Galera(GRTX) - 2021 Q4 - Annual Report

FORM 10-K Filing Information Registrant Details Galera Therapeutics, Inc. filed its 2021 Form 10-K, identifying as a Delaware-incorporated non-accelerated filer, smaller reporting, and emerging growth company listed on Nasdaq GRTX - Galera Therapeutics, Inc. filed its annual report on Form 10-K for the fiscal year ended December 31, 2021[2] Registrant Classification | Classification | Status | | :------------- | :----- | | Well-known seasoned issuer | NO | | Required to file reports | YES | | Filed all required reports | YES | | Submitted Interactive Data File | YES | | Large accelerated filer | NO | | Accelerated filer | NO | | Non-accelerated filer | YES | | Smaller reporting company | YES | | Emerging growth company | YES | - The aggregate market value of voting and non-voting common equity held by non-affiliates was approximately $161.6 million as of June 30, 2021[4] - As of March 4, 2022, 26,795,172 shares of Common Stock were outstanding[5] Documents Incorporated by Reference Portions of the 2022 Proxy Statement are incorporated by reference into Part III of this Annual Report on Form 10-K - Portions of the registrant's definitive Proxy Statement for the 2022 Annual Meeting of Stockholders are incorporated by reference into Part III of this Annual Report on Form 10-K[7] Cautionary Note Regarding Forward Looking Statements This report contains forward-looking statements subject to risks and uncertainties, with no obligation for public updates unless legally required - All statements other than historical facts are forward-looking, identifiable by terms like 'may,' 'will,' 'expect,' 'plan,' 'anticipate,' 'believe,' 'estimate,' 'predict,' 'potential,' or 'continue'[8] - Forward-looking statements are based on current expectations and projections about future events and financial trends, and are subject to risks and uncertainties described in 'Summary Risk Factors' and 'Risk Factors'[9] - The company does not plan to publicly update or revise forward-looking statements unless required by applicable law, and they are intended to be covered by safe harbor provisions of the Securities Act and Exchange Act[10] Summary Risk Factors Galera faces key risks: clinical stage status, no product sales, avasopasem dependence, funding needs, and uncertain regulatory approval - Galera Therapeutics is a clinical-stage biopharmaceutical company with a limited operating history and no product sales revenue, anticipating continued losses[13] - The company is heavily dependent on the success of its lead product candidate, avasopasem, for clinical development and regulatory approval[13] - Significant risks include the need for substantial funding, lengthy and uncertain regulatory approval processes, reliance on third parties for clinical trials and manufacturing, challenges in commercialization, and intense competition[13] Table of Contents This section outlines the major parts and items of the Form 10-K, including Business, Risk Factors, Financial Statements, and Exhibits PART I Item 1. Business Galera develops novel dismutase mimetics to reduce radiotherapy toxicity and enhance anti-cancer efficacy, with avasopasem and rucosopasem as lead candidates - Galera Therapeutics is a clinical-stage biopharmaceutical company developing novel therapeutics to reduce normal tissue toxicity and increase anti-cancer efficacy of radiotherapy[18] - Avasopasem manganese (GC4419) is the lead product candidate for reducing severe oral mucositis (SOM) in head and neck cancer (HNC) and esophagitis in lung cancer, with Breakthrough Therapy Designation for SOM[18] - Rucosopasem manganese (GC4711) is the second product candidate, in clinical development to augment anti-cancer efficacy of stereotactic body radiation therapy (SBRT) in non-small cell lung cancer (NSCLC) and locally advanced pancreatic cancer (LAPC)[18] Overview Galera develops superoxide dismutase mimetics; avasopasem showed efficacy in Phase 3 SOM, and rucosopasem enhances SBRT efficacy in cancer - Avasopasem manganese (GC4419) is in development for reducing severe oral mucositis (SOM) in head and neck cancer (HNC) and esophagitis in lung cancer, holding FDA Breakthrough Therapy Designation for SOM[18] - Corrected topline efficacy results from the Phase 3 ROMAN trial showed a statistically significant 16% relative reduction in SOM incidence (p=0.045) and a 56% relative reduction in days of SOM (median 18 days vs. 8 days in avasopasem arm)[19] - Rucosopasem manganese (GC4711) is being developed to increase the anti-cancer efficacy of SBRT, with positive Phase 1/2 pilot trial results in LAPC showing improvements in overall survival, progression-free survival, local tumor control, and time to distant metastases[22] Our Strategy Galera's strategy focuses on completing avasopasem development, building U.S. commercial infrastructure, advancing rucosopasem, and seeking collaborations - Complete development and obtain FDA approval of avasopasem for radiotherapy-induced toxicities, leveraging its Breakthrough Therapy Designation and positive Phase 3 ROMAN trial results[29] - Build a specialized U.S. sales and marketing organization of approximately 40 representatives to target 5,000 radiation oncologists for avasopasem commercialization, and potentially rucosopasem[29] - Advance rucosopasem development in combination with SBRT to increase anti-cancer efficacy, based on preclinical and pilot LAPC trial data, and explore new applications and formulations for dismutase mimetics[29] Background on Superoxide and Superoxide Dismutase Superoxide damages cells; SOD enzymes convert it to less toxic hydrogen peroxide, reducing radiotherapy toxicity and enhancing anti-cancer efficacy - Superoxide (O2•-) is a reactive oxygen species that damages biological molecules, constantly produced in living cells and exacerbated by radiotherapy[31][32] - Superoxide dismutase (SOD) enzymes rapidly convert superoxide to hydrogen peroxide, which is less toxic to normal cells and may increase anti-cancer efficacy in cancer cells[31][33] - Limitations of native SODs for therapeutic use include large size, inability to enter cells, immunogenicity, short half-lives, and inactivation by reactive oxygen species[34][35] Our Superoxide Dismutase Mimetics Galera's dismutase mimetics are small, stable drugs converting superoxide to hydrogen peroxide, reducing radiotherapy toxicity and enhancing anti-cancer efficacy - Galera's dismutase mimetics are small molecules designed to mimic native SODs, featuring a pentaaza macrocyclic core with a manganese atom for rapid and selective superoxide conversion[37][38] - Key features include rapid catalytic rate (2 × 10^7 molecules/second), high selectivity for superoxide, stability, observed safety in preclinical and clinical studies, and efficient manufacturing[39] - These mimetics reduce normal tissue toxicity from radiotherapy and have the potential to increase anti-cancer efficacy of SBRT by generating high daily doses of hydrogen peroxide, as demonstrated in preclinical models[40][41] Disease Overview and Our Product Pipeline Galera's pipeline targets radiotherapy toxicities (avasopasem for SOM/esophagitis) and enhances anti-cancer efficacy (rucosopasem for LAPC/NSCLC) - Over 50% of cancer patients treated with radiotherapy experience toxicities, with mucositis (oral and esophageal) being common and debilitating[44][45] - Severe Oral Mucositis (SOM) affects approximately 70% of locally advanced HNC patients receiving standard-of-care radiotherapy, with 20-30% developing Grade 4 OM, leading to severe pain, dehydration, malnutrition, and treatment interruptions[49][52] - Radiotherapy-induced esophagitis affects about 50% of lung cancer patients receiving radiotherapy, causing severe symptoms and potentially requiring hospitalization[96] Reducing Radiotherapy-Induced Toxicities in Patients with Cancer (Radioprotection) Radiotherapy-induced toxicities like oral mucositis and esophagitis are common; avasopasem aims to reduce these by mitigating superoxide production Oral Mucositis Oral mucositis is a severe radiotherapy complication with limited treatments; avasopasem aims to be the first FDA-approved drug to reduce SOM, supported by clinical data - SOM is defined as Grade 3 or Grade 4 OM, causing severe pain, dehydration, malnutrition, and treatment interruptions, with no FDA-approved drugs for its treatment in HNC