / Lectin Pathway (OMS721) Ab Stem Cell Transplant-Associated TMA

MASP-2 / Lectin Pathway (OMS721) Ab Lupus Nephritis & Other Renal Diseases

PDE10 (OMS824) S M Huntington's and Schizophrenia

PPARγ (OMS405) S M Opioid and Nicotine Addiction

Urology (OMS201) S M Ureteroscopy

Preclinical Programs

PDE7 (OMS527) S M Addictions and Compulsive Disorders; Movement Disorders

MASP-3 / Alternative Pathway (OMS906) Ab PNH and a Wide Range of Other Alternative Pathway Disorders

Plasmin (OMS616) Protein Surgical and Traumatic Bleeding

MASP-2, MASP-3, MASP-2/3 andC-1 / Classical Pathway

S M Disorders of Lectin, Alternative and Classical Pathways of Complement

GPR151, GPR161, GPR174, GPR183, OPN4 S M CNS; Oncology; Immuno-oncology; SAD

and Sleep Disorders

GPCR Platform S M CNS, Metabolic, CV, Oncologic, Musculoskeletal & Other Disorders

Antibody Platform Ab Metabolic, CV, Oncologic, Musculoskeletal & Other Disorders

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Experienced Management with Deep Industry Experience

Position Background

Gregory Demopulos, MD Chairman, President & CEO Stanford and Duke Departments of Orthopedic Surgery

Leonard Blum Chief Business and Commercial Officer Theravance, ICOS, Merck

Chris Bral, PhD, DABT VP, Nonclinical Development Arrowhead Research, Vertex, Schering-Plough Research Institute

Dan Canafax, PharmD, FCCP VP, Medical Affairs & Clinical Research Theravance, Xenoport, ARYx, Medimmune

Tim Duffy VP, Business Development MDRNA, Prometheus, Procter & Gamble

Timi Edeki, MD, PhD VP, Clinical AstraZeneca, Abbott, Drexel University

George Gaitanaris, MD, PhD Chief Scientific Officer Nura, Primal, NCI

Michael Jacobsen Chief Accounting Officer & Treasurer Sarepta, ZymoGenetics, ICOS, Onvia, Mosaix

Marcia Kelbon, JD General Counsel and Secretary Christensen O’Connor Johnson Kindness

William J. Lambert, PhD VP, Chemistry, Manufacturing and Controls MedImmune, Pacira, Eisai, Pfizer, Upjohn

Catherine Melfi, PhD Chief Regulatory Officer Eli Lilly, Indiana University

J. Steven Whitaker, MD, JD Chief Medical Officer Allon Therapeutics, ICOS

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OMIDRIA®

Ophthalmological Surgery

OMIDRIA® (phenylephrine and ketorolac intraocular solution) 1%/0.3%

First and only FDA-approved intraocular product to prevent miosis and to reduce postoperative ocular pain

First and only FDA-approved NSAID-containing product forintraocular administration during cataract surgery

Proven effective, safe, and well tolerated

Strong post-launch (“real-world”) clinical data

Room-temperature storage; 4-year shelf life

Issued patents through 2033, pending patents through 2035

FDA approved sNDA for pediatric label expansion in December 2017

- Additional six months of marketing exclusivity

Market Scope survey of practicing ophthalmologists conducted in March 2017 states OMIDRIA was being used in 8% of U.S. cataract procedures1

Pursuing continued separate payment by CMS

1 Market Scope 2017 Annual Cataract Surgeon Survey Report

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OMIDRIA®

Quarter-Over-Quarter Sell-Through Growth (Vials)

0

10,000

20,000

30,000

40,000

50,000

60,000

2015-Q1 2015-Q2 2015-Q3 2015-Q4 2016-Q1 2016-Q2 2016-Q3 2016-Q4 2017-Q1 2017-Q2 2017-Q3

OM

IDRI

A Vi

als

Quarter

OMIDRIA Vials Purchased by ASCs and Hospitals by Quarter

$21.7M net revenue in 3Q 2017 – 27% increase over 2Q 2017 and 92% over 3Q 2016;sell-through increase of 20% over 2Q 2017 and 116% over 3Q 2016

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Irrigation solution

OMIDRIA®

Fits Easily into the Surgical Workflow

Proprietary combination of:

● Phenylephrine

● Ketorolac

Once added to irrigation solution, no change in surgical procedure

4 mL

Dilute in

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OMIDRIA®

Importance of a Well-Dilated Pupil

Despite every advance (e.g., phaco, ECCE, femto) in cataract surgery over the past four decades, small pupils are still a factor associated with cataract surgery complications

Poor visualization increases the risk of complications

Capsulorrhexis Phacoemulsification Cortical Clean-Up Lens Implantation

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p<0.0001

p=0.0004

47%

35%

22%

6%0

5

10

15

20

25

30

35

40

45

50

Vehicle(n=53)

Ketorolac(n=52)

Phenylephrine(n=49)

OMIDRIA(n=49)

p=0.0216

OMIDRIA® Phase 2b ResultsAnti-Miotic Effects of OMIDRIA and Its Components

Percent of Patients with Pupil Diameter < 6 mm at Any Time During Surgery

Post hoc analysis. p-values are versus OMIDRIA.

*All patients, including vehicle-treated patients, received standardized preoperative mydriatics and anesthetics.

OMIDRIA was well tolerated; adverse events were similar to those of vehicle.

Perc

ent

of P

atie

nts

*

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OMIDRIA®

Portal to the Operative Field

Pupil diameter < 6 mm is associated with a multiply increased risk of complications (e.g., posterior capsule tears, iris trauma, retained lens fragments, vitreous loss)

Effect of ~2.5-mm Decrease in Pupil Diameter

Diameter = 8 mm

Diameter = 6 mm

Diameter = 5.5 mm

Over 50% reduction in operative field

Diameter = 3.5 mm

66% reduction in operative field

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OMIDRIA® Phase 3 TrialsDecrease in Pupil Diameter ≥ 2.5 mm

*All patients, including placebo-treated patients, received standard preoperative mydriatics and anesthetics

Perc

ent

of P

atie

nts

0

10

20

30

OMIDRIA Placebo

28%(n=50)

0

10

20

30

OMIDRIA Placebo

p<0.0001

(n=195) (n=200)

3%(n=6) 1%

(n=2)

27%(n=53)

Study 1 Study 2

p<0.0001

(n=184) (n=180)* *

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OMIDRIA® Phase 3 TrialsPupil Diameter < 6 mm at Start of Lens Implantation

Pupil diameter <6 mm is associated with a multiply increased rate of complications (e.g., posterior capsule tears, iris trauma, retained lens fragments, vitreous loss)

Perc

ent

of P

atie

nts

Study 2

0

5

10

15

20

25

30 OMIDRIA Placebo

4%(n=8)

p<0.0001

23%(n=46)

0

5

10

15

20

25

30 OMIDRIA Placebo

p<0.0001

4%(n=7)

Study 1

23%(n=41)

(n=184) (n=180) (n=195) (n=200)

*All patients, including placebo-treated patients, received standard preoperative mydriatics and anesthetics

* *

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OMIDRIA® Phase 3 TrialsEarly Postoperative Ocular Pain

*All patients, including placebo-treated patients, received standardized preoperative mydriatics and anesthetics.

Perc

ent

of P

atie

nts

Pain-Free Patients(VAS = 0 At All Time Points)

0

5

10

15

20

25

30 OMIDRIA Placebo*

26%(n=104)

p=0.0027

17%(n=69)

0

5

10

15

20

25

30 OMIDRIA Placebo*

7%(n=29)

p=0.0014

14%(n=57)

Patients Experiencing Moderate-to-Severe Pain

(VAS ≥ 40 At Any Time Point)

(n=403) (n=403) (n=403) (n=403)

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OMIDRIA® Phase 3 ResultsPain Medication Use

Analgesic Use on Day of Surgery

0

10

20

30

40

50

35.1%(n=142)

24.6%(n=99)

Placebo(n=405)

OMIDRIA(n=403)

p=0.001

Perc

ent

of P

atie

nts

Post hoc analysis

*

*All patients, including placebo-treated patients, received standardized preoperative mydriatics and anesthetics.

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OMIDRIA®

Post-Launch Clinical Experience

Physician-Conducted Studies

Use of OMIDRIA has resulted in statistically significant:

Reduction in complication rates associated with small pupils1

Decrease in use of pupil-expanding devices1,2,3

Prevention of miosis during femtosecond laser-assisted surgery4

Reduction in surgical times1,3

Improvement in uncorrected visual acuity on day after surgery1

1 Rosenberg ED, et al. Clin Ophthalmology. 2018;12:21-28. 2 Bucci, et al., Clin Ophthalmology. 2017; 11: 1039-1043; 3 Visco D. Effect of Phenylephrine/Ketorolac on Iris Fixation Ring Use and Surgical Times in Patients at Risk of Intraoperative Miosis. Clin Ophthalmology (in press). 4Gayton JL. E-Poster at the 15th International Congress on Vision Science and Eye; 2017 Aug 10-11; London, UK.

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OMIDRIA®

Publications and Videos

Publications and Videos Multiple publications summarizing clinical trial data andpost-launch physician experience

– Lindstrom RL, et al., Clin Ophthalmol. 2014; 8: 1735-1744

– Grob SR, et al., Clin Ophthalmol. 2014; 8: 1281-1289

– Osher RH, et al., Expert Rev. Ophthalmol. 2015; 10(2): 91–103

– Hovanesian J., et al., J Cataract Refract Surg. 2015; 41: 2060-2068

– Lawuyi LE, Gurbaxani A. Clin Ophthalmol. 2015; 9: 1249-1254

– Gonzalez-Salinas R, et al., Patient Prefer Adherence 2016; 10:1795-1801

– Waterbury LD, JOPT. 2017; 33: 3-4

– Waterbury LD, JOPT. 2017; 34: 1-7

– Bucci, et al., Clin Ophthalmol. 2017; 11: 1039-1043

– Donnenfeld, et al., JCRS. 2017; 43: 597-605

– Rosenberg, et al., Clin Ophthalmol. 2018; 12: 21-28

– Visco D, Clin Ophthalmol (in press)

Additional manuscripts submitted and in preparation detailing post-launch physician experience from case-controlled studies

Multiple OMIDRIA videos by thought-leaders available on internet

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Pipeline ProgramsOMS721: MASP-2 Antibody

Overview Specifically blocks the lectin pathway (LP) Omeros controls worldwide exclusive rights to the inhibition

of MASP-2 and to all MASP-2 antibodies FDA orphan, fast track, and breakthrough therapy designations Phase 3 programs underway in aHUS and IgA nephropathy Phase 3 program for HCT-associated TMA initiated Phase 2 programs ongoing in other renal diseases >150 subjects have received OMS721 with no safety concerns Small molecule inhibitors of MASP-2 under development

OMS721 vs. C5 Inhibitor Classical pathway unaffected Subcutaneous or intravenous dosing vs. intravenous infusion No vaccination required Role in coagulation cascade

Other Potential Indications

Glomerulonephropathies Age-related macular degeneration (AMD)

Paroxysmal nocturnal hemoglobinuria (PNH)

Disseminated intravascular coagulation (DIC)

Traumatic brain injury/stroke Transplant

Diabetic complications Joint disease

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OMS721 Targets MASP-2: Protease Required for Lectin Pathway Function

Classical Pathway

Immune Complex Infection, Tissue Injury

C3a

Factor D

AlternativePathway

Thrombin

Coagulation

OMS721

MASP-2 C1r/s

Lectin Pathway

C4, C2

C4b/2a

C3 C3b Factor B

Platelet ActivationLeukocyte Recruitment

Cell Lysis

C5aMAC

C5b

C1q MBL, Ficolins, CL-11

C5

Soliris®

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OMS721: MASP-2 Antibody Phase 1 Clinical Program and Chronic Toxicology

Evaluated safety, tolerability, pharmacodynamics and pharmacokinetics of OMS721 in healthy subjects

Both intravenous and subcutaneous administration yields sustained lectin pathway inhibition

Have not reached a maximum tolerated dose (MTD)

Phase 1 Clinical Program

Safety and Toxicology Toxicology program supports chronic clinical administration via multiple routes for all potential indications

No adverse findings were identified in a chronic toxicology study in primates up to and including the highest doses administered

FDA and EMA concurrence regarding nonclinical development

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OMS721: MASP-2 Antibody Phase 2 Trial in Thrombotic Microangiopathies

Open-label, three-stage trial in adult patients with TMAs

– aHUS

– HCT-TMA

Objectives are to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity

Trial is ongoing in US, EU, and Asia Pacific

Overview

Design Stage 1 (dose escalation)

– IV weekly x 4 weeks

– Three cohorts (low-, mid-, and high-dose)

Stage 2 (cohort expansion)

– aHUS cohort (12 weeks)

– HCT-TMA cohort (4 weeks)

Stage 3 (extended treatment)

– aHUS cohort (12 weeks)

– HCT-TMA cohort (4 weeks)

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OMS721: MASP-2 Antibody Summary of aHUS Program

Improvements in TMA markers (mean platelets, LDH and haptoglobin) were observed in aHUS patients

Three aHUS patients were able to discontinue dialysis

Three others on chronic dialysis were deemed eligible for renal transplant, with one successfully transplanted to date

OMS721 was well tolerated with good safety profile

Data presented at World Congress of Nephrology, Mexico City, April 2017

Phase 2 Results

Fast track and orphan designations from FDA

Phase 3 trial in newly diagnosed or ongoing aHUS targeting:– ~40 patients for EMA full approval and US accelerated approval

– ~80 patients for US full approval

Agreement with FDA and EMA on one single-arm (i.e., no control group), open-label trial to satisfy both agencies

Clinical package for biologics license application (BLA) similar to that which formed basis of approval for Soliris®

Safety can be demonstrated across range of diseases

FDA and EMA agreement on CMC and nonclinical safety / tox plans

Pursuing US accelerated approval and European full approval

Phase 3 Program

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OMS721: MASP-2 Antibody HCT-Associated TMA

HCT-TMA is a serious and potentially fatal complication of HCT caused by endothelial injury

In 2015, more than 20,000 HCT were performed in the US and approximately 40,000 HCT in Europe

Incidence of HCT-TMA as high as approximately 40%

Mortality can be >90% in severe cases

Survivors have increased risk of renal impairment and ESRD

No treatments approved for HCT-TMA; eculizumab treatment has been reported to be effective but with increased risk of infection-related mortality

Laskin et al, Blood (2011) 118:1452-62; D'Souza A, Zhu X. Current Uses and Outcomes of Hematopoietic Cell Transplantation (HCT): CIBMTR Summary Slides, 2016. Available at: http://www.cibmtr.org; Passweg et al, Bone Marrow Transplantation (2017) 52:811-17; Jodele et al, Blood Rev (2015) 29:191-204; Jodele et al, Biol Blood Marrow Transplant (2016) 22:307-15; Bohl et al, Biology of Blood and Marrow Transplantation (2017) 23(12): 2172-2177.

Overview

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OMS721: MASP-2 AntibodyProposed HCT Pathophysiology

24

OMS721: MASP-2 AntibodyProposed HCT Pathophysiology

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OMS721: MASP-2 Antibody Summary of HCT-Associated TMA Program

Marked improvements in clinical status and TMA markers in many patients

Steroid-refractory GVHD resolved following OMS721 treatment in one patient

OMS721 well tolerated with good safety profile

Data presented at:

– ASBMT meetings, Orlando, FL, February 2017

– EBMT annual meeting, Spain, October 2017

– EBMT Complications Course, Spain, October 2017

Continuing trial enrollment in US, EU, and Asia Pacific

Phase 2 Results

Phase 3 program initiated

Phase 2 protocol to be amended following FDA/EMA discussion to transition to Phase 3 trial

Pursuing breakthrough therapy designation from FDA and Priority Medicines status in Europe

Next Steps

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Capriole et al. 2017 EBMT Presentation, Granada, ES

OMS721: MASP-2 Antibody HCT: GVHD Resolution

History

OMS721 Treatment

46 year-old male with a history of ALL

Underwent unrelated HLA 9/10 allogeneic HCT

Developed gastrointestinal GVHD three times

– Twice developed Grade 4 disease; initially steroid-responsive, but later steroid-refractory requiring investigational treatment

– Last episode Grade 2 – not treated due to steroid-refractory history

Developed HCT-TMA that did not respond to tapering of immunosuppressives at the time of third GVHD episode

Developed co-existing neurogenic bladder and tetraparesis with axonal sensorimotor and autonomic polyneuropathy

Patient was hospitalized and bed-ridden at study entry

Initiated OMS721 treatment

TMA and GVHD resolved after just two OMS721 doses

Improvement in neurological function noted after just four 4 doses with continued improvement after treatment completion

Patient is at home and working part-time at last follow-up

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Zecca et al. 2017 EBMT Poster, Marseille, FR

OMS721: MASP-2 Antibody HSCT: Compassionate Use Case Report

15 year-old girl post-HSCT for Diamond-Blackfan anemia

Developed TMA and responded to eculizumab treatment

Developed pulmonary edema associated with eculizumab, which was discontinued

TMA relapsed and treatment with low-dose eculizumab –developed life-threatening diffuse alveolar hemorrhage, which did not resolve with corticosteroids

Patient required daily platelet transfusions and 3x/week hemodialysis for several months

History

OMS721 Treatment Treated with OMS721 3x/week and dialysis discontinuedafter a few weeks

Platelets recovered; transfusions tapered, then discontinued

During taper of OMS721, patient developed a viral infection that reactivated her HSCT-TMA; successfully treated with restoration of original OMS721 dose

As of last follow-up, patient doing well and remained free of both dialysis and transfusions

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OMS721: MASP-2 AntibodyIgA Nephropathy (IgAN)

Caused by deposition of galactose-deficient IgA1 molecules in the glomerulus causing inflammation and progressive kidney disease

C3a stimulation of mesangial cells produces a proliferative and secretory phenotype (pro-inflammatory and pro-fibrotic cytokines)

Collectin-11 (CL-11) – a lectin pathway recognition molecule –linked to proteinuria and renal inflammation

Most common form of primary glomerulonephritis and responsible for 10% of patients on dialysis

Approximately 150,000-180,000 people in the US have IgAN

Up to 40% of patients with IgAN develop end-stage renal disease and require dialysis within 20 years of diagnosis

No therapies are approved for the treatment of IgAN

Renal biopsies demonstrate evidence of lectin pathway activation

Magistroni et al., Kidney Intl (2015) 88:974-89; Wyatt and Julian, New Engl J Med (2013) 368:2402-14;Ibels and Gyory, Medicine (1994) 73:79-102; Data on file

Overview

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OMS721: MASP-2 AntibodyOutcome in IgAN Correlated to Proteinuria

Proteinuria in IgAN patients is associated with renal outcomes and the degree of proteinuria is the best predictor of renal risk

Coppo et al, Kidney Intl (2014) 86:828-36; Reich et al, J Am Soc Nephrol (2007) 3177-83

Approximately 60-70% of patients with IgAN have proteinuria of1 g/day or greater

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OMS721: MASP-2 AntibodyIgA Nephropathy and Complement

Predominance of IgA deposits (alone or with IgG/IgM) in glomerular mesangium

Abnormally glycosylated IgA1 binds MBL and activates MASP-2

Complement C4, MBL, MASP-2, and the terminal complement complex (C5b–C9) are often detected in biopsies and are indicative of lectin pathway activation

MBL staining in biopsy is associated with more severe proteinuria

Patients with high urinary MBL levels have an unfavorable prognosis

Absence of C1q suggests that classical pathway is not activated

C3a stimulation of mesangial cells produces a proliferative and secretory phenotype (pro-inflammatory and pro-fibrotic cytokines)

CL-11 is a driver of proteinuria and renal inflammation

Immunofluorescence microscopy reveals granular deposits of IgA in the glomerular mesangium

Magistroni et al., Kidney Intl (2015) 88:974-89; Roos et al., J Am Soc Nephrol (2006) 17:1724-34; Wan et al. J Cell Physiol2007;213(2):495-501;Endo et al., Nephrol Dial Transplant (1998) 13:1984-90; Liu et al., Clin Exp Immunol (2012) 169:148-55; Zhang et al. ClinExpImmunol2017 Mar 15. doi:10.1111/cei.12961. 0

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Circulating galactose-deficient IgA (GdIgA) antibodies

MBL/MASP-2 complexes bind to GdIgAand deposit on mesangial cells

MESANGIAL CELLS• MBL/MASP-2 lectin-mediated complement activation• Activation of secretory phenotype and cell proliferation

Pro-inflammatory & Pro-fibrotic cytokines

TUBULAR EPITHELIAL AND INTERSTITIAL CELL INJURY

UPREGULATION OF COLLECTIN-11

INCREASED INFLAMMATION THROUGH MASP-2-MEDIATED LECTIN PATHWAY ACTIVATION

PROGRESSIVE RENAL DYSFUNCTION

OMS721: MASP-2 AntibodyProposed IgA Nephropathy Pathophysiology

PODOCYTE INJURY

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OMS721: MASP-2 Antibody Phase 2 Trial in Glomerulonephritis

Safety and tolerability in patients with renal disease

– IgAN

– Membranous nephropathy

– Lupus nephritis

– C3 glomerulopathy

Patients were on steroids and RAS blockade

Study design

– 1-month run-in to establish baseline

– 12-week treatment period including corticosteroid tapering

– 6-week follow-up period

Urine albumin/creatinine ratio (uACR) change from baseline by disease

24-hour urine protein change from baseline by disease

Corticosteroid dose needed to maintain stable renal function by disease

Study Overview

Assessments

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OMS721: MASP-2 AntibodyPhase 2 and Follow-up Results – IgAN Patients: uACR

uACR over Time by Patient

During the trial, the mean uACR decreased 77% (p = 0.026)

0

200

400

600

800

1000

1200

1400

1600

1800

Baseline Study Follow‐Up 1(13 weeks after first

dose)

End of Study (18weeks after first

dose)

20‐24 weeks afterfirst dose

25‐35 weeks afterfirst dose

50‐52 weeks afterfirst dose

60‐62 weeks afterfirst dose

mg/g

Patient 1 Patient 2 Patient 3 Patient 4

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OMS721: MASP-2 Antibody IgA Nephropathy Phase 2 Results: 24-Hr Urine Protein

24-H

our U

rine

Prot

ein

(mg/

day)

35

OMS721: MASP-2 AntibodyPhase 2 and Follow-up Results – IgAN: eGFR

eGFR over Time by Patient

At up to one-year follow-up, sustained GFR improvement (as much as 57%) seen in 3 out of 4 patients

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OMS721: MASP-2 Antibody Glomerulonephritis Phase 2 Trial Results

Clinically and statistically significant treatment effect in IgAN as assessed by both uACR and 24-hour urine protein

– Steroids completely eliminated for all patients

– Data presented at ERA-EDTA Congress, Madrid, June 2017 and at ASN annual meeting, New Orleans, November 2017

Four of five lupus nephritis patients showed substantial (mean of 69%) decrease in 24-hour urine protein

– Majority of patients were able to taper steroid dosing

Mixed results in membranous nephropathy – an inherently variable disease

OMS721 well tolerated with good safety profile

Positive post-trial follow-up data (up to approx. one year)

– Proteinuria in three of four patients remained reducedat 14%, 23% and 24% of pre-treatment baseline values

– Glomerular filtration rate (GFR) slightly improved in two patients, 57% increase in third

Continuing enrollment of IgAN patients not on steroids indouble-blind, vehicle-controlled cohort

Summary

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OMS721: MASP-2 AntibodyPhase 3 Program in IgA Nephropathy

Granted breakthrough therapy designation (BTD) and orphan drug designation from FDA

– First IgAN investigational treatment to receive BTD

Agreement reached with FDA on protocol for single Phase 3 randomized, double-blind, placebo-controlled trial

– Adaptive design

– 140 patients per group for proteinuria at 24 weeks (primary endpoint)

– Full or accelerated approval possible from either general population or high-proteinuria patient subset (≥ 2 g/day)

– In full approval scenario, eGFR is only a safety endpoint and can provide potential label claim

– Accelerated approval would allow marketing of OMS721 during collection of confirmatory eGFR data

Phase 3 patient enrollment expected to open in February 2018

In EU, pursuing orphan status and Priority Medicines program

Highlights

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Pipeline ProgramsOMS906: MASP-3 Antibody

Overview Identified MASP-3 as key activator of alternative pathway

Highly potent and selective antibodies against MASP-3

OMS906 blocks conversion of pro-factor D to factor D

Manufacturing scale-up process underway

Small-molecule inhibitors of MASP-3 under development

Potential Indications Paroxysmal nocturnal hemoglobinuria (PNH)

Age-related macular degeneration (AMD)

Multiple sclerosis Asthma

Arthritis Dense deposit disease

Traumatic brain injury Behcet’s disease

Neuromyelitis optica Aspiration pneumonia

Pauci-immune necrotizing crescentic glomerulonephritis

Endophthalmitis

Disseminated intravascular coagulation

Thrombotic microangiopathy

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Inci

denc

e (%

)

OMS906 reduced the incidence of arthritis by 86%

OMS906: MASP-3 AntibodyCAIA Mouse Model – Incidence

p < 0.005

40

OMS906: MASP-3 AntibodyCAIA Mouse Model – Clinical Scores

OMS906 reduced the severity of the disease by 90%

p < 0.01

41

Intravascular Clearance

OMS906: MASP-3 AntibodyRed Blood Cell Clearance in PNH

Vulnerable to Complement Activity

42

Soliris

Intravascular Clearance Extravascular Clearance

Phagocytic Cell

OMS906

OMS906: MASP-3 AntibodyRed Blood Cell Clearance in PNH

43

0 2 4 6 8 10 12 141

10

100

RBC Survival

Time (days)

Crry-: Vehicle

Crry-: OMS906

Crry-: C5 mAb

Treatment of mice with C5 mAb provided no improvement over vehicle treatment in Crry-deficient RBC survival. In contrast, OMS906 treatment caused a significant improvement of Crry-

deficient RBC survival over both C5 mAb (~4-fold, p = 0.029) and vehicle-treated animals

OMS906: MASP-3 AntibodyRBC Survival in Treated Mice – PNH Model

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C4 Bypass

Omeros Has Redefined the Complement System:Lectin Pathway Effector Arms (LEA)-1 and -2

MAC

OMS721 Blocks MASP-2

Soliris® Blocks C5

OMS906 Blocks MASP-3

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OMS721 and OMS906 Intellectual Property

Broad Patents Owned or exclusively licensed by Omeros

Patents and applications effectively control the MASP-2 target

– All antibodies that are specific to MASP-2

– Omeros’ MASP-2 antibodies, including OMS721

– Methods of inhibiting MASP-2 for the treatment of a wide range of inflammatory disorders

Pending patents effectively control MASP-3 for a wide range of disorders and Omeros’ MASP-3 antibodies

Patent portfolio effectively controls inhibition of both lectin and alternative pathway activators

Established Portfolio 19 issued US patents and 271 issued foreign patents

33 pending US patents and 141 pending foreign patents

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Novel target and novel mechanism for treating addiction

Mechanism is highly conserved between humans and rodents

Works through the dopamine system

PDE7 inhibition reduces both craving and relapse

Significant effects observed in:

– Nicotine, cocaine, alcohol, and opioid addiction

– Binge eating

Issued patent broadly covers any PDE7 inhibitor for treatment of any addiction or compulsive behavior

PDE7 inhibitor for clinical development selected and toxicology studies initiated

IND/CTA submission targeted for 2018

Overview

Pipeline ProgramsOMS527: PDE7 Inhibitor

47

OMS527: Effect of PDE7 Inhibition on the Self-Administration of Nicotine

0

2

4

6

8

10

12

14

Vehicle Low Medium High

PDE7i (dose)

**

Num

ber

of r

ewar

ds (

2-hr

)

PDE7 inhibition reduces nicotine self-administration

**p: <0.01 vs Vehicle

48

0

5

10

15

20

25

30

35

40Le

ver

Resp

onse

s (1

-hr)

PDE7i (dose)

Extinction Vehicle LowVery low

**p: < 0.01 vs. Vehicle##p: < 0.01 vs. Extinction

##

**

**

Yohimbine

PDE7 inhibition reduces stress-induced relapse to nicotine seeking

OMS527: Effect of PDE7 Inhibition on Stress-Induced Relapse to Nicotine Seeking

49

OMS527: Effects of PDE7 Inhibition onDopamine Levels in Rat Nucleus Accumbens

VehiclePDE7i

0 60 120 180

100

125

150

175

200

Time (min)

Basa

l DA

leve

ls (

%)

Nicotine

PDE7 inhibition reduces nicotine-induced increase of extracellular dopamine levels in the nucleus accumbens

50

Issued patents: 6 US patents and 88 foreign patents

Pending patent applications: 3 US patent applications and 36 foreign patent applications

Candidate compounds patented internationally

Method patents issued and pending internationally

– Patents broadly claim the use of any PDE7 inhibitor for treatment of addiction and impulse control disorders and for the treatment of movement disorders

– Claim use of specific compounds tested and exhaustive list of other published PDE7 inhibitors

Overview

OMS527: PDE7 Inhibitor Intellectual Property

51

Pipeline Program: GPCRs Significant Potential as Drug Targets

GPCRs

Annual Worldwide Drug Market$700B+

Nuclear receptors Ligand-gated ion

channels Voltage-gated

ion channels Penicillin-binding

protein Myelo-

peroxidase-like Sodium

neurotransmittersymporter

Type II DNAtopoisomerase

Fibronectin type III Cytochrome P450 Other

GPCRs: The Premier Drug Targets

Characteristics Advantages

Modulation of numerous

physiological procedures

Impacts broad range of diseases

High specificity and limited to specific tissues

Limited side effects

Expressed on cell surface Easily accessible

by drugs

L-DOPA

52

Promising targets, but drugdiscovery difficult

GPCRs as Drug Targets

363 Non-Sensory GPCRs

30-40% of all marketed drugs target only 46

GPCRs

TodayMarketed

Drugs

Ligand required for assay development Signaling pathway not known Laborious fractionation for natural

ligand identification Current technologies limited only to

agonist screening

The Challenge

The Opportunity

Up to 60+ new drug targets

119

116

82

No knownligands

Knownligands

244

“Orphans”

Not yet drugtargets

In development

Marketed drugs

53

Unlocking Class A oGPCRs

0

10

20

30

40

50

60

Omeros Other Worldwide(Surrogate Ligand)

Other Worldwide(Natural Ligand)

Deorphanizations Over the Same Three-Year Period

54

44

Num

ber

of R

ecep

tors

54

Orphan GPCRs Unlocked To Date

GPCR Metabolic & Cardiovascular Indications

GPR12 Obesity, cognitive impairments

GPR21 Obesity, diabetes

GPR22 Cardiovascular diseases, anxiety

GPR25 Arterial stiffness

GPR37L1 Hypertension

GPR39 Diabetes

GPR45 Obesity

GPR50 Metabolic disorders

GPR61 Eating disorders

GPR82 Appetite, body weight

GPR101 Appetite and eating disorders

GPR132 Atherosclerosis

GPR146 Dyslipidemia, diabetes

GPR171 Eating disorders

GPR176 Atherosclerosis

SREB1/GPR27 Diabetes, schizophrenia

GPCR Oncology Indications

GPR19 Melanoma, lung cancer

GPR20 Gastro-intestinal stromal tumors, acute myeloid leukemia

GPR65 Renal cell carcinoma, ovarian cancer, inflammation

GPR68 Ovarian cancer, prostate cancer, osteoporosis

GPR80 Hepatocellular carcinoma

GPR87 Squamous cell carcinomas

GPR150 Ovarian cancer

GPR161 Triple-negative breast cancer, sarcomas

GPR174 Regulatory T-cell modulation

LGR4 Cancer stem cells, bone diseases

LGR5Cancer stem cells, esophageal adenocarcinoma

P2Y8 Leukemias, lymphomas

55

Orphan GPCRs Unlocked To Date (continued)

GPCR CNS Indications

GPR17 Myelin disorders, multiple sclerosis

GPR31 Anxiety disorders

GPR37 Parkinson’s disease

GPR52 Schizophrenia

GPR63 Autism

GPR78 Bipolar disorder, schizophrenia

GPR139 Motor disorders

GPR141 Autism

GPR151 Schizophrenia, cognition

GPR153 Schizophrenia

MAS1 Cognitive impairments

MRGE Pain

OPN4 SAD, jet lag, photophobia, sleep disorders

SREB2/GPR85 Schizophrenia, obesity

SREB3/GPR173 Schizophrenia, obesity

GPCRs with Unknown Indications

GPR135 GPR182

GPR162 MRGF

OPN5

GPCR Miscellaneous Indications

GPR15 HIV enteropathy, rheumatoid arthritis

GPR32 Acute inflammatory responses

GPR83 Autoimmune diseases, PTSD

GPR183 Osteoporosis and EBV

CCRL2 Rheumatoid arthritis

LGR6 Hair follicle stem cells, wound repair

56

GPCRs: Expanding Intellectual Propertyand Advancing Specific Targets

Three levels of intellectual property

1. Linked to signaling profile – independent of indication

2. Linked to knock-out mice/phenotypes – indication-specific

3. Medicinal chemistry – composition of matter

Also applies to recalcitrant non-orphan GPCRs

Expect to obtain broad IP allowing Omeros to control the receptor and compounds targeting it

Intellectual Property

Specific Targets Advancing through compound optimization with animal data

GPR151 – Schizophrenia and cognition

GPR161 – Triple-negative breast cancer

GPR174 – Cytokine and regulatory T-Cell (“T-reg”) modulation

GPR183 – Osteoporosis and EBV-related diseases

OPN4 – seasonal affective and mood disorders, photophobia, sleep disorders

57

N=3*p<0.05**p<0.01

Human T-Reg Cells

FoxP

3+H

elio

s+(%

)

0.00

0.20

0.40

0.60

0.80

1.00

1.20

1.40

1.60

1.80

Vehicle Very low Low Medium

[GPR174i]

*

****

0

500

1000

1500

2000

2500

3000

Vehicle Very low Low Medium High

IL-2

(pg

/ml)

*****

*** ***

**p<0.01***p<0.001

[GPR174i]

IL-2

Effects of GPR174 Inhibitory Compoundson Human Peripheral Blood Mononuclear Cells

58

GPR174 A Novel Cancer Immunotherapy Target

GPR174 inhibition

– Potentiates the immune system, in particular Th1 responses that promote cytotoxic T cells

– Reduces the number of T-regs

The combined effects on cytokine stimulation and T-reg reduction represent a new mechanism for cancer immunotherapy

GPR174 small-molecule inhibitors could provide meaningful benefits over other cancer immunotherapies and a significant advance for patients

– Oral administration vs injection (checkpoint inhibitors) or involved procedure (CAR-T)

– Broader indications – not limited by the presence ofspecific cancer markers

– Potentially safer therapies due to short half life

Establishing broad intellectual property position

Advancing development of small-molecule inhibitors of GPR174

Overview

59

Pipeline behindMarketed OMIDRIA®

Program (Product) Molecule Targeted Disease / Procedure Pre-clinical Phase 1 Phase 2 Phase 3 FDA

ApprovalEconomic

Rights

Clinical Programs

MASP-2 / Lectin Pathway (OMS721) Ab Atypical Hemolytic Uremic Syndrome

MASP-2 / Lectin Pathway (OMS721) Ab IgA Nephropathy

MASP-2 / Lectin Pathway (OMS721) Ab Stem Cell Transplant-Associated TMA

MASP-2 / Lectin Pathway (OMS721) Ab Lupus Nephritis & Other Renal Diseases

PDE10 (OMS824) S M Huntington's and Schizophrenia

PPARγ (OMS405) S M Opioid and Nicotine Addiction

Urology (OMS201) S M Ureteroscopy

Preclinical Programs

PDE7 (OMS527) S M Addictions and Compulsive Disorders; Movement Disorders

MASP-3 / Alternative Pathway (OMS906) Ab PNH and a Wide Range of Other Alternative Pathway Disorders

Plasmin (OMS616) Protein Surgical and Traumatic Bleeding

MASP-2, MASP-3, MASP-2/3 andC-1 / Classical Pathway

S M Disorders of Lectin, Alternative and Classical Pathways of Complement

GPR151, GPR161, GPR174, GPR183, OPN4 S M CNS; Oncology; Immuno-oncology; SAD

and Sleep Disorders

GPCR Platform S M CNS, Metabolic, CV, Oncologic, Musculoskeletal & Other Disorders

Antibody Platform Ab Metabolic, CV, Oncologic, Musculoskeletal & Other Disorders

60

Next-Generation TherapeuticsTransforming Patient Care Today