Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage
biotechnology developing allogeneic CAR T and in vivo gene
correction therapies with its ARCUS® genome editing platform, and
SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage
biopharmaceutical company focused on developing life-changing
medicines for patients with severe rare diseases and cancer, today
announced they have entered into a clinical trial collaboration
agreement. Per the agreement, PBCAR269A, Precision BioSciences’
wholly-owned investigational allogeneic chimeric antigen receptor
(CAR) T cell therapy candidate targeting B-cell maturation antigen
(BCMA), will be evaluated in combination with nirogacestat,
SpringWorks’ investigational gamma secretase inhibitor (GSI), in
patients with relapsed or refractory multiple myeloma.
“Based on recent clinical data using GSIs in combination with
BCMA-targeted therapies, it is exciting to combine these agents in
patients who have a need for better therapies,” said Nina Shah,
M.D., study Principal Investigator and Associate Professor in the
Department of Medicine at the University of California, San
Francisco. “I look forward to the data generated from this
investigational study to see if PBCAR269A plus nirogacestat
improves clinical outcomes in patients with multiple myeloma.”
Gamma secretase inhibition has been shown preclinically to
enhance the activity of BCMA-targeted therapies by preventing the
cleavage and shedding of BCMA from the surface of myeloma cells,
which increases the cell surface density of BCMA and reduces levels
of soluble BCMA. Via this mechanism, nirogacestat may enhance the
activity of BCMA-targeted therapies.1 Emerging clinical data also
suggest that a GSI may increase antitumor efficacy of BCMA-targeted
autologous CAR T therapy in patients with relapsed or refractory
multiple myeloma.2,3
“In June, we initiated our Phase 1/2a clinical trial of
PBCAR269A, which targets BCMA for the treatment of relapsed or
refractory multiple myeloma and has demonstrated anti-tumor
activity in preclinical disease models,” said Chris Heery, M.D.,
Chief Medical Officer at Precision BioSciences. “Preclinical data
from our own program as well as others have suggested the
importance of gamma secretase inhibition to unlock the full
potential of BCMA targeted therapies. We look forward to further
evaluating this in the clinic.”
Under the terms of the agreement, Precision BioSciences will
assume all development costs of the expanded Phase 1/2a study of
PBCAR269A to include nirogacestat and evaluate the safety and
preliminary clinical activity of the combination therapy. Precision
BioSciences and SpringWorks will form a joint development committee
to oversee the clinical study, which is expected to commence in the
first half of 2021, pending discussions with regulators.
“Patients with multiple myeloma are in great need of treatment
advances,” said Saqib Islam, Chief Executive Officer of SpringWorks
Therapeutics. “We continue to believe that nirogacestat has the
potential to become a cornerstone of BCMA combination therapy for
these patients and are pleased to work with Precision BioSciences
and their leading group of scientific advisors and clinical
investigators to evaluate the combination of our gamma secretase
inhibitor with their ‘off-the-shelf’ CAR T therapy.”
About PBCAR269APBCAR269A is an allogeneic
BCMA-targeted CAR T cell therapy candidate being evaluated for the
safety and preliminary clinical activity in a Phase 1/2a
multicenter, nonrandomized, open-label, parallel assignment,
single-dose, dose-escalation, and dose-expansion study of adults
with relapsed or refractory multiple myeloma. The starting dose of
PBCAR269A is 6 x 105 CAR T cells/kg body weight with subsequent
cohorts receiving escalating doses to a maximum dose of 6 x 106 CAR
T cells/kg body weight.
PBCAR269A is the company’s third CAR T candidate to advance to
the clinic and is part of a pipeline of cell-phenotype optimized
allogeneic CAR T therapies derived from healthy donors and then
modified via a simultaneous TCR knock-out and CAR T knock-in step
with the Company’s proprietary ARCUS® genome editing technology.
Precision BioSciences optimizes its CAR T therapy candidates for
immune cell expansion in the body by maintaining a high proportion
of naïve and central memory CAR T cells.
The U.S. Food and Drug Administration (FDA) recently granted
Fast Track Designation to PBCAR269A for the treatment of relapsed
or refractory multiple myeloma for which the FDA previously granted
Orphan Drug Designation. The PBCAR269A clinical trial will be
conducted at multiple U.S. sites. For more information, visit
www.clinicaltrials.gov, study identifier number NCT04171843.
About NirogacestatNirogacestat is an
investigational, oral, selective, small molecule, gamma secretase
inhibitor in Phase 3 clinical development for desmoid tumors, which
are rare and often debilitating and disfiguring soft-tissue tumors.
Gamma secretase cleaves multiple transmembrane protein complexes,
including Notch, which is believed to play a role in activating
pathways that contribute to desmoid tumor growth.
In addition, gamma secretase has been shown to directly cleave
membrane-bound BCMA, resulting in the release of the BCMA
extracellular domain, or ECD, from the cell surface. By inhibiting
gamma secretase, membrane-bound BCMA can be preserved, increasing
target density while reducing levels of soluble BCMA ECD, which may
serve as decoy receptors for BCMA-directed therapies.
Nirogacestat’s ability to enhance the activity of BCMA-directed
therapies has been observed in preclinical models of multiple
myeloma. SpringWorks is evaluating nirogacestat as a BCMA
potentiator and has four collaborations with industry-leading BCMA
developers to evaluate nirogacestat in combinations across
modalities, including with an antibody-drug conjugate, two CAR T
cell therapies and a bispecific antibody. In addition, SpringWorks
and Fred Hutchinson Cancer Research Center have entered into a
sponsored research agreement to further characterize the ability of
nirogacestat to modulate BCMA and potentiate BCMA directed
therapies using a variety of preclinical and patient-derived
multiple myeloma models developed by researchers at Fred Hutch.
Nirogacestat has received Orphan Drug Designation from the U.S.
Food and Drug Administration (FDA) for the treatment of desmoid
tumors (June 2018) and from the European Commission for the
treatment of soft tissue sarcoma (September 2019). The FDA also
granted Fast Track and Breakthrough Therapy Designations for the
treatment of adult patients with progressive, unresectable,
recurrent or refractory desmoid tumors or deep fibromatosis
(November 2018 and August 2019).
About Precision BioSciences, Inc.Precision
BioSciences, Inc. is a clinical stage biotechnology company
dedicated to improving life (DTIL) with its novel and proprietary
ARCUS® genome editing platform. ARCUS is a highly specific and
versatile genome editing platform that was designed with
therapeutic safety, delivery, and control in mind. Using ARCUS, the
Company’s pipeline consists of multiple “off-the-shelf” CAR T
immunotherapy clinical candidates and several in vivo gene
correction therapy candidates to cure genetic and infectious
diseases where no adequate treatments exist. For more information
about Precision BioSciences please
visit www.precisionbiosciences.com.
About SpringWorks TherapeuticsSpringWorks is a
clinical-stage biopharmaceutical company applying a precision
medicine approach to acquiring, developing and commercializing
life-changing medicines for underserved patient populations
suffering from devastating rare diseases and cancer. SpringWorks
has a differentiated portfolio of small molecule targeted oncology
product candidates and is advancing two potentially registrational
clinical trials in rare tumor types, as well as several other
programs addressing highly prevalent, genetically defined cancers.
SpringWorks’ strategic approach and operational excellence in
clinical development have enabled it to rapidly advance its two
lead product candidates into late-stage clinical trials while
simultaneously entering into multiple shared-value partnerships
with industry leaders to expand its portfolio. For more
information, visit www.springworkstx.com and follow
@SpringWorksTx on Twitter and LinkedIn.
Precision Forward-Looking StatementsThis press
release contains forward-looking statements within the meaning of
the Private Securities Litigation Reform Act of 1995. All
statements contained in this press release that do not relate to
matters of historical fact should be considered forward-looking
statements, including, without limitation, statements regarding the
Company’s timing of clinical trials and results therefrom involving
PBCAR269A and the expected benefits of producing clinical trial
material at the Company’s in-house manufacturing facility. In some
cases, you can identify forward-looking statements by terms such as
“anticipate,” “believe,” “could,” “expect,” “should,” “plan,”
“intend,” “estimate,” “target,” “mission,” “may,” “will,” “would,”
“should,” “could,” “target,” “project,” “predict,” “contemplate,”
“potential,” or the negative thereof and similar words and
expressions.
Forward-looking statements are based on management’s current
expectations, beliefs and assumptions and on information currently
available to us. Such statements are subject to a number of known
and unknown risks, uncertainties and assumptions, and actual
results may differ materially from those expressed or implied in
the forward-looking statements due to various important factors,
including, but not limited to: our ability to become profitable;
our ability to procure sufficient funding and requirements under
our current debt instruments; our operating expenses and our
ability to predict what those expenses will be; our limited
operating history; the success of our programs and product
candidates in which we expend our resources; our dependence on our
ARCUS technology; the initiation, cost, timing, progress,
achievement of milestones and results of research and development
activities, preclinical or greenhouse studies and clinical or field
trials; public perception about genome editing technology and its
applications; competition in the genome editing, biopharmaceutical,
biotechnology and agricultural biotechnology fields; our or our
collaborators’ ability to identify, develop and commercialize
product candidates; pending and potential liability lawsuits and
penalties against us or our collaborators related to our technology
and our product candidates; the U.S. and foreign regulatory
landscape applicable to our and our collaborators’ development of
product candidates; our or our collaborators’ ability to obtain and
maintain regulatory approval of our product candidates, and any
related restrictions, limitations and/or warnings in the label of
an approved product candidate; our or our collaborators’ ability to
advance product candidates into, and successfully design, implement
and complete, clinical or field trials; potential manufacturing
problems associated with the development or commercialization of
any of our product candidates; our ability to achieve our
anticipated operating efficiencies at our manufacturing facility;
delays or difficulties in our and our collaborators’ ability to
enroll patients; if our product candidates do not work as intended
or cause undesirable side effects; risks associated with applicable
healthcare, data privacy and security regulations and our
compliance therewith; the rate and degree of market acceptance of
any of our product candidates; the success of our existing
collaboration agreements, and our ability to enter into new
collaboration arrangements; our current and future relationships
with third parties including suppliers and manufacturers; our
ability to obtain and maintain intellectual property protection for
our technology and any of our product candidates; potential
litigation relating to infringement or misappropriation of
intellectual property rights; our ability to effectively manage the
growth of our operations; our ability to attract, retain, and
motivate key scientific and management personnel; market and
economic conditions; effects of natural and manmade disasters,
public health emergencies and other natural catastrophic events
effects of the outbreak of COVID-19, or any pandemic, epidemic or
outbreak of an infectious disease; insurance expenses and exposure
to uninsured liabilities; and other important factors discussed
under the caption “Risk Factors” in our Quarterly Report on Form
10-Q for the quarterly period ended June 30, 2020, as any such
factors may be updated from time to time in our other filings with
the SEC, which are accessible on the SEC’s website at www.sec.gov
and the Investors & Media page of our website at
investor.precisionbiosciences.com.
All forward-looking statements speak only as of the date of this
press release and, except as required by applicable law, we do not
plan to publicly update or revise any forward-looking statements
contained herein, whether as a result of any new information,
future events, changed circumstances or otherwise.
SpringWorks Forward-Looking StatementsThis
press release contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995, as
amended, including, without limitation, statements regarding
SpringWorks’ clinical trials and its strategy, business plans and
focus. The words “may,” “will,” “could,” “would,” “should,”
“expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,”
“predict,” “project,” “potential,” “continue,” “target” and similar
expressions are intended to identify forward-looking statements,
although not all forward-looking statements contain these
identifying words. Any forward-looking statements in this press
release are based on management’s current expectations and beliefs
and are subject to a number of risks, uncertainties and important
factors that may cause actual events or results to differ
materially from those expressed or implied by any forward-looking
statements contained in this press release, including, without
limitation, those related to SpringWorks’ financial results, the
timing for completion of SpringWorks’ clinical trials of its
product candidates, whether and when, if at all, SpringWorks’
product candidates will receive approval from the U.S. Food and
Drug Administration, or FDA, or other foreign regulatory
authorities, uncertainties and assumptions regarding the impact of
the COVID-19 pandemic on SpringWorks’ business, operations,
clinical trials, supply chain, strategy, goals and anticipated
timelines, competition from other biopharmaceutical companies, and
other risks identified in the section entitled “Risk Factors” in
Item 1A of Part II of SpringWorks’ Quarterly Report on Form 10-Q
for the quarter ended June 30, 2020, as well as discussions of
potential risks, uncertainties and other important factors in
SpringWorks’ subsequent filings with the Securities and Exchange
Commission. SpringWorks cautions you not to place undue reliance on
any forward-looking statements, which speak only as of the date
they are made. SpringWorks disclaims any obligation to publicly
update or revise any such statements to reflect any change in
expectations or in events, conditions or circumstances on which any
such statements may be based, or that may affect the likelihood
that actual results will differ from those set forth in the
forward-looking statements. Any forward-looking statements
contained in this press release represent SpringWorks’ views only
as of the date hereof and should not be relied upon as representing
its views as of any subsequent date.
Contact:
Maurissa MessierSenior Director, Corporate
CommunicationsMaurissa.messier@precisionbiosciences.com
Kim DiamondVice President, Communications and
Investor Relations(203) 561-1646kdiamond@springworkstx.com
References
1 Eastman S, Shelton C, Gupta I, Krueger J,
Blackwell C, Bojczuk. Synergistic activity of belantamab mafodotin
(anti-BCMA immuno-conjugate) with PF-03084014 (gamma-secretase
inhibitor) in Bcma-expressing cancer cell lines. Blood.
2019;134(supplement_1):4401. doi.org/10.1182/blood-2019-123705.2
Cowan AJ, Pont M, Sather BD, et al. Efficacy and safety of fully
human Bcma CAR T cells in combination with a gamma secretase
inhibitor to increase Bcma surface expression in patients with
relapsed or refractory multiple myeloma. Blood.
2019;134(supplement_1):204. doi.org/10.1182/blood-2019-129405.3
Pont MJ, Hill T, Cole GO, et al. γ-Secretase inhibition increases
efficacy of BCMA-specific chimeric antigen receptor T cells in
multiple myeloma. Blood. 2019;134(19):1585-1597.
doi:10.1182/blood.2019000050
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