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April, 27 2023 • Articles

SparingVision Presents Progress of its Lead Gene Therapy Program SPVN06 at ARVO 2023

Paris, April 27, 2023 – SparingVision (“the Company”), a clinical-stage genomic medicine company developing vision-saving treatments for ocular diseases,

shares progress in its lead gene therapy program, SPVN06, and research on retinitis pigmentosa. These updates were presented at the Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting, 23-27 April 2023.

In the first of three poster presentations, SparingVision presented nonclinical safety and pharmacokinetic data on its breakthrough gene therapy approach, SPVN06, from three studies conducted in non-human primates (NHPs). The data demonstrated the absorption and shedding of SPVN06, which was transiently observed in blood and tears, and high tropism for the retina). These studies also demonstrated reasonable safety margins across the full clinical dose range, supporting the Company’s ongoing Phase I/II clinical trial of SPVN06, PRODYGY.

Dr Mehdi Gasmi, Chief Operating Officer of SparingVision, said: “We are pleased to have been selected once again to highlight the progress of our lead program SPVN06 at ARVO’s Annual Meeting. The robust preclinical data package that we have built to date, as well as the clinical information collected from our ongoing natural history study PHENOROD2, were instrumental in helping us design our first-in-human Phase I/II clinical trial, PRODYGY. This trial received IND and CTA approval at the end of 2022- early 2023 and is currently enrolling patients.”

The second poster highlighted the importance of appropriate pharmacology animal model selection in order to establish functional proof of concept and inform dose selection, which is especially crucial in gene therapy where patients cannot be redosed. SparingVision evaluated two mouse models of RCD, rd10 and P23H/+, and compared rd10 mice breed in normal light conditions versus darkness. The Company eventually selected the dark-reared rd10 mouse model for the pharmacological assessment of SPVN06, as it provided the appropriate biological framework to evaluate a slow-down in visual acuity upon therapeutic intervention.

In the final presentation, SparingVision provided an update on its ongoing prospective natural history study, PHENOROD2, assessing RCD progression. The Company demonstrated no substantial change in mobility or balance, assessed respectively using a MOST-based modular maze and the Sensory Organization Test (SOT), after two years of follow-up. The impact of RCD on functional vision has not been well characterized to date and these findings indicate that a MOST-based mobility test could be used to indirectly assess cone function; however, it may not be able to capture short-term changes in patients with slowly progressive RCD. Longer follow-up may be needed to allow for the detection of changes in disease progression and inform potential treatment effects in interventional clinical trials, including selecting relevant clinical efficacy endpoints.

More details of the presentations can be found below:

Poster Presentation: Nonclinical safety and pharmacokinetic assessment of SPVN06, an AAV-based gene therapy for the treatment of rod-cone dystrophies

Presenter: Anne-Sophie Gautron, PhD

Three studies were conducted in non-human primates (NHP) in order to evaluate safety and biodistribution upon bilateral subretinal injection of SPVN06 at dose levels ranging from 6E9 to 3E11 vg/eye. This included two 3-month GLP1 studies evaluating SPVN06 absorption, biodistribution and shedding. The safety evaluation showed SPVN06-related ocular changes were found at dose levels ≥1E11 vg/eye and limited to the photoreceptors and RPE2 due to transgene overexpression in the healthy retina and/or overload of vector parties. A transient immune response against the AAV capsid was observed but no immune response against the transgenes was detected. A No Observed Adverse Effect Level (NOAEL) of 6E10 vg/eye was recognized, supporting the clinical dose range for the Phase I/II PRODYGY trial.
[1] GLP: Good Laboratory Practices

[2] RPE: Retinal Pigment Epithelium

Poster Presentation: Mouse model selection for pharmacological evaluation of AAV-based therapeutic agents for the treatment of rod-cone dystrophies (RCD)

Presenter: Melanie Marie, PhD

To assess SPVN06 pharmacological activity, two mouse models of RDC (rd10 and P23H/+) were evaluated. Functional and structural characterization of the retinal generation was performed in both models. While cone and rod function were drastically reduced in both models compared to wild-type (WT) mice, visual acuity was reduced by 25% as early as P38 and ~50% at P45 in rd10 mice which were housed in darkness from birth to P30. In contrast, visual acuity in the P23H/+ model was generally comparable to WT mice until P220. The dark-reared rd10 model was ultimately selected for the definitive pharmacological assessment, with the housing condition enabling rapid onset of retinal degeneration following light exposure, allowing the evaluation of a slow-down of degeneration.
Poster Presentation: Mobility and postural testing in patients with rod-cone dystrophy enrolled in the prospective natural history study PHENOROD2

Presenter: Mylène Poujade

A subset of 30 subjects enrolled in the PHENOROD2 study performed a series of mobility and postural tests using the Artificial Street platform at the Streetlab facility (Paris, France). After 2 years of follow-up, the changes in mobility performance score and postural outcomes were negligible. No significant differences were reported between the three genotypes within the cohort, for mobility or postural assessment. At enrollment, visual acuity was mildly to moderately affected.

**ENDS**