Initiate at OW: Round P2 – Fight! DT-216 re-enters clinic with P2 reformulation; improved PK appears positioned to show initial increases in frataxin

Research evidence excerpt

Initiate at OW: Round P2 – Fight! DT-216 re-enters clinic with P2 reformulation; improved PK appears positioned to show initial increases in frataxin

May 12, 2026

How can we differentiate signal from noise in frataxin measures?

Unfortunately, depending on the literature reference, assay used, and

sample source, there appears to be a wide range of estimates of natural,

within-patient variability in frataxin levels. While, as a group, frataxin levels

appear generally consistent over time, this relationship breaks down in very

small sample sizes.

2013 Plasterer reported an assay coefficient of variation (%CV, standard

deviation / mean) of ~16-18% for total frataxin in whole blood, but some

patients showed 50-300% changes over a period of 15 weeks.

2023 Lynch highlights that whole-blood measures can be influenced by

cell counts, which are highly variable; whole-blood measures usually use

whole-blood lysate, platelets provide the majority of mature frataxin in

whole blood, and platelet levels can vary, affecting outcomes and leaving

intracellular protein levels unobservable.

Even Design’s own observational muscle biopsy data from their August

2023 materials show that from one visit to the next, frataxin protein can

vary +/- 25%.

Because of these aspects, we think a 20-30% increase in whole-blood

protein and in muscle is potentially on the cusp of differentiating from

natural within-patient variability, but we would look to patient and cohort

trends for further support.

Our view on the GeneTAC platform holistically: the mechanism is sound,

delivery is key

After extensive diligence across the academic literature, company data, and

our own PK/PD modeling, we believe the biology underlying GeneTAC is

sound, but clinical success depends on optimizing PK: