SparingVision Presents Validating Data of its Lead Gene Therapy Programs, SPVN06 and SPVN20, at ESGCT 2022
Data supports progression into first-in-human clinical trial with SPVN06
Paris, October 13, 2022 – SparingVision (“the Company”), a genomic medicine company developing vision-saving treatments for ocular diseases, has presented data on its two lead gene-independent assets, SPVN06 and SPVN20, at the European Society of Gene and Cell Therapies (ESGCT) 29th Congress held in Edinburgh, UK, this week (11-14 October).
In two of the posters, SparingVision presented data from murine models of rod-cone dystrophies (RCDs) which demonstrated proof of concept of the Company’s breakthrough lead gene therapy products, SPVN06 and SPVN20. SPVN06 and SPVN20 act independently of the causative gene mutation and are potentially capable of addressing mutations in the more than 70 genes known to cause retinitis pigmentosa (RP), a leading cause of blindness worldwide and the most common form of RCD.
Following subretinal administration of SPVN06, encoding the short and long forms of the rod-derived cone viability factor (RdCVF/RdCVFL), highly significant slowing-down of visual acuity loss in the treated animals compared to controls was observed. In addition, the subretinal administration of SPVN20, encoding the G protein-coupled inwardly-rectifying potassium channel (GIRK) showed restoration of cone photosensitivity and significant visual improvements in treated animals.
In a third poster, the Company will present the results of nonclinical studies evaluating the toxicology and pharmacokinetics of SPVN06, including its most recent 3-month GLP studies in Non-Human Primates (NHP) which was the driver for setting the clinical dose levels for the planned SPVN06 clinical trial. A No Observed Adverse Effect Level (NOAEL) of 6E10 vg/eye was established in this study and sustained expression of high levels of mRNA transgenes were measured.
In addition, collaborator Charles River presented data showing the successful development and qualification of the early steps of a potency assay for SPVN06.
The data presented at ESGCT supported the Company’s Investigational New Drug (IND) application and Clinical Trial Authorisation (CTA) submission for SPVN06, ahead of its first-in-human trial expected to start before the end of the year.
Mehdi Gasmi. Ph.D., Chief Operating Officer at SparingVision, said: “There is a significant unmet need for people affected by RCDs as there is only one existing therapy addressing a specific gene, benefiting about 1-3% of all RCD patients. Our gene independent treatments, on the other hand, are designed to target a wider array of RCD-affected individuals. The data we are presenting provide further evidence of their potential and we are excited at the prospect of taking our lead candidate SPVN06 to the clinic by the end of the year.”
More details of the presentations can be found below:
Poster Presentation: Gene-independent strategies for cone preservation in inherited rod-cone dystrophies (Poster #P225)
Presenter: Laure Blouin
- Studies provided proof of concept for SPVN06 and SPVN20 as RdCVF/RdCVFL and GIRK gene-independent therapies, respectively, using animal models of rod-code dystrophies (RCD).
- SPVN06: Bilateral subretinal injections at Postnatal Day18 (P18) of SPVN06 at 1E8vg/eye in the rd10 mouse model demonstrated highly significant protection of visual acuity loss at P45.
- SPVN20: Unilateral subretinal injection with AAV-GIRK at P15 in the huP347S+/- mouse model of RP demonstrated improved visual acuity and photopic response as measured by optokinetic reflex and electroretinogram. Results demonstrated functionality of remaining cone opsins which were able to induce a light response when combined with GIRK expression in RP mice and, therefore, provided proof of concept of SPVN20 in restoring photosensitivity in dormant cones.
Poster Presentation: AAV delivery of G protein gated K+ channel increases cone-mediated vision in the rd10 mouse model of Retinitis Pigmentosa (Poster #P219)
Presenter: Hanen Khabou, Ph.D
- In an autosomal recessive model of retinitis pigmentosa (rd10 mouse), the exogenous expression of human GIRK1 F137S in degenerating cones resulted in significant restoration of cone-mediated responses and cortical integration. GIRK1 F137S was selected as a previously described human GIRK1 variant with a point mutation with enhanced properties.
- Improvement of cone function as a result of GIRK channel expression is the underlying mechanism of the SPVN20 gene-agnostic approach to treating RP.
Poster Presentation: Development and qualification of a relative potency assay for SPVN06, a recombinant AAV vector for the treatment of inherited retinal disorders (Poster #P347)
Presenter: Charles River in collaboration with SparingVision
- Data describes the development and qualification of a phase-appropriate, relative potency assay for SPVN06, measuring the levels of mRNA transcripts for RdCVF and RdCVFL compared to a standardized reference control vector.
- The team successfully developed and qualified a relative potency assay (with intermediate precision for RdCVF and RdCVFL of 11.2% and 20.4%, respectively) for use in release testing for batch-to-batch consistency evaluation and in stability studies.
Poster Presentation: Nonclinical safety and pharmacokinetic assessment of SPVN06, an AAV-based gene therapy for the treatment of rod-cone dystrophies (Poster #P228)
Presenter: Anne-Sophie Gautron, Ph.D.
- Three studies (a one-month pilot non-GLP study and two 3-month GLP toxicology and biodistribution studies) in non-human primates (NHP) evaluated dose levels of SPVN06 ranging from 6E9 to 3E11 vg/eye administered via a single bilateral subretinal injection.
- High and sustained levels of SPVN06 and RdCVF/RdCVFL mRNA (up to three months) were measured in the retina, with limited expression in non-ocular tissues and a transient presence in tears and blood.
- Results showed SPVN06 was well tolerated with no-observed-adverse-effect level (NOAEL) of 6E10 vg/eye in the 3-month GLP study, which was the driver for setting the clinical dose levels for the upcoming clinical trial.