Cassava Sciences, Inc. (Nasdaq: SAVA), a biopharmaceutical company,
today reported positive top-line clinical results of its lead drug
candidate for Alzheimer’s disease, PTI-125. The Alzheimer’s brain
is characterized by a misfolded protein called Filamin A (FLNA);
PTI-125 binds to FLNA and restores its normal shape and function.
In a Phase 2a study funded by the National Institutes of Health
(NIH), treatment with PTI-125 for 28 days significantly reduced
biomarkers of Alzheimer’s disease pathology, neuroinflammation and
neurodegeneration in patients.
“Based on these encouraging biomarker results,
this new treatment could be an important part of the research
dialogue in Alzheimer’s disease,” said Dr. Jeffrey
Cummings, Research Professor of the Department of Brain
Health, UNLV and Director of the Center for Neurodegeneration and
Translational Neuroscience of the Cleveland Clinic Lou Ruvo Center
for Brain Health. “This drug candidate appears to target some of
the more toxic components of the illness. Results will need to be
replicated in larger studies to prove it’s a definitive advance in
the field.”
The Phase 2a study achieved a 100% responder
rate, with all patients responding to PTI-125. A key objective of
this first-in-patient study was to measure drug effects on
biomarkers in the brain (i.e., in cerebrospinal fluid, or CSF)
before and after 28 days of treatment with PTI-125.
Key results include:
- Total tau (T-tau) decreased 20%
(p<.001)
- Phosphorylated tau (P-tau)
decreased 34% (p<.0001)
- Neurofilament light chain (NfL), a
marker for neurodegeneration, decreased 22% (p<.0001)
- Neurogranin, a marker for cognitive
decline, decreased 32% (p<.0001)
- Neuroinflammatory marker YKL-40, an
indicator of microglial activation, decreased 9% (p<.0001)
- Proinflammatory Interleukin 6
(IL-6) decreased 14% (p<.0001)
- Proinflammatory Interleukin 1 beta
(IL-1β) decreased 11% (p<.0001)
- Proinflammatory Tumor necrosis
factor alpha (TNFα) decreased 5% (p=.001)
- The ratio of CSF P-tau to Aβ42, a
widely accepted biochemical value of Alzheimer’s disease, improved
in all evaluable patients (p<.001).
“We conclude from this study that PTI-125 was
able to reduce biomarkers of neurodegeneration and
neuroinflammation in Alzheimer’s patients at a dose that appears
safe and well-tolerated,” said Nadav Friedmann, PhD, MD, Chief
Medical Officer of Cassava Sciences. “To our knowledge, no other
drug has shown such promising results on objective, validated
biomarkers of disease.”
Cognition was not assessed in this
first-in-patient study; however, published studies show that
elevated levels of CSF biomarkers P-tau and total tau/Aβ42 ratio
correlate with deficiencies on a range of memory and sustained
attention assessments.
“We are excited to lead the way in the effort to
bring a new treatment paradigm to Alzheimer’s, a disease that has
seen few scientific advancements to date despite massive research
efforts,” said Remi Barbier, President & CEO of Cassava
Sciences. “The relationship between biomarkers and Alzheimer’s
disease is crucial, well-known and widely published. As a result,
we’re cautiously optimistic that PTI-125 moves us closer towards
the goal of a disease-modifying treatment. And as always, we are
grateful for the support of our collaborators, advisors and NIH,
whose peer-review system of evaluation has enabled us to advance
PTI-125 step-wise from basic research to clinical testing within 10
years.”
Next Step: Initiation of a Phase 2b
Study in Q3 2019Based on these positive Phase 2a results,
Cassava Sciences plans to initiate a Phase 2b study of PTI-125.
This Phase 2b study will also be funded by NIH. A key objective of
the Phase 2b study will be to replicate the beneficial effects of
PTI-125 on biomarkers of Alzheimer’s disease in a larger, blinded
study. Phase 2b is designed as a blinded, randomized,
placebo-controlled, multicenter, dose-response, research study in
approximately 60 patients with mild-to-moderate Alzheimer’s
disease. Study patients will be dosed with PTI-125 100 mg, 50 mg,
or matching placebo, twice daily for 28 continuous days. The
primary efficacy endpoint is improvement in biomarkers of
Alzheimer’s disease. Enrollment is expected to take approximately
12 months.
Phase 2a Study DesignPhase 2a
was a first-in-patient, open-label, multi-center, safety,
pharmacokinetic and biomarker study of PTI-125 in the U.S. Thirteen
patients with mild-to-moderate Alzheimer’s disease, age 50-85,
received 100 mg oral PTI-125 twice daily for 28 days. A diagnosis
of Alzheimer’s disease was confirmed with Mini-Mental State
Examination (MMSE) ≥ 16 and ≤ 24 and a CSF T-tau/Aβ42 ratio ≥ 0.30.
Safety was assessed by ECGs, clinical labs, adverse event
monitoring and physical examinations. CSF was drawn from patients
before dosing started and again after 28 continuous days of dosing
with PTI-125. CSF samples were then analyzed for biomarkers of
Alzheimer’s pathology (T-tau, P-tau, Aβ42); neurodegeneration (NfL,
neurogranin); and neuroinflammation (YKL-40, IL-6, IL-1β and TNFα).
A consulting biostatistician conducted an independent analysis of
the data set.
Cassava Sciences expects to present a full data
set from this Phase 2a study at Clinical Trials on Alzheimer’s
Disease (CTAD), a conference for the medical and scientific
community being held in San Diego, CA, December 4-7th, 2019.
Cassava Sciences’ Phase 2a study was supported
by the National Institute on Aging at NIH under award AG060878.
About PTI-125 and Cassava’s Scientific
ApproachThe target of PTI-125 is an altered form of
filamin A (FLNA), a scaffolding protein. Altered FLNA in the
brain disrupts the normal function of neurons, leading to
Alzheimer’s pathology, neurodegeneration and neuroinflammation.
Cassava’s lead drug candidate, PTI-125, is a small molecule drug
that restores the normal shape of FLNA in the brain. This action
improves the function of certain receptors in the brain and exerts
powerful anti-neuroinflammatory effects.
Cassava Sciences is also developing a
biomarker/diagnostic to detect Alzheimer’s disease with a simple
blood test. This program, called PTI-125Dx, also receives
significant scientific and financial support from NIH.
The underlying science for Cassava Sciences’
programs in neurodegeneration is published in several prestigious
peer-reviewed technical journals, including Journal of
Neuroscience, Neurobiology of Aging, and Journal of Biological
Chemistry. As previously announced, in 2018 NIH awarded Cassava two
research grants following an in-depth, confidential review of its
science and technology. These two NIH grants represent up to $6.7
million of non-dilutive financing.
About Alzheimer's
DiseaseAlzheimer’s disease is a progressive brain disorder
that destroys memory and thinking skills. Currently, there are no
drug therapies to halt Alzheimer’s disease, much less reverse its
course. In the U.S. alone, approximately 5.8 million people are
currently living with Alzheimer’s disease, and approximately
487,000 people age 65 or older will develop Alzheimer’s in
2019.1 The number of people living with Alzheimer’s disease is
expected to grow dramatically in the years ahead due to an aging
population, which may also result in growing social and economic
burden of Alzheimer’s.2
___________________________
1, 2 Source: Alzheimer’s Association. 2019
Alzheimer’s Disease Facts and Figures. Available online at:
https://www.alz.org/media/documents/alzheimers-facts-and-figures-2019-r.pdf
About Cassava Sciences,
Inc.The mission of Cassava Sciences is to detect and treat
neurodegenerative diseases, such as Alzheimer’s disease. Over the
past ten years, Cassava Sciences has combined state-of-the-art
technology with new insights in neurobiology to develop novel
solutions for Alzheimer’s disease.
Cassava Sciences owns worldwide development and
commercial rights to its research programs in Alzheimer’s disease,
and related technology, without royalty obligations to any
third-party.
Declared Interest. Dr. Cummings
is a paid consultant for Cassava Sciences.
For More Information
Contact:Eric Schoen, Chief Financial OfficerCassava
Sciences, Inc.eschoen@CassavaSciences.com(512) 501-2450
For Media Inquiries
Contact:Kirsten Thomas, SVP The Ruth
Groupkthomas@TheRuthGroup.com (508) 280-6592
Note Regarding Forward-Looking
Statements: This press release contains forward-looking
statements for purposes of the Private Securities Litigation Reform
Act of 1995 (the "Act"). Cassava Sciences disclaims any intent
or obligation to update these forward-looking statements and claims
the protection of the Safe Harbor for forward-looking statements
contained in the Act. Examples of such statements include, but
are not limited to, statements regarding the timing of initiation
or completion of Phase 2 clinical studies; the interpretation of
clinical results; and potential benefits of the Company’s drug
programs in neurodegeneration, including Alzheimer’s disease. The
Company cautions that forward-looking statements are inherently
uncertain. Such statements are based on management's current
expectations, but actual results may differ materially due to
various factors. Such statements involve risks and uncertainties,
including, but not limited to, those risks and uncertainties
relating to the ability to demonstrate the specificity, safety,
efficacy or potential health benefits of our product candidates and
including those described in the section entitled “Risk Factors” in
Cassava’s Annual Report on Form 10-K for the year ended December
31, 2018. Existing and prospective investors are cautioned not
to place undue reliance on these forward-looking statements, which
speak only as of the date hereof. Except as required by law, the
Company disclaims any intention or responsibility for updating or
revising any forward-looking statements contained in this press
release. For further information regarding these and other
risks related to our business, investors should consult our filings
with the U.S. Securities and Exchange Commission (SEC), which are
available on the SEC's website at www.sec.gov.
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