Why Multiple Drug Programs for Phelan-McDermid Syndrome need to be Moving Forward at Once
If you've recently received more invitations than usual to join clinical research or drug trials for Phelan-McDermid syndrome (PMS), you're not imagining it. Four different drug programs are now in or approaching human testing — at the same time. That's not a coincidence, and it's not a sign that the field is scattered or unfocused. It's a deliberate strategy that rare-disease researchers, drug developers, and investors call taking multiple shots on goal: pursuing several different scientific approaches in parallel instead of betting everything on one.
Here's what's happening, why it's happening, and why families should see it as good news.
The Four Programs Currently in Motion
Two PMS-specific drug trials are already in the public eye:
Ercanetide (NNZ-2591) — an oral medication from Neuren Pharmaceuticals
JAG201 — a SHANK3 gene therapy from Jaguar Gene Therapy
Two more are close behind, expected to enter clinical trials soon:
PYC-002 — an antisense oligonucleotide, or ASO, from PYC Therapeutics
BA102 — a small-molecule drug from NeuroNOS
How These Four Approaches Differ — and Why That's a Strength
Although all four programs aim to help people with PMS, they work in genuinely different ways, and that's the point:
The gene therapy delivers a synthetic copy of the SHANK3 gene to boost protein levels directly.
The ASO doesn't add a new gene copy — it helps the body use the existing gene copy more efficiently.
Ercanetide and BA102 take a different approach altogether, aiming to repair downstream biological processes that go wrong when SHANK3 is reduced, rather than targeting the gene itself.
Because clinical drug trials specifically for PMS are still quite new, no one yet knows how well any single treatment will work across the full spectrum of PMS, or whether combining treatments might work even better. Each clinical trial can only test one drug at a time — but once drugs are approved, physicians are free to prescribe more than one. That opens the door to combination treatment in real-world practice, not just in trials.
There's a helpful comparison already playing out in another genetic disorder: spinal muscular atrophy (SMA). Three different SMA drugs are now approved in the U.S. — a gene therapy, an ASO, and an oral medication — and real-world experience shows they often serve different roles at different points in a patient's life, with combination treatment becoming increasingly common.
Why Multiple Shots on Goal Matter for PMS Families
For the PMS community, the urgency here isn't abstract — there are currently no approved treatments for PMS. Every additional program in development is another chance that something eventually reaches approval.
It also reflects a basic biological reality: PMS isn't one uniform condition. Deletion size varies from one person to the next, some individuals have a SHANK3 sequence changes rather than a deletion, and the presentation of the condition may vary across different ages and stages of life. A single mechanism is unlikely to serve the whole community equally well. Having several approaches in development at once gives different people with PMS a better chance that one of them will be the right fit.
How Biopharma Companies and Investors See It
"Multiple shots on goal" isn't just a hopeful phrase — it's an established strategy in rare disease drug development and investing. Different treatment approaches carry different risks, different manufacturing challenges, and different regulatory paths, so companies working on PMS aren't really racing head-to-head against each other. They're each filling a different niche in a field where the need is still far from met.
For investors, deliberately funding several different approaches for the same disease — rather than concentrating on one — is now considered a sound, well-established way to manage risk. CureSHANK's long-term vision reflects exactly this: supporting PMS drug programs that use different strategies, different technologies, and sit at different stages of development, so the investment community sees a portfolio of opportunities rather than a single high stakes bet.
A Model From a Related Rare Disease: Angelman Syndrome
PMS isn't the first rare neurodevelopmental disorder to take this approach. The Angelman syndrome patient advocacy group, FAST, has built a network of drug developers running more than a dozen programs — spanning gene therapy, ASOs, gene editing, RNA interference, enzyme replacement, and small molecules. The goal is explicit: de-risk the field as a whole, rather than concentrate hope on a single program.
Notably, three different companies currently have separate ASO programs for Angelman syndrome in final-stage clinical testing, with the hope that at least one will become commercially available soon.
How CureSHANK Is Driving This Strategy for PMS
CureSHANK is working with every drug developer currently active in the PMS field — named and not-yet-named — with one shared goal: keeping all partners moving forward and progressing toward real treatments. To support this further, CureSHANK has launched a Drug Development Accelerator, aimed at encouraging even more innovation and diversity of approach.
Across patients, companies, and investors, the reasoning all points the same direction, even if each group arrives there differently: patients need it because PMS isn't a uniform disease; biopharma companies need it because no single approach has proven itself yet, so the risks of the science and the risks of the technology should be spread separately; and investors need it because, in rare disease, portfolio-level risk is best managed through multiple, independent shots — not a single asset riding on one outcome.
Ralf Schmid is the Chief Scientific Officer (CSO) at CureSHANK and can be reached at research@cureshank.org
