DSGN

• Introduced Design Therapeutics’ GeneTAC small molecule genomic medicine platform, targeting monogenic disorders like Friedreich Ataxia, Fuchs Endothelial Corneal Dystrophy, Huntington’s Disease, and Myotonic Dystrophy.
• DT-216 for Friedreich Ataxia: Took lead molecule into clinical trials, announced new drug product DT-216P2 with improved pharmacokinetics and injection site reaction profile, planning Phase 1 clinical trial in healthy volunteers.
• Fuchs Endothelial Corneal Dystrophy: IND cleared to proceed, plan to initiate Phase 1 development for DT-168 in 2024, and conduct observational study in patients with FECD.
• Huntington’s Disease: Identified small molecule candidates with allele selective reduction of Mutant Huntington expression, plan to choose development candidate.
• Myotonic Dystrophy: Identified compounds with allele selective inhibition of Mutant DMPK, aim to advance to development candidates.

• Plan to conduct Phase 1 clinical trial in healthy volunteers for DT-216P2 to confirm pharmacokinetics and injection site tolerability.
• Initiate Phase 1 development for DT-168 in Fuchs Endothelial Corneal Dystrophy in 2024.
• Choose development candidates for Huntington’s Disease and Myotonic Dystrophy programs.
• Cash runway of approximately $281 million supports generating clinical proof of concept on up to four programs.

No distinct product segments with financial revenue contribution percentages discussed; focus is on programs in Friedreich Ataxia, Fuchs Endothelial Corneal Dystrophy, Huntington’s Disease, and Myotonic Dystrophy.

None explicitly detailed in the transcript provided, but forward-looking statements are subject to risks and uncertainties due to various factors including those described in the risk factors section of the most recently filed Form 10-K.

Q: Could you tell us more about the tissue distribution relative to the plasma distribution for DT-216P2 in all of the relevant tissue types for patients affected by FA? And have you gone back and tested the ISR profile for the original formulation of DT-216, as well as the new one?

A: On the exposure profile, the levels of drug required in tissue are similar to the in vitro EC90. The new drug product DT-216P2 is well behaved with no disconnect between plasma and tissue levels. Non-clinical studies show injection site reactions were attributable to excipients in the prior formulation, and the new formulation resolves injection site issues.

Q: How are you thinking about designing your Phase 1 for DT-216P3? And if you show frataxin expression increases in patients, do you think that might potentially open a path forward for accelerated approval? And should we also expect similar patient numbers to the original SAT in that study?

A: Plan to first conduct a Phase 1 PK study in healthy volunteers to confirm the PK profile of DT-216P2, then conduct patient studies in 2025. No specific comments on FDA accelerated approval path, and no indication of similar patient numbers to original study.

Q: You were working on new method development with respect to frataxin and detection on a protein level. Can you share details on where that methodology stands and timing? And about Fuchs, where does it shake out in terms of measurements for progression or loss of vision?

A: Working on improving measurement of frataxin protein, with robust assays for RNA already in use. For Fuchs, observational study will include measures of visual quality, anterior eye tomography, and microscopic visualization of the corneal endothelium to understand disease progression.