Newly launched PulseSight Therapeutics SAS, an ophthalmic biotech company, is planning to develop disruptive non-viral gene therapies with minimally-invasive delivery technology.
First, give me a rundown on PulseSight.
Based in Paris, France, PulseSight launched on Feb. 28 with seed financing from two venture capital funds: Zurich, Switzerland-based Pueros Bioventures, an exclusive investor of private innovative drug companies, and California-based ND Capital, which specializes in investing in disruptive technologies.
Its purpose: to clinically validate its proprietary delivery platform via advancing two first-in-class, late-stage preclinical drug candidates for:
- Wet age-related macular degeneration (AMD)
- Dry AMD
- Includes geographic atrophy (GA)
Now talk about this platform.
The company’s non-viral gene therapy ocular platform encompasses an electro-transfection system (delivery device, really) that delivers DNA plasmids encoding therapeutic proteins into the ciliary muscle in order to treat major eye diseases (including AMD).
How does it work, exactly?
According to PulseSight, the platform features four main components that enable its operations:
- Proprietary DNA plasmid
- Plasmid technology with no cargo size limitation, allowing for safe / long-term expression of therapeutic proteins
- Minimally-invasive administration
- Includes a user-friendly device for introducing plasmid into the ciliary muscle
- Efficient delivery
- Ciliary muscle permeability amplified via electric pulse, allowing plasmid to spread from the muscle to the retina
- Long-lasting protein expression
- Eye generates its own therapeutic proteins (with proven expression in the retina)
Gotcha. Now explain these two programs.
The company’s lead and second programs include:
- PST-809 (wet AMD; lead program)
- Previously known as EYS611
- PST-611 (dry AMD; second program)
Let’s start with PST-809.
What it is: a dual-gene encoding plasmid a potent anti-VEGF, aflibercept, together with decorin—a natural protein with an anti-angiogenic and anti-fibrotic effect (click here for details)—that targets choroidal neovascularization (CNV), vascular leakage, and subretinal fibrosis.
Its potential: improved efficacy in wet AMD patients; improved compliance via reducing need for anti-vascular endothelial growth factor (VEGF) injections.
Its uniqueness: an ability to target both VEGF and VEGF-independent pathways.
And how does it do that?
Per PulseSight, preclinical research has found that “decorin, among other targets, inhibits the TGF-β pathogenic cascade involved in the expression of angiogenic-related molecules and mediating inflammation and subretinal fibrosis formation.”
In other words: by inhibiting or blocking TGF-β signaling, CNV formation is decreased.
Tell me more about this clinical research on PST-809.
PulseSight reported that PST-809 demonstrated efficacy and durability by:
- Exhibiting ongoing reduction in both vascular leakage and CNV lesion size
- Significantly promoted the repair of retinal pigment epithelium (RPE) wounds over CNV lesions
- Indicates potential to promote disease regression and reduce need for retreatment
Gotcha. Now talk about PST-611.
What it is: contains a plasmid that encodes the human transferrin (TF) protein, which is a natural iron transporter involved in controlling the eye’s iron levels (needed for retinal cell metabolism).
- Note: iron overload is linked with degenerative retinal diseases like AMD, retinitis pigmentosa (RP), and glaucoma
Its potential: to effectively address GA / dry AMD-associated complex pathophysiological pathways while simultaneously benefiting from re-treatment only every 6 months.
On a greater scope: potential treatment for other neurodegenerative retinal disorders like glaucoma or RP.
- Note: PST-611 was previously granted the FDA’s Orphan Drug Designation (ODD) in the U.S.
And its preclinical research so far?
PulseSight reported that preclinical experiments across various disease models indicate positive effects of transferrin for the following:
- Removing iron
- Reducing oxidative stress
- Preserving RPE integrity
- Preventing retinal degeneration and vision loss
Lastly, what else should I know?
Take note of the company’s newly appointed team of experts:
- CEO Judith Grecie, PharmD
- Previous CEO of Onxeo; president of Eisai France
- Chief Scientific Officer (CSO) Thierry Bordet, PhD
- Devices Director Alan Wirbisky
- Previously engineering team manager at Flex Medical
- Francine Behar-Cohen, MD, PhD
- Inventor of PulseSight’s technology
- PulseSight Board Independent Chair Dirk Sauer
- Previous head of Ophthalmology a Novartis
See here for additional details.