Cortexyme Announces Preclinical Data Highlighting Potential Therapeutic Benefits of Atuzaginstat for the Treatment of High-Risk Oral Potentially Malignant Disorders
March 09 2022 - 07:00AM
Business Wire
First-in-class lysine gingipain inhibitor,
atuzaginstat, has the potential to reduce the malignant progression
of oral potentially malignant disorders (OPMD)
In vitro study results demonstrate that PD-L1
is induced by P. gingivalis and can be blocked by atuzaginstat
Atuzaginstat ready to begin a Phase 2 trial for
expansion into high-risk OPMD indication; IND submission expected
in the first half of 2022
Cortexyme, Inc. (Nasdaq: CRTX), a clinical-stage
biopharmaceutical company pioneering upstream therapeutic
approaches to improve the lives of patients diagnosed with
degenerative diseases, today provided an update on both proprietary
preclinical research and peer-reviewed publications supporting the
potential of atuzaginstat (COR388) to treat patients with high-risk
oral potentially malignant disorders (OPMDs), including oral/head
and neck squamous cell cancer (O/HNSCC), high-risk oral
pre-malignant dysplasia (PmD), proliferative verrucous leukoplakia
(PVL), and carcinoma-in-situ (CIS).
“The infectious bacterium P. gingivalis and its secreted
virulence factor proteases, gingipains, may promote the progression
of high-risk oral potentially malignant disorders to oral/head and
neck cancer and are associated with reduced overall survival rates
in O/HNSCC,” said Chris Lowe, Cortexyme’s interim chief executive
officer. “Based upon the mechanism of action and non-clinical
evidence demonstrating the benefits of atuzaginstat in reducing P.
gingivalis-driven tumor growth and pathway activation, as well as
PD-L1 expression, Cortexyme sees an opportunity to apply our
expertise in gingipain inhibition where P. gingivalis infection
plays a central role in disease progression. We look forward to
strategically advancing the development of atuzaginstat for the
potential treatment of high-risk OPMDs through both internal and
external development opportunities.”
Cortexyme is finalizing a Phase 2 trial design for its lysine
gingipain inhibitor, atuzaginstat (COR388), as a potential new
indication to prevent the development of O/HNSCC. The company has
completed a pre-IND (Investigational New Drug application) meeting
with U.S. Food and Drug Administration (FDA) and plans to submit an
IND to the Division of Oncology 2 in the first half of 2022.
A Role for P. gingivalis in OMPDs
The evidence supporting the development of a gingipain inhibitor
for the potential treatment of OMPDs includes the following
peer-reviewed publications and proprietary preclinical
research:
- P. gingivalis implicated in tumor growth: Published
research shows that unresolved P. gingivalis infections can lead to
tumorigenesis (Geng, et al., 2017; Perera, et al., 2016) and that
there is a significant association between oral squamous cell
carcinoma (OSCC) and P. gingivalis infection (Katz, et al.,
2011).
- P. gingivalis associated with decreased overall
survival: P. gingivalis in human OSCC is associated with a
significant decrease in overall survival (Wen, et al., 2020). The
presence of P. gingivalis gingipains (Kgp) is also associated with
significantly decreased overall survival in esophageal cancer (Gao,
et al., 2016).
- P. gingivalis induces immune evasion mechanism:
Published research indicates that PD-L1 is highly expressed in
human oral pre-malignant dysplasia progressing to cancer (Dave, et
al. 2020) where the PD-1/PD-L1 pathway negatively regulates tumor
immune recognition. PD-L1 is induced on tumor cells, but also
tumor-associated macrophages (TAMs) and dendritic cells, blocking
tumor immune surveillance. P. gingivalis infection induces PD-L1
expression, which may facilitate immune evasion of infected cells.
Cortexyme in vitro studies have demonstrated that PD-L1 induced by
P. gingivalis can be blocked by atuzaginstat.
- P. gingivalis promotes oral dysplasia malignant
transformation: P. gingivalis is associated with multiple
tumorigenic pathways, including activation of the β-catenin pathway
(Reyes, et al. 2020), which is associated with increased
progression of PmD, providing further biological rationale for the
use of atuzaginstat in PmD.
- P. gingivalis is present in nearly all human high-risk
OPMDs: Cortexyme has demonstrated that the target of
atuzaginstat, gingipain, is present in nearly all human high-risk
OPMDs in a large human histopathologic IHC study, which underscores
atuzaginstat’s potential to fundamentally interrupt the disease
process.
Merrill Biel, MD, PhD, Cortexyme’s oncology advisory board chair
and a leading expert in O/HNSCC and adjunct professor of
Otolaryngology at the University of Minnesota, commented, “Nearly
all cases of O/HNSCC are preceded by asymptomatic high-risk OPMDs.
At the present time, there are no FDA-approved treatments for
high-risk OPMDs. Present treatment consists of clinical observation
or surgical resection. Both are associated with high rates of
recurrence and surgery can involve significant morbidity, including
difficulty speaking, swallowing, and chewing. There is an urgent
need for an effective, targeted, non-invasive modality for treating
P. gingivalis-positive, high-risk OPMD lesions that will reduce the
incidence of malignant transformation of OPMDs to invasive oral
squamous cell carcinoma without the limiting side effects
associated with surgery. I am excited and encouraged by the growing
evidence that supports the potential of atuzaginstat for the
treatment of P. gingivalis-positive, high-risk OPMDs. In addition,
for the first time there is the possibility for a medical treatment
to reduce the incidence of O/HNSCC.”
About Cortexyme
Cortexyme, Inc. (Nasdaq: CRTX) is a clinical stage
biopharmaceutical company pioneering upstream therapeutic
approaches designed to improve the lives of patients diagnosed with
degenerative diseases, including Alzheimer’s disease,
periodontitis, and oral potentially malignant disorders, among
others. Cortexyme’s innovative approach targets a specific,
infectious pathogen called P. gingivalis found in the brain of
Alzheimer’s patients and other organs and tied to degeneration and
inflammation in humans and animal models. The company’s causation
evidence for Alzheimer’s disease and the mechanism of its novel
therapeutic has been independently replicated and confirmed by
multiple laboratories around the world, as well as published in
peer-reviewed scientific journals. To learn more about Cortexyme,
visit or follow @Cortexyme on Twitter.
Forward-Looking Statements
Statements in this news release contain “forward-looking
statements” that are subject to substantial risks and
uncertainties. Forward-looking statements contained in this news
release may be identified by the use of words such as “can,”
expect,” “plans,” “will,” “may,” “potential,” “demonstrate,”
“promote, “ “opportunity,” “confirmed” or other similar words.
Examples of forward-looking statements include, among others, the
strategic development path for atuzaginstat; its business plans,
internal and external development of the pipeline, strategy,
planned FDA submissions and clinical trials and timeline,
prospects, and milestone expectations; the timing and success of
the company’s clinical trials and related data, including plans and
the ability to initiate, conduct and/or complete current and
additional studies; the potential of atuzaginstat to treat
Alzheimer’s disease and other indications including oral
potentially malignant disorders (OPMDs), including oral/head and
neck squamous cell cancer (O/HNSCC), high-risk oral pre-malignant
dysplasia (PmD), proliferative verrucous leukoplakia (PVL), and
carcinoma-in-situ (CIS); the timing of announcements and updates
relating to its clinical trials and related data; the potential
therapeutic benefits, safety and efficacy of the company’s product
candidate or library of compounds; and statements about its ability
to obtain, and the timing relating to, further development of
atuzaginstat and other programs or indications, regulatory
submissions and interactions with regulators, and related response
and decisions, and approvals with respect to the company’s drug
product candidate. Forward-looking statements are based on
Cortexyme’s current expectations and are subject to inherent
uncertainties, risks, and assumptions that are difficult to predict
and could cause actual results to differ materially from what the
company expects. Further, certain forward-looking statements are
based on assumptions as to future events that may not prove to be
accurate. Factors that could cause actual results to differ
include, but are not limited to, the risks and uncertainties
described in the section titled “Risk Factors” in Cortexyme’s
Annual Report on Form 10-K filed with the Securities and Exchange
Commission (SEC) on March 1, 2022, its Quarterly Report on Form
10-Q filed with the SEC on October 29, 2021, and other reports as
filed with the SEC. Forward-looking statements contained in this
news release are made as of this date, and Cortexyme undertakes no
duty to update such information except as required under applicable
law.
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version on businesswire.com: https://www.businesswire.com/news/home/20220309005301/en/
Stacy Roughan Cortexyme, Inc. Vice President, Corporate
Communications & Investor Relations ir@cortexyme.com
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