Episode Overview

Podcast: The Blind Life Podcast
Host: Sam Seavey
Guest: John Tobin, Vice President of Clinical Operations at Splice Bio
Episode: Ep. 46 — Splice Bio And The Future Of Vision Loss Treatment | Gene Therapy For Stargardt Disease
Date: September 9, 2025

Theme:
Sam Seavey welcomes John Tobin from Splice Bio to discuss the latest advancements in gene therapy for Stargardt disease, focusing on Splice Bio's cutting-edge approach. They explore how the company’s innovative technology could halt the progression of vision loss, the importance of genetic testing, and how listeners can participate in these groundbreaking studies.

Key Discussion Points & Insights

1. John Tobin’s Background and Role at Splice Bio

• John has worked in the pharmaceutical and biotech sector for 30 years, with the last decade focused on inherited retinal disease and gene therapy (01:35-02:33).
• His experience spans multiple medical areas, ultimately specializing in ophthalmology and rare retinal diseases.

2. About Splice Bio

• Splice Bio is a growing biotech company based in Barcelona, with around 45–50 people, dedicated to gene therapies for ophthalmology, especially for rare diseases caused by mutations in large genes like ABCA4 (02:42-05:40).
• John is based near London but frequently collaborates with the Barcelona team.

3. Gene Therapy for Stargardt Disease: The Science & Innovation

• The Problem:
  • Stargardt's is caused by mutations in the ABCA4 gene, which is notably large, with hundreds of possible mutations (06:44-07:40).
  • The ABCA4 protein helps clear toxic waste byproducts from the retina’s visual cycle. Without it, cells get sick and die.
• The Challenge:
  • Viruses used as gene therapy vectors have a limited capacity and can’t naturally carry the entire ABCA4 gene.
• Splice Bio’s Solution:
  • They split the gene into two fragments, package each into separate vectors, and inject both (07:40-11:46).
  • Extra DNA is added that acts as “glue” (technically called an intein) to re-join the protein halves inside cells—this process is called “splicing,” thus the name Splice Bio.
• Goal:
  • Enable production of a functioning ABCA4 protein inside photoreceptor cells to halt progression of Stargardt’s.
• Efficacy:
  • Designed to be a “one and done” treatment; the new gene sequence should persist and function for the life of the cell (13:05-13:58).

Quote:

*"The gene, that sequence of DNA, will sit in the cells for the rest of the patient's life in theory... You only need one injection into the eye." — John Tobin (13:14)

4. Realistic Expectations: Curing or Halting Vision Loss

• The best possible outcome is to arrest further degeneration rather than regain already lost vision, since dead photoreceptor cells cannot be revived (13:58-14:54).
• Early intervention, ideally at diagnosis or before significant cell loss, is most effective.

Quote:

*"If we can arrest that growth completely, then that really is ideal. If we can slow the growth down significantly so it makes a difference to the subjects, that's a good outcome as well." — John Tobin (14:10)

5. The Clinical Development Program: Polaris and Astra Studies

• Polaris Study:
  • Observational (“natural history”) study to collect data on the disease’s progression and refine outcome measurements before commencing gene therapy. Participants attend frequent follow-ups (17:27-20:09).
  • This preparation ensures trials are well-targeted and informative.
• Astra Study:
  • The ongoing gene therapy clinical trial, focused initially on verifying safety, then progressing to efficacy as more subjects are enrolled and data accrue.

Quote:

*"Before we even embark on a gene therapy trial, we run an observational trial ... bring the patients in, get them into a study, and then have them visit ... pretty regularly, and start to really start to understand, you know, what their progression looks like." — John Tobin (17:27)

6. Who Can Participate & Global Scope

• Sites are active in both the US and Europe. Patients from other regions can be considered if records and diagnosis are verified; Splice Bio covers travel for eligible participants (20:36-22:31).
• Genetic testing is strongly advised for anyone interested in participating or for those with inherited retinal disease in general.

Quote:

*"The importance of getting genetically tested is really important ... You've got a real advantage if you've got a genetic report that can tell a doctor ... exactly what your genetic profile is." — John Tobin (21:49)

• For Splice Bio’s Stargardt's therapy, the approach is "mutation agnostic"—any ABCA4 mutation qualifies, unlike other platforms that target only specific variants (24:38).

7. Altruism and Innovation in Clinical Studies

• Participation in clinical studies is described as “an altruistic act”—it benefits both current patients and future generations (22:33-23:45).
• The importance of ongoing research and volunteer participants is emphasized.

Quote:

*"They are really consistently the heroes in this environment because without them, we've got no chance, and generations to come have got no chance." — John Tobin (23:10)

8. Critical Advice: Get Genetic Testing

• Genetic testing is sometimes free and critical for knowing eligibility for trials and treatments.
• Testing technology is always improving, so retesting in future years may reveal more precise information (24:38-25:49).

Quote:

*"Talk to your geneticists as well, because the genetic testing that you may do today, in 5, 10 years' time will be far more improved and they'll get even more information." — John Tobin (25:35)

Notable Quotes & Memorable Moments

• On Splitting the Gene:

  • “We cut the gene in half ... and then inject both halves into the patient ... Once in the cell, those two bits of glue then go looking for each other like a plus or minus on a magnet.” — John Tobin (09:44)

• On Participation:

  • “We’re inviting [participants] to take part ... for hopefully what will be the good of them, but more often the good of their kids, the good of the generations to come, and just the benefit of medical advancements.” — John Tobin (23:13)

• On the Origin Story of Splitting Genes:

  • [Joking about a kid suggesting splitting the gene:]
    “I’ve never heard it, but I’m going to say yes because it’s a good story. And kids are smart, right? ... There’s probably all these really very clever scientists all thinking the same thing, but too scared to come up with it because it’s a stupid idea. But, no, it’s a brilliant idea.” — John Tobin (16:43-17:22)

How to Learn More or Participate

• Visit: www.splice.bio and fill out the clinical interest form.
• Email: clinicaltrials@splice.bio
• Mention “The Blind Life” when applying as a study source.
• Investigational sites in the US and Europe—travel from other regions can be arranged, eligibility permitting (20:36-22:31).

Timestamps for Important Segments

• 01:35 — John Tobin’s background and focus on ophthalmology
• 02:42 — Introduction to Splice Bio’s mission and technology
• 06:44 — Stargardt’s disease and gene therapy basics
• 09:44 — The innovation of splitting the gene and splicing technology
• 13:05–13:14 — “One and done” potential of the treatment
• 14:10 — Discussion of realistic outcomes: halting vs. reversing vision loss
• 17:27–20:09 — The structure of Polaris (observational) and Astra (treatment) studies
• 21:49 — Critical importance of genetic testing
• 22:33–23:45 — On the altruism and importance of clinical research volunteers
• 24:38–25:49 — Mutation-agnostic therapy and evolving genetic testing

Final Takeaways

This episode delivers a hopeful and detailed view of how gene therapy is advancing for inherited retinal disease, specifically Stargardt’s. Splice Bio’s unique technology may halt vision loss with a single treatment, regardless of the mutation type, bringing long-awaited optimism to the blind and visually impaired community. Both guests emphasize the vital importance of genetic testing and the selfless contributions of trial participants in driving medical breakthroughs forward.