Sio Gene Therapies Announces CSF Reductions in GM1 Ganglioside from Clinical Trial of AXO-AAV-GM1 Gene Therapy
May 13 2021 - 7:00AM
Sio Gene Therapies Inc. (NASDAQ: SIOX), a clinical-stage company
focused on developing gene therapies to radically transform the
lives of patients with neurodegenerative diseases, will present new
biomarker data from the Company’s study of AXO-AAV-GM1, its
adeno-associated viral vector (AAV)9-based gene therapy candidate
for the treatment of GM1 gangliosidosis, at the 24th Annual Meeting
of the American Society of Gene & Cell Therapy (ASGCT), today,
May 13, 2021 at 6:15 PM EDT.
Dr. Cynthia Tifft, Deputy Clinical Director of the National
Human Genome Research Institute (NHGRI) and Principal Investigator
in the study, will review patient-level data on safety and efficacy
at six-months follow-up from the low-dose cohort of the Company’s
ongoing Phase 1/2 clinical study, with a focus on new six-month
biomarker data from cerebrospinal fluid (CSF).
Previously reported data from the clinical study demonstrated
that AXO-AAV-GM1 was well-tolerated with a favorable safety profile
and provided early indications of clinical disease stability. In
the low-dose cohort, five patients with late-infantile and juvenile
GM1 gangliosidosis received a 1.5x1013 vg/kg intravenous (IV)
infusion of AXO-AAV-GM1. At 6 months following gene transfer, serum
beta-galactosidase enzyme activity approximately doubled and was
restored to 23-57% of the lower limit of the normal reference range
in the low-dose cohort. All five children demonstrated signs of
clinical stabilization as assessed by measures of development
including the Vineland-3 Adaptive Behavior, Upright and Floor
Mobility, and Clinical Global Impression scales. To date, there
have been no serious adverse events attributed to gene therapy in
any patients receiving either the low-dose or the high-dose of
AXO-AAV-GM1.
“AAV9 is one of the best-studied vector systems currently in
development. These new 6-month CSF biomarker data are an important
update to the growing body of evidence for AXO-AAV-GM1 where we now
provide direct evidence of biodistribution and biochemical effect
in the CNS at the lowest dose, similar to what we saw in prior
translational studies with naturally occurring animal models,” said
Gavin Corcoran, M.D., Chief R&D Officer of Sio Gene Therapies.
“Intravenous administration is likely to impact the disease in the
periphery, where the disease burden is substantial. Today’s CSF
data, indicating a biomarker response in the CNS, provides the
first indication that intravenous administration of AXO-AAV-GM1 may
be able to treat both the systemic and neurological manifestations
of this progressive, multisystem disease. We are proud to continue
to lead the way in the development of a potentially transformative
treatment for patients and families affected by GM1 gangliosidosis
and look forward to the upcoming 12-month data readout later this
year to provide further evidence regarding the durability of our
AAV9 gene therapy and its potential to slow or halt the progression
of GM1 gangliosidosis.”
Key findings from the new biomarker
analysis:
- 18-49% reductions from baseline in accumulated substrate, GM1
ganglioside, were observed in CSF of 4 out of 5 children in the
low-dose cohort at 6 months
- 3 out of 5 children demonstrated CSF GM1 ganglioside levels
less than 100 ng/mL at the 6-month follow-up visit
- One child, whose disease was the most advanced at baseline and
who worsened on certain clinical parameters, exhibited an increase
in CSF GM1 ganglioside of 19% from baseline at 6 months
- Literature reported mean levels of normal GM1 ganglioside in
CSF range from 29.7- 52.3 ng/ml in healthy children 1 month to 18
years of age (Izumi 1993, Kaye 1992, Ginns 1980)
- These data represent the first direct evidence in humans that
intravenously administered AXO-AAV-GM1 gene therapy exerts a
measurable biochemical effect on GM1 ganglioside accumulation
within the central nervous system (CNS)
- Builds upon previous findings of widespread CNS transfection,
disease modification, and improved survival in naturally occurring
feline models. These preclinical studies suggest progressive
normalization of GM1 ganglioside content in brain regions beginning
at 4 months after intravenous gene therapy (when animals were 5
months of age) and continuing until 42 months of age
- Additional evidence from a murine model of GM1 gangliosidosis
suggests that the blood-brain barrier is more permeable than
healthy controls due to local neuroinflammation (Jeyakumar 2003),
supporting the view that intravenous (systemic) administration of
AAV9 may enable widespread CNS distribution in GM1
gangliosidosis
Dr. Tifft said, “These data are highly encouraging and
underscore the potential of Sio’s gene therapy program for GM1
gangliosidosis. I have been involved in the clinical and research
aspects of this disease for more than 10 years and have seen
first-hand a disease that only gets worse, so I am proud to share
this clinical update for a trial where we have seen kids remain
stable and most children have shown some overall improvement.”
Upcoming Milestones
- 12-month data from the low-dose cohort in the second half of
2021;
- 12-month data from the first two children dosed in the
high-dose cohort in Q1 2022; and
- In the first half of 2022, meeting with the U.S. Food and Drug
Administration to discuss the registrational pathway for
AXO-AAV-GM1
The clinical study (NCT03952637) is designed to evaluate the
safety, tolerability, and potential efficacy of AXO-AAV-GM1
delivered intravenously in children with Type I and Type II GM1
gangliosidosis. Stage 1 is a dose-escalation study in which the
low-dose cohort is evaluating 1.5x1013 vg/kg and the high-dose
cohort is evaluating a dose of 4.5x1013 vg/kg in early infantile,
late infantile, and juvenile children.
GM1 gangliosidosis is a progressive and fatal pediatric
lysosomal storage disorder caused by mutations in the GLB1 gene
that cause impaired production of the β-galactosidase enzyme.
Currently, there are no FDA-approved treatment options for GM1
gangliosidosis.
About AXO-AAV-GM1
AXO-AAV-GM1 delivers a functional copy of
the GLB1 gene via an adeno-associated viral (AAV) vector,
with the goal of restoring β-galactosidase enzyme activity for the
treatment of GM1 gangliosidosis. The gene therapy is delivered
intravenously, which has the potential to broadly transduce the
central nervous system and treat peripheral manifestations of the
disease as well. Preclinical studies in murine and a
naturally-occurring feline model of GM1 gangliosidosis have
supported AXO-AAV-GM1’s ability to improve β-galactosidase enzyme
activity, reduce GM1 ganglioside accumulation, improve
neuromuscular function, and extend survival.
AXO-AAV-GM1 has received both Orphan Drug Designation and Rare
Pediatric Disease Designation from the Food and Drug
Administration and is the only gene therapy in clinical
development for all pediatric forms of GM1 gangliosidosis.
In 2018, Sio licensed exclusive worldwide rights from
the University of Massachusetts Medical School for the
development and commercialization of gene therapy programs for GM1
gangliosidosis and GM2 gangliosidosis, including Tay-Sachs and
Sandhoff diseases.
About Sio Gene TherapiesSio Gene
Therapies combines cutting-edge science with bold imagination
to develop genetic medicines that aim to radically improve the
lives of patients. Our current pipeline of clinical-stage
candidates includes the first potentially curative AAV-based gene
therapies for GM1 gangliosidosis and Tay-Sachs/Sandhoff diseases,
which are rare and uniformly fatal pediatric conditions caused by
single gene deficiencies. We are also expanding the reach of gene
therapy to highly prevalent conditions such as Parkinson’s disease,
which affects millions of patients globally. Led by an experienced
team of gene therapy development experts, and supported by
collaborations with premier academic, industry and patient advocacy
organizations, Sio is focused on accelerating its candidates
through clinical trials to liberate patients with debilitating
diseases through the transformational power of gene therapies. For
more information, visit www.siogtx.com.
Forward-Looking Statements
This press release contains forward-looking statements for the
purposes of the safe harbor provisions under The Private Securities
Litigation Reform Act of 1995 and other federal securities laws.
The use of words such as “believe,” "estimate, " “may be,” and
other similar expressions are intended to identify forward-looking
statements. For example, all statements Sio makes regarding costs
associated with its operating activities, funding requirements
and/or runway to meet its upcoming clinical milestones, and timing
of its upcoming clinical milestones are forward-looking. All
forward-looking statements are based on estimates and assumptions
by Sio’s management that, although Sio believes to be reasonable,
are inherently uncertain. All forward-looking statements are
subject to risks and uncertainties that may cause actual results to
differ materially from those that Sio expected. Such risks and
uncertainties include, among others, the impact of the Covid-19
pandemic on our operations; the actual funds and/or runway required
for our clinical and product development activities and anticipated
upcoming milestones; actual costs related to our clinical and
product development activities and our need to access additional
capital resources prior to achieving any upcoming milestones; the
initiation and conduct of preclinical studies and clinical trials;
the availability of data from clinical trials; the development of a
suspension-based manufacturing process for Axo-Lenti-PD; the
scaling up of manufacturing, the expectations for regulatory
submissions and approvals; the continued development of our gene
therapy product candidates and platforms; Sio’s scientific approach
and general development progress; and the availability or
commercial potential of Sio’s product candidates. These statements
are also subject to a number of material risks and uncertainties
that are described in Sio’s most recent Quarterly Report on Form
10-Q filed with the Securities and Exchange Commission on February
9, 2021, as updated by its subsequent filings with the Securities
and Exchange Commission. Any forward-looking statement speaks only
as of the date on which it was made. Sio undertakes no obligation
to publicly update or revise any forward-looking statement, whether
as a result of new information, future events or otherwise, except
as required by law.
Contacts:
Media
Josephine Belluardo, Ph.D. LifeSci Communications(646)
751-4361jo@lifescicomms.cominfo@siogtx.com
Investors and Analysts
Parag V. MeswaniSio Gene Therapies Inc.Chief Commercial
Officerinvestors@siogtx.com
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