GenSight Biologics Announces Publication of Positive Safety Data from Phase I/II Trial of GS010 in the JAMA Ophthalmology

Intravitreal administration of GS010 in patients with LHON was safe and
well tolerated

PARIS–(BUSINESS WIRE)–Regulatory News:

GenSight Biologics (Euronext: SIGHT, ISIN: FR0013183985, PEA-PME
eligible), a biopharma company focused on discovering and developing
innovative gene therapies for retinal neurodegenerative diseases and
central nervous system disorders, today announced publication of
detailed safety data from the Phase I/II clinical trial of GS010 in
Leber Hereditary Optic Neuropathy (LHON) patients in the Journal of
the American Medical Association (JAMA) Ophthalmology
. This study
demonstrates that GS010 (rAAV2/2-ND4) is both safe and well
tolerated 2 years after a single unilateral intravitreal administration.

The study was an open-label single-center Phase I/II clinical trial that
included 4 dose-escalation cohorts and an extension cohort. Fifteen
subjects with LHON carrying the ND4-G11778A mutation were
prospectively enrolled. Each subject received a single intravitreal
injection of rAAV2/2-ND4 in the worse-seeing eye. The study
design included an initial follow-up period of 48 weeks, followed by
longer-term follow-up for an additional 4 years. The primary objective
was to ascertain the safety and tolerability of escalating doses of
rAAV2/2-ND4. Secondary objectives included bio-dissemination and
immunogenicity of rAAV2/2-ND4 and evaluation of visual functions.

The analysis included 15 patients (mean [SD] age, 47.9 [17.2] years; 13
men and 2 women) enrolled in the 5 cohorts of the clinical trial.
Thirteen patients experienced intraocular inflammation after rAAV2/2-ND4
administration. Mild anterior chamber inflammation and vitritis were
reported at all doses, and all cases were responsive to treatment. A
maximum ocular inflammation score (OIS) of 9.5 was observed in a patient
with history of idiopathic uveitis. Overall, OIS was not associated with
the viral dose administered. No neutralizing antibodies (NAb) against
AAV2 were detected in aqueous humor before treatment. Two patients
tested positive for cellular immune response against AAV2 at baseline
and after treatment. Humoral immune response was not associated with
either the dose administered or with the immune status of patients at
baseline. No association was found between OISs and serum NAb titers.

Dr. Barrett Katz, Chief Medical Officer of GenSight, commented “Our
findings have implications for all gene therapies employing viral
vectors that are administered intravitreally. The tolerability of our
vector and safety of our drug offer further support for the application
of this technology to future trials. This confirms our confidence in
continuing this journey searching for answers in blinding diseases for
which adequate treatment is wanting.

The publication entitled “Immune Response and Intraocular
Inflammation in Patients With Leber Hereditary Optic Neuropathy Treated
With Intravitreal Injection of Recombinant Adeno-Associated Virus 2
Carrying the ND4 Gene: A Secondary Analysis of a Phase 1/2 Clinical
is available online at

About GenSight Biologics

GenSight Biologics S.A. is a clinical-stage biopharma company focused on
discovering and developing innovative gene therapies for retinal
neurodegenerative diseases and central nervous system disorders.
GenSight Biologics’ pipeline leverages two core technology platforms,
the Mitochondrial Targeting Sequence (MTS) and optogenetics to help
preserve or restore vision in patients suffering from blinding retinal
diseases. GenSight Biologics’ lead product candidate, GS010, is in Phase
III trials in Leber Hereditary Optic Neuropathy (LHON), a rare
mitochondrial disease that leads to irreversible blindness in teens and
young adults. Using its gene therapy-based approach, GenSight Biologics’
product candidates are designed to be administered in a single treatment
to affected eyes by intravitreal injection to offer patients a
sustainable functional visual recovery.

About GS010

GS010 targets Leber Hereditary Optic Neuropathy (LHON) by leveraging a
mitochondrial targeting sequence (MTS) proprietary technology platform,
arising from research conducted at the Institut de la Vision in Paris,
which, when associated with the gene of interest, allows the platform to
specifically address defects inside the mitochondria using an AAV vector
(Adeno-Associated Virus). The gene of interest is transferred into the
cell to be expressed and produces the functional protein, which will
then be shuttled to the mitochondria through specific nucleotidic
sequences in order to restore the missing or deficient mitochondrial

About Leber Hereditary Optic Neuropathy (LHON)

Leber Hereditary Optic Neuropathy (LHON) is a rare maternally inherited
mitochondrial genetic disease, characterized by the degeneration of
retinal ganglion cells that results in brutal and irreversible vision
loss that can lead to legal blindness, and mainly affects adolescents
and young adults. LHON is associated with painless, sudden loss of
central vision in the 1st eye, with the 2nd eye
sequentially impaired. It is a symmetric disease with poor functional
visual recovery. 97% of patients have bilateral involvement at less than
one year of onset of vision loss, and in 25% of cases, vision loss
occurs in both eyes simultaneously. The estimated incidence of LHON is
approximately 1,400 to 1,500 new patients who lose their sight every
year in the United States and Europe.


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