Novel, investigational drug
JZP815 inhibited tumor growth in several RAS- and BRAF-mutated
solid tumor models, and demonstrated enhanced activity when
combined with other MAPK pathway inhibitors
Jazz plans to submit an investigational new
drug application (IND) for JZP815 this year
DUBLIN, April 8, 2022 /PRNewswire/ -- Jazz
Pharmaceuticals plc (Nasdaq: JAZZ) and collaboration partner Redx
Pharma (AIM: REDX) today presented data showing the pan-RAF
kinase inhibitor, JZP815, was active in multiple RAF- and
RAS-mutant tumor pre-clinical models, with a pharmacokinetic
profile that may provide drug exposure required for target
engagement in humans.
"As a precision pan-RAF inhibitor with a differentiated
mechanism of action, JZP815 is a promising drug candidate for
several types of difficult-to-treat solid tumors, including
colorectal cancer, non-small cell lung cancer, melanoma and ovarian
cancer," said Rob Iannone, M.D.,
M.S.C.E., executive vice president, global head of research and
development of Jazz Pharmaceuticals. "By not inducing paradoxical
pathway activation, which can stimulate the growth of certain
cancers, JZP815 may offer a significant advancement in the pan-RAF
inhibitor class with the potential to address unmet patient need.
We look forward to submitting the investigational new drug
application for JZP815 this year."
JZP815 targets specific components of the mitogen-activated
protein kinase (MAPK) pathway, namely all three RAF proteins –
ARAF, BRAF and CRAF – that when activated by oncogenic mutations,
can be a frequent driver of human cancer.
Pre-clinical data of JZP815 administered orally as both a
monotherapy and in combination with mitogen-activated protein
kinase (MAPK) pathway inhibitors were presented at the American
Association for Cancer Research 2022 Annual Meeting (AACR). Key
findings of several pre-clinical models include1:
- JZP815 inhibited all 3 RAF kinase family members (ARAF, BRAF,
CRAF) at low-to-sub nanomolar potencies in biochemical assays.
- JZP815 did not induce significant paradoxical pathway
activation, observed with approved first generation BRAF-selective
inhibitors, while demonstrating equivalent cellular potencies for
MAPK pathway inhibition driven by either mutant RAF monomers or
dimers or mutant RAS-induced RAF dimers in tumor cells.
- JZP815 significantly inhibited tumor growth, including inducing
tumor regression, as a single agent in multiple mouse xenograft
solid tumor models harboring RAS and/or BRAF mutations.
- JZP815's pharmacokinetic profile sustained on-target pathway
pharmacodynamic responses in a predictable dose and time dependent
manner.
- JZP815 demonstrated enhanced activity when combined with
inhibitors of other MAPK pathway components including MEK1/2, SOS1,
SHP2 and EGFR inhibitors in both
class 2 and class 3 mutant BRAF patient-derived tumor cells ex
vivo, and KRAS mutant NSCLC and colorectal cancer xenografts
in vivo.
The full Jazz presentation abstract, titled, "JZP815, a potent
and selective pan-RAF inhibitor, demonstrates efficacy in RAF and
RAS mutant tumor pre-clinical models" is available at
https://www.abstractsonline.com/pp8/#!/10517/presentation/15283.
Jazz acquired JZP815 from Redx Pharma, and the two companies are
collaborating on this pre-clinical research. Jazz plans to submit
an IND for JZP815 this year.
About JZP815
JZP815 is an investigational, pre-clinical stage pan-RAF kinase
inhibitor that was discovered and developed using state-of-the-art
screening methodologies and medicinal chemistry. JZP815 targets
specific components of the mitogen-activated protein kinase (MAPK)
pathway that, when activated by oncogenic mutations, can be a
frequent driver of human cancer. JZP815 potently inhibits both
monomer- and dimer-driven RAF signaling (e.g., RAS-induced),
prevents paradoxical pathway activation induced by BRAF selective
inhibition, and is active against class 1, class 2, and class 3
BRAF mutants, as well as BRAF fusions and CRAF mutants. JZP815 is
not currently approved for use anywhere in the world. JZP815 is
part of Jazz's growing early-stage R&D pipeline focused on
precision oncology in solid tumors.
About Jazz Pharmaceuticals plc
Jazz Pharmaceuticals
plc (NASDAQ: JAZZ) is a global biopharmaceutical company whose
purpose is to innovate to transform the lives of patients and their
families. We are dedicated to developing life-changing medicines
for people with serious diseases—often with limited or no
therapeutic options. We have a diverse portfolio of marketed
medicines and novel product candidates, from early- to late-stage
development, in neuroscience and oncology. Within these therapeutic
areas, we are identifying new options for patients by actively
exploring small molecules and biologics, and through innovative
delivery technologies and cannabinoid science. Jazz is
headquartered in Dublin, Ireland
and has employees around the globe, serving patients in nearly 75
countries. For more information, please visit
www.jazzpharmaceuticals.com and follow @JazzPharma on Twitter.
Caution Concerning Forward-Looking Statements
This press release contains forward-looking statements, including,
but not limited to, statements related to Jazz Pharmaceuticals'
belief in the potential of JZP815 to provide a potentially new
therapeutic option for multiple solid tumor types; progressing
JZP815 to the clinic and other statements that are not historical
facts. These forward-looking statements are based on Jazz
Pharmaceuticals' current plans, objectives, estimates, expectations
and intentions and inherently involve significant risks and
uncertainties. Actual results and the timing of events could differ
materially from those anticipated in such forward-looking
statements as a result of these risks and uncertainties, which
include, without limitation, effectively registering JZP815 with
FDA and initiating clinical trials; launching and commercializing
new products; obtaining and maintaining adequate coverage and
reimbursement for the company's products; delays or problems in the
supply or manufacture of the company's products; and other risks
and uncertainties affecting the company, including those described
from time to time under the caption "Risk Factors" and elsewhere in
Jazz Pharmaceuticals' Securities and Exchange Commission filings
and reports (Commission File No. 001-33500), including Jazz
Pharmaceuticals' Annual Report on Form 10-K for the year ended
December 31, 2021 and future filings
and reports by Jazz Pharmaceuticals. Other risks and uncertainties
of which Jazz Pharmaceuticals is not currently aware may also
affect Jazz Pharmaceuticals' forward-looking statements and may
cause actual results and the timing of events to differ materially
from those anticipated. The forward-looking statements herein are
made only as of the date hereof or as of the dates indicated in the
forward-looking statements, even if they are subsequently made
available by Jazz Pharmaceuticals on its website or otherwise. Jazz
Pharmaceuticals undertakes no obligation to update or supplement
any forward-looking statements to reflect actual results, new
information, future events, changes in its expectations or other
circumstances that exist after the date as of which the
forward-looking statements were made.
Media Contact:
Kristin
Bhavnani
Head of Global Corporate Communications
Jazz Pharmaceuticals plc
CorporateAffairsMediaInfo@jazzpharma.com
Ireland +353 1 637 2141
U.S. +1 215 867 4948
Investors:
Andrea N.
Flynn, Ph.D.
Vice President, Head, Investor Relations
Jazz Pharmaceuticals plc
investorinfo@jazzpharma.com
Ireland +353 1 634 3211
U.S. +1 650 496 2717
References
1 Hauptschein, R. et al. JZP815, a potent and
selective pan-RAF inhibitor, demonstrates efficacy in RAF and RAS
mutant tumor pre-clinical models. American Association for Cancer
Research 2022 Annual Meeting. Available at
www.abstractsonline.com/pp8/#!/10517/presentation/15283. Accessed
April 2022.
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