Nov. 25 at 11:59 PM
$WVE — SUMMARY (vs Peers) going into two major Q4 catalysts, HD and INHBE. While some have intimated that WVE has no assets, its clinical pipeline is rich, albeit with limited patient numbers; they've already established proof of concept with best-in-class in at least one indication.
🧠 Huntington’s Disease (HD) — WVE-003
Wave (WVE-003):
• Best-in-class allele-selective mHTT lowering (~46%) with wtHTT preserved.
• Imaging shows slowed caudate atrophy → real biologic activity.
• Clean safety, reversible dosing, scalable.
Peers:
• PTC518: Strong dataset + Big Pharma partner, but non-selective HTT lowering.
• AMT-130: One-and-done AAV gene therapy, but FDA pushback + neurosurgical risk.
Takeaway:
➡️ WVE-003 is the most precision-targeted HD drug in the clinic.
➡️ Peers have more data, but not the same selectivity or regulatory clarity.
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🫁 AATD — WVE-006 (RNA Editing)
Wave (WVE-006):
• First therapeutic RNA editor in humans.
• Achieves ~13 µM AAT w/ >60% healthy M-AAT; strong Z-AAT reduction.
• Maintains natural physiologic AAT response.
• Reversible & titratable.
Peer (Beam-302):
• Potent DNA base editing; very high M-AAT % early on.
• Permanent genome edits → longer-term safety risk unknown.
Takeaway:
➡️ Wave = safer, reversible editing with real clinical proof.
➡️ Beam = more potent but carries permanent-edit risk.
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💪 Duchenne (Exon 53) — WVE-N531
Wave (WVE-N531):
• ~5.5% unadjusted dystrophin at 24 weeks.
• ~9% muscle-adjusted dystrophin.
• Strong PK + consistent expression across patients.
Peers:
• Viltolarsen: ~5.3% at 25 weeks.
• Golodirsen: ~1% at 48 weeks.
Takeaway:
➡️ Wave matches or beats best-in-class exon 53 drugs.
➡️ Needs larger functional dataset → big upside if confirmed.
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⚖️ Obesity / Metabolic — WVE-007 (INHBE/Activin E)
Wave (WVE-007):
• First-in-human INHBE/Activin E knockdown.
• Up to 85% Activin E reduction.
• 6-month durability from a single dose.
• Weight-loss data expected next.
Peers:
• Arrowhead, Vial, iBio all preclinical or early PD.
• No one else has Wave’s human biomarker dataset.
Takeaway:
➡️ Wave leads the Activin E / fat-selective weight-loss race.
➡️ Massive optionality once weight-loss readouts hit.
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🔥 OVERALL
• Wave has first-in-human wins in RNA editing + INHBE biology.
• Best biomarker clarity in Huntington’s (allele-selective).
• Competitive or superior dystrophin restoration in DMD.
• Peers generally have bigger datasets, but often with more safety or regulatory friction (gene therapy, DNA editing).
