What changed in this filing

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Item 1. Business

2022-03-01 compared with 2021-03-01 · 211 added, 269 removed, 707 unchanged (40% of the section changed)

We are a commercial-stage biopharmaceutical company committed to discovering, developing and commercializing small-molecule and protein therapeutics for large-market as well as orphan indications targeting inflammation, complement-mediated diseases, disorders of the central nervous system and immune-related diseases, including cancers.

Our drug product OMIDRIA® is marketed in the United States for use during cataract surgery or intraocular lens replacement for adult and pediatric patients.

Our drug candidate narsoplimab is the subject of a biologics license application (“BLA”) under priority review by the U.S.

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”).

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

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 have also initiated a Phase 1 clinical program 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.

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.

We also possess a proprietary-asset-enabled antibody-generating technology.

We have retained control of all commercial rights for OMIDRIA and each of our product candidates and programs.

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

OMIDRIA 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.

Outside the U.S., we have received approval from the European Commission (“EC”) to market OMIDRIA in the European Economic Area (“EEA”), for use during cataract surgery and other IOL replacement procedures for maintenance of intraoperative mydriasis (pupil dilation), prevention of intraoperative miosis and reduction of acute postoperative ocular pain.

OMIDRIA is a proprietary drug product containing two active pharmaceutical ingredients (“APIs”):

ketorolac, an anti-inflammatory agent, and phenylephrine, a mydriatic, or pupil dilating, agent.

Cataract and other lens replacement surgery involves replacement of the original lens of the eye with an artificial intraocular lens.

OMIDRIA is added to standard irrigation solution used during cataract and lens replacement surgery and is delivered intracamerally, or within the anterior chamber of the eye, to the site of the surgical trauma throughout the procedure.

Preventing pupil constriction is essential for these procedures and, if miosis occurs, the risk of damaging structures within the eye and other complications increases, as does the operating time required to perform the procedure.

United States .

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.

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 sell OMIDRIA primarily through wholesalers which, in turn, sell to ASCs and hospitals.

CMS, the federal agency responsible for administering the Medicare program, granted transitional pass-through reimbursement status for OMIDRIA in 2014, effective from January 1, 2015 through December 31, 2017 and, in March 2018, Congress extended pass-through reimbursement status for a small number of drugs, including OMIDRIA, for an additional two years, running from October 1, 2018 through September 30, 2020.

Pass-through status allows for separate payment (i.e., outside the packaged payment rate for the

surgical procedure) under Medicare Part B.

In CMS’ CY2021 Hospital Outpatient Prospective Payment System (HOPPS) and Ambulatory Surgical Center (ASC) Payment System Final Rule, CMS confirmed that OMIDRIA, as an otherwise policy packaged drug following OMIDRIA’s expiration of pass-through status on October 1, 2020, qualifies for separate payment when used on Medicare Part B patients in the ASC setting under CMS’ policy for non-opioid pain management surgical drugs.

CMS made separate payment for OMIDRIA effective retroactively as of October 1, 2020.

CMS’ current non-opioid separate payment policy and, as a result, separate payment for OMIDRIA thereunder, like other CMS policies in the OPPS and ASC systems, can be changed by CMS through its OPPS/ASC annual rulemaking and comment process.

We believe that CMS will continue its separate payment policy for non-opioid pain management surgical drugs, which has been in effect since 2019, and that OMIDRIA will continue to be separately reimbursed when used in the ASC setting.

We have implemented a variety of programs and arrangements to facilitate the availability of OMIDRIA to cataract and IOL replacement patients in the U.S., including the following:

● various purchase volume-discount programs for OMIDRIA;

● agreements to enable discounts on qualifying purchases of OMIDRIA by certain U.S.

government purchasers and other eligible entities, such as 340B-eligible hospitals and clinics;

● the OMIDRIAssure ® Reimbursement Services Program, which we refer to as OMIDRIAssure.

OMIDRIAssure provides coverage and reimbursement support services for surgeons and facilities to help remove uncertainties about coding, billing and coverage of OMIDRIA and to enable better access to the drug for patients facing financial barriers.

Under our “Equal Access” patient assistance program, financially eligible uninsured and government-insured patients receive OMIDRIA free of charge for use during surgery.

Through our “We Pay the Difference” program we pay the facility, on behalf of commercially insured patients, the difference between the facility’s acquisition cost for OMIDRIA, after accounting for any applicable volume discounts, and the amount covered by the patient’s insurance.

European Union and other International Territories.

In July 2018, we placed OMIDRIA on the market in the European Union (“EU”) on a limited basis and continue to maintain the ongoing validity of the Marketing Authorization for OMIDRIA in EU member states and EEA countries.

Decisions about price and reimbursement for OMIDRIA are made on a country-by-country basis and may be required before marketing may occur in a particular country.

At this time we do not expect to see significant sales of OMIDRIA in any countries within the EEA or other international territories if we are unable to complete a broad sales launch in any such country either independently or through partnerships for the marketing and distribution of OMIDRIA.

Our Product Candidates and Development Programs

Our clinical product candidates consist of the following:

Product Candidate/Program

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.

Our Drug Candidates and Development Programs

Our clinical drug candidates consist of the following:

Drug Candidate/Program

Targeted Disease(s)

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Pivotal Trial Complete;

BLA under priority review

FDA’s PDUFA Action Date July 17, 2021

CRL received;

BLA pending before FDA

BLA resubmission

(In-licensed)

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Immunoglobulin A Nephropathy (IgAN)

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

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

(In-licensed)

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Narsoplimab (OMS721/MASP-2)

Lectin Pathway Disorders

Lupus Nephritis and other renal diseases

Determine whether to initiate Phase 3 program

(In-licensed)

Narsoplimab (OMS721/MASP-2)

Severe COVID-19 requiring mechanical ventilation

Complete clinical trial and/or obtain regulatory authorization

Read out data from platform clinical trial

(In-licensed)

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Addictions and compulsive disorders;

Advance clinical development pending availability of resources

Initiate Phase 2 clinical program pending availability of resources

(Compounds In-licensed)

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Paroxysmal Nocturnal Hemoglobinuria (PNH) and other alternative pathway disorders

Read out Phase 1 clinical trial data and initiate Phase 2 trial

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

PPARγ (OMS405) -

Opioid and nicotine addiction

Further refine development path

Evaluate data from investigator-sponsored trial in patients with cocaine use disorder

Our pipeline of development programs consists of the following:

Product Candidate/Program

Drug Candidate/Program

Targeted Disease(s)

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aHUS, IgAN, HSCT-TMA and age-related macular degeneration

Optimize compounds

Identify drug development candidate for clinical trials

(In-licensed)

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Long-acting second generation antibody targeting lectin pathway disorders

Complete preclinical toxicology studies and manufacturing scale-up;

submit IND and/or CTA to initiate clinical trials

Preclinical/Phase 1

CTA submission

MASP-3 - Small-

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PNH and other alternative pathway disorders

Continue medicinal chemistry and advance co-crystallization efforts

Immuno-oncologic and wide range of tumors

Optimize compounds

GPCR Platform, including GPR151, GPR161, and other Class A Orphan GPCRs

Identify drug development candidate for clinical trials

GPR174 Inhibitors and Related Therapeutics

Wide range of cancers

Identify drug development candidate for clinical trials

Chimeric Antigen Receptor (CAR) T-Cell and Adoptive T-Cell Therapies

Wide range of cancers

Scale up and clinical trial initiation

> 50 other GPCR targets

Immuno-oncologic,

metabolic, CNS, cardiovascular, musculoskeletal & other disorders

Continue drug discovery and selected medicinal chemistry for Class A Orphan GPCRs

Identify drug development candidate for clinical trials

MASP Inhibitor Clinical Programs

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Three main pathways can activate the complement system:

classical, alternative and lectin.

classical, lectin, and alternative.

MASP-2 is recognized as the effector enzyme of the lectin pathway and is required for the function of this pathway.

Importantly, inhibition of MASP-2 has been demonstrated not to interfere with the antibody-dependent classical complement activation pathway, a critical component of the acquired immune response to infection the abnormal function of which is associated with a wide range of autoimmune disorders.

Our proprietary, patented lead human monoclonal antibody targeting MASP-2, which we have referred to as OMS721, has been assigned the nonproprietary name narsoplimab.

The current development focus for narsoplimab is diseases in which the lectin pathway has been shown to contribute to significant tissue injury and pathology.

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

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

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.

Thrombotic Microangiopathies

In November 2020, we completed the rolling submission to FDA of our BLA for narsoplimab for the treatment of HSCT-TMA, a frequently lethal complication of HSCT.

The BLA has been accepted for filing by FDA and granted priority review with an FDA action date under the Prescription Drug User Fee Act (“PDUFA”) of July 17, 2021.

In October 2020, we reported final clinical data from our pivotal trial of narsoplimab in HSCT-TMA.

The single-arm, open-label trial included safety and efficacy endpoints that were previously agreed to with FDA.

These endpoints were assessed for (1) all 28 patients who received at least one dose of narsoplimab and (2) patients who received the protocol-specified dosing of at least four weeks of narsoplimab.

In October 2020, we reported final clinical data from our pivotal trial of narsoplimab in HSCT-TMA, a frequently lethal complication of HSCT.

In November 2020, we completed the rolling submission of our BLA for narsoplimab for the treatment of HSCT-TMA and FDA accepted the BLA for filing in January 2021 under its Priority Review program.

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.

This is referred to as the “complete response rate.” The primary laboratory markers that were evaluated were platelet count and lactate dehydrogenase (“LDH”), levels, while improvement in clinical status was evaluated based on organ function and transfusions.

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.

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

In Europe, the EMA has confirmed narsoplimab’s eligibility for 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.

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) priority review for the HSCT-TMA BLA, (3) orphan drug designation for the prevention (inhibition) of complement-mediated TMAs, and (4) orphan drug designation for the treatment of HSCT-TMA.

The EC also granted narsoplimab designation as an orphan medicinal product for treatment in hematopoietic stem cell transplantation.

We have an ongoing Phase 3 clinical program in patients with aHUS with active sites in the U.S., Europe and Asia.

The single-arm, open-label Phase 3 clinical trial in patients with newly diagnosed or ongoing aHUS is enrolling.

This trial is targeting approximately 40 patients for EU approval and U.S.

accelerated approval with 80 patients required for full approval in the U.S.

The trial includes multiple sites in the U.S., Asia and Europe, and is actively enrolling, though enrollment has been slowed in part due to prioritizing the use of resources within our narsoplimab programs on HSCT-TMA, IgA nephropathy, and COVID-19.

Dosing consists of an initial IV loading

followed by daily subcutaneous dosing.

Based on discussions with FDA and the EMA, we expect that the clinical package for the BLA would be similar to that which formed the basis of approval for Soliris ® (eculizumab), which is marketed by Alexion Pharmaceuticals, Inc.

The FDA has granted to 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 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.

Renal Disease

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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 with 24-hour urine protein excretion greater than 1 g/day at baseline on optimized renin-angiotensin system blockade.

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.

This trial includes a run-in period.

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

Phase 2 Clinical Trial - Renal Diseases .

We have been conducting a Phase 2 clinical trial in patients with complement-associated renal diseases, specifically designed to cover:

(1) IgA nephropathy;

(2) membranous nephropathy;

and (3) lupus nephritis.

An initial open-label cohort of patients completed treatment in May 2017.

In August 2020, a manuscript detailing the results of the Phase 2 clinical trial in patients with IgA nephropathy was published in the peer-reviewed journal Kidney International Reports .

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 COVID-19 patients treated with narsoplimab under compassionate use, all with acute respiratory distress syndrome (“ARDS”) and requiring continuous positive airway pressure (“CPAP”) or intubation.

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.

During the course of the compassionate use program, institutional guidelines at the treating hospital were updated to require that all COVID-19 patients in the hospital receive steroids.

One patient treated with narsoplimab did not receive steroids.

Of the five narsoplimab-treated patients who received steroids, two initiated them after already improving such that CPAP was no longer required or was discontinued the following day.

The study evaluated CEC counts in a separate group of four patients receiving only steroids for a short duration, and the counts were found to be unaffected by steroid administration.

This suggests that any beneficial

effect of steroids on COVID-19-associated endothelial damage may be delayed and had little effect on the recovery course of the narsoplimab-treated patients who initiated steroid treatment after improving.

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

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

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

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, such as cognitive impairment or cardiac, pulmonary or other organ disorder, commonly seen following resolution of initial COVID-19 symptoms.

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.

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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 nine more patients in Italy and four patients in the U.S.

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

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.

Narsoplimab is also the only complement inhibitor included in the I-SPY COVID-19 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 trial utilizes Quantum Leap Healthcare Collaborative's adaptive platform trial design, which is intended to increase trial efficiency by minimizing the number of participants and time required to evaluate potential treatments.

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 as well as international regulatory authorities and global healthcare organizations continue to progress.

government agencies continue to progress.

Licensing Arrangements .

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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.

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.

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

paroxysmal nocturnal hemoglobinuria (“PNH”);

multiple sclerosis;

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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 completed all of the intravenous dosing cohorts in the single-ascending-dose study and expect to begin subcutaneous dosing in March 2021.

Initial data from the Phase 1 trial are expected in the second quarter of 2021.

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.

Licensing Arrangements.

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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, which we are targeting for initiation of clinical trials in early 2022.

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.

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We hold an exclusive license to certain PDE7 inhibitors claimed in patents and pending patent applications owned by Daiichi Sankyo Co., Ltd.

(“Daiichi Sankyo”), as successor-in-interest to Asubio Pharma Co., Ltd., or, for use in the treatment of movement, addiction and compulsive disorders as

well as other specified indications.

(“Daiichi Sankyo”), as successor-in-interest to Asubio Pharma Co., Ltd., or, for use in the treatment of movement, addiction and compulsive disorders as well as other specified indications.

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

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The published results of the heroin study demonstrated that, although not altering the reinforcing or positive subjective effects of heroin, the PPARγ agonist significantly reduced heroin craving and overall anxiety.

The National Institute on Drug Abuse provided substantially all of the funding for these clinical trials and solely oversaw the conduct of these trials.

The National Institute on Drug Abuse (“NIDA”) provided substantially all of the funding for these clinical trials and solely oversaw the conduct of these trials.

We have the right or expect to be able to reference the data obtained from these studies for subsequent submissions to FDA and continue to retain all other rights in connection with the PPARγ program.

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, decreased cravings and protection of brain white matter) from a Phase 2 clinical trial conducted by an independent investigator evaluating the effects of a PPARγ agonist in patients with cocaine use disorder.

An investigator-sponsored study on the prevention of relapse following treatment of cocaine use disorder is expected to begin enrolling in March 2021.

The study is funded by the National Institute on Drug Abuse (“NIDA”).

An investigator-sponsored study evaluating the effects of a PPARγ agonist on the prevention of relapse following treatment of cocaine use disorder is ongoing.

The study is funded by NIDA.

Patent Assignment Agreement with Roberto Ciccocioppo, Ph.D.

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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.

As of December 31, 2020, we had 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.

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.

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.

Based on our data, we believe that GPR174 controls a major pathway in cancer and modulation of the receptor could provide a seminal advance in immuno-oncologic treatments for a wide range of tumors.

Our recent discoveries suggest a new approach to cancer immunotherapy that targets inhibition of GPR174 and can be combined with and significantly improve the tumor-killing effects of adenosine pathway inhibitors.

Based on our data, we believe that GPR174 controls a major, previously unrecognized pathway in cancer and modulation of the receptor could provide a seminal advance in immuno-oncologic treatments for a wide range of tumors.

Our studies in mouse models of melanoma and colon carcinoma found that GPR174-deficiency resulted in significantly reduced tumor growth and improved survival of the animals versus normal mice.

Our discoveries suggest a new approach to cancer immunotherapy that targets inhibition of GPR174 and can be combined with and significantly improve the tumor-killing effects of other oncologic agents, including radiation, adenosine pathway inhibitors and checkpoint inhibitors.

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.

In November 2019, we announced that our studies in mouse models of melanoma and colon carcinoma found that GPR174-deficiency resulted in significantly reduced tumor growth and improved survival of the animals versus normal mice.

We are developing both small-molecule and antibody inhibitors of GPR174 with the objective of moving compounds into human trials and exploring several of our other GPCR targets as well.

We have also conducted in vitro and in vivo preclinical efficacy studies and engaged in compound optimization for a number of targets including GPR151, which is linked to schizophrenia, cognition and obesity, and GPR161, which is associated with triple negative breast cancer and various sarcomas.

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.

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Sales and Marketing

We have retained all worldwide marketing and distribution rights to OMIDRIA, our product candidates and our development programs.

This allows us to market and sell OMIDRIA and any product candidates that is approved in the future, either independently, through arrangements with third parties, or via some combination of these approaches.

With respect to OMIDRIA in the U.S., we have developed our own internal marketing and sales capabilities and, as of December 31, 2020, we employed 63 sales and reimbursement team members.

In July 2018 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 for a period of three years and we expect to continue to market the product within Europe on a limited basis for purposes of maintaining the marketing authorization.

At this time we do not expect to generate, in the near-term, significant sales of OMIDRIA outside of the U.S.

We have retained all worldwide marketing and distribution rights to our drug candidates and our development programs.

As such, we will be able to market any drug candidate that is approved in the future independently, through arrangements with third parties, or via some combination of these approaches.

We maintained internal marketing and sales capabilities with respect to OMIDRIA until the completion of the divestiture of that product on December 23, 2021.

As part of the divestiture, substantially all of our OMIDRIA sales and marketing team members accepted employment with Rayner and were separated from their employment at Omeros, effective as of December 31, 2021.

Manufacturing, Supply and Commercial Operations

We use third parties to produce, store and distribute OMIDRIA and currently do not own or operate manufacturing facilities.

Our agreements with these third parties include confidentiality and intellectual property provisions to protect our proprietary rights related to OMIDRIA.

We require manufacturers that produce APIs and finished drug products to operate in accordance with current Good Manufacturing Practices (“cGMPs”) and all other applicable laws and regulations.

We have an agreement with Hospira Worldwide, Inc.

(“Hospira”), a wholly owned subsidiary of Pfizer, Inc., to provide commercial supply of OMIDRIA.

Under the agreement with Hospira (the “Hospira OMIDRIA Agreement”), Hospira has agreed to manufacture and supply, and we have agreed to purchase, a minimum percentage of our requirements of OMIDRIA for commercial sales and clinical supplies for the development of additional therapeutic indications in the U.S.

In addition, Hospira has agreed to manufacture and supply a portion of our requirements of OMIDRIA in the EU, with there being no minimum purchase and supply requirement in the EU if the parties do not enter into such an amendment to the agreement.

We have not yet entered into such an agreement with Hospira relating to the supply of OMIDRIA for the EU.

The Hospira OMIDRIA Agreement expires in February 2022, but may be terminated prior to the end of its term upon the occurrence of certain specified events, including without limitation an uncured breach of the agreement or bankruptcy or dissolution of a party.

Upon termination of the Hospira OMIDRIA Agreement, except in the case of termination for an uncured breach by Hospira, we will be required to purchase all of Hospira’s inventory of OMIDRIA and, if applicable, all work-in-progress inventory and to reimburse Hospira for all supplies purchased or ordered based on firm purchase orders or our estimates of its requirements of OMIDRIA.

We have used multiple suppliers for the APIs for OMIDRIA in the past and we intend to leverage Hospira’s sourcing of APIs in the future under the Hospira OMIDRIA Agreement.

Given the large amount of these APIs manufactured annually by these and other suppliers, and the quantities of these APIs that we have on hand, we anticipate that we will be capable of addressing our commercial API supply needs for OMIDRIA in the near-term.

We have not yet signed commercial agreements with suppliers for the supply of all of our anticipated commercial quantities of these APIs for OMIDRIA, although we may elect to do so in the future.

In addition to our supply agreement with Hospira, we have executed an agreement with a second manufacturing partner for supply of OMIDRIA.

Work to bring the second manufacturer online is ongoing and we anticipate OMIDRIA to be available from this manufacturer beginning in 2021.

In the U.S., we sell OMIDRIA through a limited number of wholesalers that distribute the product to ASCs and hospitals.

Title transfers upon delivery of OMIDRIA to the wholesaler.

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

We currently do not own or operate manufacturing facilities.

We utilized contract manufacturers to produce, store and distribute OMIDRIA and currently rely on third parties to produce sufficient quantities of our drug candidates for use in pre-clinical and clinical studies and for the manufacture of narsoplimab for commercial use following regulatory approval.

We assigned or otherwise transitioned to Rayner our agreements with the third parties that produced, stored and distributed OMIDRIA.

We required manufacturers that produced active pharmaceutical ingredients (“API s”) and finished drug products to operate in accordance with current Good Manufacturing Practices (“cGMPs”) and all other applicable laws and regulations.

In the U.S., we sold OMIDRIA through a limited number of wholesalers that distributed the product to ASCs and hospitals.

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.

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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.

Product Candidates .

We have laboratories in-house for analytical method development, bioanalytical testing, formulation, stability testing and small-scale compounding of laboratory supplies of product candidates.

We utilize contract manufacturers to produce sufficient quantities of product candidates for use in preclinical and clinical studies and to store and distribute our product candidates.

Drug Candidates .

We have laboratories in-house for analytical method development, bioanalytical testing, formulation, stability testing and small-scale compounding of laboratory supplies of drug candidates.

We utilize contract manufacturers to produce sufficient quantities of drug candidates for use in preclinical and clinical studies and to store and distribute our drug candidates.

We require manufacturers that produce APIs and finished drug products for clinical use to operate in accordance with cGMPs and all other applicable laws and regulations.

We anticipate that we will rely on contract manufacturers to develop and manufacture our product candidates for commercial sale.

We maintain agreements with potential and existing manufacturers that include confidentiality and intellectual property provisions to protect our proprietary rights related to our product candidates.

We anticipate that we will rely on contract manufacturers to develop and manufacture our drug candidates for commercial sale.

We maintain agreements with potential and existing manufacturers that include confidentiality and intellectual property provisions to protect our proprietary rights related to our drug candidates.

In July 2019, we entered into a master services agreement with Lonza Biologics Tuas Pte.

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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.

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or EU and is subject to automatic renewal for an additional four-year term unless we provide notice of non-renewal at least three years prior to the end of the initial term.

In addition, either party may terminate the agreement, subject to

applicable notice and cure periods under certain circumstances.

Other than our agreement for commercial supply of narsoplimab, we have not yet entered into a commercial supply agreement for any of our product candidates.

In addition, either party may terminate the agreement, subject to applicable notice and cure periods under certain circumstances.

Other than our agreement for commercial supply of narsoplimab, we have not yet entered into a commercial supply agreement for any of our drug candidates.

License and Development Agreements

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We have also agreed to make total milestone payments of up to $3.8 million to Dr.

Ciccocioppo upon the occurrence of certain development events, such as patient enrollment in a Phase 1 clinical trial and receipt of marketing approval of a product candidate covered by any patents that issue from the patent applications that we acquired from him.

Ciccocioppo upon the occurrence of certain development events, such as patient enrollment in a Phase 1 clinical trial and receipt of marketing approval of a drug candidate covered by any patents that issue from the patent applications that we acquired from him.

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.

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Ciccocioppo ends when there are no longer any valid and enforceable patents related to the intellectual property rights we acquired from him, provided that either party may terminate the agreement earlier in case of an uncured breach by the other party.

Under the terms of the

agreement, we have agreed to pay a portion of the payments due to Dr.

Under the terms of the agreement, we have agreed to pay a portion of the payments due to Dr.

Ciccocioppo to the Università di Camerino without any increase to our payment obligations.

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dosing of human subjects in Phase 1, 2 and 3 clinical trials;

receipt of marketing approval of a PDE7 inhibitor product candidate;

receipt of marketing approval of a PDE7 inhibitor drug candidate;

and reaching specified sales milestones.

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The term of our payment obligations to LSDF is the same as that under our agreement with Vulcan.

We entered into settlement agreements and consent judgments with (1) Par Pharmaceutical, Inc.

and its subsidiary, Par Sterile Products, LLC (collectively, “Par”) and (2) Lupin Ltd.

and Lupin Pharmaceuticals, Inc.

(collectively, “Lupin”) in October 2017 and May 2018, respectively.

Under the terms of the settlement agreements and consent judgments, Par and Lupin are each prohibited from launching a generic version of OMIDRIA prior to a specified entry date.

Par’s entry date is the earlier of (1) April 1, 2032 or (2) the date on which we or a third-party, through licensing or any future final legal judgment, should one ever exist, with respect to our Orange Book listed patents, is able to launch a generic version of OMIDRIA.

Lupin’s entry date is the earlier of (A) April 1, 2032 if Par has forfeited its six month first-ANDA filer exclusivity, (B) October 1, 2032 if Par has not forfeited its six month first-ANDA filer exclusivity, or (C) a date on which we or a third party (other than Par), through licensing of, any future final legal judgment regarding, or the delisting, abandonment or expiration of our U.S.

OMIDRIA patents, is able to launch a generic version of OMIDRIA.

Under the settlement agreements, we granted each of Par and Lupin a non-exclusive, non-sublicensable license to make, sell and distribute a generic version of OMIDRIA between their applicable entry dates and the latest expiration of our U.S.

patents related to OMIDRIA (i.e., October 23, 2033).

During this period, Par and Lupin, as applicable, are each required to pay us a royalty equal to 15% of net sales of its generic version of OMIDRIA.

The pharmaceutical and biotechnology industry is highly competitive and characterized by a number of established, large pharmaceutical and biotechnology companies as well as smaller companies like ours.

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If we fail to stay at the forefront of technological change, we may be unable to compete effectively.

We are not aware of any product that directly competes with OMIDRIA and is FDA-approved for intraoperative delivery in irrigation solutions during surgical procedures;

however, OMIDRIA could face competition from products that are delivered intraoperatively, but that do not include a non-steroidal anti-inflammatory agent, as well as from preoperative and postoperative treatments for mydriasis, pain or inflammation.

Our primary competition for OMIDRIA comes from surgeons’ current practices, which may include use of products obtained from distributors or

compounding pharmacies at a relatively low cost.

Title I (the “Compounding Quality Act”) of the Drug Quality and Security Act, which was enacted in November 2013, added Section 503B to the FDCA establishing a distinct category of drug compounders known as “outsourcing facilities.” Among other provisions, the Compounding Quality Act imposes restrictions on the materials that may be compounded at registered outsourcing facilities and traditional compounders and places conditions on the compounding of bulk substances.

Surgeons may perceive that, since the enactment of the Compounding Quality Act, compounding pharmacies, particularly those that are registered as “outsourcing facilities,” are subject to rigorous regulatory oversight that assures the safety and manufacturing quality of compounded products, notwithstanding the relatively high frequency of recall events, warning letters and findings of unsanitary conditions issued by FDA following inspection of registered outsourcing facilities.

In addition, we anticipate that there are some surgeons who do not use intraoperative mydriatics and may not agree with the value proposition of maintaining pupil dilation and inhibiting miosis during the procedure, or with the use of a nonsteroidal anti-inflammatory drug intraoperatively to inhibit inflammation, prevent miosis and reduce postoperative pain.

Although we are not aware of any companies developing similar approaches for maintenance of intraoperative pupil size and postoperative pain reduction as an FDA-approved product, such strategies may develop.

In Europe, an inexpensive mydriatic and local anesthetic combination product is available but, unlike OMIDRIA, this product does not include an anti-inflammatory agent.

Product 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.

Soliris ® (eculizumab) and Ultomiris ® (ravulizumab-cwvz) are monoclonal complement inhibitors administered intravenously and approved for commercial use with which our lead MASP-2 inhibitor, narsoplimab (OMS721), and/or our MASP-3 inhibitor OMS906 will compete, if either is approved for any indication(s) for which Soliris ® and/or Ultomiris ® are also approved.

Alexion Pharmaceuticals, Inc., the manufacturer of Soliris ® and Ultomiris ® , initiated a Phase 3 trial of Ultomiris ® for HSCT-TMA in the fourth quarter of 2020.

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.

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

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Intellectual Property

We have retained control of all worldwide manufacturing, marketing and distribution rights for OMIDRIA and each of our product candidates and programs.

Some of our products and product candidates and programs are based on inventions and other intellectual property rights that we acquired through assignments, exclusive licenses or acquisitions described in further detail under “License and Development Agreements” below.

We have retained control of all worldwide manufacturing, marketing and distribution rights for each of our drug candidates and programs.

Some of our drug candidates and programs are based on inventions and other intellectual property rights that we acquired through assignments, exclusive licenses or acquisitions described in further detail under “License and Development Agreements” below.

As of February 9, 2022, we owned or held worldwide exclusive licenses to a total of 80 issued patents and 56 pending patent applications in the U.S.

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our available resources, the size of the commercial market, the presence of a potential competitor or a contract manufacturer in the market and whether the legal authorities in the market effectively enforce patent rights.

● OMIDRIA-Ophthalmology.

OMIDRIA is encompassed by our PharmacoSurgery patent portfolio.

The relevant patents and patent applications in this portfolio are directed to combinations of agents, generic and/or proprietary to us or to others, drawn from therapeutic classes such as pain and inflammation inhibitory agents, mydriatic agents and agents that reduce intraocular pressure, delivered locally and intraoperatively to the site of ophthalmological procedures, including cataract and lens replacement surgery.

As of February 10, 2021, we owned eight issued U.S.

patents and three pending U.S.

patent applications and 99 issued patents and 55 pending patent applications in foreign markets that are directed to OMIDRIA.

Our OMIDRIA patents have terms that will expire as late as October 23, 2033 and, if currently pending patent applications are issued, as late as November 30, 2035.

● MASP-2 Program - Narsoplimab (OMS721).

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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 10, 2021, we exclusively controlled two issued patents and five pending patent applications in the U.S.

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

and 150 issued and 86 pending patent applications in foreign markets that are related to our MASP-3 program.

● PPARγ Program - OMS405 .

As of February 10, 2021, we owned two issued patents and one pending patent application in the U.S., and 35 issued patents and 11 pending patent applications in foreign markets, directed to our discoveries linking PPARγ and addictive disorders.

As of February 9, 2022, we owned three issued patents and one pending patent application in the U.S., and 37 issued patents and 7 pending patent applications in foreign markets, directed to our discoveries linking PPARγ and addictive disorders.

● PDE7 Program - OMS527 .

As of February 10, 2021, we owned two issued patents and one pending patent application in the U.S., and 61 issued patents and three pending patent applications in foreign markets directed to our discoveries linking PDE7 to movement disorders, as well as one issued patent and two pending patent applications in the U.S., and 49 issued patents and 13 pending patent applications in foreign markets directed to the link between PDE7 and addiction and compulsive disorders.

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.

patents and 61 issued and one pending patent application in foreign markets that are directed to proprietary PDE7 inhibitors.

patents and 62 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 10, 2021, we owned seven issued patents and 12 pending patent applications in the U.S., and 56 issued patents and one pending patent application 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.

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.

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

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

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

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 products and product 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 products and product 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 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.

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.

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Accordingly, we cannot predict the breadth of claims that may be allowed or enforced in the patents that we own or have licensed or in third-party patents.

We sell OMIDRIA under trademarks that we consider in the aggregate to be important to our operations.

We have registered, and intend to maintain, the trademarks “OMEROS”, “OMIDRIA”, “OMIDRIASSURE” and “PHARMACOSURGERY” with the U.S.

Patent and Trademark Office in connection with the products and services we

We are not aware of any material claims of infringement or other challenges to our right to use the “OMEROS,” “OMIDRIA,” “OMIDRIASSURE” or “PHARMACOSURGERY” trademarks in the U.S.

We have registered, and intend to maintain, the trademark “OMEROS” within the U.S.

Patent and Trademark Office in connection with the products and services we offer.

We are not aware of any material claims of infringement or other challenges to our right to use the “OMEROS” trademark in the U.S.

Government Regulation

Government authorities in the U.S., the EU and other countries extensively regulate the research, development, testing, manufacture, labeling, promotion, advertising, distribution, marketing, and export and import of drug and biologic products such as OMIDRIA and the product candidates that we are developing.

Government authorities in the U.S., the EU and other countries extensively regulate the research, development, testing, manufacture, labeling, promotion, advertising, distribution, marketing, and export and import of drug and biologic products including the drug candidates that we are developing.

Failure to comply with applicable requirements, both before and after receipt of regulatory approval, may subject us, our third-party manufacturers, and other partners to administrative and judicial sanctions, such as warning letters, product recalls, product seizures, a delay in approving or refusal to approve pending applications, civil and other monetary penalties, total or partial suspension of production or distribution, injunctions, and/or criminal prosecutions.

In the U.S., our products and product candidates are regulated by FDA as drugs or biologics under the FDCA and implementing regulations and under the Public Health Service Act (“PHSA”).

In Europe, our products and product 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.

OMIDRIA has received marketing approval from FDA and from the applicable regulatory authorities in the EU.

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

In the U.S., our drug candidates are regulated by FDA as drugs or biologics under the FDCA and implementing regulations and under the Public Health Service Act (“PHSA”).

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.

The steps required before a product may be approved for marketing by FDA, or the applicable regulatory authorities outside of the U.S., typically include the following:

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If the necessary clinical trials are successfully completed, the results of the preclinical trials and the clinical trials, together with other detailed information, including information on the manufacture and composition of the product, are submitted to FDA in the form of an NDA or a BLA, as applicable, and to the EMA or national regulators in the form of an MAA, requesting approval to market the product for a specified indication.

In the EU, an MAA may be submitted to the EMA for review and, if the EMA gives a positive opinion, the EC may grant a

marketing authorization that is valid across the EU (centralized procedure).

In the EU, an MAA may be submitted to the EMA for review and, if the EMA gives a positive opinion, the EC may grant a marketing authorization that is valid across the EU (centralized procedure).

Alternatively, an MAA may be submitted to one or more national regulators in the EU according to one of several national or decentralized procedures.

The type of submission in Europe depends on various factors and must be cleared by the appropriate authority prior to submission.

For most of our product candidates, the centralized procedure will be either mandatory or available as an option.

For most of our drug candidates, the centralized procedure will be either mandatory or available as an option.

If the regulatory authority determines that the application is not acceptable, it may refuse to accept the application for filing and review, outlining the deficiencies in the application and specifying additional information needed to file the application.

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

In addition, even if a product candidate satisfied its endpoints with statistical significance during clinical trials, FDA could determine that the overall balance of risks and benefits for the product 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.

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.

If approval is obtained changes to the approved product such as adding new indications, manufacturing changes, or additional labeling claims will require submission of a supplemental application, referred to as a variation in the EU, or, in some instances, a new application, for further review and approval.

The testing and approval process requires substantial time, effort, and financial resources, and we cannot be sure that any future approval will be granted on a timely basis, if at all.

Some of our drug products may be eligible for NDA submissions to FDA for approval under the Section 505(b)(2) process.

Section 505(b)(2) applications are a type of NDA that may be submitted for drug products that represent a modification, such as a new indication or new dosage form, of a previously approved drug.

Section 505(b)(2) applications may rely on FDA’s previous findings for the safety and effectiveness of the previously approved drug along with additional clinical data and information obtained by the 505(b)(2) applicant to support the modification of the previously approved drug.

Preparing Section 505(b)(2) applications may be less costly and time-consuming than preparing an NDA that is based entirely on new data and information.

Some of our product candidates, such as those from our MASP-2 and MASP-3 programs, are considered biologics because they are derived from natural sources as opposed to being chemically synthesized.

Some of our drug candidates, such as those from our MASP-2 and MASP-3 programs, are considered biologics because they are derived from natural sources as opposed to being chemically synthesized.

The added complexity associated with manufacturing biologics may result in additional monitoring of the manufacturing process and product changes.

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

We must 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.

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Fast-Track and Priority Review Designations.

Section 506(b) of the FDCA provides for the designation of a drug as a fast-track product if it is intended, whether alone or in combination with one or more other drugs, for the treatment of a

serious or life-threatening disease or condition, and it demonstrates the potential to address unmet medical needs for such a disease or condition.

Section 506(b) of the FDCA provides for the designation of a drug as a fast-track product if it is intended, whether alone or in combination with one or more other drugs, for the treatment of a serious or life-threatening disease or condition, and it demonstrates the potential to address unmet medical needs for such a disease or condition.

A program with fast-track status is afforded greater access to FDA for the purpose of expediting the product’s development, review and potential approval.

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Studies that are conducted to demonstrate a drug’s effect on a surrogate or intermediate clinical endpoint for accelerated approval must be adequate and well-controlled as required by the FDCA.

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 and describe the clinical benefit of the product, and FDA may impose restrictions on distribution to assure safe use.

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.

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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.

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There are also an increasing number of state laws that require manufacturers to make reports to states on pricing and marketing information or impose other special requirements for the sale and marketing of drug products.

Many of these

laws contain ambiguities as to what is required to comply with the laws.

Many of these laws contain ambiguities as to what is required to comply with the laws.

In addition, federal and state “transparency laws” require manufacturers to track and report certain payments made to health care providers and, under some state laws, other information concerning our products.

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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.

A marketing authorization will cease to be valid if a product previously placed on the market is no longer actually present on the market for three consecutive years and we expect to make OMIDRIA available in the European market on a limited basis to the extent necessary to continue the validity of our marketing authorization.

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.

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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.

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.

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A certification that the new drug will not infringe the already approved drug’s listed patents or that such patents are invalid or unenforceable is called a Paragraph IV certification.

the ANDA or 505(b)(2) applicant does not include a Paragraph IV certification, the ANDA or 505(b)(2) application will not be approved until all of the listed patents claiming the referenced drug have expired, except for any listed patents that only apply to uses of the drug not being sought by the ANDA or 505(b)(2) applicant.

If the ANDA or 505(b)(2) applicant does not include a Paragraph IV certification, the ANDA or 505(b)(2) application will not be approved until all of the listed patents claiming the referenced drug have expired, except for any listed patents that only apply to uses of the drug not being sought by the ANDA or 505(b)(2) applicant.

If the ANDA or 505(b)(2) applicant has made a Paragraph IV certification, the applicant must also send notice of a Paragraph IV Notice Letter to the NDA and patent holders once the ANDA or 505(b)(2) application has been accepted for filing by FDA.

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Specifically, FDA may not accept a biosimilar application referencing data from a pioneer biologic (i.e., one approved through a full BLA) until four years have elapsed from the date of first licensure of the pioneer biologic.

FDA may not approve a biosimilar application

referencing data from a pioneer biologic until 12 years have elapsed since the date of first licensure of the pioneer biologic.

FDA may not approve a biosimilar application referencing data from a pioneer biologic until 12 years have elapsed since the date of first licensure of the pioneer biologic.

There are certain restrictions and limitations on the types of BLAs that are eligible for biologics exclusivity as well as what constitutes the date of first licensure for a pioneer biologic.

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Healthcare compliance laws .

In the U.S., commercialization of OMIDRIA and our product candidates, if approved, is subject to regulation and enforcement under a number of federal and state healthcare compliance laws administered and enforced by various agencies.

In the U.S., commercialization of our drug candidates, if approved, is subject to regulation and enforcement under a number of federal and state healthcare compliance laws administered and enforced by various agencies.

These include, but are not limited to, the following:

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Pharmaceutical Pricing and Reimbursement

and foreign markets, our ability to commercialize our products and product candidates successfully, and to attract commercialization partners for our products and product candidates, depends in significant part on the availability of adequate financial coverage and reimbursement from third-party payers including, in the U.S., managed care organizations and other private health insurers as well as governmental payers such as the Medicare and Medicaid programs.

and foreign markets, our ability to commercialize our drug candidates successfully, and to attract commercialization partners for our drug candidates, depends in significant part on the availability of adequate financial coverage and reimbursement from third-party payers including, in the U.S., managed care organizations and other private health insurers as well as governmental payers such as the Medicare and Medicaid programs.

Reimbursement by a third-party payer may depend on a number of factors, including the payer’s determination that use of a product is:

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Third-party private and governmental payers are increasingly challenging the prices charged for medicines and examining their cost-effectiveness in addition to their safety and efficacy.

We may need to conduct expensive pharmacoeconomic studies in order to demonstrate the cost effectiveness of our products or product candidates.

Even with the availability of such studies, third-party private and/or governmental payers may not provide coverage and reimbursement for our products or product candidates, in whole or in part.

We may need to conduct expensive pharmacoeconomic studies in order to demonstrate the cost effectiveness of our products or drug candidates.

Even with the availability of such studies, third-party private and/or governmental payers may not provide coverage and reimbursement for our drug candidates, in whole or in part.

United States.

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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.

In December 2018, a federal district court judge in Texas found the ACA’s individual mandate to be unconstitutional and, therefore, the entire law to be invalid.

In December 2019, the Fifth Circuit affirmed the ruling regarding the individual mandate but remanded the case to the district court for additional analysis of the question of severability and whether portions of the law remain valid.

The case is currently pending at the Supreme Court, and a decision is expected by mid-2021.

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

The incoming 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.

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.

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Governments in the various member states of the EU influence or control the price of medicinal products in their countries through their pricing and reimbursement rules and control of national healthcare systems that fund a large part of the cost of those products to consumers.

To obtain reimbursement or pricing approval, some of these countries may require the completion of clinical trials or pharmacoeconomic studies that assess the cost-effectiveness of a product or product candidate relative to currently available therapies or relative to a specified standard.

To obtain reimbursement or pricing approval, some of these countries may require the completion of clinical trials or pharmacoeconomic studies that assess the cost-effectiveness of a product or drug candidate relative to currently available therapies or relative to a specified standard.

The downward pressure on healthcare costs in general, and prescription medicines in particular, has become very intense and is creating increasingly high barriers to the entry of new products in these markets.

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As of December 31, 2021, we had 213 full-time employees, 135 of whom are in research and development, 24 of whom are in sales and marketing and 54 of whom are in finance, legal, business development and administration.

Our full-time employees include eight with M.D.s and 38 with Ph.Ds., of whom one and 22, respectively, are in research and development.

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

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.

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

Information about Our Executive Officers and Significant Employees

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Vice President, Chief Commercial Officer

Vice President, Business Development

Gaitanaris, M.D., Ph.D.

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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.

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in Marketing from Rutgers University.

Duffy has served as our vice president, business development since March 2010.

From November 2008 to March 2010, Mr.

Duffy served as the managing director of Pacific Crest Ventures, a life science consulting firm that he founded.

From June 2004 through September 2008, Mr.

Duffy served at MDRNA, Inc.

(formerly Nastech Pharmaceutical Company, Inc.), a biotechnology company.

At MDRNA, he held roles of increasing responsibility in marketing and business development, most recently as the chief business officer.

Prior to MDRNA, Mr.

Duffy served as vice president, business development at Prometheus Laboratories, Inc., a specialty pharmaceutical company, and as a customer marketing manager at The Procter & Gamble Company.

Duffy received his B.S.

from Loras College.

Gaitanaris, M.D., Ph.D.

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Gaitanaris received his Ph.D.

in cellular, molecular and

biophysical studies and his M.Ph.

in cellular, molecular and biophysical studies and his M.Ph.

from Columbia University and his M.D.

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Our principal executive offices are located at 201 Elliott Avenue West, Seattle, Washington, 98119, and our telephone number is (206) 676-5000.

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 website address is www.omeros.com.

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.

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of this Annual Report on Form 10-K.

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

● the commercial success of OMIDRIA and whether we will continue to maintain separate payment for OMIDRIA;

● 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 our products;

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

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.

● 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

● 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;

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● 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 investigational and marketed drugs for clinical and commercial use;

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

● 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;

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

● failure to capitalize on product candidates or indications;

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

● 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;

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

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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