The Visual Cycle and Why It Fails
Every act of vision begins with a photon striking a photoreceptor cell in the retina. That photon is captured by a molecule called retinal, which is bound to a protein called opsin. The interaction between retinal and opsin triggers a cascade of electrochemical signals — the visual cycle — that ultimately produces the experience of sight.
In a healthy eye, this cycle runs continuously and efficiently. In patients with inherited retinal diseases, a genetic mutation disrupts one or more steps in this process. The photoreceptors degrade. Vision deteriorates. In many cases, the patient eventually loses sight altogether.
The conditions All Model Pty Ltd is targeting all share this common mechanism: photoreceptor degeneration caused by dysfunction in the visual cycle.
Target Conditions
Leber Congenital Amaurosis (LCA) is one of the earliest-onset inherited retinal dystrophies, causing severe visual impairment from birth or early infancy. It is caused by mutations in any of more than 25 genes involved in photoreceptor function and the visual cycle. There is currently only one approved gene therapy for one genetic subtype of LCA (voretigene neparvovec, approved by the TGA and FDA for RPE65-associated LCA). The vast majority of LCA patients have no approved treatment.
Stargardt disease is the most common inherited macular dystrophy, affecting approximately 1 in 8,000 to 1 in 10,000 people. It is caused primarily by mutations in the ABCA4 gene, which leads to toxic accumulation of byproducts in the retinal pigment epithelium and progressive loss of central vision. No approved treatments currently exist.
Retinitis Pigmentosa (RP) is a group of inherited disorders causing progressive degeneration of the rod photoreceptors, leading to night blindness followed by loss of peripheral and eventually central vision. RP affects approximately 1 in 4,000 people worldwide. It is one of the leading causes of blindness in working-age adults, and no disease-modifying treatments are approved for most genetic subtypes.
A Differentiated Approach
Every current competitor in the opsin therapeutic space — including programmes at GenSight Biologics, Bionic Sight, and Nanoscope Therapeutics — delivers opsin-encoding genes into retinal cells using adeno-associated virus (AAV) vectors. This gene therapy approach has significant limitations: it requires complex viral vector manufacturing, it cannot easily be re-dosed, it carries immunogenicity risks from the viral vector itself, and the regulatory pathway for novel gene therapies is less predictable than for small molecules.
All Model Pty Ltd's approach is structurally different. Rather than delivering opsin-encoding DNA, the company is developing retinal analog compounds — molecules that function like retinal, the natural chromophore at the centre of the visual cycle. Beginning with peptides that mimic opsin function and graduating to small molecule mimetics, this approach offers several meaningful advantages:
- Re-dosable — small molecules can be administered repeatedly, allowing dose optimisation and ongoing treatment rather than a single irreversible intervention
- Lower manufacturing complexity — chemical synthesis is more scalable than viral vector production, which faces significant global capacity constraints
- Familiar safety profile — small molecules carry a well-characterised risk profile for prescribers and regulators
- Open IP landscape — while competitors are claiming the opsin protein sequence space via gene therapy patents, the peptide and small molecule mimetic space remains substantially open
The Compounds
All Model Pty Ltd has synthesised two novel retinal analog compounds — 8-0-3b and 3-0-8a — each representing 50 per cent of the therapeutic mixture. Both are retinal analogs that function like retinal: they absorb light and are capable of initiating the visual cycle in the eye. Both are patent pending worldwide.