☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15 (d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-43080 ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2025 OR UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-K (Mark one) Polaryx Therapeutics, Inc. (Exact name of registrant as specified in its charter) (State or other jurisdiction of (I.R.S. Emplo ...

Core Insights - The U.S. FDA has granted Fast Track Designation to PLX-200 for treating Late-Infantile Neuronal Ceroid Lipofuscinosis (LINCL/CLN2 disease), marking a significant regulatory milestone for Polaryx Therapeutics [1][3] Company Overview - Polaryx Therapeutics, Inc. is a clinical-stage biotechnology company focused on developing therapies for rare pediatric lysosomal storage disorders (LSDs) [6] - Founded in 2014, the company aims to deliver safe and effective treatments that address the underlying pathophysiology of these diseases [6][7] Product Development - PLX-200, the lead drug candidate, is an orally available compound derived from gemfibrozil, which is FDA-approved for lipid regulation [4] - The drug's ability to cross the blood-brain barrier has been documented, potentially addressing significant unmet needs in multiple rare LSDs [4][7] Clinical Trials - The SOTERIA Phase 2 trial is designed to evaluate the safety, tolerability, and clinical activity of PLX-200 across four LSDs: CLN2, CLN3, Krabbe disease, and Sandhoff disease [5] - The trial is set to begin in the third quarter of 2026, with sites in the U.S., Europe, and Asia [5] - SOTERIA will incorporate analyses comparing treated arms to natural history data as a control, enhancing the robustness of the trial [5]

Core Insights - Polaryx Therapeutics, Inc. is actively participating in events to support the Krabbe disease community, demonstrating its commitment to advancing research and engaging with stakeholders [1][5] Event Participation - The company will attend the 2026 Krabbe Translational Research Network (KTRN) meeting from March 18-20, 2026, in Minneapolis, Minnesota, with key executives present [2] - The KTRN meeting aims to accelerate Krabbe research through focused, data-driven sessions that integrate insights across various aspects of the disease [3][4] - Polaryx will also participate in the 2026 Putt-Putt to CureKrabbe event on March 20, 2026, hosted by KrabbeConnect, to raise awareness and strengthen community engagement [5] Clinical Development - Polaryx is advancing the SOTERIA trial, a Phase 2, open-label, single-arm study to evaluate the safety, tolerability, and clinical activity of its lead candidate, PLX-200, across four rare lysosomal storage disorders (LSDs) [6][8] - The SOTERIA trial is designed to be flexible and resource-efficient, aiming to gather important data for PLX-200's future clinical development [8] - The trial is set to initiate in the first half of 2026, with sites in the United States, Europe, and Asia, following a safe to proceed letter from the FDA received in October 2025 [8][9] Scientific Insights - Recent findings on PLX-200 as a potential therapeutic approach for Krabbe disease have received positive feedback from the Krabbe community, emphasizing the importance of community engagement in clinical development [7] - Krabbe disease is caused by mutations in the GALC gene, leading to severe neurological decline due to the accumulation of toxic metabolites [7] Company Overview - Polaryx Therapeutics focuses on developing small molecule and gene therapy treatments for rare orphan lysosomal storage disorders, aiming to address significant unmet medical needs [10] - The company was founded in 2014 and seeks to deliver effective treatments that target the underlying pathophysiology of these diseases [10]

Core Insights - Premarket trading is showing notable activity with significant price movements indicating potential opportunities for traders before the market opens [1] Group 1: Premarket Gainers - Domo, Inc. (DOMO) is up 39% at $6.13 [3] - Auna SA (AUNA) is up 17% at $5.67 [3] - TMD Energy Limited (TMDE) is up 16% at $2.39 [3] - Acurx Pharmaceuticals, Inc. (ACXP) is up 14% at $3.31 [3] - Atomera Incorporated (ATOM) is up 11% at $5.58 [3] - Oracle Corporation (ORCL) is up 9% at $163.42 [3] - UniFirst Corporation (UNF) is up 8% at $280.84 [3] - Adial Pharmaceuticals, Inc. (ADIL) is up 8% at $1.99 [3] - VCI Global Limited (VCIG) is up 7% at $3.22 [3] - XTI Aerospace, Inc. (XTIA) is up 5% at $3.19 [3] Group 2: Premarket Losers - Raytech Holding Limited (RAY) is down 22% at $3.40 [4] - MiNK Therapeutics, Inc. (INKT) is down 15% at $11.39 [4] - ESGL Holdings Limited (OIO) is down 15% at $3.26 [4] - Trailblazer Holdings, Inc. (TBMC) is down 14% at $10.13 [4] - Groupon, Inc. (GRPN) is down 12% at $10.16 [4] - AeroVironment, Inc. (AVAV) is down 10% at $198.24 [4] - Brand Engagement Network, Inc. (BNAI) is down 10% at $32.83 [4] - Polaryx Therapeutics, Inc. (PLYX) is down 7% at $5.50 [4] - TIC Solutions, Inc. (TIC) is down 6% at $8.00 [4] - ENDRA Life Sciences Inc. (NDRA) is down 5% at $3.32 [4]

Core Insights - Polaryx Therapeutics is committed to developing disease-modifying therapies for rare pediatric lysosomal storage disorders (LSDs) and raising awareness within the rare disease community [2][4] Company Overview - Polaryx Therapeutics, founded in 2014, focuses on small molecule and gene therapy treatments for rare orphan LSDs, aiming to address significant unmet medical needs [8] - The company's lead candidate, PLX-200, is designed to target multiple LSDs and is currently advancing through clinical trials [8] Clinical Trials - The SOTERIA trial is a Phase 2, open-label, single-arm study aimed at evaluating the safety, tolerability, and clinical activity of PLX-200 across four rare LSDs: CLN2, CLN3, Krabbe disease, and Sandhoff disease [7] - The trial is expected to begin in the first half of 2026, with sites in the United States, Europe, and Asia [7] - SOTERIA is designed to be flexible and resource-efficient, potentially validating PLX-200's preclinical science while gathering important data for future clinical development [7] Rare Disease Context - LSDs are a group of over 50 inherited metabolic diseases caused by genetic mutations, affecting approximately 1 in 5,000 births [3][4] - The National Organization for Rare Diseases (NORD) defines a rare disease as one affecting fewer than 1 in 2,000 people globally, with about 70% starting in childhood [4] - More than 300 million people worldwide are affected by rare diseases, highlighting the urgent need for new treatments [4]

Core Viewpoint - Polaryx Therapeutics Inc. has made significant progress in its clinical programs, particularly with the announcement of the SOTERIA Phase 2 basket trial for its lead candidate, PLX-200, which targets multiple lysosomal storage disorders [1][2] Group 1: Clinical Development - The SOTERIA trial will utilize a control arm based on natural history data to compare against the treated arm receiving PLX-200, an orally available compound derived from gemfibrozil [2] - This trial is designed to be flexible and resource-efficient, potentially leading to conditional marketing authorization if compelling clinical activity is demonstrated [1][2] Group 2: Market Reaction - Following the announcement, Polaryx Therapeutics shares increased by 46.06%, reaching a price of $3.52, although the stock is still near its 52-week low of $2.20 [3]

Core Insights - Polaryx Therapeutics, Inc. has selected a leading contract research organization (CRO) for its SOTERIA trial, marking a significant milestone in the clinical development of its lead candidate, PLX-200, aimed at treating rare pediatric lysosomal storage disorders (LSDs) [1][2] Company Overview - Polaryx Therapeutics is a clinical-stage biotechnology company founded in 2014, focused on developing small molecule and gene therapy treatments for rare orphan LSDs [6][7] - The company aims to deliver safe and effective treatments that address the underlying pathophysiology of these diseases, integrating both small molecule therapies and gene therapy [6] Product Information - PLX-200 is an orally available compound based on gemfibrozil, an FDA-approved lipid-regulating agent, which has shown the ability to cross the blood-brain barrier (BBB) [4] - The drug is positioned to potentially address significant unmet needs in multiple rare LSD indications due to its mechanism of action and established safety profile in adults [4] Trial Details - The SOTERIA trial is a Phase 2, open-label, single-arm study designed to evaluate the safety, tolerability, and clinical activity of PLX-200 across four LSDs: CLN2, CLN3, Krabbe disease, and Sandhoff disease, which represent approximately 25% of the LSD patient population [5] - The trial is designed to be flexible and resource-efficient, with plans to initiate in the first half of 2026 in the United States, Europe, and Asia [3][5] - A safe to proceed letter from the FDA was received in October 2025, allowing the company to move forward with the trial [3][5]

Core Insights - Premarket trading is showing notable activity with significant price movements indicating potential investment opportunities before the market opens [1] Premarket Gainers - TG-17, Inc. (OBAI) has increased by 123% to $6.98 [3] - Polaryx Therapeutics, Inc. (PLYX) is up 78% at $4.29 [3] - ZIM Integrated Shipping Services Ltd. (ZIM) has risen by 34% to $29.97 [3] - Masimo Corporation (MASI) is up 33% at $173.80 [3] - Ocular Therapeutix, Inc. (OCUL) has increased by 26% to $11.21 [3] - Empery Digital Inc. (EMPD) is up 15% at $4.34 [3] - Digital Brands Group, Inc. (DBGI) has risen by 12% to $5.40 [3] - Kennedy-Wilson Holdings, Inc. (KW) is up 9% at $10.82 [3] - urban-gro, Inc. (UGRO) has increased by 8% to $3.89 [3] - Neo-Concept International Group Holdings Limited (NCI) is up 6% at $2.55 [3] Premarket Losers - JIADE Limited (JDZG) has decreased by 48% to $1.98 [4] - AIM ImmunoTech Inc. (AIM) is down 19% at $1.01 [4] - Founder Group Limited (FGL) has fallen by 16% to $15.10 [4] - Mega Fortune Company Limited (MGRT) is down 12% at $6.53 [4] - Moolec Science SA (MLEC) has decreased by 9% to $7.80 [4] - Creative Global Technology Holdings Limited (CGTL) is down 8% at $2.68 [4] - Danaher Corporation (DHR) has fallen by 7% to $196.00 [4] - Westwood Holdings Group, Inc. (WHG) is down 7% at $16.37 [4] - Psyence Biomedical Ltd. (PBM) has decreased by 6% to $2.90 [4] - Healthcare Triangle, Inc. (HCTI) is down 5% at $8.10 [4]

Core Insights - Polaryx Therapeutics presented new data on PLX-200, a reformulated gemfibrozil, for treating Krabbe disease at the WORLDSymposium™ 2026, highlighting its potential as a disease-modifying therapy for lysosomal storage disorders (LSDs) [1][2][3] Company Overview - Polaryx Therapeutics is a clinical-stage biotechnology company focused on developing therapies for rare pediatric lysosomal storage disorders, aiming to address significant unmet medical needs [12] Scientific Findings - Preclinical studies showed that gemfibrozil, when administered orally in a mouse model of Krabbe disease, improved motor functions and increased lifespan by activating PPARβ and PPARα, leading to enhanced lysosome biogenesis and reduced neuroinflammation [2][5][6] - PLX-200 promotes the expression of anti-inflammatory genes and protects neuronal cells, contributing to its therapeutic potential in neurodegenerative diseases [6][10] Clinical Development - The SOTERIA trial, a Phase 2 open-label study, is set to evaluate the safety and efficacy of PLX-200 across multiple LSDs, with plans to initiate in the first half of 2026 following FDA approval [11][8] - The trial is designed to be flexible and resource-efficient, allowing for the collection of valuable data to inform future development pathways for PLX-200 [11][7] Market Context - Krabbe disease is caused by mutations in the GALC gene, leading to toxic metabolite accumulation and severe neurological decline, highlighting the critical need for effective treatments [9][10]

Core Insights - Polaryx Therapeutics, Inc. has appointed three new members to its Board of Directors, enhancing its expertise in scientific research, clinical development, finance, and corporate strategy as it progresses as a public company [1][2][3] Board Appointments - Mitchel Berger, M.D., Francis A. Braun III, CPA, and Charles Ryan, J.D., Ph.D. have been appointed to the Board, effective January 29, 2026, while Andrew O has ceased to serve [1][2] - The new board members bring extensive experience: Dr. Berger is a prominent figure in neuro-oncology, Mr. Braun has a strong background in finance and advisory roles, and Dr. Ryan has significant experience in biotechnology and regulatory affairs [3][4][5][6] Company Milestones - Polaryx is advancing its lead candidate, PLX-200, into an IND-approved SOTERIA Phase 2 basket trial, marking a significant near-term milestone for the company [2][3] - The company focuses on developing therapies for rare, pediatric lysosomal storage disorders (LSDs), aiming to address significant unmet medical needs [7]