Design Therapeutics, Inc. · NASDAQ:DSGN
Design Therapeutics — Investor Presentation (2026)
45 slides from Design Therapeutics's investor presentation, 2026
Slide 1: Designing a Novel Class of Genomic Medicines for Genetic Disorders
DESIGNING A NOVEL CLASS OF GENOMIC MEDICINES FOR GENETIC DISORDERS 3Q 2026 1
Slide 2: Disclaimers
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 no
Slide 3: Challenging the status quo of genomic medicines with small molecules
Challenging the status quo of genomic medicines with small molecules (GeneTAC ® molecules) that dial up or dial down transcription… …to treat significant monogenic disorders BECAUSE WE BELIEVE YOUR FATE DOESN’T HAVE TO BE WRITTEN IN YOUR GENES 3
Slide 4: Advancing four GeneTAC molecule programs
Advancing four GeneTAC® molecule programs Status + Expected Gene Monogenic disease Differentiated profile Market Overview Milestone Timing Friedreich GAA repeat Restoration RESTORE-FA positive $7.3B Ataxia FRATAXIN of endogenous 4-week data Biogen acquired expansion leads to 12-week data 1Q 27 (FXN)
Slide 5: GeneTAC molecules can distribute widely, overcoming a central challenge
GeneTAC® molecules can distribute widely, overcoming a central challenge for traditional genomic medicines GeneTAC® Small Molecule Oligonucleotide Protein Gene Therapy MOLECULAR SIZE 1,000-3000 6,000- 50,000- 4,000,000- (Dalton) 15,000 100,000 5,000,000 Broad distribution LIMITED LIMITED LIMITED Dis
Slide 6: DT-216P2 for Friedreich Ataxia
DT-216P2 for Friedreich Ataxia 6
Slide 7: Pathogenic Cascade in Friedreich Ataxia and Clinical Biomarker Strategy
Pathogenic Cascade in Friedreich Ataxia and Clinical Biomarker Strategy Friedreich Ataxia Healthy 1 FXN DNA 2 FXN pre-mRNA Same endogenous spliced Measured for 3 FXN mRNA mRNA (levels low in FA) supportive data Endogenous blood 4 FXN protein FXN protein primary endpoint 5 Protein function (e.g. Cis-
Slide 8: FA GeneTAC molecules normalized FXN levels in FA patient cells
FA GeneTAC® molecules normalized FXN levels in FA patient cells but did not alter FXN levels in healthy cells GeneTAC® molecules FA PATIENT (two expanded copies) normalized levels Ligand Linker DNA-targeting moiety moiety Relative FXN mRNA (%) 100 DRUG CANDIDATE DNA 50 0 – Drug candidate TRANSCRIPTI
Slide 9: Endogenous blood FXN protein forms the foundation of natural history studies in FA
Endogenous blood FXN protein forms the foundation of the natural history studies in FA Large scale natural history evaluation Conclusion of endogenous blood frataxin protein: • Blood samples taken from patients in the FACOMS and FACHILD natural history “FRATAXIN LEVELS directly correlate studies wit
Slide 10: RESTORE-FA MAD study in FA patients: 4-week cohorts completed
RESTORE-FA MAD study in FA patients: 4-week cohorts completed Weekly Biomarker endpoints Exploratory clinical Dosing duration IV infusion (target cohort size ≥ 4) Endogenous FXN biomarkers endpoints 1. Whole blood mRNA and 1. mFARS2 protein 2. Upright Stability Score 2. Muscle biopsy mRNA and (USS)
Slide 11: Baseline characteristics
Baseline characteristics Cohort 1 Cohort 2 Cohort 3 Cohort 4 Total 0.1 mg/kg IV 0.3 mg/kg IV 0.6 mg/kg IV 1.0 mg/kg IV (N = 16) (n = 4) (n = 4) (n = 4) (n = 4) Age (years), Mean (SD) 43.5 (16.8) 39.5 (5.3) 26.75 (6.7) 34.75 (10.3) 36.125 (11.6) Age at onset (years), Mean (SD) 26.5 (19.9) 18.75 (7.4)
Slide 12: Endogenous FXN Protein: Increases in multiple isoforms of blood frataxin protein
Endogenous FXN Protein: Increases in multiple isoforms of blood frataxin protein Whole blood (FXN-M) Whole blood (FXN-E) Percent of baseline (SE) p = 0.005* p < 0.001* p = 0.002* p < 0.001* 125 ns* 125 ns* 100 100 0.1 mpk 0.3 mpk 0.6 mpk 1.0 mpk 1.0 mpk 0.1 mpk 1.0 mpk 1.0 mpk 2 weeks 4th dose 2 wee
Slide 13: Endogenous FXN mRNA: Increases observed in multiple tissues
Endogenous FXN mRNA: Increases observed in multiple tissues Percent of baseline (SE) 175 p < 0.001* 150 Whole blood 125 Sensitive assay with ns* separation between 100 patients and carriers 0.1 mpk 0.3 mpk 0.6 mpk 1.0 mpk Percent of baseline (SE) 150 p = 0.015* Muscle ns* 125 Confirms activity multi
Slide 14: Historical placebo effect on mFARS and USS
Historical placebo effect on mFARS and USS USS shows the least variability and is resistant to placebo effects Peak mean mFARS placebo cohort effects observed is 3 points 1 point improvement is beyond 95% confidence interval in previous placebo groups Source: Rummey, Christian, et. al. 2026. “Domain
Slide 15: Ataxia measurement: mFARS and upright stability score improvement observed
Ataxia measurement: mFARS and upright stability score improvement observed mFARS Upright Stability Score Worsening p =0.021* p = 0.033* 2 ns* ns* Change from Baseline (SE) Change from Baseline (SE) 1.9 0 0 1.1 0.3 0.0 0.2 0.4 Improving -0.6 -1.0 -1.6 -1.5 -2 -5 -1.8 -4 -4.0 -6.4 -2.7 -3.6 PBO Omav D
Slide 16: Fatigue: Change from baseline in PROMIS fatigue scale
Fatigue: Change from baseline in PROMIS fatigue scale (T-score) PROMIS time course 1.0 mpk Worsening Change from baseline 0.6 mpk (SE) [T-score] 0 0.3 mpk 0.1 mpk Minimal important change = 3 5-point improvement responders -5 5-point improvement Improving (post 4th dose) 1.0 mpk 3/4 p = 0.039* 0.6 m
Slide 17: Safety data
Safety data • DT-216P2 was generally well-tolerated • No serious adverse events • No study discontinuations • All adverse events were mild to moderate • Adverse events possibly or probably considered related to DT-216P2 occurring in more than one patient: • Three patients experienced transient asymp
Slide 18: Possible registration paths – update on registrational plans in 4Q
Possible registration paths – update on registrational plans in 4Q Potential approval frameworks based on Accelerated Traditional Initial approval based on surrogate marker reasonably likely to predict Approval based on clinical efficacy clinical benefit Followed by clinical confirmatory study FXN e
Slide 19: RESTORE-FA Patient Study: 12-week cohorts
RESTORE-FA Patient Study: 12-week cohorts Data following 12 weeks of dosing expected 1Q 2027 • Continuing evaluation Weekly Primary efficacy Dosing duration of 1 mpk as the IV infusion endpoint planned go-forward 1 mpk (50-80 mg) Percent change from 12 weeks plus planned dose in 10 patients baseline
Slide 20: Observations in mFARS across FA landscape
Observations in mFARS across FA landscape (modified Friedreich Ataxia Rating Scale) • The mFARS is a clinician-administered tool to measure neurologic dysfunction and disease progression in FA • Omaveloxolone (SKYCLARYS ) pivotal trial (MOXIE study) used mFARS as the primary endpoint • Omaveloxolone
Slide 21: Activity of FA GeneTAC molecules compared with other compounds
Activity of FA GeneTAC molecules compared with other compounds that have purportedly increased frataxin FXN mRNA (1 day) FXN Protein (3 days) 150 15 FXN (pg/ug protein input) Percent of Healthy Control FXN (%) 100 10 50 5 0 -4 -2 0 2 4 6 0 Log Concentration (uM) H G irin .1u ) R x o l e (3 . 2 u ) h
Slide 22: DT-168 for Fuchs Endothelial Corneal Dystrophy
DT-168 for Fuchs Endothelial Corneal Dystrophy 22
Slide 23: FECD is a progressive corneal disease caused by a single gene mutation
FECD is a progressive corneal disease caused by a single gene mutation in a majority of cases Increasing Endothelial Cell Dysfunction — Loss of cells, pump function, corneal edema Diagnosed by Loss of visual Patient can’t Corneal transplant community optometrist quality stand symptoms surgery ~2M di
Slide 24: DT-168 reduction of nuclear foci observed in primary CECs
DT-168 reduction of nuclear foci observed in primary CECs isolated from patients with FECD with high potency (<5nM foci IC50) CECs treated daily for Nuclei Foci Merge 6 or 14 days with DT-168 Cells taken from discarded FECD Foci per nucleus corneal endothelium used to evaluate Vehicle Percent of unt
Slide 25: DT-168 left wild-type TCF4 transcripts unaffected while improving spliceopathy
Treatment with DT-168 left wild-type TCF4 transcripts unaffected in primary control and FECD CECs while improving spliceopathy TCF4 mRNA Patient-derived FECD CECs + DT-168 Percent of untreated 6d treatment; percent spliced Cells taken from discarded FECD corneal endothelium used to evaluate efficacy
Slide 26: DT-168 Phase 1 SAD/MAD study in healthy participants
DT-168 Phase 1 SAD/MAD study in healthy participants assessed safety, tolerability, and systemic PK • DT-168 eye drops were well-tolerated in all subjects • There were no serious adverse events, no ocular adverse events, or participant discontinuations due to adverse events1 • All observed adverse e
Slide 27: Splicing biomarker is measurable in surgically removed corneal endothelial cells
Splicing biomarker is measurable in surgically removed corneal endothelial cells • Design conducted reference range studies showing consistently different splicing between unaffected eyes and mutant TCF4 FECD surgical samples • Design has developed RNA biomarker measurements potentially suitable Cel
Slide 28: DT-168 Phase 2 biomarker study with data in 2027
DT-168 Phase 2 biomarker study with data in 2027 Objectives: Safety and tolerability; corneal endothelial biomarkers TCF4+ FECD patients FECD corneal endothelium scheduled for surgery Unaffected corneal endothelium Corneal Corneal endothelium endothelium Tissues removed during Tissue from corneal tr
Slide 29: Myotonic Dystrophy Type 1 (DM1)
Myotonic Dystrophy Type 1 (DM1) 29
Slide 30: DT-818 summary
DT-818 summary Summary Phase 1 • Initiated dosing DM1 patients in Phase 1 MAD • DT-818 nominated as development trial of DT-818 candidate for the treatment of DM1 with • Injectable (initially once weekly IV, potential best-in-disease profile; designed to exploring subcutaneous route) selectively tar
Slide 31: DM1 (Myotonic dystrophy type 1)
DM1 (Myotonic dystrophy type 1) 1 Mechanism of disease 2 Preclinical human cells 4 Longer DMPK CTG repeats in affected tissues cause disease Myoblasts Myocytes Myotubes DM1 patient myotube model CTG repeat number Foci = mutant DMPK RNA Sequestered MBNL protein • Similar spliceopathy and repeat lengt
Slide 32: DM1 clinical stage programs
DM1 clinical stage programs Degrading siRNA linked Blocking ASO Blocking ASO RNAi linked to ASO linked to Approach1 to transferrin linked to linked to cyclic targeting transferrin receptor mAb peptide peptide ligand >100kDa >50kDa receptor Fab >10kDa >10kDa >10kDa Stage of Registrational trials Regi
Slide 33: Designing a better DM1 approach
Designing a better DM1 approach Design hypothesis Features designed into DT-818 We believe reduction of toxic foci in human Greater than 90% reduction of toxic foci and myotubes is a better predictor of clinical splicing restoration of splicing in human myotubes biomarker observations – Human geneti
Slide 34: DT-818 foci reduction leads to improvement in splicing regardless of repeat length
DT-818 treatment results in foci reduction, leads to improvement in splicing, regardless of repeat length or patient genetics DT-818 reduces toxic RNA DT-818 corrects splicing in DM1 nuclear foci in DM1 myotubes myotubes Foci per nucleus Splice index Percent change relative to untreated (FISH) Index
Slide 35: DT-818 reduces toxic RNA foci and liberates MBNL1 protein
DT-818 treatment reduces toxic RNA foci and liberates MBNL1 protein in DM1 patient myotubes Vehicle DT-818 Nuclei RNA Foci MBNL1 Foci Merge 35
Slide 36: DT-818 best-in-disease potential for foci reduction in patient cell line
DT-818 treatment shows best-in-disease potential for foci reduction in patient cell line with 2,600 repeats Estimated*1 ~55% Estimated*2 ~30% Foci per nucleus Percent change relative to untreated (FISH) Repeat administration at these dose levels was Repeat administration at these dose levels was fou
Slide 37: DT-818 selectively targets mutant DMPK
DT-818 selectively targets mutant DMPK Allele-specific mechanism spares DMPK protein DM1 patients have two DMPK alleles Mutant allele Healthy allele Percent change relative to untreated Normalized to total protein CTG expansion No CTG expansion DMPK Protein Repeat administration Repeat administratio
Slide 38: Splicing and myotonia improved in HSALR mice treated with DT-818
Splicing and myotonia improved in actin repeat (HSALR) mice treated with DT-818 Vehicle DT-818 Myotonia Foci 38
Slide 39: DT-818 shows good exposure and long half-life
DT-818 shows good exposure and long half-life NHP PK Single IV dose nM DT-818 in plasma Repeat administration at these dose levels was found to be well tolerated 39
Slide 40: DT-818 summary
DT-818 summary Summary Phase 1 • Initiated dosing DM1 patients in Phase 1 MAD • DT-818 nominated as development trial of DT-818 candidate for the treatment of DM1 with • Injectable (initially once weekly IV, potential best-in-disease profile; designed to exploring subcutaneous route) selectively tar
Slide 41: Huntington's Disease (HD)
Huntington’s Disease (HD) 41
Slide 42: GeneTAC molecules selectively reduce mutant Huntingtin and spare the normal allele
Huntington’s Disease (HD) GeneTAC® molecules selectively reduce mutant Huntingtin and spare the normal Huntingtin allele Normal HTT gene — thought to be important to normal state GeneTAC® molecules preserve transcription at the wild type locus • Causes brain atrophy due to death of neurons wtHTT Pol
Slide 43: Allele-specific reductions of RNA and protein in zQ175DN HD mouse model
Allele-specific reductions of RNA and protein observed in the brain in zQ175DN HD mouse model after 8 weeks of systemic administration HTT RNA level in striatum HTT protein level in striatum 13 Note: mice were treated with Candidate 1 or Candidate 2 for 8 weeks, vehicle group treated for 4 weeks. Pe
Slide 44: GeneTAC HD candidates have significant advantages over other HTT lowering approaches
GeneTAC® HD candidates have significant advantages over other HTT lowering therapeutic approaches Allele-selective Non-selective Reduce both normal and Reduce mutant Huntingtin and spare the normal Huntingtin mutant Huntingtin GeneTAC® HD candidates WVE-003 Small molecule ASO Modality Facilitate dru
Slide 45: Strong financial position to enable programs and platform
Strong financial position to enable programs and platform PLATFORM • Proprietary GeneTAC® platform designed to generate blockbuster products with first/best-in-class profiles for severe monogenic disorders • Three clinical-stage programs (FA, FECD, and DM1) in 2026 PROGRAMS o DT-216 restores endogen