From Lab Trick to Clinical Program: The Splice Bio Story (and the Playbook Behind It)

Split inteins, subretinal first, ruthless execution—and a syndicate built across time zones: how Splice Bio got from slide to surgery.

TL;DR

In a hurry? Here are the essentials at a glance:

• Start with a real edge: split-intein AAV overcomes cargo limits where it matters.

• Pick a tractable first proof: subretinal delivery in Stargardt disease, not systemic DMD.

• Treat seed as an execution test: spend ~€2M to turn in vitro promise into in vivo data.

• Syndicate for the long haul: $57M Series A (NEA, UCB Ventures, Gilde, Novartis VF, Ysios), then a global Series B (EQT, Sanofi, RO).

• Founder <> VC compact: team proposes, board pressure-tests; investors don’t operate.

• Go global on capital: diverse geographies = perspectives, talent pipelines, and follow-on $$.

• Expect (many) no’s; learn without taking it personally—and don’t pitch your #1 first.

• Execution, resilience, and small wins compound into the next round.

Session summary with Sylvain Sachot (Partner, Asabys Partners) and Miquel Vila-Perelló (Co-founder & CEO, Splice Bio).

From academia to company: the split-intein insight

Protein splicing began as a lab trick at Princeton—great for making complex proteins, but the killer app emerged elsewhere: gene therapy. Split inteins could reassemble over-large genes inside cells, neatly side-stepping AAV’s cargo cap.

“In gene therapy… our technology basically solved a key problem… the limited cargo capacity of AAVs.” —Miquel Vila-Perelló

The team re-focused from immuno-oncology conjugates to gene therapy, re-branding ProteoDesign to Splice Bio and re-incorporating with new backers.

Picking the first hill to climb

Early on, DMD was tempting (dystrophin is huge). But systemic delivery multiplies risk, cost, and CMC complexity. Splice Bio and Asabys chose a different first hill: ophthalmology—small volumes, local administration, clear readouts.

“The idea was to prove inteins in gene therapy—not prove inteins in IV systemic gene therapy… go subretinal, low dose, and show it works.” —Sylvain Sachot

They selected Stargardt disease (inherited retinal dystrophy) as the first indication, where the platform’s size advantage is decisive and development risk more contained.

Seed as execution test: ~€2M to in vivo

The seed was small—about €2M—and the brief was clear: turn in vitro promise into in vivo data and show the team can execute on plan, budget, and time.

“Investors eventually invest a lot of money—but first they need to see you do what you said you’d do. That’s how trust is built.” —Miquel Vila-Perelló

The company ran lean experiments with EU/US partners, while quietly sketching the people and plans needed for the next phase.

Series A before the window shut

In 2022—just before markets tightened—Splice Bio closed a $57M Series A led by UCB Ventures and Ysios, with NEA’s first investment in Spain, Gilde Healthcare, and Novartis Venture Fund.

“It wasn’t just the size—it was the quality of partners…and having existing investors continue is a big validation.” —Miquel Vila-Perelló

The raise funded completion of non-clinical packages, IND/CTAs (US/EU), and the build-out of clinical, regulatory, and CMC teams.

Series B and first-in-human

With clinical ops in place, the company dosed its first Stargardt patient and expanded sites across the US and Europe. A global Series B brought in EQT, Sanofi, and RO Venture Fund, with strong insider support.

“Our focus now is executing Phase 1/2 readouts—safety and efficacy are the next value inflection points—while advancing a focused pipeline in ophthalmology and select neuro areas.” —Miquel Vila-Perelló

The platform continues to broaden, but with discipline: local administration first, then adjacencies (e.g., inner ear), avoiding “beautiful platform, no product” traps.

How VCs decided to keep leaning in

Continuation wasn’t automatic; it was earned. Data quality, on-time/on-budget delivery, and organizational scaling from 4 people to dozens mattered.

“We were already convinced on AAV cargo limits; the question was: does this team scale the company as well as the science? The answer was yes.” —Sylvain Sachot

Syndicate signals helped too: corporates joining, new global funds anchoring, and insiders re-upping.

Roles and boundaries: who proposes, who challenges

Founders propose; boards interrogate. Investors see patterns and share ideas, but they’re not operators.

“The expectation should be that management comes with the plan. If it’s bold, we’ll debate it—but investors shouldn’t run the company.” —Miquel Vila-Perelló

That clarity kept brainstorming productive and accountability intact—even on unconventional paths.

Go global on capital (and perspective)

A cross-border cap table brought differing lenses, talent networks, and deeper follow-on capacity.

“As broad as possible—more pockets for talent, more pockets for money… and better board debates.” —Sylvain Sachot

Caveat: align with any non-dilutive schemes that have shareholder restrictions; otherwise, global is upside.

How many no’s? A lot. What to do with them.

Outreach was founder-led; “cold” approaches were rare. The count? Dozens and dozens of no’s at seed; still many at A/B.

“You need thick skin. Most no’s aren’t about you—portfolio fit, timing, prior exposure… learn, don’t take it personally.” —Miquel Vila-Perelló

Tactical tip: don’t open with your #1 target—practice the pitch first.

If we did it again: what would change?

The process worked, but in today’s environment the team would start even earlier—and plan for longer cycles.

“Maybe we underestimated how long it would take. Investors want to see the movie, not a picture.” —Miquel Vila-Perelló

Personal note: protect the CEO’s energy. Burnout is the worst outcome for everyone.

FAQ