PYC - General Discussion, page-102

Thanks TB. This news about Dyne Therapeutics provides an excellent example of what is possible for PYC.

Nasdaq-listed Dyne Therapeutics (DYN) has already been identified by PYC as a comparable peer company (see slide below from PYC AGM Presentation, November 2020)



Like PYC, Dyne is an early clinical stage platform technology biotech developing PMO antisense therapies for the treatment of rare genetically-driven diseases. Dyne’s PMO drugs are conjugated with proprietary antigen-binding fragments with the aim of enhancing delivery and hence efficacy while simultaneously using much lower and safer doses than with standard naked antisense drugs. These drugs also offer the potential for less frequent dosing intervals.

Dyne’s pipeline focus is on genetically-driven muscular diseases and its two lead assets, which are at dosing escalation stage in Phase 1/2 trials, target Type 1 myotonic dystrophy (DM1) and Duchenne muscular dystrophy (DMD) amenable to Exon 51 skipping.

Dyne is currently in the news because sources suggest that the company has received takeover interest from larger pharma since releasing its first interim clinical data in its two lead programs on 3 January. The early results were stunning and Dyne immediately seized the opportunity to raise a further US$345m to advance its pipeline. Hence the headline that the company is now “weighing its options” as the company now has more options since its back is no longer against the financial wall. (At Sep 30 2023, Dyne had US$158m in cash and securities and a quarterly cash burn of US$62m.)

Crucially, Dyne’s first clinical data from its two Phase 1/2 trials, both of which commenced in September 2022, have already demonstrated proof-of-concept.

Its first drug, DYNE-101 in DM1, demonstrated early dose-dependent results, including in correction of splicing, the key biomarker for DM1, as well as meaningful improvement in myotonia at the lowest dose.

The initial efficacy data comes from a study in 32 adult DM1 patients in a randomized, placebo-controlled, multiple ascending dose portion of a Phase 1/2 trial and includes 6-month data from the lowest-dose 1.8 mg/kg cohort (n=16) and 3-month data from the next 3.4 mg/kg Q4W cohort (n=16).

Enrolment is now complete through the 5.4 mg/kg Q8W cohort of the trial (48 total patients enrolled), and approximately 300 doses have been administered to date, supporting dose escalation up to 6.8 mg/kg.

The Phase 1/2 global clinical trial consists of a 24-week multiple ascending dose period, a 24-week open-label extension and a 96-week long-term extension. The trial, which is designed to be registrational, is expected to enrol approximately 64 adult patients with DM1.

Dyne’s second drug, Dyne-251 in DMD amenable to exon 51 skipping, reported initial efficacy based on 6-month data from 6 male patients enrolled in the 5 mg/kg cohort of the randomized, placebo-controlled dose-escalating portion of a Phase 1/2 trial trial. Patients were randomized to receive either DYNE-251 (n=4) or placebo (n=2) once every four weeks.

Once every 4-week administration of DYNE-251 reached levels of dystrophin expression, exon skipping and percent dystrophin positive fibres that exceeded levels reported in a clinical trial for the current weekly standard of care for DMD exon 51 (Sarepta's eteplirsen) at 6 months with a 24-fold lower total PMO dose.

Enrolment is now complete through the 20 mg/kg cohort (40 total patients enrolled), supporting dose escalation up to 40 mg/kg.

To date, both drugs have reported favourable safety profiles, with no related serious adverse events reported.

Dyne anticipates reporting data for multiple, higher dose cohorts from both trials in the second half of 2024.

Exactly 3 months ago (27 October 2023), Dyne’s market cap was ~US$400m (A$608m). The market cap climbed to UD$800m at the beginning of this month, just prior to Dyne announcing its interim trial data. While the DYN shareprice initially rose 50% on the positive announcement, the market cap pulled back to US$950 m (A$ 1.45bn) following the capital raise announcement. However, following yesterday’s Bloomberg article suggesting pharma takeover interest, the DYN stock price sharply jumped, with Dyne ending the week with a US$1.9bn (A$2.9bn) market cap.