Summary of Design Therapeutics Conference Call Company Overview - **Company**: Design Therapeutics (NasdaqGS:DSGN) - **Focus**: Development of therapies for Friedreich's Ataxia (FA) and Fuchs' Corneal Dystrophy (FECD) using GeneTAC technology Key Points on Friedreich's Ataxia (FA) - **Therapeutic Goal**: Increase levels of normal endogenous frataxin, which is crucial as FA is caused by low levels of this protein [3][4] - **RESTORE-FA Study**: Ongoing multiple-dose study aimed at generating data to confirm an increase in frataxin levels, which would be a significant advancement in treatment [3][11] - **Measurement Techniques**: Both mRNA and protein levels will be measured in whole blood and affected tissues (muscle biopsies) to assess treatment efficacy [4][5] - **Safety and Tolerability**: Previous studies confirmed safety and a dose-to-exposure relationship, allowing for the continuation of multiple ascending dose studies [10][19] - **Expected Data**: Anticipated results from the RESTORE-FA study in the second half of the year, focusing on frataxin response after 12 weeks of dosing [11][23] Key Points on Fuchs' Corneal Dystrophy (FECD) - **Therapeutic Goal**: Development of an eye drop to slow or stop the progression of FECD, aiming to maintain visual quality for patients diagnosed early [24][25] - **Biomarker Study**: An exploratory study using discarded corneal tissue to identify potential biomarkers for target engagement, although limitations exist due to the nature of the tissue samples [25][26] - **Expected Results**: Results from the biomarker study are also anticipated in the second half of the year [30] Key Points on DM1 (Myotonic Dystrophy Type 1) - **Unique Approach**: DT-818 is a small molecule designed to reduce the expression of the mutant DMPK allele while sparing the wild-type allele, differing from other oligonucleotide-based therapies [31][32] - **Pharmacology**: Observed over 90% reduction in toxic DMPK RNA, which correlates with improvements in splice index, indicating potential efficacy [32][33] - **Administration Routes**: Focus on intravenous (IV) administration, with potential for subcutaneous (sub-Q) delivery, which could enhance adoption compared to other therapies [34] Financial Position - **Cash Reserves**: Company has over $200 million in cash, projected to sustain operations into 2029, with a focus on achieving positive clinical proof of concept in at least one therapeutic area [41] Additional Insights - **GeneTAC Technology**: The company is leveraging its proprietary technology to create bifunctional molecules that can either enhance or repress gene expression, tailored to specific genetic conditions [36][37] - **Operational Challenges**: The timeline for data release from studies may vary based on operational factors, indicating a need for flexibility in planning [23] This summary encapsulates the critical aspects of Design Therapeutics' current projects, financial health, and strategic direction as discussed in the conference call.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ☒ 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 ☐ 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 001-40288 Design Therapeutics, Inc. (Exact name of Registrant as specified in its Charter) Delaware 82-3929248 (State or other jurisdicti ...

Exhibit 99.1 Design Therapeutics Reports Fourth Quarter and Full Year 2025 Financial Results and Recent Business Updates Trials for DT-216P2 (RESTORE-FA) and DT-168 (FECD) Ongoing; DT-818 (DM1) Dosing in Patients Expected in the First Half of 2026 Cash and Securities of $219.8 Million as of Year-End Supports Ongoing Clinical Execution Carlsbad, Calif., March 9, 2026 - Design Therapeutics, Inc. (Nasdaq: DSGN), a clinical-stage biotechnology company developing treatments for serious degenerative genetic disea ...

Core Insights - Design Therapeutics, Inc. is advancing its GeneTAC® portfolio with three clinical programs, including DT-818 for myotonic dystrophy type-1 (DM1), DT-216P2 for Friedreich ataxia (FA), and DT-168 for Fuchs endothelial corneal dystrophy (FECD) [2][5] Clinical Programs - The company is expected to initiate patient dosing in the Phase 1 trial of DT-818 in DM1 in the first half of 2026, with results anticipated in 2027 [2][6] - Ongoing trials include RESTORE-FA for DT-216P2, with an update on frataxin levels expected in the second half of 2026, and a Phase 2 biomarker trial for DT-168, with data also anticipated in the second half of 2026 [6] Financial Performance - For Q4 2025, research and development expenses were $13.4 million, while general and administrative expenses were $4.7 million, leading to a net loss of $16.0 million [4][10] - For the full year 2025, total operating expenses reached $79.5 million, with a net loss of $69.8 million [10] - As of December 31, 2025, the company reported cash and securities of $219.8 million, which is expected to fund operations into 2029 [6][11] Pipeline Development - The company is also advancing preclinical characterization for several candidate molecules targeting Huntington's disease and exploring multiple genomic medicine discovery efforts [5][7]

DESIGNING A NOVEL CLASS OF GENOMIC MEDICINES FOR GENETIC DISORDERS 1Q2026 1 Disclaimers This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to projections from early-stage programs, preclinical data and early-stage clinical data; the therapeutic potential of DT-216P ...

Summary of Design Therapeutics FY Conference Call Company Overview - **Company**: Design Therapeutics (NasdaqGS:DSGN) - **Focus**: Development of small molecule genetic medicines targeting diseases caused by single gene mutations [2][3] Key Programs and Clinical Trials 1. **Friedreich's Ataxia (FA)** - **Trial**: RESTORE-FA trial, focusing on increasing endogenous frataxin expression [3] - **Expected Data**: Anticipated in the second half of 2026 [3][23] - **Mechanism**: DT-216 targets abnormally long GAA repeats in the frataxin gene to enhance frataxin production without gene editing [5][7] - **Previous Findings**: Limited duration of exposure observed in 2023 trials, with 8-10 nanomolar levels in muscle biopsies [6] 2. **Fuchs' Corneal Dystrophy (FECD)** - **Study**: Exploratory biomarker study using DT-168 eye drops to assess splicing impact [4][10] - **Market Size**: Approximately 2 million diagnosed cases in the U.S. [9] - **Mechanism**: DT-168 aims to reduce toxic RNA production caused by CTG expansions in the TCF4 gene [10][11] - **Safety**: Phase 1 study showed no significant adverse events [11] 3. **Myotonic Dystrophy Type 1 (DM1)** - **Trial**: Phase 1 multiple ascending-dose study with DT-818, expected to start in the first half of 2026 [22][23] - **Mechanism**: Targets abnormally long CTG repeats in the DMPK gene to reduce toxic RNA tangles [13][19] - **Expected Data**: Initial results anticipated in 2027 [22][36] - **Market Opportunity**: DM1 is considered 10 times more prevalent than FA, indicating a significant market potential [17] Financial Position - **Cash Reserves**: Ended the third quarter with $206 million, providing a strong runway for ongoing clinical programs [23] Market Insights - **Friedreich's Ataxia Market**: Despite existing treatments, there is a significant unmet need as current therapies do not address the genetic root cause [29] - **Clinical Translation**: The relationship between toxic RNA levels and clinical outcomes is being explored, with potential implications for splicing correction and overall treatment efficacy [30][33] Additional Considerations - **GeneTAC Approach**: The small molecule platform is still in early stages of clinical proof of concept, with different molecules targeting distinct genetic mutations [36] - **Future Outlook**: Positive data from any of the ongoing trials could significantly enhance shareholder value and advance treatment options in these areas of unmet medical need [3][23]

Group 1: Market Movements - Several biotech and healthcare companies experienced notable gains in after-hours trading, driven by earnings updates, guidance announcements, and broader investor sentiment [1] - FibroBiologics, Inc. (FBLG) led with a 7.68% increase, closing at $0.41, suggesting speculative interest or technical momentum [1] - Nyxoah SA (NYXH) advanced 3.94% to $5.28 after reporting preliminary results for Q4 and full year 2025, along with revenue guidance for Q1 2026 [2] - Fortress Biotech, Inc. (FBIO) climbed 6.90% to $4.49, continuing a trend of volatility despite no new news [2] - Revvity, Inc. (RVTY) gained 4.92% to close at $109.00, with investors likely reacting to a previous collaboration announcement with Eli Lilly [3] - Option Care Health, Inc. (OPCH) rose 3.28% to $33.11 after releasing preliminary unaudited financial results for Q4 and full year 2025, along with guidance for 2026 [4] - Actinium Pharmaceuticals, Inc. (ATNM) added 3.02% to close at $1.34, reflecting investor activity in the broader biotech sector [4] - Design Therapeutics, Inc. (DSGN) gained 1.97% to $9.30, indicating continued interest despite no specific news [5] Group 2: Company-Specific Developments - FibroBiologics, Inc. (FBLG) showed a significant rise without any company-specific news, indicating potential speculative interest [1] - Nyxoah SA (NYXH) provided revenue guidance for Q1 2026, which bolstered investor confidence in its growth trajectory [2] - Revvity, Inc. (RVTY) is expanding access to predictive models through a collaboration with Eli Lilly, aimed at accelerating AI-enabled drug discovery [3] - Option Care Health, Inc. (OPCH) released preliminary financial results and guidance, contributing to its positive after-hours reaction [4]

Summary of Design Therapeutics FY Conference Call Company Overview - Design Therapeutics (NasdaqGS:DSGN) focuses on gene expression modulation using small molecules, targeting significant monogenic diseases [2][3] Clinical Development Programs - The company is in clinical development for three major diseases: - **Friedreich Ataxia (FA)**: Ongoing trial named Restore FA, aiming to increase endogenous Frataxin levels, with data expected in the second half of 2026 [3][4] - **Myotonic Dystrophy Type 1 (DM1)**: Plans to begin multiple-dose studies in the first half of 2026, with data anticipated in 2027 [4] - **Fuchs Corneal Dystrophy**: Eye drop formulation targeting the mutant TCF4 gene, with a phase two biomarker study expected to yield data in the second half of 2026 [3][4] Friedreich Ataxia (FA) Program - The molecule DT-216 aims to increase Frataxin expression, with a new formulation (DT-216P2) showing over 10x increase in exposure and resolved vein thrombophlebitis issues [6][8] - The trial design includes dose escalation studies, with a focus on measuring Frataxin levels in whole blood and muscle [13][14] - The goal is to achieve Frataxin levels comparable to carriers, which would indicate restoration of cellular function [18][19] Fuchs Corneal Dystrophy Program - The company has developed a potential biomarker for splicing in corneal tissue, allowing for the assessment of treatment efficacy [22][23] - Patients scheduled for corneal transplants will receive eye drops prior to surgery, with the aim of demonstrating the drug's ability to fix splicing [24][25] Myotonic Dystrophy Type 1 (DM1) Program - The company is developing a small molecule that can penetrate cells effectively, targeting the mutant DMPK RNA responsible for the disease [30][31] - Data shows over 90% reduction in mutant RNA without affecting wild type protein expression, indicating selectivity and potential efficacy [31][32] Financial Position - Design Therapeutics reported a strong cash position of over $200 million, providing a runway into 2029 to gather clinical data and advance its programs [35]

Summary of Design Therapeutics FY Conference Call Company Overview - **Company**: Design Therapeutics (NasdaqGS:DSGN) - **Event**: FY Conference on December 03, 2025 Key Updates on Products and Programs DT-818 for DM1 - **Clinical Development**: DT-818 is set to enter clinical studies in the first half of 2026 for the DM1 program [3][16] - **Mechanism of Action**: DT-818 is a gene-targeted chimera designed to reduce the expression of mutant toxic DMPK RNA, which is the genetic cause of DM1. It targets the long CTG repeats in the mutant allele, aiming to restore cellular health [3][4] - **Differentiation**: Unlike other oligonucleotide-based therapies, DT-818 distributes widely to all affected tissues, including the CNS, potentially offering broader therapeutic benefits [5][6] - **Efficacy in Preclinical Models**: DT-818 demonstrated over 90% reduction in mutant RNA foci in preclinical models, significantly outperforming competitors that achieved only 30%-55% reduction [6][8] - **Clinical Translation**: There is a correlation between toxic foci reduction and clinical benefits, with existing literature supporting the link between splicing improvements and clinical outcomes [13][14] DT-216P2 for Friedreich's Ataxia (FA) - **Clinical Hold Lifted**: The company is off clinical hold and is conducting the RESTOR-FA study to evaluate DT-216P2's effect on increasing endogenous frataxin expression [22][23] - **Study Design**: The study is a multiple ascending dose study, measuring frataxin levels in whole blood and muscle tissue [30][32] - **Expected Data**: Results from the RESTOR-FA study are anticipated in the second half of 2026, with a focus on significant increases in frataxin levels being a potential regulatory endpoint [28][38] DT-168 for Fuchs' Dystrophy - **Study Design**: A biomarker phase two study is ongoing, where patients scheduled for corneal transplants will use DT-168 eye drops to assess splicing effects in corneal endothelial cells [40][41] - **Innovative Approach**: The study utilizes discarded corneal tissue to measure the drug's efficacy, marking a novel approach in the field [41] - **Observational Study**: Concurrently, an observational study is evaluating endpoints like visual quality and corneal edema to inform future clinical studies [42] Financial Position - **Cash Balance**: The company reported over $200 million in cash, providing a runway into 2029 [43] Conclusion - Design Therapeutics is advancing multiple innovative therapies targeting rare genetic diseases, with significant clinical studies planned for 2026. The company maintains a strong financial position to support its research and development efforts.

Core Insights - Design Therapeutics, Inc. is a clinical-stage biotechnology company focused on developing treatments for serious degenerative genetic diseases [2] - The company utilizes its GeneTAC platform to create therapies that target specific disease-causing genes [2] - Upcoming investor conferences will feature management participation in fireside chats, with live webcasts available [1][3] Company Overview - Design Therapeutics is developing a new class of therapies based on GeneTAC gene targeted chimera small molecules [2] - Current clinical-stage programs include DT-216P2 for Friedreich ataxia, DT-168 for Fuchs endothelial corneal dystrophy, and DT-818 for myotonic dystrophy type-1 [2] - The company is also advancing a program for Huntington's disease and exploring multiple genomic medicine discovery efforts [2]