What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2023-03-13 compared with 2022-03-01 · 244 added, 283 removed, 635 unchanged (45% of the section changed)

Omeros Corporation (“Omeros,” the “Company” or “we”) is an innovative biopharmaceutical company committed to discovering, developing and commercializing small-molecule and protein therapeutics for large-market and orphan indications targeting immunologic diseases, including complement-mediated diseases and cancers related to dysfunction of the immune system, as well as addictive and compulsive disorders.

Our lead drug candidate narsoplimab is the subject of a biologics license application (“BLA”) currently pending before the U.S.

Food and Drug Administration (“FDA”) for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (“HSCT-TMA”).

On October 18, 2021, we announced the receipt of a Complete Response Letter (“CRL”) from FDA regarding the BLA.

In the CRL, FDA expressed difficulty in estimating the treatment effect of narsoplimab in HSCT-TMA and asserted that additional information will be needed to support regulatory approval.

In February 2022, we had a Type A meeting with FDA to discuss the CRL, including each of the review issues that FDA identified as presenting difficulties interpreting the treatment response in the pivotal trial.

We are currently awaiting FDA’s response to our rebuttals to each of those review issues.

We continue to believe that our BLA, as submitted, merits approval and that the data meet or exceed the threshold for substantial evidence of effectiveness.

We also have multiple Phase 3 and Phase 2 clinical-stage development programs in progress with narsoplimab, which are focused on:

complement-mediated disorders, including immunoglobulin A (“IgA”) nephropathy, atypical hemolytic uremic syndrome (“aHUS”) and COVID-19.

We are also initiating a Phase 1b clinical program in paroxysmal nocturnal hemoglobinuria (“PNH”) for our MASP-3 inhibitor OMS906 targeting the alternative pathway of complement and have successfully completed a Phase 1 study in our phosphodiesterase 7 (“PDE7”) program focused on addiction.

In addition, we have a diverse group of preclinical programs, including GPR174, a novel target in immuno-oncology that modulates a new cancer immunity axis that we discovered.

Small-molecule and antibody inhibitors of GPR174 are part of our proprietary G protein-coupled receptor (“GPCR”) platform through which we control 54 GPCR drug targets and their corresponding compounds.

Omeros Corporation (“Omeros,” the “Company” or “we”) is a clinical-stage biopharmaceutical company committed to discovering, developing and commercializing small-molecule and protein therapeutics for large-market as well as orphan indications targeting immunologic disorders including complement-mediated diseases, cancers, and addictive and compulsive disorders.

The lead drug candidate in our pipeline of complement-targeted therapeutics is narsoplimab (OMS721), a proprietary, patented human monoclonal antibody targeting mannan-binding lectin-associated serine protease 2 (“MASP-2”), the key activator of the lectin pathway of complement.

Clinical development of narsoplimab is currently focused primarily on hematopoietic stem cell transplant-associated thrombotic microangiopathy (“HSCT-TMA”) and immunoglobulin A (“IgA”) nephropathy.

We expect to read out 36-week proteinuria data from our Phase 3 clinical trial evaluating narsoplimab for the treatment of IgA nephropathy, ARTEMIS-IGAN, later this year .

We successfully completed a pivotal clinical trial for narsoplimab in HSCT-TMA and previously submitted to the U.S.

Food and Drug Administration (“FDA”) a biologics licensing application (“BLA”) seeking marketing approval for narsoplimab in this indication.

In late 2021, FDA issued a complete response letter (“CRL”) with respect to the BLA in which the agency indicated that additional information would be needed to support regulatory approval.

We appealed FDA’s decision to issue the CRL through a formal dispute resolution process that concluded in late 2022.

Although our appeal was denied, the decision identified potential paths for resubmission of the BLA based on both response data and survival data from the completed pivotal trial versus a historical control group, with or without an independent literature analysis.

We have requested a meeting with the review division at FDA to confirm the additional information required to be included in the resubmission to support approval of the BLA.

There can be no guarantee that the specific requirements for resubmission, when determined through interaction with the FDA review division, will be satisfactory in terms of the time and/or expenditure required, and there can be no guarantee that any resubmission will result in approval of narsoplimab for HSCT-TMA.

We are also developing OMS1029, a long-acting, next-generation antibody targeting MASP-2 and the lectin pathway.

Dosing of all cohorts in a single-ascending dose Phase 1 clinical trial of OMS1029 was successfully completed in early 2023.

OMS1029 was well tolerated with no safety concerns identified.

Preliminary pharmacokinetic (“PK”) and pharmacodynamic (“PD”) data show dose-proportional exposure and sustained lectin pathway inhibition, consistent with potentially quarterly intravenous or subcutaneous dosing.

Our pipeline of clinical-stage complement-targeted therapeutic candidates also includes OMS906, a proprietary, patented monoclonal antibody targeting mannan-binding lectin-associated serine protease 3 (“MASP-3”), the key activator of the alternative pathway of complement.

We believe OMS906 has the potential to treat a wide range of alternative pathway-related diseases and that its attributes favorably differentiate OMS906 from other marketed and in-development alternative pathway inhibitors.

Clinical development of OMS906 is currently focused on rapidly obtaining proof-of-concept data in multiple alternative pathway-related disorders, including paroxysmal nocturnal hemoglobinuria (“PNH”) and complement 3 glomerulopathy (“C3G”).

Following the successful completion of a Phase 1 single-ascending-dose study of OMS906 in healthy subjects, we initiated clinical programs evaluating OMS906 in PNH and C3G.

In late 2022, we began enrolling in a Phase 1b clinical trial evaluating OMS906 for the treatment of PNH.

The first treatment-naïve PNH patients were dosed with OMS906 in early 2023.

We have also begun enrolling a Phase 1b clinical trial evaluating OMS906 in PNH patients who have had an unsatisfactory response to the C5 inhibitor ravulizumab.

We have completed several regulatory and ethics committee submissions for a Phase 1b clinical trial evaluating OMS906 in patients with C3G and expect to begin enrolling patients next month following receipt of regulatory and ethics committee approvals.

Our development pipeline also includes OMS527, our phosphodiesterase 7 (“PDE7”) inhibitor focused on addiction and movement disorders, for which we have successfully completed a Phase 1 study.

We are evaluating OMS527 in a clinically predictive primate model of levodopa-induced dyskinesias (“LID”), a common and debilitating side effect of long-term levodopa dosing in patients with Parkinson’s disease.

We also have a diverse group of preclinical programs, including GPR174, a novel target in immuno-oncology that modulates a new cancer immunity axis that we discovered.

Inhibitors of GPR174 are part of our proprietary G protein-coupled receptor (“GPCR”) platform through which we control 54 GPCR drug targets and their corresponding compounds.

We are also developing novel adoptive T cell/CAR-T therapies and novel immunotherapeutics and cancer vaccines as part of our immuno-oncology platform.

We previously developed and commercialized OMIDRIA ® (phenylephrine and ketorolac intraocular solution) 1%/0.3%, which is approved by FDA for use during cataract surgery or intraocular lens (“IOL”) replacement to maintain pupil size by preventing intraoperative miosis (pupil constriction) and to reduce postoperative ocular pain.

We marketed OMIDRIA in the United States (“U.S.”) from the time of its commercial launch in 2015 until December 2021.

We marketed OMIDRIA in the United States (the “U.S.”) from the time of its commercial launch in 2015 until December 2021.

On December 23, 2021, we completed the sale of OMIDRIA and certain related assets and liabilities to Rayner Surgical Inc.

(“Rayner”) pursuant to an Asset Purchase Agreement, dated December 1, 2021 (the “Asset Purchase Agreement”).

We received approximately $126.0 million in cash at the closing and we will receive a royalty of 50% of the net revenue, as defined in the Asset Purchase Agreement, from sales of OMIDRIA in the U.S.

between the closing date and the earlier of January 1, 2025 or the payment of the $200.0 million milestone described below.

After such date, we will receive a royalty of 30% of the net revenue from sales of OMIDRIA in the U.S.

until the expiration or termination of the last issued and unexpired patent with respect to OMIDRIA in the U.S.

base royalty rate is subject to a reduction down to 10% upon the occurrence of certain events described in the Asset Purchase Agreement, including during any specific period in which OMIDRIA is no longer eligible for separate payment (i.e., outside the packaged payment rate for the surgical procedure) under Medicare Part B.

We will also will receive a royalty of 15% of the net revenue from sales of OMIDRIA outside the U.S.

on a country-by-country basis between the closing date and the expiration or termination of the last issued and unexpired patent with respect to OMIDRIA in such country.

we will receive a $200.0 million milestone payment if, prior to January 1, 2025, separate payment for OMIDRIA is secured under Medicare Part B for a continuous period of at least four years.

We launched OMIDRIA in the U.S.

in the second quarter of 2015 and sold OMIDRIA primarily through wholesalers which, in turn, sold to Ambulatory Surgical Centers (“ASC”) and hospitals.

The Centers for Medicare & Medicaid Services (“CMS”), the federal agency responsible for administering the Medicare program, granted transitional pass-through reimbursement status for OMIDRIA from January 1, 2015 through December 31, 2017.

In March 2018, Congress extended pass-through reimbursement status for OMIDRIA through September 30, 2020 when used during procedures performed on Medicare Part B fee-for-service patients.

Pass-through reimbursement for OMIDRIA under Medicare Part B expired on October 1, 2020.

In December 2020, in its calendar year 2021 Outpatient Prospective Payments System (“OPPS”) and ASC Payments System final rule, CMS determined that, under its policy applicable to certain non-opioid pain management surgical drugs, OMIDRIA qualifies for separate payment when used on Medicare Part B patients in the ASC setting.

CMS’ policy of separately reimbursing non-opioid pain management surgical drugs was first adopted in 2019 and became applicable to OMIDRIA upon the expiration of the drug’s pass-through reimbursement on October 1, 2020.

In November 2021, CMS issued its final OPPS and ASC Payments Systems rule for calendar year 2022 which reconfirmed CMS’ policy regarding non-opioid pain management surgical drugs and states that OMIDRIA will continue to receive separate payment when used on Medicare Part B patients in the ASC setting.

Under the Asset Purchase Agreement, we are entitled to receive royalties based on Rayner’s sales of OMIDRIA for the life of the patents covering OMIDRIA in the relevant jurisdiction.

From the closing date through the occurrence in late 2022 of the milestone event that resulted in our receipt of a $200 million milestone payment (the “Milestone Payment”) in early 2023, the applicable royalty rate on net revenue from OMIDRIA sales in the U.S.

Per the terms of the Asset Purchase Agreement, the applicable royalty rate was reduced to 30% of the net revenue from sales of OMIDRIA in the U.S.

following the occurrence of the milestone event.

On September 30, 2022, we sold to DRI Healthcare Acquisitions LP (“DRI”) an interest in a portion of our future OMIDRIA royalty receipts and received $125.0 million in cash consideration.

DRI receives their prorated monthly cap amount before we receive any royalty proceeds.

DRI is not entitled to carry-forward or to recoup any shortfall if the royalties paid by Rayner for an annual period are less than the cap amount applicable to each discrete calendar year.

Additionally, DRI has no recourse to or security interest in our assets other than our OMIDRIA royalty receipts, and we retain all royalty receipts in excess of the respective cap in any given calendar year.

Please refer to Part II, Item 8, “Note 9 – OMIDRIA Royalty Obligation ” to our Consolidated Financial Statements in this Annual Report on Form 10-K for information regarding the OMIDRIA royalty obligation .

Our Drug Candidates and Development Programs

2 unchanged sentences

Targeted Disease(s)

Development Status

Next Expected

Narsoplimab (OMS721/MASP-2) -

Lectin Pathway Disorders

(MASP-2 / Lectin Pathway)

Hematopoietic stem-cell transplant-associated thrombotic microangiopathy (HSCT-TMA)

Pivotal trial complete;

CRL received;

BLA pending before FDA

BLA resubmission

(In-licensed)

Narsoplimab (OMS721/MASP-2) -

Lectin Pathway Disorders

Drug Candidate/Program

Targeted Disease(s)

Next Expected

(MASP-2 / Lectin Pathway)

Immunoglobulin A Nephropathy (IgAN)

Complete Phase 3 patient enrollment and perform 36-week assessment of proteinuria

(In-licensed)

Narsoplimab (OMS721/MASP-2) -

Lectin Pathway Disorders

Atypical Hemolytic Uremic Syndrome (aHUS)

Complete Phase 3 patient enrollment

(In-licensed)

Narsoplimab (OMS721/MASP-2)

Read out data from 36-week assessment of proteinuria

(MASP-2 / Lectin Pathway)

Severe COVID-19 requiring mechanical ventilation

Read out data from platform clinical trial

(In-licensed)

PDE7 (OMS527)

Continue ongoing discussions with U.S.

government agencies regarding use of narsoplimab in acute, severe COVID-19, post-acute sequelae of SARS-CoV-2 infection (PASC, i.e., long COVID) and other causes of acute respiratory distress syndrome (ARDS);

continue developing companion diagnostic for lectin pathway involvement in COVID-19

(MASP-2 / Lectin Pathway)

Long-acting second-generation antibody targeting lectin pathway disorders

Submit IND and commence Phase 1 multiple-ascending-dose study

(MASP-3 / Alternative Pathway)

Paroxysmal nocturnal hemoglobinuria (PNH), complement 3 glomerulopathy (C3G) and other alternative pathway disorders

Read out data from Phase 1b clinical trial in PNH patients

Addictions and compulsive disorders;

Initiate Phase 2 clinical program pending availability of resources

(Compounds In-licensed)

MASP-3 (OMS906) -

Alternative Pathway Disorders

Paroxysmal Nocturnal Hemoglobinuria (PNH) and other alternative pathway disorders

Initiate Phase 1b clinical trial in PNH patients with suboptimal response to the C5 inhibitor ravulizumab

PPARγ (OMS405) -

Assess data in primate study of OMS527 in levodopa-induced dyskinesias (LID);

continue discussions regarding external funding for development in addictive disorders

Opioid and nicotine addiction

10 unchanged sentences

Identify drug development candidate for clinical trials

(In-licensed)

MASP-2 – Second Generation Antibody

Long-acting second generation antibody targeting lectin pathway disorders

Preclinical/Phase 1

CTA submission

MASP-3 - small-

7 unchanged sentences

Wide range of cancers

Scale up and clinical trial initiation

Scale up and initiate clinical trials

Immunotherapeutics

Wide range of cancers

Scale up and initiate clinical trials

> 50 other GPCR targets

3 unchanged sentences

MASP Inhibitor Clinical Programs

MASP-2 Program - Narsoplimab (OMS721) - Lectin Pathway Disorders

Mannan-binding lectin-associated serine protease-2 (“MASP-2”), is a novel pro-inflammatory protein target involved in activation of the complement system, which is an important component of the immune system.

MASP-2 Program - Lectin Pathway Disorders

MASP-2 is a novel pro-inflammatory protein target involved in activation of the complement system, which is an important component of the immune system.

The complement system plays a role in the body’s inflammatory response and becomes activated as a result of tissue damage or trauma or microbial pathogen invasion.

7 unchanged sentences

When not treated, these diseases are typically characterized by significant end-organ damage, such as kidney or central nervous system injury.

We have completed our pivotal clinical trial for narsoplimab in HSCT-TMA and Phase 3 clinical programs are in process for narsoplimab in IgA nephropathy and aHUS.

Narsoplimab is also being evaluated for

treatment of COVID-19 in a nationwide adaptive platform trial and has been used under compassionate use to treat COVID-19 patients in Italy and in the U.S.

We have completed our pivotal clinical trial for narsoplimab in HSCT-TMA and expect later this year to read out 36-week proteinuria data from our Phase 3 clinical program evaluating narsoplimab in IgA nephropathy.

Narsoplimab has also been evaluated for treatment of COVID-19 in a nationwide adaptive platform trial and has been used under compassionate use to treat COVID-19 patients in Italy and in the U.S.

Our MASP-2 inhibitor program also includes OMS1029, our long-acting, next-generation antibody targeting the lectin pathway.

Dosing of all cohorts in a single-ascending dose Phase 1 clinical trial of OMS1029 was successfully completed in early 2023.

OMS1029 was well tolerated with no safety concerns identified.

Preliminary PK and PD data show dose-proportional exposure and sustained lectin pathway inhibition, consistent with potentially quarterly intravenous or subcutaneous dosing.

This next-generation MASP-2 inhibitor is intended to be complementary to narsoplimab, enabling us to pursue chronic indications in which dosing convenience would be of significant benefit to patients.

We are preparing to submit an IND to initiate a multiple-ascending-dose Phase 1 study of OMS1029 in healthy subjects.

Thrombotic Microangiopathies

2 unchanged sentences

In October 2021, we received a CRL from FDA regarding the BLA.

In the CRL, FDA expressed difficulty in estimating the treatment effect of narsoplimab in HSCT-TMA and asserted that additional information will be needed to support regulatory approval.

In January 2022 we submitted a response to the CRL comprising a comprehensive briefing package addressing the points raised by FDA in the CRL and a request for a Type A meeting with FDA to discuss the CRL.

We are currently awaiting FDA’s response to our rebuttals to each of those review issues.

We continue to believe that our BLA, as submitted, merits approval and that the data meet or exceed the threshold for substantial evidence of effectiveness.

The final clinical data from our pivotal trial of narsoplimab in HSCT-TMA in October 2020 was obtained from a single-arm, open-label trial The company worked closely with FDA on design of the single-arm trial to support approval and the definition of response as the primary endpoint.

The primary efficacy endpoint in the trial was the proportion of patients who achieved designated “responder” status based on improvement in HSCT-TMA laboratory markers and clinical status.

The primary laboratory markers evaluated were platelet count and lactate dehydrogenase (“LDH”) levels, while improvement in clinical status was evaluated based on organ function and transfusions.

Each patient was required to show improvement in both laboratory markers and clinical status to be considered a responder.

All others were considered non-responders.

Among patients who received at least one dose of narsoplimab, the complete response rate was 61% (95% confidence interval [CI] 40.6 to 78.5;

p<0.0001), while the complete response rate among patients who received the protocol-specified narsoplimab treatment of at least four weeks of dosing was 74% (95% CI 51.6 to 89.8;

The response rates and their respective lower levels of the 95% confidence intervals are a multiple of the pre-specified efficacy threshold of 15%.

Secondary endpoints in the trial were survival rates and change from baseline in HSCT-TMA laboratory markers.

Among all treated patients, 68% survived for at least 100 days following HSCT-TMA diagnosis, while 83% of patients who received treatment for at least four weeks and 94% of the responders achieved this endpoint.

Median overall survival was 274 days among all patients and 361 days among patients who received the protocol-specified treatment of at least four weeks.

Median survival could not be estimated for responders because more than half of the responders were alive at last follow-up.

Results also included statistically significant improvements in platelet count, LDH and haptoglobin.

The treated population had multiple high-risk features that portend a poor outcome, including the persistence of HSCT-TMA despite modification of immunosuppression (which was a criterion for entry into the trial), graft-versus-host disease, significant infections, non-infectious pulmonary complications and neurological findings.

The most common adverse events observed in the trial were nausea, vomiting, diarrhea, hypokalemia, neutropenia and fever, which are all common in stem-cell transplant patients.

Six deaths occurred during the trial.

These were due to sepsis, progression of the underlying disease, and graft-versus-host disease with TMA.

All of these are common causes of death in this patient population.

In Europe, the EMA has confirmed narsoplimab’s eligibility for the EMA’s centralized review of a single MAA that, if approved, authorizes the product to be marketed in all EU member states and EEA countries.

We are targeting to complete our MAA submission in 2022.

In the U.S., FDA has granted narsoplimab (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 HSCT-TMA.

The European Commission (“EC”) also granted narsoplimab designation as an orphan medicinal product for treatment in hematopoietic stem cell transplantation.

We have a Phase 3 clinical program in patients with aHUS for which patient recruitment is ongoing.

The trial includes multiple sites in the U.S., Asia and Europe;

however, enrollment has been slowed due, in large part, to prioritizing the use of resources within our complement programs to narsoplimab in HSCT-TMA and IgA nephropathy, and to OMS906 in PNH.

FDA has granted narsoplimab orphan drug designation for the prevention (inhibition) of complement-mediated TMAs and fast-track designation for the treatment of patients with aHUS.

In the CRL, the FDA review division expressed difficulty in estimating the treatment effect of narsoplimab in HSCT-TMA and asserted that additional information would be needed to support regulatory approval.

In June 2022, we appealed the issuance of the CRL through a formal dispute resolution process and requested that FDA’s Office of New Drugs (“OND”) direct the FDA review division to accept a Class 1 resubmission of the existing BLA and to commence labeling discussions with Omeros immediately thereafter.

In November 2022 we received OND’s decision denying our appeal.

Although the decision denied our request for immediate resubmission of the BLA and commencement of labeling discussions, it also proposed paths forward to resubmission based on submission of both response and survival data from our completed pivotal trial compared to an appropriate historical control group, with or without an independent literature analysis.

We have requested a meeting with the review division at FDA to confirm the additional information required to be included in the resubmission to support approval of the BLA.

We expect to complete our MAA submission following the resubmission of our BLA to FDA.

The European Commission (the “EC”) also granted narsoplimab designation as an orphan medicinal product for treatment in hematopoietic stem cell transplantation.

We have a Phase 3 clinical program to evaluate narsoplimab in patients with aHUS.

Enrollment in this trial has been challenging and, for commercial reasons specific to the aHUS market, we have prioritized the use of resources to other clinical programs within our complement portfolio.

Currently there is one clinical site in the U.S.

that remains open for patient enrollment.

Renal Disease

Phase 3 Program - IgA Nephropathy .

Patient enrollment is ongoing in our Phase 3 clinical trial evaluating narsoplimab in IgA nephropathy, which is referred to as ARTEMIS-IGAN.

The single Phase 3 trial design is a randomized, double-blind, placebo-controlled multicenter trial in patients at least 18 years of age with biopsy-confirmed IgA nephropathy and 24-hour urine protein excretion greater than 1 g/day at baseline on optimized renin-angiotensin system blockade.

In our Phase 3 clinical trial evaluating narsoplimab in IgA nephropathy, which is referred to as ARTEMIS-IGAN, we expect to read out 36-week proteinuria data later this year.

renin-angiotensin system blockade.

This trial includes a run-in period.

2 unchanged sentences

The primary endpoint, which could suffice for full or accelerated approval depending on the effect size, is reduction in proteinuria at 36 weeks after the start of dosing.

The trial is designed to allow intra-trial adjustment in sample size.

For the purposes of safety and efficacy assessments, the initial sample size for the proteinuria endpoint is estimated at 140 patients in each of the treatment and placebo groups.

This will include a subset of patients with high levels of proteinuria ( i.e.

, equal to or greater than 2 g/day) at baseline, and a substantial improvement at 36 weeks in this subset of patients alone could potentially form the basis for approval.

We believe that the trial design will allow assessment for either full or accelerated approval at 36 weeks based on proteinuria results either (1) across the general population of study patients or (2) in the high-proteinuria subset of patients.

The trial is designed to allow intra-trial adjustments in sample size.

The initial sample size for the proteinuria endpoint remains unchanged at 140 patients in each of the treatment and placebo groups following a blinded sample-size re-estimation.

A subset of patients with high levels of proteinuria ( i.e.

, equal to or greater than 2 g/day) at baseline, and a substantial improvement at 36 weeks could potentially form the basis for approval.

An additional sample-size re-estimation for the eGFR endpoint will take place at the time of the 36-week primary endpoint analysis to ensure that the study is adequately powered for the eGFR readout at the end of the trial.

We believe that the trial design will allow assessment for either full or accelerated approval at 36 weeks based on proteinuria results in the high-proteinuria subset of patients.

In the event of full approval, estimated glomerular filtration rate (“eGFR”) becomes a safety endpoint only.

In the event that the primary endpoint at 36 weeks results in accelerated approval from FDA, change in eGFR is expected to be assessed at approximately two years after the start of dosing.

These eGFR data, if satisfactory, would then likely form the basis for full approval.

In response to investigators’ concerns about extended withholding of narsoplimab treatment from any high-proteinuria patient initially randomized to the placebo-treated group, FDA will allow patients in that sub-population open-label treatment with narsoplimab after at least 1 year of blinded treatment.

These eGFR data, if satisfactory, would then likely form the basis for full approval, which could be in the high-proteinuria subset or the general IgAN population.

In the U.S., narsoplimab has received breakthrough therapy and orphan drug designations from FDA for the treatment of IgA nephropathy.

In Europe, narsoplimab has received orphan drug designation from the EMA in patients with IgA nephropathy.

In March 2020, in response to a request from physicians at the Papa Giovanni XXIII Hospital in Bergamo, Italy, we initiated a compassionate use program for narsoplimab to treat patients with severe COVID-19 requiring mechanical ventilation.

The initial cohort treated under this compassionate use program included a total of six patients with severe COVID-19 treated with narsoplimab under compassionate use, all with acute respiratory distress syndrome (“ARDS”) and requiring continuous positive airway pressure (“CPAP”) or intubation.

At baseline, circulating endothelial cell (“CEC”) counts and serum levels of interleukin-6 (“IL-6”), interleukin-8 (“IL-8”), C-reactive protein (“CRP”), LDH, D-dimer and aspartate aminotransferase (“AST”) were markedly elevated.

Narsoplimab treatment was associated with rapid and sustained reduction across all of these markers of endothelial damage and inflammation.

In addition, massive bilateral pulmonary thromboses, seen in two of the patients, resolved while on narsoplimab.

All six narsoplimab-treated patients recovered, survived and were discharged.

Narsoplimab was well tolerated and no adverse drug reactions were reported.

Two control groups with similar baseline characteristics were used for retrospective comparison, both showing substantial mortality rates of 32% and 53%.

detailing the results of the initial cohort of Bergamo patients treated with narsoplimab was published in the peer-reviewed journal Immunobiology .

(Rambaldi A, Gritti G, Micò MC, et al.

Endothelial injury and thrombotic microangiopathy in COVID-19:

Treatment with the lectin-pathway inhibitor narsoplimab.

Immunobiology.

2020;225(6):152001.)

All six patients were evaluated five to six months after cessation of narsoplimab treatment.

None of them showed any clinical or laboratory evidence of long-term effects of COVID-19 or post-acute sequelae of SARS-CoV-2 infection (“PASC”), such as cognitive impairment or cardiac, pulmonary or other organ disorder, commonly seen following resolution of initial COVID-19 symptoms.

Endothelial damage and resultant thromboses are significant to the pathophysiology of COVID-19, and we believe these data illustrate the importance of inhibiting the lectin pathway to treat critically ill COVID-19 patients.

Endothelial damage activates the lectin pathway of complement.

We believe the results observed following narsoplimab treatment in critically ill COVID-19 patients at Papa Giovanni were consistent with those seen in HSCT-TMA and underscore the pathophysiologic similarities between these two disorders.

Narsoplimab has been shown to inhibit lectin pathway activation and to block the MASP-2-mediated conversion of prothrombin to thrombin, microvascular injury-associated thrombus formation and the activation of factor XII as well as the MASP-2-mediated activation of kallikrein.

We believe that the anticoagulant effects of narsoplimab may provide therapeutic benefits in both HSCT-TMA and COVID-19.

Following treatment of the initial six patients under the compassionate use program in Italy, we have continued compassionate-use treatment with 13 more patients in Italy and four patients in the U.S.

All of these patients prior to receiving narsoplimab were severely ill, intubated (16) or on CPAP (one), had multiple comorbidities, and had failed other therapies, including anti-virals, targeted anti-inflammatory therapeutics, convalescent plasma and steroids.

Following treatment with narsoplimab, the laboratory improvements and clinical outcomes of these patients are similar to those seen in the initial cohort of Bergamo patients.

Two manuscripts from Omeros’ laboratories at the University of Cambridge are expected to be published soon detailing several of our discoveries related to the pathophysiology of COVID-19.

The first, submitted for peer-reviewed publication, covers the discovery of a profile of complement markers of broad complement dysfunction seen in all patients examined during the acute phase of severe COVID-19.

This dysfunction appears to be driven by hyperactivation of the lectin pathway.

Narsoplimab restores complement function in these severe COVID-19 patients while, in patients not treated with narsoplimab, the broad complement dysfunction persists throughout the hospitalization or until death.

The second manuscript, under final review at another peer-reviewed journal, demonstrates that the complement dysfunction in severe COVID-19 patients reported in the first manuscript results in impairment of the adaptive immune response necessary to fight infection, leading to an increased risk of life-threatening secondary infection.

Here again treatment with narsoplimab normalizes the adaptive immune response, which should restore the body’s ability to prevent or fight secondary infection and reduce COVID-19 mortality.

Narsoplimab is also the only complement inhibitor included in the I-SPY COVID-19 adaptive platform trial sponsored by Quantum Leap Healthcare Collaborative, which is evaluating drugs and investigational products for the treatment of critically ill COVID-19 patients.

The narsoplimab treatment arm of the I-SPY COVID-19 trial has now concluded.

Once all data are available, they will be analyzed and the outcome shared publicly.

Discussions regarding the use of narsoplimab in COVID-19 with leaders across various U.S.

government agencies continue to progress.

Narsoplimab also has been administered under compassionate use to treat COVID-19 patients in Italy and in the U.S.

and was the only complement inhibitor included in the I-SPY COVID-19 trial, a nationwide, late-stage adaptive platform trial evaluating multiple agents as potential treatments for COVID-19, sponsored by Quantum Leap Healthcare Collaborative (“Quantum Leap”), in which results of the narsoplimab treatment arm were reported in September 2022.

The I-SPY COVID-19 trial was designed for rapid screening of agents that show promise for two primary endpoints in critically ill COVID-19 patients:

the time to recovery (defined as reduction in oxygen demand) and the risk of mortality.

The study utilized Quantum Leap’s adaptive platform trial design methodology, which focuses on the simultaneous, efficient assessment of multiple investigational agents.

To streamline enrollment and allow rapid assessment of multiple drugs as required during the pandemic, the platform trial’s initial design included a requirement that patients be randomized prior to consenting to trial participation.

Because such analyses are known to create a risk of bias, Quantum Leap also prespecified analyses based on all randomized patients (the industry-standard intent-to-treat population).

Substantial imbalance in the consented population was detected and created a marked and statistically significant bias against the narsoplimab arm, rendering analysis of the consented population meaningless.

Although the narsoplimab treatment arm was terminated prior to accrual of the maximum of 125 patients on the basis of analysis in the pre-consented population in which substantial bias was detected, analysis in the randomized patient population showed that the addition of narsoplimab to treatment of critically ill patients with COVID-19 reduces the mortality risk (hazard ratio [HR]=0.81, with probability [HR <1] equal to 0.77).

In approximately half of the patients who died in the narsoplimab group, narsoplimab was not given or was prematurely stopped, with those patients dying 9 to 35 days later.

Neither the trial’s futility nor graduation criteria had been met in the analysis of the randomized population at the time the narsoplimab arm was terminated.

Narsoplimab was not observed to shorten the time to recovery in critically ill patients with COVID-19 in this study.

The study did not identify any new safety signals for narsoplimab in the setting of critically ill COVID-19 patients.

Next steps in the development of narsoplimab for COVID-19 are dependent on the availability of government or other external funding and support.

We continue to engage in discussions with the U.S.

government regarding its preparedness strategy for the current and potential future pandemics, including anticipated future funding programs and opportunities intended to advance development of therapeutics for COVID-19 and other infectious diseases.

we are developing an assay platform to identify hyperactivation of the lectin pathway in COVID-19 and post-acute sequelae SARS-CoV-2 (PASC).

Licensing Arrangements .

We hold worldwide exclusive licenses to rights related to MASP-2, the antibodies targeting MASP-2 and the therapeutic applications for those antibodies from the University of Leicester, from its collaborator, the Medical Research Council at Oxford University (“MRC”), and from Helion Biotech ApS (“Helion”).

For a more detailed description of these licenses, see “License and Development Agreements” below.

MASP-3 Program - OMS906 - Alternative Pathway Disorders

As part of our MASP program, we have identified mannan-binding lectin-associated serine protease 3 (“MASP-3”), which has been shown to be the key activator of the complement system’s alternative pathway (“APC”), and we believe that we are the first to make this and related discoveries associated with the APC.

As part of our program to develop complement-targeted therapeutics, we have identified MASP-3, which has been shown to be the key activator of the complement system’s alternative pathway (“APC”), and we believe that we are the first to make this and related discoveries associated with the APC.

The complement system is part of the immune system’s innate response, and the APC is considered the amplification loop within the complement system.

MASP-3 is responsible for the conversion of pro-factor D to factor D;

converted factor D is necessary for the activation of the APC.

Based on our alternative pathway-related discoveries, we have expanded our intellectual property position to protect our inventions stemming from these discoveries beyond MASP-2 associated inhibition of the lectin pathway to include inhibition of the alternative pathway.

Our current primary focus in this program is developing MASP-3 inhibitors for the treatment of disorders related to the APC.

MASP-3 is responsible for the conversion of pro-factor D to mature factor D;

which is necessary for the activation of the APC.

We believe that MASP-3 inhibitors have the potential to treat patients suffering from a wide range of diseases and conditions, including:

12 unchanged sentences

The program has also generated positive data in a well-established animal model of arthritis.

In September 2020 we began enrollment and dosing in a placebo-controlled, double-blind, single-ascending-dose and multiple-ascending-dose Phase 1 clinical trial to evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of OMS906.

We have dosed subjects across all dosing cohorts in the single-ascending dose study and reported preliminary data from the Phase 1 trial in June 2021.

OMS906 has been well tolerated at all doses tested and preliminary human pharmacokinetic and pharmacodynamic data are consistent with once-monthly subcutaneous dosing and every-other-month or less frequent IV dosing.

Recent data show high level suppression of alternative pathway activity.

We have determined to forego the multiple-ascending dose portion of our Phase 1 trial in healthy subjects and plan to move directly into a Phase 1b clinical trial in patients with PNH who have an unsatisfactory response to the C5 inhibitor ravulizumab.

A successful meeting was held between Omeros and the Medicines and Healthcare products Regulatory Agency (MHRA) to discuss the design and conduct of the Phase 1b trial.

Enrollment is expected to begin this summer.

We expect that this will accelerate our overall clinical development program for OMS906 in PNH.

Clinical development of OMS906 is currently focused on rapidly obtaining proof-of-concept data in multiple APC-related disorders, including PNH and C3G.

Clinical results of a placebo-controlled, double-blind, single-center Phase 1 clinical trial evaluating the safety, tolerability, pharmacodynamics and pharmacokinetics of single-ascending intravenous (“IV”) and subcutaneous (“SC”) doses of OMS906 in healthy subjects were presented at the American Society of Hematology Annual Meeting in December 2022.

Subjects were randomized into escalating single-ascending dose cohorts that received 0.1 to 5.0 mg/kg IV and 3.0 to 8.0 mg/kg SC of either OMS906 or placebo via infusion.

Overall, 72 subjects were enrolled, and demographics were generally balanced between the dosing cohorts, and between the OMS906 versus placebo groups.

OMS906 was well tolerated at all doses tested with no safety concerns.

OMS906 displayed consistent pharmacokinetic properties with dose proportionality (with non- linearity) for both IV and SC administration.

A long half-life (geometric mean range 94–406 hours) was observed, with measurable drug concentrations detected at Day 85 for both the IV (3 and 5 mg/kg) and SC (3, 5 and 8 mg/kg) OMS906 cohorts.

The key pharmacodynamic marker for MASP-3 inhibition – mature complement factor D – showed a dose-proportional response with rapid suppression and a substantial degree of suppression of long duration in subjects receiving 3 and 5 mg/kg OMS906 IV versus placebo.

The observed pharmacokinetic and pharmacodynamic profiles showed predictable systemic exposure, evidence of high levels of alternative pathway inhibition, and a long duration of action consistent with once-monthly to once-quarterly SC or IV dosing.

In late 2022 we began enrolling in a Phase 1b clinical trial evaluating OMS906 for the treatment of PNH.

The first treatment-naïve PNH patients were dosed with OMS906 in early 2023.

We have also begun enrolling a Phase 1b clinical trial evaluating OMS906 in PNH patients who have had an unsatisfactory response to the C5 inhibitor ravulizumab.

OMS906 received designation from FDA as an orphan drug for the treatment of PNH in July 2022.

Licensing Arrangements.

We jointly own and hold worldwide exclusive license rights related to therapeutic applications for inhibiting MASP-3 from the University of Leicester.

We also hold an exclusive license from Xencor, Inc.

for the application of certain antibody technology to OMS906.

For a more detailed description of these licenses, see “License and Development Agreements” below.

2 unchanged sentences

We have generated positive preclinical data from MASP-2 inhibition in in vivo models of AMD, myocardial infarction, diabetic neuropathy, stroke, ischemia-reperfusion injury, and other diseases and disorders.

We are also developing a longer-acting second generation antibody targeting MASP-2, OMS1029 which is expected to enter the clinic this summer.

All first-in-human-enabling toxicology studies have been completed, and no findings of concern were identified.

Based on pharmacokinetic/pharmacodynamic data to date, dosing in humans is expected to be once-monthly to once-quarterly by subcutaneous or intravenous administration.

Development efforts are also directed to a small-molecule inhibitor of MASP-2 designed for oral administration, as well as small-molecule inhibitors of MASP-3 and bispecific small- and large-molecule inhibitors of MASP-2/-3.

5 unchanged sentences

Data generated in preclinical studies support the use of PDE7 inhibitors in both of these therapeutic areas.

In September 2019, we reported positive results from our completed Phase 1 clinical trial designed to assess the safety, tolerability and pharmacokinetics of the compound in healthy subjects.

In September 2019, we reported positive results from our completed Phase 1 clinical trial designed to assess the safety, tolerability and pharmacokinetics of our lead PDE7 inhibitor in healthy subjects.

In the double blind, randomized Phase 1 study, the study drug, referred to as OMS182399, met the primary endpoints of safety and tolerability and showed a favorable and dose-proportional pharmacokinetic profile supporting once-daily dosing.

There was no apparent food effect on plasma exposure to OMS182399.

Continued clinical development in our PDE7 program is subject to allocation of financial and other resources, which are currently prioritized for other programs.

Research collaborators at Emory University are currently evaluating, in a clinically predictive primate model, the potential of our PDE7 inhibitors to improve levodopa-induced dyskinesias.

Levodopa-induced dyskinesias are crippling, involuntary movements in patients with Parkinson’s disease that are caused by prolonged treatment with levodopa, the most prescribed therapy for Parkinson’s disease.

More than 10 million patients are living with Parkinson’s disease worldwide .

Reportedly 50 percent or more of levodopa-treated patients with Parkinson’s disease suffer from LID.

Additionally, we are engaged in discussions with third parties regarding external funding for development of our PDE7 inhibitors as a treatment for addictive disorders.

Exclusive License Agreement with Daiichi Sankyo Co., Ltd.

21 unchanged sentences

Preclinical Programs and Platforms

GPCR Platform

GPCRs, which are cell surface membrane proteins involved in mediating both sensory and nonsensory functions, comprise one of the largest families of proteins in the genomes of multicellular organisms.

Sensory GPCRs are involved in the perception of light, odors, taste and sexual attractants.

Non-sensory GPCRs are involved in metabolism, behavior, reproduction, development, hormonal homeostasis and regulation of the central nervous system.

The vast majority of GPCR drug targets are non-sensory.

Although GPCRs form a super-family of receptors, individual GPCRs display a high degree of specificity and affinity for the functionally active molecules, or ligands, that bind to a given receptor.

Ligands can either activate the receptor (agonists) or inhibit it (antagonists and inverse agonists).

When activated by its ligand, the GPCR interacts with intracellular G proteins, resulting in a cascade of signaling events inside the cell that ultimately leads to the particular function linked to the receptor.

Without a known ligand, there is no template from which medicinal chemistry efforts can be readily initiated, nor a means to identify the GPCR’s signaling pathway and, therefore, drugs are very difficult to develop against orphan GPCRs.

“Unlocking” these orphan GPCRs by identifying one or more of their respective ligands could lead to the development of drugs that act at these new targets.

To our knowledge, Omeros’ technology is the first commercially viable technology capable of identifying ligands of orphan GPCRs in high throughput.

We have developed a proprietary cellular redistribution assay (“CRA”), which we use in a high-throughput manner to identify synthetic ligands, including antagonists, agonists and inverse agonists, that bind to and affect the function of orphan GPCRs.

We have screened Class A orphan GPCRs against our small-molecule chemical libraries using the CRA and have identified and confirmed compounds that interact with 54 of the 81 Class A orphan GPCRs linked to a wide range of indications including cancer as well as metabolic, cardiovascular, immunologic, inflammatory and central nervous system disorders.

GPCR Platform and GPR174

We have developed a proprietary cellular redistribution assay which we use in a high-throughput manner to identify synthetic ligands, including antagonists, agonists and inverse agonists, that bind to and affect the function of orphan GPCRs.

We have screened Class A orphan GPCRs against our small-molecule chemical libraries using the cellular redistribution assay and have identified and confirmed compounds that interact with 54 of the 81 Class A orphan GPCRs linked to a wide range of indications including cancer as well as metabolic, cardiovascular, immunologic, inflammatory and central nervous system disorders.

One of our priorities in this program is GPR174, which is involved in the modulation of the immune system.

The GPR174 program is part of our immuno-oncology platform.

In ex vivo human studies, our small-molecule inhibitors targeting GPR174 upregulate the production of cytokines, block multiple checkpoints and tumor promoters, and suppress regulatory T cells.

3 unchanged sentences

These discoveries include (1) identification of cancer-immunity pathways controlled by GPR174, (2) the identification of phosphatidylserine as a natural ligand for GPR174, (3) a collection of novel small-molecule inhibitors of GPR174 and (4) a synergistic enhancement of “tumor-fighting” cytokine production by T cells following the combined inhibition of both GPR174 and the adenosine pathway, another key metabolic pathway that regulates tumor immunity.

We are developing both small-molecule and antibody inhibitors of GPR174 with the objective of moving compounds into human trials.

In addition to GPR174 inhibitors, we also are developing other cancer therapeutics as well as novel platforms for generating more effective CAR-T and adoptive T-cell therapies.

In addition to Class A orphan GPCRs, we have screened orphan and non-orphan Class B receptors.

Class B GPCRs have large extracellular domains and their natural ligands are generally large peptides, making the development of orally active, small-molecule drugs against these receptors, such as glucagon and parathyroid hormone, a persistent challenge.

Our CRA technology finds functionally active small molecules for GPCRs, which we believe could lead to the development of oral medications for many of the Class B GPCRs.

While our focus to date has remained on Class A orphan GPCRs, we have identified and confirmed sets of compounds that interact selectively with, and modulate signaling of, a small subset of Class B GPCRs, namely glucagon-like peptide-1 receptor and parathyroid hormone 1 receptor.

We are developing, and are considering advancing to clinical trials, inhibitors of GPR174 and of the pathways affected by this receptor and/or adenosine receptors.

GPCR Platform Funding Agreements with Vulcan Inc.

3 unchanged sentences

For a more detailed description of these agreements, see “License and Development Agreements” below.

Immuno-Oncology Platform

We are advancing preclinical research on potential molecular and cellular therapies for cancer.

On the molecular front, we have developed novel biologic platforms to target cancer cells specifically and kill them directly or indirectly through the potentiation of the immune system.

Our novel molecules combine tumor antigens with a potent adjuvant and show high levels of killing in cancer cells.

We believe that some of these molecules could function as therapeutic vaccines against a broad range of tumors, potentially transforming treatment of both solid tumors and hematologic cancers.

On the cellular front, we are evaluating novel approaches for both CAR T and adoptive T cell therapies.

We have identified specific T cell signaling pathways, which, once inhibited, significantly and preferentially enhance the expansion of memory T cells that distinctively recognize and efficiently kill tumor cells.

We continue to develop and validate our novel approach, which we believe could improve response rates for patients receiving either engineered or native T cell therapies for liquid or solid tumors.

Sales and Marketing

10 unchanged sentences

Title transferred upon delivery of OMIDRIA to the wholesaler.

We used a single third-party logistics provider to handle warehousing and final packaging of our commercial supply of OMIDRIA in the U.S.

and to ship OMIDRIA to our wholesalers.

Our third-party logistics provider also performs certain support services on our behalf.

Virtually all of our revenues for the last three fiscal years were generated from OMIDRIA product sales in the U.S.

Our four major distributors--AmerisourceBergen Corporation, Cardinal Health, Inc., McKesson Corporation and FFF Enterprises, Inc.--together with entities under their common control each accounted for 10% or more, and nearly 100% in aggregate, of our total revenue in 2021.

For additional information regarding our major customers, see Part II, Item 8, “Note 2—Significant Accounting Policies” to our Consolidated Financial Statements in this Annual Report on Form 10-K.

For additional information, see Part II, Item 8, “Note 3—Discontinued Operations” to our Consolidated Financial Statements in this Annual Report on Form 10-K.

Drug Candidates .

8 unchanged sentences

We will purchase narsoplimab that meets agreed specifications in batches, with the price per batch varying according to the total number of batches ordered for serial production in a single manufacturing campaign.

We are obligated to purchase a minimum number of batches annually beginning on a specified

anniversary of the first commercial sale of narsoplimab in either the U.S.

We are obligated to purchase a minimum number of batches annually beginning on a specified anniversary of the first commercial sale of narsoplimab in either the U.S.

We may be obligated to pay certain fees to Lonza upon cancellation of purchase orders.

5 unchanged sentences

MASP Program .

Under our exclusive license agreements with the University of Leicester and MRC, we have agreed to pay royalties to each of the University of Leicester and MRC that are a percentage of any proceeds we receive from the licensed MASP-2 technology during the terms of the agreements.

Our exclusive license agreement with the University of Leicester, but not our agreement with the MRC, also applies to other MASPs.

The continued maintenance of these agreements requires us to undertake development activities.

Under our exclusive license agreement with the University of Leicester, we have agreed to pay royalties to the University of Leicester that are a percentage of any proceeds we receive from the licensed MASP-2 technology during the term of the agreement.

The agreement also applies to other MASPs and continued maintenance of the agreement requires us to undertake development activities.

We must pay low single-digit percentage royalties with respect to proceeds that we receive from products incorporating certain intellectual property within the licensed technology that are used, manufactured, directly sold or directly distributed by us, and we must pay royalties, in the range of a low single-digit percentage to a low double-digit percentage, with respect to proceeds we receive from sublicense royalties or fees that we receive from third parties to which we grant sublicenses to certain intellectual property within the licensed technology.

We did not make any upfront payments for these exclusive licenses nor are there any milestone payments or reversion rights associated with these license agreements.

We retain worldwide exclusive licenses from these institutions to develop and commercialize any intellectual property rights developed in the sponsored research.

The term of each license agreement ends when there are no longer any pending patent applications, applications in preparation or unexpired issued patents related to any of the intellectual property rights we are licensing under the agreement.

Both of these license agreements may be terminated prior to the end of their terms by us for convenience or by one party if the other party (1) breaches any material obligation under the agreement and does not cure such breach after notice and an opportunity to cure or (2) is declared or adjudged to be insolvent, bankrupt or in receivership and materially limited from performing its obligations under the agreement.

We did not make any upfront payments for the exclusive license, nor are there any milestone payments or reversion rights associated with the license agreement.

We retain a worldwide exclusive license from the University of Leicester to develop and commercialize any intellectual property rights developed in the sponsored research.

The term of the agreement ends when there are no longer any pending patent applications, applications in preparation or unexpired issued patents related to any of the intellectual property rights we are licensing under the agreement.

The license agreement may be terminated prior to the end of its term by us for convenience or by one party if the other party (1) breaches any material obligation under the agreement and does not cure such breach after notice and an opportunity to cure or (2) is declared or adjudged to be insolvent, bankrupt or in receivership and materially limited from performing its obligations under the agreement.

In April 2010, we entered into an exclusive license agreement with Helion, pursuant to which we received a royalty-bearing, worldwide exclusive license to all of Helion’s intellectual property rights related to MASP-2 antibodies, polypeptides and methods in the field of inhibition of mannan-binding lectin-mediated activation of the complement system for the prevention, treatment or diagnosis of any disease or condition.

3 unchanged sentences

The agreement may be terminated sooner by either party following a material breach of the agreement by the other party that has not been cured within 90 days.

In August 2020, we entered into a technology license agreement with Xencor, Inc., pursuant to which we received an exclusive license to apply Xencor’s Xtend Fc technology to OMS906 and options to access exclusive licenses to apply Xtend Fc technology to additional antibodies (the “Xencor Agreement”).

Exercise of an option to access additional licenses would require payment of a $3.0 million upfront license fee.

With respect to each antibody for which we license the Xencor technology we are obligated to make milestone payments of up to $65.0 million, comprised of $15.0 million in development milestones, $25.0 million in regulatory milestones and $25.0 million in sales milestones.

We are obligated on a product-by-product and country-by-country basis to pay Xencor royalties in the mid-single digit

percentage range on net sales of any product covered by the license so long as there is a valid, subsisting and enforceable claim in any patents or patent applications covering the licensed technology.

Thereafter, the royalty rate is reduced to the low single-digit percentage range, if the applicable licensed product is covered by Xencor know-how, or to zero, if the applicable licensed product is not covered by Xencor know-how.

The term of the Xencor Agreement continues on a product-by-product basis until the later of (i) expiration for the last-to-expire patent covering the licensed technology or (ii) five years from the date of first commercial sale of the applicable product.

We acquired the patent applications and related intellectual property rights for our PPARγ program in February 2009 from Roberto Ciccocioppo, Ph.D.

8 unchanged sentences

If we notify Dr.

Ciccocioppo that we have abandoned all research and development and commercialization efforts related to the patent applications and intellectual property rights we acquired

from him, Dr.

Ciccocioppo that we have abandoned all research and development and commercialization efforts related to the patent applications and intellectual property rights we acquired from him, Dr.

Ciccocioppo has the right to repurchase those assets from us at a price equal to a double-digit percentage of our direct and indirect financial investments and expenditures in such assets.

18 unchanged sentences

In October 2010, we entered into funding agreements for our GPCR program with Vulcan and LSDF.

We received $20.0 million and $5.0 million, respectively, under the agreements with Vulcan and LSDF.

Under these agreements, we have agreed to pay Vulcan and LSDF tiered percentages of the net proceeds, if any, that we derive from the GPCR program.

Under these agreements, we have

agreed to pay Vulcan and LSDF tiered percentages of the net proceeds, if any, that we derive from the GPCR program.

The percentage rates of net proceeds payable to Vulcan and LSDF decrease as the cumulative net proceeds reach specified thresholds, and the blended percentage rate payable to Vulcan and LSDF in the aggregate is in the mid-teens with respect to the first approximately $1.5 billion of cumulative net proceeds that we receive from our GPCR program.

19 unchanged sentences

We expect to compete for market share against large pharmaceutical and biotechnology companies, smaller companies that are collaborating with larger pharmaceutical companies, new companies, academic institutions, government agencies and other public and private research organizations.

In addition, the pharmaceutical and biotechnology industry is characterized by rapid technological change.

In addition, the pharmaceutical and

biotechnology industry is characterized by rapid technological change.

Because our research approach integrates many technologies, it may be difficult for us to remain current with the rapid changes in each technology.

2 unchanged sentences

Drug Candidates, Development Programs and Platforms.

With respect to our development of therapeutics targeting complement-mediated disorders, there are multiple companies developing potential therapies targeting the complement system.

Although none of these potential therapies, to our knowledge, selectively inhibit the lectin pathway, there are other companies developing alternative pathway inhibitors.

There are also a number of complement-targeted therapeutics that have been approved for commercial use, including Soliris ® (eculizumab), Ultomiris ® (ravulizumab-cwvz), Empaveli ® (pegcetacoplan) and Tavneos ® (avocopan), with which narsoplimab and/or OMS906 will compete if either is approved for any indication(s) for which one or more of these products are also approved.

There are a number of complement-targeted therapeutics that are in advanced stages of clinical development, or which have been approved for commercial use.

These include Soliris ® (eculizumab), Ultomiris ® (ravulizumab-cwvz), Empaveli ® (pegcetacoplan), Tavneos ® (avocopan) and iptacopan.

Narsoplimab, OMS1029 and/or OMS906 will face competition from one or more of these products if approved for any indication(s) for which one or more of these potentially competitive products are also approved.

We are aware of other companies attempting to de-orphanize orphan GPCRs.

13 unchanged sentences

We own and exclusively control under a license from the University of Leicester all rights to methods of treating various disorders and diseases by inhibiting MASP-3.

As of February 9, 2022, we exclusively controlled three issued patents and five pending patent applications in the U.S.

As of February 15, 2023, we exclusively controlled three issued patents and seven pending patent applications in the U.S.

and 171 issued and 108 pending patent applications in foreign markets that are related to our MASP-3 program.

2 unchanged sentences

● PDE7 Program - OMS527 .

As of February 9, 2022, we owned two issued patents and one pending patent application in the U.S., and 61 issued patents and twoe pending patent applications in foreign markets directed to our discoveries linking PDE7 to movement disorders, as well as two issued patent and two pending patent applications in the U.S., and 49 issued patents and 11 pending patent applications in foreign markets directed to the link between PDE7 and addiction and compulsive disorders.

Additionally, under a license from Daiichi Sankyo, we exclusively control rights to three issued U.S.

As of February 15, 2023, we owned two issued patents and one pending patent application in the U.S., and 61 issued patents and two pending patent applications in foreign markets directed to our discoveries linking PDE7 to movement disorders, as well as three issued patent and two pending patent applications in the U.S., and 53 issued patents and 8 pending patent applications in foreign markets directed to the link between PDE7 and addiction and compulsive disorders.

Additionally, under a license from Daiichi

Sankyo, we exclusively control rights to three issued U.S.

patents and 53 issued patents in foreign markets that are directed to proprietary PDE7 inhibitors.

For a more detailed description of our agreement with Daiichi Sankyo, see “License and Development Agreements” below.

● GPCR Platform.

As of February 9, 2022, we owned seven issued patents and 12 pending patent applications in the U.S., and 56 issued patents and 24 pending patent applications in foreign markets, which are directed to previously unknown links between specific molecular targets in the brain and a series of CNS disorders, to our CRA and to other research tools that are used in our GPCR program, and to orphan GPCRs and other GPCRs for which we have identified functionally interacting compounds using our CRA.

● GPCR Platform and Immuno-oncology Program.

As of February 15, 2023, we owned six issued patents and 13 pending patent applications in the U.S., and 57 issued patents and 26 pending patent applications in foreign markets, which are directed to previously unknown links between specific molecular targets in the brain and a series of CNS disorders, to potential cancer therapies, to our CRA and to other research tools that are used in our GPCR program, and to orphan GPCRs and other GPCRs for which we have identified functionally interacting compounds using our CRA.

Two of the pending patent applications in the U.S.

and the 24 pending patent applications in foreign markets are directed to GPR174.

and 24 of the pending patent applications in foreign markets are directed to GPR174.

Three of the pending patent applications in the U.S.

and two pending applications in foreign markets are directed to potential cancer therapies.

All of our employees enter into our standard employee proprietary information and inventions agreement, which includes confidentiality provisions and provides us ownership of all inventions and other intellectual property made by our employees that pertain to our business or that relate to our employees’ work for us or that result from the use of our resources.

Our commercial success will depend in part on obtaining and maintaining patent protection and trade secret protection of the use, formulation and structure of our drug candidates and the methods used to manufacture them, as well as on our ability to defend successfully these patents against third-party challenges.

Our ability to protect our drug

candidates from unauthorized making, using, selling, offering to sell or importing by third parties is dependent on the extent to which we have rights under valid and enforceable patents that cover these activities.

Our ability to protect our drug candidates from unauthorized making, using, selling, offering to sell or importing by third parties is dependent on the extent to which we have rights under valid and enforceable patents that cover these activities.

The patent positions of pharmaceutical, biotechnology and other life sciences companies can be highly uncertain and involve complex legal and factual questions for which important legal principles remain unresolved.

13 unchanged sentences

In the EU, our drug candidates are regulated by the EMA and national medicines regulators under the rules governing medicinal products in the EU as well as national regulations in individual countries.

The marketing authorization for OMIDRIA in the U.S.

has been transferred to Rayner and the marketing authorizations in the EU and United Kingdom are in process of being transferred to Rayner, as required by the Asset Purchase Agreement pursuant to which Omeros divested OMIDRIA and related assets, including such marketing approvals, in December 2021.

Our drug candidates are in various stages of testing and none of our drug candidates has received marketing approval from FDA or the applicable regulatory authorities in the EU.

27 unchanged sentences

Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified personnel and must be conducted in accordance with local regulations and GCPs.

Clinical trials are conducted under protocols detailing, for example, the parameters to be used in monitoring patient safety and the efficacy criteria, or endpoints, to be evaluated.

Clinical trials

are conducted under protocols detailing, for example, the parameters to be used in monitoring patient safety and the efficacy criteria, or endpoints, to be evaluated.

Each trial must be reviewed and approved by an independent institutional review board or ethics committee for each clinical site at which the trial will be conducted before it can begin.

24 unchanged sentences

The FDA may refer the NDA or BLA to an advisory committee for review and recommendation as to whether the application should be approved and under what conditions.

The FDA is not bound by the recommendation of an advisory committee, but it generally follows such recommendation.

The FDA is not bound by the recommendation of an advisory

committee, but it generally follows such recommendation.

In addition, even if a drug candidate satisfied its endpoints with statistical significance during clinical trials, FDA could determine that the overall balance of risks and benefits for the drug candidate is not adequate to support approval, or only justifies approval for a narrow set of clinical uses and/or subject to restricted distribution or other burdensome post-approval requirements or limitations.

5 unchanged sentences

For example, we must establish a pharmacovigilance system and are required to report adverse reactions and production problems, if any, to the regulatory authorities.

If any of our drug

candidates are approved, we will be required to also comply with certain requirements concerning advertising and promotion for our products.

If any of our drug candidates are approved, we will be required to also comply with certain requirements concerning advertising and promotion for our products.

The regulatory authorities may impose specific obligations as a condition of the marketing authorization, such as additional safety monitoring, or the conduct of additional clinical trials or post-marketing safety studies, or the imposition of a Risk Evaluation and Mitigation Strategy (“REMS”), which could include significant restrictions on distribution or use of the product.

18 unchanged sentences

Accelerated Approval .

The FDA may grant accelerated approval to a product for a serious or life-threatening condition that provides a meaningful therapeutic advantage to patients over existing treatments based upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit.

The FDA may grant accelerated approval to a product for a serious or life-threatening condition that provides a meaningful therapeutic advantage to patients over existing treatments based upon a

determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit.

The FDA may also grant accelerated approval for such a condition when the product has an effect on an intermediate clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality and that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit.

2 unchanged sentences

Following accelerated approval, FDA requires that the company provide confirmatory evidence, which may include certain adequate and well-controlled post-marketing clinical studies to verify the clinical benefit of the product, and FDA may impose restrictions on distribution to assure safe use.

Confirmatory studies are typically required to be underway at the time of the accelerated approval.

Pursuant to new statutory authority under the Food and Drug Omnibus Reform Act of 2022, FDA can require confirmatory studies to be underway at the time of the accelerated approval.

If the required confirmatory studies fail to verify the clinical benefit of the drug, or if the applicant fails to perform the required confirmatory studies with due diligence, FDA may withdraw approval of the drug under streamlined procedures in accordance with the Agency’s regulations.

39 unchanged sentences

In general, our labeling and promotion must not be false or misleading in any particular, and claims that we make must be adequately substantiated.

In addition, our approved labeling must include adequate directions to physicians for

each intended use of our products.

In addition, our approved labeling must include adequate directions to physicians for each intended use of our products.

Failure to comply with these requirements can result in adverse publicity, warning letters, corrective advertising, injunctions and potential civil and criminal penalties.

17 unchanged sentences

For products and transactions falling within DSCSA’s scope, manufacturers are required to verify that purchasers of the manufacturers’ products are appropriately licensed.

Further, under the DSCSA, covered manufacturers have drug product investigation, quarantine, disposition, and notification responsibilities for product that is reasonably believed or that credible evidence shows to be counterfeit, diverted, stolen, intentionally adulterated such that the product would result in serious adverse health consequences or death, the subject of fraudulent transactions or otherwise unfit for distribution such that they would be reasonably likely to result in serious health consequences or death.

to result in serious health consequences or death.

Anti-counterfeiting and serialization requirements similar to those under the DSCSA have also been adopted in the EU and became effective in February 2019.

2 unchanged sentences

The foreign regulatory approval processes include similar requirements and many of the risks associated with FDA and/or the EU approval process described above, although the precise requirements may vary from country to country.

In the EU, once an MAA is granted, the product must be “placed on the market” in at least one EEA country within three years of the date of authorization.

“Placed on the market” is defined as when the medicinal product is “released into the distribution chain,” i.e.

, out of the direct control of the marketing authorization holder.

In July 2021, we placed OMIDRIA on the market in the EU, on a limited basis, which maintained the ongoing validity of the European marketing authorization for OMIDRIA.

The EU marketing authorization is in the process of being transferred to Rayner as required under the Asset Purchase Agreement pursuant to which we divested OMIDRIA and related assets to Rayner in December 2021.

Hatch-Waxman Act.

3 unchanged sentences

In this case the original NDA, i.e., the pioneer drug, is known as the “listed” drug or “reference-listed” drug.

An ANDA provides for marketing of a drug that has the same active ingredients and, in some cases ( e.g., ophthalmology), also the same inactive ingredients, in the same strengths, route of administration and dosage form as the listed drug and has been shown

through testing to be bioequivalent to the listed drug or receives a waiver from bioequivalence testing.

An ANDA provides for marketing of a drug that has the same active ingredients and, in some cases, also the same inactive ingredients, in the same strengths, route of administration and dosage form as the listed drug and has been shown through testing to be bioequivalent to the listed drug or receives a waiver from bioequivalence testing.

ANDA applicants are generally not required to conduct or submit results of preclinical or clinical tests to prove the safety or effectiveness of their drug, other than the requirement for bioequivalence testing.

41 unchanged sentences

In addition to these federal law requirements, several U.S.

states have enacted similar laws requiring periodic reporting and/or disclosure related to our marketing, sales and other activities, or regulating certain sales and marketing activities, such as provision of meals, gifts or entertainment to certain health care providers.

We may also be subject to federal or state privacy laws if we receive protected patient health information.

21 unchanged sentences

For example, the 2010 Affordable Care Act (the “ACA”), is intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add transparency requirements for the healthcare and health insurance industries, impose new taxes and fees on the health industry and impose additional health policy reforms.

Other legislative changes included a two percent across-the-board reduction to Medicare payments to providers, effective April 1, 2013, which, due to subsequent legislative amendments, will stay in effect through fiscal year 2029 unless additional congressional action is taken.

(A temporary suspension of this reduction during the public health emergency for the pandemic is currently scheduled to expire on March 31, 2022.) The American Taxpayer Relief Act of 2012, among other things, reduced Medicare payments to several providers, and increased the period for the government to recover overpayments to providers from three to five years.

Other legislative changes included a two percent across-the-board reduction to Medicare payments to providers, effective April 1, 2013, which, due to subsequent legislative amendments, will begin to increase gradually starting in April 2030, reaching 4 percent in April 2031 and continuing until the reduction ends in October 2031, unless additional

congressional action is taken.

The American Taxpayer Relief Act of 2012, among other things, reduced Medicare payments to several providers, and increased the period for the government to recover overpayments to providers from three to five years.

In December 2017, portions of the ACA dealing with the individual mandate insurance requirement were effectively repealed by the Tax Cuts and Jobs Act of 2017.

The latest court challenge to the ACA failed in June 2021, when the United States Supreme Court held that the individual plaintiffs and states lacked standing to challenge the constitutionality of the ACA.

In November 2020, CMS issued an interim final rule through the CMS Innovation Center whereby Medicare Part B reimbursement for “certain high-cost prescriptions drugs” would be no more than most-favored-nation price (i.e., the lowest price) after adjustments, for a pharmaceutical product that the drug manufacturer sells in a member country of the Organization for Economic Cooperation and Development that has a comparable per-capita gross domestic product.

In December 2020, the U.S.

District Court in Northern California issued a nationwide preliminary injunction against implementation of the interim final rule.

The Biden administration subsequently withdrew the interim final rule.

The Biden administration has indicated that lowering prescription drug prices is a priority, but it is not yet clear what steps the administration will take or whether such steps will be successful.

We cannot predict the ultimate content, timing or effect of any healthcare reform legislation or executive order or the impact that the resulting changes may have on us.

Containment of healthcare costs has been a priority of federal, state, and foreign governments, and the prices of drug products have been a focus of this effort.

Governments have shown significant interest in implementing cost-containment programs.

This interest has resulted in significant proposed and enacted reform measures affecting healthcare reimbursement and drug pricing, including the enactment in August 2022 of significant changes to potential Medicare drug product reimbursement through government negotiation of certain drug prices, as well as manufacturer discount and inflation rebate obligations under the Inflation Reduction Act (the “IRA”).

We are unable to predict what additional legislation, regulations, policies or court orders, if any, relating to the healthcare industry or coverage and reimbursement may be enacted or imposed in the future or what effect such legislation, regulations, policies or court orders would have on our business.

13 unchanged sentences

As of December 31, 2022, we had 196 full-time employees, 130 of whom are in research and development, 19 of whom are in sales and marketing and 47 of whom are in finance, legal, business development and administration.

Our full-time employees include five with M.D.s and 39 with Ph.Ds., of whom one and 23, respectively, are in research and development.

Our full-time employees include five with M.Ds and 36 with Ph.Ds., of whom four and 36, respectively, are in research and development.

None of our employees are represented by a labor union, and we consider our employee relations to be good.

8 unchanged sentences

Significant Employees:

Christopher S.

Vice President, Nonclinical Development

Vice President, Chief Business Development Officer

Vice President, Chief Commercial Officer

Dimitrova, Ph.D.

Vice President, Chemistry, Manufacturing and Controls

Gaitanaris, M.D., Ph.D.

Vice President, Science and Chief Scientific Officer

Bruce Meiklejohn, Ph.D.

Vice President, Chemistry, Manufacturing and Controls

Vice President, Regulatory Affairs & Quality Systems and Chief Regulatory Officer

6 unchanged sentences

founded our company and has served as our president, chief executive officer and chairman of the board of directors since June 1994.

He also served as our chief financial officer and treasurer from

January 2009 to October 2013 in an interim capacity and as our chief medical officer from June 1994 to March 2010.

He also served as our chief financial officer and treasurer from January 2009 to October 2013 in an interim capacity and as our chief medical officer from June 1994 to March 2010.

Prior to founding Omeros, Dr.

27 unchanged sentences

from Saint Michael’s College.

Christopher S.

has served as our vice president, nonclinical development since October 2015.

From April 2014 to October 2015, Dr.

Bral was the executive director, toxicology at Arrowhead Research Corporation, a biopharmaceutical company.

From June 2008 to April 2014, Dr.

Bral served as director, drug safety evaluation at Vertex Pharmaceuticals, a biotechnology company.

Prior to Vertex, Dr.

Bral held various pre-clinical drug safety positions of increasing responsibility at Schering-Plough Research Institute including associate director, drug safety evaluation.

Bral received his Ph.D.

in biochemistry and biophysics from Texas A&M University and his B.S.

in chemistry from John Carroll University.

He has been board-certified in toxicology through the American Board of Toxicology since 2000.

Bowes, MBEE has served as our chief business development officer since September 2022.

Bowes brings over 30 years of industry experience in corporate and product strategic planning, global licensing and business development.

Prior to joining Omeros, Ms.

Bowes served as a fractional executive for several small biotechnology companies through Chevy Chase BioPartners, LLC, periodically between 2006 to 2022.

From 2016 to 2019 she served as the chief business officer for the CARMA cell therapy drug development division of Maxcyte, Inc., a provider of cell-engineering platform technologies.

From 2011 to 2013 Ms.

Bowes served as the vice president of licensing and commercial strategy for CBLI Pharma, an orphan disorder company.

From 2003 to 2006 she served as MedImmune’s senior director of strategic planning, overseeing corporate and new product planning.

Prior to MedImmune, Ms.

Bowes held several roles of increasing responsibility for Amylin, Agouron/Pfizer, Centocor/Johnson & Johnson and Hybritech/Eli Lilly & Company.

She holds a Masters in Biotechnology Enterprise and Entrepreneurship (MBEE) from Johns Hopkins University, a B.S.

in biology from the University of Cincinnati and a medical technology certification from the American Society of Clinical Pathologists.

Nadia Dac has served as our chief commercial officer since January 2021.

10 unchanged sentences

in Marketing from Rutgers University.

Dimitrova, Ph.D., has served as our vice president chemistry, manufacturing, and controls (“CMC”) since October 2022.

Prior to joining Omeros in this role, Dr.

Dimitrova had 20 years of pharmaceutical experience with CMC leadership spanning formulation development, drug product and device development, drug delivery and Human Factors engineering, analytical sciences, process development, and clinical manufacturing.

In her career, Dr.

Dimitrova contributed to the development of a number of monoclonal antibodies, Fc-fusion proteins, PEG-proteins, bispecific molecules, cytokines, DNA, peptides, and small molecules at Amgen Inc., MedImmune (Astra Zeneca), Biogen, and Jazz Pharmaceuticals.

Dimitrova contributed to the commercialization of nine patient-convenient drug/device combination products for the treatment of autoimmune, respiratory, neurodegenerative, hematology, and infectious diseases.

Most recently, from May 2019 to September 2022, Dr.

Dimitrova was vice president of product and device development at Akero Therapeutics, developing Fc-FGF21 fusion protein for treatment of NASH.

Prior to her industry work, Dr.

Dimitrova spent five years in academia, including at the National Heart, Lung, and Blood Institute at the National Institutes of Health and the National Institute of Advanced Industrial Science and Technology (AIST) in Japan.

Dimitrova holds a Ph.D.

in Biophysics and Biological Sciences from the Bulgarian Academy of Sciences and the AIST, and a M.S.

in Chemistry from Kliment Ohridski University in Bulgaria.

Gaitanaris, M.D., Ph.D.

10 unchanged sentences

from the Aristotelian University of Greece.

Bruce Meiklejohn, Ph.D .

has served as our vice president, chemistry, manufacturing and controls (“CMC”) since October 2019.

Prior to joining Omeros in this role, Dr.

Meiklejohn was an expert CMC consultant for several biotechnology companies, including Omeros.

His consulting work followed a career of over 27 years at Eli Lilly and Company, where he held a number of CMC leadership roles including head of Lilly’s biopharmaceutical product development division and senior research fellow in regulatory affairs CMC.

While at Lilly, Dr.

Meiklejohn led or played a key role in CMC activities for a number of multibillion-dollar drugs, including Trulicity ® , Cialis ® , Alimta ® , Forteo ® , and Cymbalta ® .

Meiklejohn earned his Ph.D.

in analytical chemistry and his B.S.

in biology and chemistry at Colorado State University.

has served as our vice president, regulatory affairs and quality systems since October 2012 and has served as our chief regulatory officer since April 2016.

1 unchanged sentence

Prior to joining Eli Lilly, Dr.

Melfi held various faculty and research positions at Indiana University, including appointments in its Economics Department, in the School of Public and Environmental Affairs, and in the Indiana University School of Medicine.

Melfi held various faculty and research positions at Indiana

University, including appointments in its Economics Department, in the School of Public and Environmental Affairs, and in the Indiana University School of Medicine.

Melfi received her Ph.D.

37 unchanged sentences

Our website address is www.omeros.com.

We make available, free of charge through our investor relations website at investor.omeros.com, our annual report on Form 10-K, our quarterly reports on Form 10-Q, our current reports on Form 8-K and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act, including exhibits to those

reports, as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC.

Our websites and the information contained therein or incorporated therein are not intended to be incorporated into this Annual Report on Form 10-K.

6 unchanged sentences

Risks related to our drug candidates, programs and operations include, but are not limited to, the following:

● the magnitude and duration of future royalties paid to us based on net sales by Rayner of OMIDRIA, which are heavily dependent on the continuation of separate payment for OMIDRIA under Medicare Part B, as well as Rayner’s ability to successfully market and sell OMIDRIA in the U.S.

● the magnitude and duration of future royalties paid to us based on net sales by Rayner of OMIDRIA, which are dependent on Rayner’s ability to successfully market and sell OMIDRIA;

● lack of adequate coverage or reimbursement from government and/or private payers for OMIDRIA or any of our drug candidates that we commercialize in the future;

● whether any of our drug candidates will successfully complete clinical development or be suitable for successful commercialization or generation of revenue;

● failure to obtain and maintain regulatory approval for marketing of future commercial products in the U.S.

or in foreign jurisdictions;

● the success of our clinical trials evaluating narsoplimab for treatment of COVID-19 and, even if successful, our ability to manufacture narsoplimab in quantities adequate

● the impact of the COVID-19 pandemic on our business, operations and financial results as well as significant uncertainty around the evaluation of narsoplimab as a potential treatment for critically ill COVID-19 patients;

● lack of adequate coverage or reimbursement from government and/or private payers for any drug candidates that we commercialize in the future;

● unpredictability of our operating results;

● our ability to raise capital when needed;

● any failure to comply with current or future government regulations;

● lack of internal manufacturing capacity and reliance on third parties to manufacture, finish, store and ship supplies of our drug candidates for clinical and, after approval, commercial use;

● ability to acquire ingredients, excipients, test kits and other materials to manufacture our drug candidates on commercially reasonable terms;

● inability to acquire ingredients, excipients, test kits and other materials to manufacture our drug candidates on commercially reasonable terms;

● delays, suspensions or terminations of our clinical trials or clinical protocols;

● failure to capitalize on drug candidates or indications;

● whether our drug candidates will successfully complete clinical development or be suitable for successful commercialization or generation of revenue;

● unpredictability of our operating results;

● inability to raise capital when needed;

● any failure to comply with current or future government regulations;

● substantial costs as a result of commercial disputes, claims, litigation or other legal proceedings;

● ability to protect our intellectual property and proprietary technologies;

● inability to protect our intellectual property and proprietary technologies;

● our indebtedness and liabilities, which could limit the cash flow available for our operations;

8 unchanged sentences

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business