[Second Supplemental Indenture Overview](index=1&type=section&id=Second%20Supplemental%20Indenture) This document outlines the agreement establishing the 9.50% Convertible Senior Notes due 2029 and amending the Base Indenture [Preamble](index=1&type=section&id=Preamble) The preamble identifies the parties, the new 9.50% Notes due 2029, and its amendment to the 2020 Base Indenture Indenture Details | Item | Detail | | :--- | :--- | | **Document Type** | Second Supplemental Indenture | | **Issuer** | Omeros Corporation | | **Trustee** | Computershare Trust Company, National Association | | **Security** | 9.50% Convertible Senior Notes due 2029 | | **Effective Date** | May 14, 2025 | | **Base Indenture Date** | August 14, 2020 | [Article 1: Definitions and Interpretation](index=6&type=section&id=Article%201.%20Definitions%3B%20Rules%20of%20Construction%3B%20Scope%20and%20Interpretation%20of%20Base%20Indenture) This article defines key terms for the Notes and clarifies the interpretive rules and scope relative to the Base Indenture [Definitions](index=6&type=section&id=Section%201.01.) This section provides critical definitions for the Notes, superseding the Base Indenture for terms like conversion and corporate events Key Note Terms | Term | Definition | | :--- | :--- | | **Notes** | 9.50% Convertible Senior Notes due 2029 | | **Issue Date** | May 14, 2025 | | **Maturity Date** | June 15, 2029 | | **Interest Payment Dates** | June 15 and December 15, commencing December 15, 2025 | | **Initial Conversion Rate** | 161.8122 shares of Common Stock per $1,000 principal amount | | **Authorized Denomination** | $1,000 or any integral multiple thereof | - A **'Fundamental Change'** is defined to include events such as a change of control where a person or group acquires over 50% of voting power, the sale of substantially all assets, stockholder approval of liquidation, or the delisting of the Common Stock from major exchanges[32](index=32&type=chunk)[33](index=33&type=chunk) [Interpretation and Scope](index=17&type=section&id=Section%201.04.) This section clarifies that this supplemental indenture's provisions for the 2029 Notes supersede any conflicting terms in the Base Indenture - The Supplemental Indenture's provisions will apply solely to the 2029 Notes and will **supersede conflicting provisions** in the Base Indenture[86](index=86&type=chunk) - Specific articles of the Base Indenture related to redemption, conversion, defaults, successors, and covenants are **explicitly replaced** by the corresponding articles in this supplemental document[88](index=88&type=chunk)[91](index=91&type=chunk) [Article 2: The Notes](index=19&type=section&id=Article%202.%20The%20Notes) This article details the terms of the Notes, including their issuance, interest accrual, and transfer and exchange procedures [Initial and Additional Notes](index=20&type=section&id=Section%202.03.) This section specifies the initial issuance amount of the Notes and allows for the future issuance of additional notes Note Issuance Details | Item | Amount | | :--- | :--- | | **Initial Aggregate Principal** | $70,785,000 | - The Company may issue **additional notes** in the future without holder consent, which will be part of the same series as the initial notes[103](index=103&type=chunk) [Accrual of Interest](index=21&type=section&id=Section%202.05.) This section details the interest accrual terms for the Notes, including the rate, payment dates, and handling of defaulted interest Interest Terms | Term | Detail | | :--- | :--- | | **Stated Interest Rate** | 9.50% per annum | | **Interest Payment Dates** | June 15 and December 15 | | **Interest Calculation Basis** | 360-day year, twelve 30-day months | | **Default Interest** | Accrues on defaulted amounts at the same 9.50% rate | [Transfers and Exchanges](index=23&type=section&id=Section%202.10.) This section governs the transfer and exchange of Notes, establishing restrictions in compliance with Rule 144 - Transfers of Notes are restricted until the 'Resale Restriction Termination Date,' which is the later of **one year after the last issuance date** or as required by law; restricted securities will bear a restrictive legend[135](index=135&type=chunk)[136](index=136&type=chunk)[139](index=139&type=chunk) - A Global Note can be exchanged for Physical Notes if the Depositary is unable to continue its services, an **Event of Default occurs**, or the Company permits it[126](index=126&type=chunk) [Article 3: Covenants](index=32&type=section&id=Article%203.%20Covenants) This article outlines the Company's ongoing obligations, including SEC reporting requirements and certifications of compliance [Exchange Act Reports](index=32&type=section&id=Section%203.02.) The Company covenants to provide the Trustee with all reports it files with the SEC under the Exchange Act - The Company must provide the Trustee with copies of its SEC filings (e.g., 10-K, 10-Q) within **15 calendar days** of the SEC filing deadline[163](index=163&type=chunk) [Compliance and Default Certificates](index=33&type=section&id=Section%203.03.) This section requires the Company to provide annual compliance certificates and prompt notice of any defaults to the Trustee - An **annual compliance certificate** must be delivered to the Trustee within 90 days of each fiscal year-end[165](index=165&type=chunk) - In the event of a Default, the Company must deliver a certificate to the Trustee describing the default within **30 days**[166](index=166&type=chunk) [Article 4: Repurchase and Redemption](index=34&type=section&id=Article%204.%20Repurchase%20and%20Redemption) This article specifies the conditions under which holders can demand repurchase or the Company can redeem the Notes [Right of Holders to Require Repurchase upon a Fundamental Change](index=34&type=section&id=Section%204.02.) Upon a Fundamental Change, holders have the right to require the Company to repurchase their Notes for cash - Upon a **Fundamental Change**, holders can force the Company to repurchase their Notes[175](index=175&type=chunk) Fundamental Change Repurchase Terms | Term | Detail | | :--- | :--- | | **Repurchase Price** | 100% of principal amount plus accrued and unpaid interest | | **Company Notice Deadline** | Within 20 calendar days after the effective date of the Fundamental Change | | **Repurchase Date** | 20 to 35 Business Days after the Company sends the notice | [Right of the Company to Redeem the Notes](index=38&type=section&id=Section%204.03.) This section grants the Company a conditional option to redeem the Notes for cash on or after June 20, 2027 - The Company **cannot redeem the Notes before June 20, 2027**[195](index=195&type=chunk) - Redemption is permitted on or after June 20, 2027, only if the Last Reported Sale Price of the Common Stock is **greater than 130% of the Conversion Price** for a specified period[196](index=196&type=chunk) - The redemption price is the **principal amount plus accrued and unpaid interest** to, but excluding, the Redemption Date[200](index=200&type=chunk) - Calling notes for redemption constitutes a **'Make-Whole Fundamental Change,'** which may increase the conversion rate for the notes being redeemed[196](index=196&type=chunk) [Article 5: Conversion](index=41&type=section&id=Article%205.%20Conversion) This article details the holders' rights to convert Notes into stock, including settlement methods, rate adjustments, and ownership limitations [Right to Convert](index=41&type=section&id=Section%205.01.) This section outlines the conditions under which holders may convert their Notes into conversion consideration - Holders may convert their notes at any time during the **'Free Convertibility Period'**[215](index=215&type=chunk) - Conversion is also permitted upon certain corporate events, such as a **Fundamental Change** or a call for redemption[212](index=212&type=chunk)[213](index=213&type=chunk) - An **'Interest Make-Whole Payment'** is payable for conversions occurring from November 14, 2025, to June 1, 2029, equal to the discounted value of remaining interest payments for up to 18 months[215](index=215&type=chunk) [Settlement upon Conversion](index=45&type=section&id=Section%205.03.) This section details the Company's options for settling conversions, which can be in shares, cash, or a combination - The Company has the right to choose the settlement method for conversions: **Physical (shares), Cash, or Combination**[226](index=226&type=chunk)[227](index=227&type=chunk) - The **Default Settlement Method is Physical Settlement**, but the Company can change it[27](index=27&type=chunk) - The number of shares issuable upon conversion is **limited by Nasdaq listing rules** until shareholder approval is obtained, which the company will use commercially reasonable efforts to obtain[230](index=230&type=chunk) [Adjustments to the Conversion Rate](index=50&type=section&id=Section%205.05.) This section provides for adjustments to the Conversion Rate to prevent dilution from certain corporate actions - The Conversion Rate will be adjusted for **stock splits, combinations, and stock dividends**[244](index=244&type=chunk) - Adjustments are also made for distributions of rights, options, warrants, spin-offs, cash dividends, and issuer tender/exchange offers where the consideration **exceeds the stock's market price**[247](index=247&type=chunk)[251](index=251&type=chunk)[260](index=260&type=chunk)[264](index=264&type=chunk) - The Company is not required to adjust the conversion rate for certain events, including stock repurchases under an approved program, issuance of shares under employee benefit plans, or a change in the par value of the Common Stock[269](index=269&type=chunk)[270](index=270&type=chunk) [Adjustments for Make-Whole Fundamental Change](index=61&type=section&id=Section%205.07.) This section provides for an increased Conversion Rate if a Make-Whole Fundamental Change occurs - Upon a Make-Whole Fundamental Change, the Conversion Rate is **increased by 'Additional Shares'** for conversions during a specific period[285](index=285&type=chunk) Make-Whole Adjustment Caps | Item | Limit | | :--- | :--- | | **Maximum Conversion Rate** | 228.6389 shares per $1,000 principal | | **Stock Price Floor** | $4.37 per share (no additional shares below this) | | **Stock Price Ceiling** | $40.00 per share (no additional shares above this) | [Beneficial Ownership Limitations](index=64&type=section&id=Section%205.09.) This section imposes a significant restriction on conversion to prevent a holder from exceeding a 9.9% ownership threshold - Holders are prohibited from converting Notes if it would result in them beneficially owning more than the **'Beneficial Ownership Limitation'**[299](index=299&type=chunk) Ownership Limitation Details | Item | Detail | | :--- | :--- | | **General Limitation** | 9.9% of outstanding Common Stock | | **Holder Adjustment** | A holder can elect a lower limit with 61 days' notice | [Article 6: Successors](index=66&type=section&id=Article%206.%20Successors) This article governs the requirements for a successor entity in the event of a merger, consolidation, or sale of assets [When the Company May Merge, Etc.](index=66&type=section&id=Section%206.01.) This section restricts the Company from major corporate transactions unless the successor assumes all obligations under the Indenture - In a merger or sale of all assets, the successor corporation must be a **U.S. entity** and must assume all obligations related to the Notes[307](index=307&type=chunk) - **No Default or Event of Default** may be continuing immediately after such a business combination[307](index=307&type=chunk) [Article 7: Defaults and Remedies](index=67&type=section&id=Article%207.%20Defaults%20and%20Remedies) This article defines events of default and outlines the corresponding remedies available to the Trustee and holders, including acceleration [Events of Default](index=67&type=section&id=Section%207.01.) This section defines the specific events that constitute a default under the Indenture - Events of Default include **non-payment of principal or interest** (with a 30-day grace period for interest)[312](index=312&type=chunk) - A cross-default on other debt of at least **$25 million**, or an uninsured final judgment of the same amount, constitutes an Event of Default[312](index=312&type=chunk)[313](index=313&type=chunk) - **Bankruptcy, insolvency, or similar proceedings** involving the Company or a Significant Subsidiary are also Events of Default[313](index=313&type=chunk)[315](index=315&type=chunk) [Acceleration](index=69&type=section&id=Section%207.02.) Upon an Event of Default, the Notes may be accelerated, making the entire principal and accrued interest immediately due - Acceleration is **automatic** upon certain bankruptcy events involving the Company[317](index=317&type=chunk) - For other defaults, the Trustee or holders of at least **25% of the principal amount** of Notes can declare acceleration[318](index=318&type=chunk) [Sole Remedy for a Failure to Report](index=69&type=section&id=Section%207.03.) This section provides a specific, limited remedy of paying Special Interest for the Company's failure to file required SEC reports Special Interest for Reporting Default | Period | Rate (per annum) | | :--- | :--- | | **First 90 days** | 0.25% | | **Days 91-180** | 0.50% | - Acceleration for a reporting default is only possible **after 181 days** if the Company elects this remedy[320](index=320&type=chunk) [Article 8: Amendments, Supplements, and Waivers](index=73&type=section&id=Article%208.%20Amendments%2C%20Supplements%20and%20Waivers) This article details the procedures for modifying the Indenture, distinguishing between changes that do and do not require holder consent [Amendments Without Consent of Holders](index=73&type=section&id=Section%208.01.) The Company and Trustee can amend the Indenture without holder consent for certain administrative or non-adverse changes - Amendments are permitted without holder consent to cure defects, add guarantees, secure the notes, or for other changes that are **not materially adverse** to holders[341](index=341&type=chunk)[342](index=342&type=chunk) [Amendments With Consent of Holders](index=74&type=section&id=Section%208.02.) This section outlines the requirements for amendments that need consent from a majority or all affected holders - Most amendments require the consent of holders of a **majority of the aggregate principal amount** of Notes[345](index=345&type=chunk) - **Unanimous consent** of all affected holders is required to: - Reduce principal or extend maturity - Reduce interest rate or extend payment time - Adversely affect conversion rights - Change the ranking of the Notes[345](index=345&type=chunk)[346](index=346&type=chunk)[350](index=350&type=chunk) [Article 9: Satisfaction and Discharge](index=77&type=section&id=Article%209.%20Satisfaction%20and%20Discharge) This article describes the process for terminating the Company's obligations under the Indenture once all Notes are paid [Termination of Company's Obligations](index=77&type=section&id=Section%209.01.) This section describes how the Company's obligations can be discharged upon payment or cancellation of all outstanding Notes - The Indenture can be discharged once all notes are paid or provided for through an **irrevocable deposit** with the Trustee[359](index=359&type=chunk) - The Notes are **not defeasible**[361](index=361&type=chunk) [Article 10: Trustee](index=78&type=section&id=Article%2010.%20Trustee) This article defines the duties, rights, compensation, and indemnification of the Trustee [Duties of the Trustee](index=78&type=section&id=Section%2010.01.) This section outlines the Trustee's duties, which are ministerial unless an Event of Default has occurred - During an Event of Default, the Trustee must act as a **'prudent person'** would[366](index=366&type=chunk) - Otherwise, the Trustee's duties are ministerial and defined solely by the **express provisions** of the Indenture[366](index=366&type=chunk) [Compensation and Indemnity](index=81&type=section&id=Section%2010.06.) The Company is obligated to compensate the Trustee for its services and indemnify it against losses and liabilities - The Company must **pay the Trustee** for its services and reimburse its expenses[385](index=385&type=chunk) - The Company must **indemnify the Trustee** against losses and liabilities, except those resulting from the Trustee's own negligence or willful misconduct[386](index=386&type=chunk) [Article 11: Miscellaneous](index=83&type=section&id=Article%2011.%20Miscellaneous) This article covers miscellaneous provisions, including governing law, jury trial waivers, and responsibility for calculations [Governing Law; Waiver of Jury Trial](index=86&type=section&id=Section%2011.06.) This section establishes that New York law governs the Indenture and that all parties waive the right to a jury trial - The Indenture and Notes are governed by the laws of the **State of New York**[411](index=411&type=chunk) - All parties **waive the right to a jury trial** for any related legal proceedings[411](index=411&type=chunk) [Calculations](index=87&type=section&id=Section%2011.12.) The Company is responsible for making all calculations required under the Indenture, which are binding absent manifest error - The **Company is responsible for all calculations** under the Indenture, including those related to conversion and pricing[417](index=417&type=chunk) - The Trustee and Conversion Agent may **rely conclusively on the Company's calculations** without independent verification[418](index=418&type=chunk) [Exhibits](index=91&type=section&id=Exhibits) This section contains the template forms for the Notes and the required legal legends [Exhibit A: Form of Note](index=91&type=section&id=Exhibit%20A%3A%20Form%20of%20Note) This exhibit provides the template form for the 9.50% Convertible Senior Notes due 2029 - Provides the **standard text and layout** for the physical Note certificates[428](index=428&type=chunk)[439](index=439&type=chunk) - Includes detachable forms for holders to exercise their rights, such as **conversion and repurchase** upon a fundamental change[456](index=456&type=chunk)[461](index=461&type=chunk)[465](index=465&type=chunk) [Exhibits B, C, and D: Legend Forms](index=102&type=section&id=Exhibit%20B%2C%20C%2C%20and%20D) These exhibits provide the specific text for legends that must be placed on the Notes and any resulting Common Stock - Exhibit B contains the legend for **Global Notes** held through a depository like DTC[468](index=468&type=chunk) - Exhibits C and D provide the **restrictive legends** required by the Securities Act for unregistered securities (Notes and converted Common Stock), outlining transfer limitations under Rule 144A and other exemptions[473](index=473&type=chunk)[477](index=477&type=chunk)

Core Viewpoint - Omeros Corporation has established the Omeros Oncology Clinical Steering Committee to advance its OncotoX biologics program targeting acute myeloid leukemia (AML), which is a highly fatal form of leukemia accounting for about 80% of acute leukemias in adults and one-third of all blood/bone marrow cancers [1][4]. Group 1: OncotoX Program Development - The OncotoX program consists of proprietary targeted, engineered molecules that deliver a toxic payload directly into cancer cells, effectively killing them [2]. - The steering committee will aid in developing the OncotoX-AML program, designing clinical trials, and interacting with institutional review boards [3]. Group 2: Efficacy and Safety - In vivo and ex vivo studies indicate that OncotoX-AML is highly effective at low doses, providing significant survival benefits compared to existing therapies like AbbVie’s Venclexta and Bristol Myers Squibb’s Vidaza [4]. - OncotoX-AML targets both AML blasts and leukemia stem cells (LSCs), which are often resistant to chemotherapy, thus addressing potential relapse [5]. - Preliminary studies show that OncotoX is well tolerated at doses significantly higher than effective doses without causing neutropenia or major changes in blood chemistry [5]. Group 3: Market Potential and Analyst Insights - Omeros is initiating IND-enabling work for OncotoX-AML, which is crucial given the limited therapeutic options for AML, especially for elderly patients or those with high-risk mutations [6]. - Analyst Jason Kolbert maintains a Buy rating on Omeros with a price target of $36, highlighting the potential of OncotoX-AML to fill gaps in AML treatment [7]. - The company plans to submit a European marketing authorization application for its lead therapy, narsoplimab, in the first half of 2025 [8].

Financial Data and Key Metrics Changes - The net loss for Q4 2024 was $31.4 million, or $0.54 per share, compared to a net loss of $32.2 million, or $0.56 per share in Q3 2024 [6][58] - For the full year 2024, the net loss was $156.8 million, or $2.70 per share [6][58] - As of December 31, 2024, the company had over $90 million in cash and investments on hand [7][59] Business Line Data and Key Metrics Changes - Research and development expenses in Q4 were heavily focused on narsoplimab and Zaltenibart [59] - OMIDRIA royalties for Q4 totaled $10.1 million based on net sales of $33.6 million, an increase from $9.3 million in Q3 [63] Market Data and Key Metrics Changes - The market size for paroxysmal nocturnal hemoglobinuria (PNH) is reported to be $3.9 billion in 2023 and projected to exceed $10 billion by 2032 [36] Company Strategy and Development Direction - The company plans to independently launch narsoplimab in the U.S. while seeking partnerships for ex-U.S. commercialization [124][126] - The focus is on restructuring the balance sheet and exploring various funding options, including partnerships and royalty monetization [8][104] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the strength of the data supporting the BLA resubmission for narsoplimab, highlighting significant survival benefits [77][78] - The company is preparing for the market launch of narsoplimab, with a strong foundation of awareness among transplant physicians [116] Other Important Information - The company is advancing Zaltenibart for C3 glomerulopathy and has received a rare pediatric disease designation from the FDA for this indication [46][47] - OMS527, aimed at treating addictions, has received funding from the National Institute on Drug Abuse for a Phase 1b clinical trial [52] Q&A Session Summary Question: Can you tell us why you believe the BLA submission is strong? - Management highlighted that the statistical analysis plan was created with FDA's agreement, and the results showed a more than three-fold improvement in survival for narsoplimab-treated patients [76][78] Question: Can you comment on pricing for narsoplimab? - Management indicated that pricing plans have not been disclosed but are expected to be in line with other complement inhibitors used in TA-TMA [91][92] Question: What is the strategy for funding and managing the balance sheet? - Management stated that they are aware of the need for balance sheet management and are exploring various options, including restructuring convertible notes and seeking additional capital [104][105] Question: Where does the company stand on manufacturing scalability for narsoplimab? - Management confirmed that they have sufficient drug supply to support the launch and initial market demand for narsoplimab [112] Question: How does the company view its long-term strategy regarding partnerships? - Management plans to launch narsoplimab independently in the U.S. while seeking partnerships for ex-U.S. commercialization, with a focus on leveraging their deep pipeline [124][126]

Product Development and Pipeline - Omeros Corporation's lead product candidate, Narsoplimab (OMS721), is focused on treating hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) and is currently in the process of resubmitting a Biologics License Application (BLA) to the FDA, with a target action date expected in September 2025[40]. - Omeros is developing zaltenibart (OMS906), a monoclonal antibody targeting MASP-3, for conditions such as paroxysmal nocturnal hemoglobinuria (PNH) and complement 3 glomerulopathy (C3G), with ongoing clinical trials[27]. - The clinical development pipeline includes OMS1029, a long-acting antibody targeting the lectin pathway, with Phase 1 studies completed and plans for Phase 2 development[34]. - The company is also advancing OMS527, a phosphodiesterase 7 (PDE7) inhibitor for addiction and movement disorders, with a Phase 1b study in adult cocaine use disorder patients initiated[28][34]. - Omeros has a diverse preclinical pipeline, including small-molecule inhibitors for MASP-2 and MASP-3, and therapies targeting a wide range of cancers[34]. - The company has generated positive preclinical data for MASP-2 inhibition in various disease models, indicating potential for significant therapeutic applications[37]. - The Phase 3 program for zaltenibart in PNH includes 120 clinical sites across 30 countries, with active comparator drug sourced and clinical site activation underway[59]. - Interim analysis from the Phase 2 trial of zaltenibart in PNH patients showed statistically significant improvements in hemolysis markers, including hemoglobin and lactate dehydrogenase[61]. - The ongoing Phase 2 clinical program for zaltenibart in C3G is expected to complete enrollment later this year, with plans for a Phase 3 trial contingent on efficacy results[64]. - The company received a $6.24 million grant from NIDA to develop the PDE7 inhibitor OMS527 for cocaine use disorder, funding a clinical study over three years[68]. - OMS527 demonstrated a reduction in adverse effects associated with cocaine in animal studies, indicating potential therapeutic benefits[69]. - The company received a funding commitment of $4.02 million from NIDA for a clinical trial assessing the safety and efficacy of the OMS527 compound, with preliminary data readout targeted by year-end 2025[70]. - In a Phase 1 clinical trial, the OMS527 compound was well tolerated with no safety concerns and showed favorable pharmacokinetics for once daily dosing[71]. - The company is evaluating an OMS527 PDE7 inhibitor for treating levodopa-induced dyskinesia (LID) in Parkinson's disease patients, with over 10 million patients affected globally[72]. - The PPARγ program has shown positive results in Phase 2 trials for addiction treatment, with significant reductions in cravings and anxiety reported[75]. Financials and Funding - The company received a milestone payment of $200 million from Rayner Surgical Inc. in February 2023 related to the sale of OMIDRIA, contingent upon its use in ambulatory surgery centers for at least four years[30]. - Omeros has entered into a Royalty Purchase Agreement with DRI Healthcare Acquisitions LP, receiving $125 million for a portion of the royalties from OMIDRIA sales, with an amended agreement in February 2024 eliminating annual caps on royalty payments[31][32]. - The company has borrowed approximately $67.1 million under a Credit and Guaranty Agreement, pledging substantially all assets as collateral, while maintaining a covenant to keep $25 million in unrestricted cash[33]. - As of December 31, 2024, the company had cash, cash equivalents, and short-term investments of $90.1 million, with cash used in operations amounting to $148.8 million and a net loss of $156.8 million for the year[170]. - The company has incurred cumulative operating losses since inception and may require additional capital to complete the development and commercialization of its product candidates[170]. - The company faces substantial doubt regarding its ability to continue as a going concern, which may materially adversely affect its share price and ability to raise new capital[169]. - The company expects to continue incurring additional losses until it generates significant revenue from commercial products or partnerships[171]. - If unable to raise additional capital, the company may have to delay, scale back, or discontinue the development of its product candidates[171]. - The company’s financial condition may limit its ability to access capital and could result in mandatory prepayments of the Initial Term Loan[171]. - The total aggregate principal amount of the company's 2026 Notes outstanding is $97.2 million, alongside $67.1 million under the Initial Term Loan and approximately $2.0 million of finance lease obligations[175]. Regulatory and Compliance - Narsoplimab has received breakthrough therapy designation and orphan drug designation from the FDA for multiple indications, including TA-TMA and complement-mediated TMAs[46]. - The European Medicines Agency confirmed narsoplimab's eligibility for centralized review, with a marketing authorization application targeted for submission in the first half of 2025[47]. - The FDA issued a Complete Response Letter (CRL) for the BLA of narsoplimab for TA-TMA, indicating the need for additional information to support regulatory approval[177]. - The regulatory environment for drug candidates is extensive, with compliance required for research, development, testing, and marketing[102]. - The FDA provides fast-track designation for drugs intended to treat serious diseases, expediting development and review processes[116]. - Breakthrough therapy designation allows for increased FDA interactions to expedite product development for serious conditions[117]. - Accelerated approval can be granted for drugs showing meaningful therapeutic advantages based on surrogate endpoints[119]. - Post-approval, the FDA requires confirmatory studies to verify clinical benefits of drugs granted accelerated approval[120]. - Orphan drug designation offers incentives for drugs treating rare diseases affecting fewer than 200,000 individuals in the U.S.[122]. - Pediatric exclusivity can extend market exclusivity by six months if pediatric studies are conducted as requested by the FDA[123]. - Expanded access allows investigational drugs to be used for patients with serious conditions when no satisfactory alternatives exist[125]. - The Drug Supply Chain Security Act mandates tracking and tracing obligations for manufacturers to ensure drug safety[129]. - The Hatch-Waxman Act provides exclusivity periods for new drugs, preventing generic applications for specified durations[135]. - The CREATES Act allows generic developers to sue brand manufacturers for access to necessary samples for product development[137]. - The company is subject to various federal and state healthcare compliance laws, including the Anti-Kickback Statute and the False Claims Act, which could impact its operations[141]. - The company operates in a highly regulated environment, with governments in the EU controlling the price of medicinal products through pricing and reimbursement rules[151]. - The company is subject to extensive government regulation, and failure to comply may result in significant penalties and operational disruptions[191]. - The company cannot guarantee timely FDA or EMA approval for narsoplimab or any other product candidates, which may require substantial time and resources[192]. Intellectual Property - As of March 31, 2025, the company owned or held exclusive licenses to a total of 81 issued patents and 64 pending patent applications in the U.S., and 1,443 issued patents and 655 pending patent applications in foreign markets[98]. - The MASP-2 program includes 42 issued patents and 33 pending patent applications in the U.S., and 861 issued patents and 474 pending patent applications in foreign markets, with patent terms expiring as late as 2043[98]. - The MASP-3 program has five issued patents and eight pending patent applications in the U.S., and 212 issued and 109 pending patent applications in foreign markets, with patent terms expiring as late as 2043[98]. - The PPARγ program includes three issued patents and one pending patent application in the U.S., and 42 issued patents and one pending patent application in foreign markets, with terms expiring as late as 2030[98]. - The PDE7 program has two issued patents and two pending patent applications in the U.S., and 61 issued patents and seven pending patent applications in foreign markets, with terms expiring as late as 2043[98]. - The oncology program has two patent applications pending in the U.S. related to potential cancer therapies[99]. - The company is operating its oncology program in stealth mode to confirm results and generate new data for intellectual property[99]. - Protecting intellectual property and proprietary technologies is challenging and costly, impacting the company's commercial success[218]. - The patent positions in the pharmaceutical and biotechnology sectors are uncertain, with potential changes in patent laws affecting the value of the company's intellectual property[219]. - The company cannot assure that its patent applications will be found patentable or that they will issue as patents, which could limit protection for its product candidates[220]. - The degree of future protection for proprietary rights is uncertain, and inability to maintain patent protection may hinder the development of follow-on indications[221]. Competition and Market Risks - The company expects to face competition from established pharmaceutical companies and new entrants in the biotechnology sector, which may impact market share[94]. - Narsoplimab and other product candidates will compete against several approved complement-targeted therapeutics, including Soliris and Ultomiris[96]. - The success of future products depends heavily on adequate coverage and reimbursement from government and private payers, which may be delayed or insufficient[180]. - The company faces significant risks in obtaining regulatory approvals outside the U.S., which may involve additional testing and data review[179]. - The operating results of the company are unpredictable and may fluctuate due to various factors, including market acceptance and pricing policies[187]. - The company may experience delays in obtaining coverage or reimbursement for newly approved products, impacting revenue and profitability[181]. - Changes in government regulations or reimbursement policies could adversely affect revenue generation and profitability[196]. - The company faces challenges in securing sufficient manufacturing capacity from contract manufacturers, which may lead to delays or inadequate supply[198]. - The availability of necessary ingredients and materials for manufacturing may not be guaranteed, potentially delaying commercialization[204]. - Clinical trials may be delayed due to various factors, including regulatory approvals and patient enrollment challenges[207]. - The company may need to establish additional manufacturing arrangements if current suppliers fail to meet requirements, which could be time-consuming and costly[199]. - There is a risk that product candidates may not successfully complete clinical development or be suitable for commercialization[212]. - The company must focus its limited resources on the most promising product candidates, potentially forgoing other opportunities[211]. Human Resources - The company had 202 full-time employees as of December 31, 2024, with 136 in research and development, 19 in sales and marketing, and 47 in finance, legal, business development, and administration[153]. - The company has built a research and development organization that includes expertise in discovery research, preclinical development, product formulation, analytical and medicinal chemistry, manufacturing, clinical development, and regulatory and quality assurance[152]. - The company is not substantially dependent on any third parties for its preclinical research and engages multiple clinical sites to conduct clinical trials[152]. - The company’s chief commercial officer has nearly three decades of international experience in the biopharmaceutical industry, having held leadership roles at various companies[157]. - The company’s vice president of chemistry, manufacturing, and controls has 20 years of pharmaceutical experience and has contributed to the commercialization of nine drug/device combination products[158].

Financial Performance - Net loss for Q4 2024 was $31.4 million, or $0.54 per share, compared to a net loss of $32.2 million, or $0.56 per share in Q3 2024[3]. - For the year ended December 31, 2024, net loss was $156.8 million, or $2.70 per share, compared to a net loss of $117.8 million, or $1.88 per share in the prior year[8]. - The company reported a net loss of $31.4 million for Q4 2024, compared to a net loss of $9.1 million in Q4 2023[21]. - The accumulated deficit increased to $910.3 million as of December 31, 2024, from $753.5 million a year earlier[23]. Cash and Investments - Cash and short-term investments available for operations and debt servicing as of December 31, 2024, were $90.1 million, a decrease of $81.7 million from December 31, 2023[9]. - Cash and cash equivalents were $3.4 million as of December 31, 2024, compared to $7.1 million at the end of 2023[23]. Revenue and Royalties - OMIDRIA royalties earned in Q4 2024 were $10.1 million on U.S. net sales of $33.6 million, compared to $9.3 million on U.S. net sales of $31.0 million in Q3 2024[10]. - Net income from discontinued operations was $5.2 million for Q4 2024, compared to $4.9 million in Q3 2024[12]. Operating Expenses - Total operating expenses for Q4 2024 were $35.7 million, slightly up from $35.4 million in Q3 2024[11]. - Significant cost outlays during 2024 totaled $42.7 million, including $21.7 million for repurchasing convertible senior notes and $19.1 million for narsoplimab drug substance delivery[9]. - Research and development expenses for Q4 2024 were $23.3 million, down from $28.9 million in Q4 2023[21]. - Selling, general and administrative expenses increased to $12.3 million in Q4 2024 from $10.9 million in Q4 2023[21]. - Interest expense decreased to $3.2 million in Q4 2024 from $4.1 million in the prior quarter, primarily due to the remeasurement of the OMIDRIA royalty obligation[11]. Drug Development and Regulatory Updates - The biologics license application (BLA) for narsoplimab was resubmitted to the FDA in March 2025, with a target action date of September 2025[4]. - The European marketing authorization application (MAA) for narsoplimab is expected to be submitted in the first half of 2025[3]. - The Phase 3 program for zaltenibart in treating paroxysmal nocturnal hemoglobinuria (PNH) has been initiated, including two studies targeting different patient populations[5]. - NIDA confirmed funding of $4.02 million for the OMS527 program, aimed at treating cocaine use disorder, starting April 1, 2025[6]. - Narsoplimab demonstrated a hazard ratio of 0.32 in overall survival compared to an external control population of TA-TMA patients, indicating significant clinical efficacy[4]. - Omeros' lead drug candidate, narsoplimab, is pending FDA review for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy[16]. Assets - Total assets decreased to $277.1 million as of December 31, 2024, down from $378.3 million a year earlier[23].

Group 1 - Omeros Corporation is set to release its fourth-quarter financial results on March 31, with analysts expecting a quarterly loss of 78 cents per share, compared to a loss of 69 cents per share in the same period last year [1] - On March 21, Omeros provided an update on its ongoing Zaltenibart Phase 3 PNH clinical trial program [1] - Omeros shares increased by 4.7%, closing at $8.92 on Thursday [1] Group 2 - Needham analyst Serge Belanger maintained a Hold rating on Omeros with an accuracy rate of 68% [4] - Cantor Fitzgerald analyst Olivia Brayer reiterated a Neutral rating on Omeros, achieving an accuracy rate of 62% [4]

Group 1 - Omeros Corporation (NASDAQ: OMER) faced a Complete Response Letter (CRL) for their HSCT-TMA molecule narsoplimab three years ago, leading to a significant decline in stock value, but it has recently shown signs of recovery [1] - The Total Pharma Tracker offers tools for DIY investors, including a software that provides extensive curated research material for any ticker [1] Group 2 - For investors seeking hands-on support, the in-house experts at Total Pharma Tracker analyze tools to identify the best investable stocks, along with buy/sell strategies and alerts [2] - A free trial is available for potential users to access the tools and evaluate the services offered by Total Pharma Tracker at no cost [2]

Core Insights - Omeros Corporation announced the completion of the primary statistical analysis for narsoplimab, a monoclonal antibody targeting TA-TMA, in agreement with the FDA [1][4] - Narsoplimab demonstrated significant improvement in overall survival for TA-TMA patients compared to an external control group [3][2] - The company plans to resubmit the Biologics License Application (BLA) for narsoplimab for TA-TMA and aims for a European marketing authorization application submission in Q2 2025 [5] Company Developments - The independent statistical analysis compared 28 TA-TMA patients treated with narsoplimab in the OMS721-TMA-001 trial to over 100 high-risk TA-TMA patients who did not receive the treatment [2][4] - Narsoplimab achieved a hazard ratio of 0.32, indicating a clinically meaningful and statistically significant improvement in overall survival [3] - Narsoplimab has shown good tolerability and no safety concerns across all clinical trials conducted to date [5] Market Reaction - Following the announcement, Omeros' stock price increased by 54.8%, reaching $11.55 [7]

Financial Data and Key Metrics Changes - The net loss for Q3 2024 was $32.2 million or $0.56 per share, a decrease from a net loss of $56 million or $0.97 per share in Q2 2024, primarily due to a $17.6 million expense related to narsoplimab in Q2 [7][49] - Cash and investments as of September 30, 2024, totaled $123.2 million, a decrease of $35.8 million from June 30, 2024 [8][49] - Operating costs from continuing operations for Q3 were $35.4 million, down $23.8 million from Q2, driven by reduced R&D expenses [49] Business Line Data and Key Metrics Changes - OMIDRIA royalties for Q3 were $9.3 million, with net sales of $31 million, compared to royalties of $10.9 million and net sales of $36.4 million in Q2, indicating a decrease in both metrics [54] - The company expects to initiate HOPD sales for OMIDRIA starting January 1, 2025, which is anticipated to significantly increase sales in the U.S. [9][10] Market Data and Key Metrics Changes - The market size for PNH is reported to be $3.9 billion in 2023 and projected to exceed $10 billion by 2032, indicating a growing opportunity for zaltenibart [32] Company Strategy and Development Direction - The company is focused on the resubmission of the Biologics License Application (BLA) for narsoplimab in TA-TMA, with expectations for a quick turnaround following FDA feedback [11][15] - Omeros is advancing its zaltenibart program with plans for Phase 3 trials in PNH and C3G, with a clear path established through discussions with FDA and European regulators [28][29] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the potential for commercial sales of narsoplimab in 2025, contingent on successful BLA resubmission [60] - The company is preparing for the initiation of Phase 3 trials for zaltenibart, with a focus on patient enrollment and leveraging previous positive data [75] Other Important Information - The FDA has established a rare disease innovation hub to facilitate the development of treatments for rare diseases, which may benefit Omeros' programs [17] - The company is also exploring additional indications for its MASP-3 inhibitor, zaltenibart, and has received a rare pediatric disease designation for C3G [33][34] Q&A Session Summary Question: Expectations for narsoplimab commercial sales - Management hopes to have narsoplimab commercially available in 2025, pending alignment on the statistical analysis plan with the FDA [60] Question: Phase 3 trial designs for zaltenibart - The Phase 3 trials will include a switch-over trial for patients not responding to ravulizumab and a trial for treatment-naive patients, with positive feedback received from regulatory agencies [66][68] Question: Strategy for the priority review voucher for pediatric C3G - Management indicated it is premature to discuss strategy regarding the voucher, considering market interest and potential internal use [69] Question: Size and cost estimates for OMS906 Phase 3 program - The Phase 3 studies are expected to be relatively small, with around 100 patients per trial, and management is confident in moving forward independently while exploring partnership opportunities [74][75]

Financial Performance - Net loss from continuing operations for the three months ended September 30, 2024, was $37.1 million, compared to a loss of $51.7 million for the same period in 2023, representing a 28.2% improvement [12]. - The company reported a net loss of $32.2 million for the three months ended September 30, 2024, compared to a net loss of $37.8 million for the same period in 2023, reflecting a 14.6% decrease [12]. - Total costs and expenses for the nine months ended September 30, 2024, were $133.6 million, an increase of 7.1% from $124.8 million for the same period in 2023 [12]. - Cash used in operations for the nine months ended September 30, 2024 was $119.8 million, which includes an $18.4 million charge for delivery of narsoplimab drug substance [163]. - The company reported a net loss of $32.2 million and $125.5 million for the three and nine months ended September 30, 2024, respectively [163]. Cash and Investments - Cash and cash equivalents at the end of the period were $1.5 million, down from $30.6 million at the end of September 2023 [17]. - The company has $123.2 million in cash, cash equivalents, and short-term investments as of September 30, 2024, with cash used in operations amounting to $119.8 million for the nine months ended September 30, 2024 [32]. - Total short-term investments amounted to $121.640 million as of September 30, 2024, with U.S. government securities and money-market funds comprising the majority [56]. - As of September 30, 2024, the company had cash, cash equivalents, and short-term investments of $123.2 million available to fund operations and service debt [146]. Research and Development - Research and development expenses for the three months ended September 30, 2024, were $24.1 million, down 24.1% from $31.7 million in the same period of 2023 [12]. - The company is focused on developing first-in-class therapeutics targeting immunologic disorders, cancers, and addictive disorders [19]. - The company is developing narsoplimab (OMS721) for TA-TMA, having completed a pivotal clinical trial and submitted a BLA to the FDA [117]. - Narsoplimab shows potential as a therapeutic for COVID-19 and ARDS, supported by in vivo animal data and proof-of-concept clinical data [118]. - OMS1029, a long-acting antibody targeting MASP-2, has completed Phase 1 trials, confirming once-quarterly low-volume dosing with no safety concerns [119]. - Zaltenibart, targeting MASP-3, is advancing to Phase 3 trials for PNH and C3G, with multiple ongoing Phase 2 trials [120][121]. - The Phase 2 trial for zaltenibart in patients unsatisfied with ravulizumab showed significant improvements in hemoglobin levels and reticulocyte counts [124]. Debt and Financing - The company entered into a Credit Agreement providing for a senior secured term loan facility of up to $92.1 million, with an initial term loan of $67.1 million [29]. - The company repurchased $118.1 million of its existing 5.25% convertible senior notes due in 2026, resulting in a $51.0 million reduction in outstanding debt [30]. - The Initial Term Loan amount outstanding was $67,077,000 as of September 30, 2024, with a total long-term debt of $92,427,000 [67]. - The company accrued $0.6 million in additional cash consideration to a certain Lender as a post-closing adjustment under the 2026 Note Repurchase Transaction [66]. - The company has a sales agreement to sell shares of common stock for up to $150.0 million to raise additional capital [34]. Discontinued Operations - The company has classified the results of OMIDRIA activities as discontinued operations following its sale to Rayner Surgical Inc. [26]. - The company recognized net income from discontinued operations of $4.881 million for the three months ended September 30, 2024, compared to $13.906 million for the same period in 2023, a decrease of approximately 65% [90]. - Cash provided by discontinued operations from operating activities was $30.619 million for the nine months ended September 30, 2024, significantly lower than $232.081 million for the same period in 2023 [92]. Stock and Compensation - Stock-based compensation expense for the nine months ended September 30, 2024, was $8.1 million, compared to $9.0 million for the same period in 2023 [17]. - The total estimated compensation expense yet to be recognized on outstanding options is $14.4 million [111]. - The share repurchase program authorized up to $50 million, with 5 million shares repurchased at an average price of $3.30 per share [105]. - As of September 30, 2024, there were 18.13 million stock options outstanding, with a weighted average exercise price of $8.41 per share [110]. Future Outlook - The company plans to resubmit the BLA for narsoplimab following FDA feedback expected in November 2024 [117]. - The company expects research and development expenses in Q4 2024 to be similar to those in Q3 2024 [151]. - The company anticipates that selling, general and administrative expenses in Q4 2024 will be similar to those in Q3 2024 [154]. - The company expects to initiate Phase 3 trials for C3G in the first half of 2025, following ongoing Phase 2 trials [127].