Oppenheimer $SRPT $CATB $PFE $SLDB We've Only Just Begun to Drug
#DMD Effectively
KOL Call Takeaways

On 09/10, we hosted a key opinion leader in the treatment of Duchenne muscular
dystrophy (DMD), Dr. H. Lee Sweeney, to discuss the DMD, its standard of care,
and emerging treatments currently in development. We walked away from the
call with several takeaways: 1) a large unmet in the disease remains with the
current standard of care; 2) CATB's edasalonexent has the potential to replace
steroid use broadly; 3) despite early promise of gene therapy treatments, meaningful
limitations remain (cardiomyopathy). During our call, we covered treatments:
deflazacort (steroid), Sarepta's eteplirsen (exon-skipping), CATB's edasalonexent
(small molecule), alternative exon-skipping agents in development, and gene therapy
programs on DMD.
■ Duchenne muscular dystrophy is a serious X-linked recessive disorder on
dystrophin gene characterized by progressive muscle loss. While the vast majority
(90%) of US patients are identified as 4–6 years of age via creatinine kinase
levels/electromyography (confirmed with genetic testing), this could trend lower
with greater awareness and novel available therapies. Few options (steroids and
eteplirsen) exist, such that patients become wheelchair-bound by adolescence,
ultimately succumbing to cardiomyopathy and loss of pulmonary function.
■ Long-term liabilities from steroids have driven a strong demand by both
physicians and parents for alternative therapies. Dr. Sweeney believes any
therapy that can demonstrate similar efficacy without the liabilities of steroid-use
(e.g., growth issues, weight gain, weak bones, high blood pressure, etc.) would
rapidly become SoC. To compound these issues, steroid use counterproductively
has been associated with muscle atrophy in healthy individuals.
■ This reads favorably for CATB's edasalonexent, which potently inhibits NF-κB
pathway, responsible for the efficacy observed from steroid usage. Edasalonexent
is an oral therapy that could remove the pause physicians and parents have
around steroid's deleterious long-term side effects. Moreover, our KOL suggested
that the long-term efficacy might stack up better than steroids in the long-run (a
reference to the Phase 2 DMD trial's long-term 12- to 72-week results).
■ Despite being "extremely optimistic" for SRPT's gene therapy program,
our KOL remains cautious on the durability of effect and need for redosing (if
possible). Our KOL emphasized the limitations of microdystrophin to protect
muscle, particularly in the case of cardiomyopathy. One solution may be localized
cardiac gene therapy, which would require a significantly reduced quantity of
vector and would target an organ that does not turnover in the same fashion as
skeletal muscle.
■ Due to the heterogeneity of patient response, DMD treatments are likely to
become more personalized consistent with the varying progressions of disease for
patients following diagnosis. That said, the current treatment landscape remains
an opportunity ripe for disruption, via a backbone steroid-sparing agent such as
edasalonexent, exon-skipping agents, or gene therapy, which each could have a
role in advancing the standard of care forward.

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