Sio Gene Therapies Announces Positive Interim Safety and Biomarker Data from Ongoing Phase 1/2 Clinical Study of AXO-AAV-GM1 Gene Therapy in GM1 Gangliosidosis
21 Oktober 2021 - 11:30AM
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, today presented
positive interim data from the Company’s ongoing Phase 1/2 study of
AXO-AAV-GM1, its adeno-associated viral vector (AAV)9-based gene
therapy candidate for the treatment of GM1 gangliosidosis, in an
oral presentation at the European Society of Gene & Cell
Therapy (ESGCT) Virtual Congress 2021, held from October 19-22,
2021. These follow-up data from five Type II (late-infantile to
juvenile) patients in the low-dose cohort and the initial two Type
II patients in the high-dose cohort demonstrate an encouraging
safety profile and a consistent dose-response in disease biomarkers
across the evaluation period.
“Our team continues to lead the industry in the development of a
new, potentially disease-modifying therapeutic option for GM1
gangliosidosis. We are extremely proud of these data, representing
our broadest dataset generated thus far, which support a dose
response and a favorable safety and tolerability profile at both
low and high doses,” said Gavin Corcoran, M.D., Chief R&D
Officer of Sio Gene Therapies. “We observed dose-dependent
responses in two key biomarkers, serum β-galactosidase and
cerebrospinal fluid (CSF) GM1 ganglioside, including normalization
of both biomarkers in the high-dose cohort. Taken together, six out
of seven patients show no evidence of overt disease progression at
the latest timepoint assessed, and we now have a better
understanding of the clinical measures that may serve as important
indicators of efficacy. Based on the results of this ongoing study,
we are working on the continued development of AXO-AAV-GM1 and plan
to engage the FDA to discuss further development, recognizing that
there is currently no approved therapy available for GM1
patients.”
Dr. Cynthia Tifft, Deputy Clinical Director of the National
Human Genome Research Institute (NHGRI) and study Principal
Investigator added, “I have dedicated my career to the care of
patients with GM1 gangliosidosis and to research efforts in the
search for a functional cure. The biomarker dose response and
favorable safety profile is a remarkable finding for the gene
therapy field. I am excited about the potential impact that
AXO-AAV-GM1 may have on the lives of these children and their
families. I look forward to seeing the longer-term data, where we
may have a chance to see not only durable disease stabilization,
but possibly even improvement.”
Key findings:
- Generally well-tolerated at both low and high doses with the
majority of adverse events considered mild to moderate
- To date, there have been no reported serious adverse events
attributed to gene therapy in any patients
- To date, there have been no adverse events leading to study
withdrawal in any patients
- No liver-related adverse events required clinical intervention
or had associated clinical sequelae
- No clinically relevant changes were observed in complement
factors, platelet count or other liver function tests
- Data demonstrate a dose-dependent improvement in key biomarkers
of disease activity: β-galactosidase enzyme activity in the serum
and GM1 ganglioside activity in the CSF
- Serum β-galactosidase activity achieved a normal range,
increasing by 12x and 17x pre-treatment levels, respectively, in
both patients in the high-dose cohort at six months
- All five patients in the low-dose cohort saw a 1.3-2.3x
increase in the same timeframe
- Levels of CSF GM1 ganglioside, the toxic substrate which
accumulates in patients with GM1 gangliosidosis and which is
associated with disease activity, were normalized in both patients
in the high-dose cohort with 42% and 72% reductions, respectively,
at six months
- In the low-dose cohort, a 18-49% decrease was seen in four out
of five patients, and a 19% increase in a single patient was seen
in the same timeframe
- GM1 ganglioside levels were below baseline in all five low-dose
patients at 12 months
- MRI assessment of total brain volume and ventricular volume,
which decrease and increase respectively in the natural history of
the disease, showed the following in the low-dose cohort at 12
months:
- Total brain volume (excluding ventricles) was maintained within
± 5% in all five patients
- Ventricular volume remained within ± 15% in four patients and
increased by 104% in one patient
- There was no clinical evidence of overt disease progression in
four of five low-dose patients at 12 months and both high-dose
patients at six months as assessed by measures of development
including the Vineland-3 Adaptive Behavior and Upright and Floor
Mobility scales
Upcoming Milestones:
- 1H 2022: Expect to provide data update from
Stage 1 of the study, including both Type I (early-infantile) and
Type II patients, at future scientific conferences
- 1H 2022: Expect to engage with the FDA to
review Stage 1 data and discuss next steps for clinical
development
Phase 1/2 Clinical Trial in GM1 Gangliosidosis:
The Phase 1/2 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 a dose of 1.5x1013 vg/kg and the
high-dose cohort is evaluating a dose of 4.5x1013 vg/kg in both
disease sub-types.
Ten patients have been dosed to date in Stage 1 of the clinical
study (including eight Type II patients and two Type I
patients)
- Longer-term evaluation of eight Type II patients in the low-
and high-dose cohort is ongoing
- Two Type I patients have received the low dose of AXO-AAV-GM1,
and screening for enrollment of Type I patients in the high dose
(4.5x1013 vg/kg) cohort is ongoing
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.
Conference Call and Webcast Details:Sio will
host a conference call and webcast today, October 21, 2021, at 8:30
a.m. EDT to review the data, with participation from Sio management
and Guangping Gao, Ph.D., Co-Director of the Li Weibo Institute for
Rare Disease Research, Director of the Horae Gene Therapy Center
and Viral Vector Core, Professor of Microbiology and Physiological
Systems and Penelope Booth Rockwell Professor in Biomedical
Research at UMass Chan Medical School, and Chief AAV Scientific
Advisor at Sio.
Thursday, October 21, 2021, at 8:30 a.m.
EDT
Toll
Free: |
877-407-0792 |
International: |
201-689-8263 |
Conference ID: |
13723622 |
Webcast: |
http://public.viavid.com/index.php?id=146710 |
A replay will be archived on the Company’s website at
www.siogtx.com after the conference call.
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 achieve a broad central
and peripheral biodistribution. Preclinical studies in murine and a
naturally-occurring feline model of GM1 gangliosidosis have
supported AXO-AAV-GM1’s ability to increase 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 UMass Chan 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 Therapies
Sio 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 "expect," "estimate," "may" 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
and outcome of its upcoming clinical and manufacturing 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 occurrence of adverse safety events
during our current and future trials; the development of a
suspension-based manufacturing process for AXO-Lenti-PD; the
scaling up of manufacturing; the outcome of interactions with
regulatory agencies and 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 August 12, 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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