Reflections from ASGCT 2025
He Wishes for the Cloths of Heaven
W. B. Yeats (first published 1899)
Had I the heavens’ embroidered cloths,
Enwrought with golden and silver light,
The blue and the dim and the dark cloths
Of night and light and the half-light,
I would spread the cloths under your feet:
But I, being poor, have only my dreams;
I have spread my dreams under your feet;
Tread softly because you tread on my dreams.
A breakthrough worth noting: an n-of-1 gene-editing therapy. Let’s celebrate the science, but keep patients and their families front-of-mind and proceed with care as we work to reform the business model.
On the flight home from New Orleans, the week’s jazz still echoing in my earbuds, a line from Yeats surfaced—“Tread softly because you tread on my dreams.” It summed up my reflection on the hopes and uncertainties that patients and families carry as they wait for the promise of cell and gene therapies.
A milestone worth celebrating
Professor Kiran Musunuru’s late-breaking CPS1 “N-of-1” base-editing success in baby KJ created much excitement and celebration. Six months from molecular diagnosis to first infusion; ammonia crises averted; a liver-transplant listing cancelled. As blueprints for bespoke in-vivo editing go, this one is pure architectural poetry.
Yet one swallow does not make a summer
Our modelling estimates, visible here pulling on published commercial GT COGs and the three-dose LNP regimen puts the price tag for this breakthrough therapy well north of US $1 million. Even if payers were willing, the bespoke CMC, analytics and logistics cannot be amortised across a wider patient pool today. KJ’s story is a beacon, not yet a bridge.
Voices that kept us grounded
In a powerful fireside panel, patient-advocate Oralea Marquardt reminded us what happens when hopes are shattered after investors pivot and trials are shelved. Prof. Don Kohn recounted how an approved ADA-SCID gene therapy survived only by shifting into a Public Benefit Corporation (Rarity Inc.) when Orchard exited. Dr Claire Booth urged proportionate regulation and innovative reimbursement, warning that repeated withdrawals erode family trust.
Their refrain? Language matters. So does honesty about timelines, affordability, and the probability that your child may not make the inclusion cut.
The industry’s unrequited love story
Capital may flow to platforms that promise scale, not to ultra-rare programmes that demonstrably save lives but defy spreadsheet logic. Until we align payment models and regulatory pathways with clinical value delivered, scientific breakthroughs will continue to outrun commercial reality. Musunuru himself flagged the need for shared reagent banks and harmonised analytics to lower entry costs for single-patient INDs.
Where Lonrú sees light
Platform-ready modular CMC dossiers – codify repeatable elements so every next bespoke therapy starts at 60 % completion.
Outcome-based annuity payments – spread the >$1 M sticker over durability, with claw-backs for under-performance.
Public-interest manufacturing co-ops – echoing Rarity’s public benefit corporation, pool idle academic clean-room capacity for ultra-rare runs.
Digital evidence commons – capture long-term real-world data to sharpen cost-effectiveness arguments and feed adaptive pricing.
Treading softly, but moving forward
Yeats’ plea is our directive: each dataset, each funding decision, each splashy headline lands on someone’s dream. Let’s celebrate KJ’s reprieve without overselling affordability and timelines for every rare disease. Let’s channel the excitement into structural fixes that let breakthrough science and sustainable business models grow in tandem.
At Lonrú, illuminating that path, from innovation to equitable impact is our raison d’être. We invite partners who share this conviction to walk with us, softly but determinedly.
- written by Lonrú Consulting’s Principal and Founder, Caoimhe Nic An tSaoir, PhD MBA
Illuminate your next step. Reach out to explore Lonrú’s VantagePoint™ frameworks.
