SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage
biopharmaceutical company focused on developing life-changing
medicines for patients with severe rare diseases and cancer,
announced today that data from two collaborator-sponsored clinical
studies evaluating nirogacestat, an investigational oral gamma
secretase inhibitor, in combination with B-cell maturation agent
(BCMA) therapies in patients with relapsed or refractory multiple
myeloma (RRMM) will be presented at the European Hematology
Association (EHA) 2023 Congress, taking place in Frankfurt, Germany
from June 8-11, 2023. Updated clinical data from the Phase 1/2
study sponsored by GSK plc (LSE/NYSE: GSK) evaluating nirogacestat
in combination with low-dose belamaf (belantamab mafodotin-blmf),
GSK’s antibody-drug conjugate targeting BCMA, in patients with RRMM
will be presented in a poster presentation. In addition, new data
from the Phase 1b clinical trial sponsored by Janssen Research
& Development, LLC (Janssen) evaluating nirogacestat in
combination with teclistamab, Janssen’s bispecific antibody
targeting BCMA and CD3, will be presented in an oral presentation.
“These data provide further validation of the mechanistic
approach supporting nirogacestat’s ability to enhance the activity
of BCMA-directed therapies across modalities. We are pleased that
updated data from the GSK-sponsored trial continue to support our
thesis that the combination with nirogacestat may further optimize
the benefit-risk profile of belamaf monotherapy. We are also
encouraged that the Janssen-sponsored trial establishes an initial
tolerability, safety and efficacy profile for combining
nirogacestat with a BCMA bispecific antibody,” said Saqib Islam,
Chief Executive Officer of SpringWorks. “Our goal is to improve the
outcomes for patients with multiple myeloma and we believe that
developing a robust clinical data set across BCMA modalities and
treatment lines can help us demonstrate where within the multiple
myeloma treatment landscape nirogacestat has the greatest
opportunity to maximize clinical benefit.”
Poster Presentation at the EHA 2023
Congress
Low-dose belantamab mafodotin (belamaf) in combination
with nirogacestat vs belamaf monotherapy in patients with
relapsed/refractory multiple myeloma (RRMM): Phase 1/2 DREAMM-5
Platform Sub-study 3
Abstract #: P913
Session Date and Time: Friday, June 9, 18:00-19:00 CEST
(12:00-1:00 p.m. ET)
This ongoing Phase 1/2 trial, which is sub-study 3 of GSK’s
DREAMM-5 platform trial (NCT04126200), aims to determine if
low-dose belamaf in combination with nirogacestat results in
similar efficacy with an improved ocular toxicity profile compared
to belamaf alone at a higher dose. Patients were randomized 1:1 to
0.95 mg/kg belamaf every three weeks (Q3W, low-dose) combined with
100 mg twice daily nirogacestat or belamaf 2.5 mg/kg Q3W
monotherapy.
Initial results from the pre-planned interim analysis were
presented at the 2022 American Society of Clinical Oncology (ASCO)
Annual Meeting. Updated data from a randomized cohort expansion in
which 34 patients received low-dose belamaf plus nirogacestat and
37 patients received belamaf monotherapy will be presented at EHA.
Patients had a median of 5 (range 3-14) prior lines of therapy. As
of the December 9, 2022 data cut-off, patients received a median of
4 (range 1-20) cycles of the combination and a median of 3 (range
1-9) monotherapy cycles.
Overall response rate (ORR) in the low-dose belamaf (0.95 mg/kg
Q3W) plus nirogacestat arm was 29%, with 1 patient (3%) achieving a
complete response (CR), 5 patients (15%) achieving a very good
partial response (VGPR), and 4 patients (12%) achieving a partial
response (PR). ORR in the belamaf monotherapy arm (2.5 mg/kg Q3W)
was 38%, with no patient achieving a CR, 5 patients (14%) achieving
a VGPR, and 9 patients (24%) achieving a PR. Per the prespecified
analysis plan, ORR was also calculated incorporating prior ORR for
low-dose belamaf plus nirogacestat from the dose exploration cohort
of this DREAMM-5 sub-study 3 and from the DREAMM-2 belamaf
monotherapy study; ORR across these studies was 36% in the low-dose
belamaf plus nirogacestat combination arm and 33% in the belamaf
monotherapy arm.
Safety results showed a substantial reduction of high-grade
ocular events in the low-dose belamaf plus nirogacestat arm
compared to the monotherapy arm of belamaf at a higher dose.
Specifically, Grade 3 ocular events were 29% for low-dose belamaf +
nirogacestat versus 59% for belamaf monotherapy (per the KVA
scale); no Grade 4 ocular events or new toxicities occurred in
either arm.
“These clinical data suggest that combining nirogacestat with a
low dose of belamaf may result in comparable efficacy to a higher
monotherapy belamaf dose, while simultaneously substantially
reducing the frequency high-grade ocular adverse events,” said Jim
Cassidy, M.D., Ph.D., Chief Medical Officer of SpringWorks. “We are
encouraged by these results and we look forward to the further
evaluation of this combination with standard of care agents in
relapsed refractory multiple myeloma as well as its potential in
earlier lines of therapy.”
Oral Presentation at the EHA 2023 Congress
Teclistamab (tec) + nirogacestat (niro) in
relapsed/refractory multiple myeloma (RRMM): the Phase 1b
MajesTEC-2 study
Session Title: MM Clinical: New combinations and novel
targets
Abstract #: S194
Session Date and Time: Saturday, June 10, 12:30-12:45 CEST
(6:30-6:45 a.m. ET)
This ongoing Phase 1b trial (NCT04722146), which is part of a
multi-arm trial being conducted by Janssen, aims to evaluate the
safety, tolerability and preliminary efficacy of nirogacestat in
combination with teclistamab in patients with RRMM. Patients in the
study had received ≥3 prior lines of therapy or were double
refractory to a proteasome inhibitor (PI) and an immunomodulatory
drug (IMiD) and triple exposed to a PI, an IMiD, and an anti-CD38
antibody, with progressive disease within 12 months of their last
line of therapy. Three dose levels were evaluated: 1) teclistamab
720 μg/kg weekly plus concurrent nirogacestat 100 mg twice daily
starting with the first dose of teclistamab (n=8); 2) teclistamab
720 μg/kg weekly plus once daily nirogacestat 100 mg starting after
teclistamab step-up dosing (n=7); and 3) 1500 μg/kg (which is the
FDA-approved dose) weekly plus once daily nirogacestat 100 mg
starting after teclistamab step-up dosing (n=13).
As of the December 16, 2022 data cut-off, 28 patients received
the combination of teclistamab and nirogacestat across three
different dose levels. Median prior lines of therapy was 4 (range
2-12) and median duration of treatment was 9.4 months (range
0.13-19.7) for teclistamab and 4.7 months for nirogacestat (range
0.16-13.0).
The most frequent (>20%) treatment-emergent adverse events
(TEAEs) for all doses were neutropenia (82%), cytokine release
syndrome, or CRS (75%), diarrhea (64%), injection-site erythema
(54%), decreased appetite (50%), fatigue (42.9%), and anemia (35%).
Of eight patients who received teclistamab 720 μg/kg plus
concurrent nirogacestat, two dose-limiting toxicities were reported
(one Grade 3 GI bleed and Grade 3 diarrhea; one Grade 3 immune
effector cell-associated neurotoxicity syndrome, or ICANS). In
addition, one patient had Grade 3 CRS and one patient had Grade 3
confusional state. These events led to the decision to delay the
starting dose of nirogacestat in subsequent cohorts. In the dose
level 2 and dose level 3 cohorts, when nirogacestat was added after
teclistamab step-up dosing and reduced to once daily, no
dose-limiting toxicities or Grade 3 CRS or neurologic adverse
events were reported.
The overall response rate was 71% for dose level 1, 57% for dose
level 2, and 92% for dose level 3. The total ORR across the three
dose levels was 78% and all responses were VGPR or better. The
percentage of patients experiencing complete response (CR) or
stringent CR (sCR) was 43%, 57% and 54%, respectively (total
percentage of CR or sCR across the three cohorts was 52%).
“This is the first clinical data set of nirogacestat in
combination with a BCMA bispecific agent. We believe these data
provide important insights into a tolerable treatment schedule and
early evidence of an encouraging ORR, including promising CR and
sCR rates, when combining nirogacestat with this BCMA modality,”
commented Dr. Cassidy. “Nirogacestat is being evaluated in
combination with three other bispecific agents and we look forward
to generating more data with these combinations.”
About Nirogacestat
Nirogacestat is an oral, selective, small molecule gamma
secretase inhibitor in Phase 3 clinical development for desmoid
tumors and in Phase 2 clinical development for ovarian granulosa
cell tumors. Nirogacestat is an investigational drug for which
safety and efficacy have not been established.
Gamma secretase cleaves multiple transmembrane protein
complexes, including Notch, which is believed to play a role in
activating pathways that contribute to growth of desmoid and
ovarian granulosa cell tumors. Gamma secretase has also been shown
to directly cleave membrane-bound B cell maturation antigen (BCMA),
resulting in the release of the BCMA extracellular domain (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 several
collaborations with industry-leading BCMA developers to evaluate
nirogacestat in combinations across modalities. SpringWorks has
also formed research collaborations with Fred Hutchinson Cancer
Research Center and Dana-Farber Cancer Institute to further
characterize the ability of nirogacestat to modulate BCMA and
potentiate BCMA-directed therapies using a variety of preclinical
multiple myeloma models.
The U.S. Food and Drug Administration (FDA) has accepted a New
Drug Application (NDA) for nirogacestat for the treatment of adults
with desmoid tumors, which is being reviewed under the FDA's
Real-Time Oncology Review program. The NDA was granted Priority
Review designation and has been given a Prescription Drug User Fee
Act (PDUFA) action date of August 27, 2023. The FDA also granted
Fast Track and Breakthrough Therapy Designations to nirogacestat
for the treatment of adult patients with progressive, unresectable,
recurrent or refractory desmoid tumors or deep fibromatosis. In
addition, nirogacestat has received Orphan Drug Designation from
the FDA for the treatment of desmoid tumors and from the European
Commission for the treatment of soft tissue sarcoma.
About SpringWorks Therapeutics
SpringWorks is a clinical-stage biopharmaceutical company
applying a precision medicine approach to acquiring, developing and
commercializing life-changing medicines for patients living with
severe rare diseases and cancer. SpringWorks has a differentiated
targeted oncology pipeline spanning solid tumors and hematological
cancers, including two late-stage clinical trials in rare tumor
types as well as several 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 innovators in industry and academia
to unlock the full potential for its portfolio and create more
solutions for patients with cancer. For more information,
visit www.springworkstx.com and follow @SpringWorksTx
on Twitter and LinkedIn.
SpringWorks Forward-Looking Statements
This press release contains “forward-looking statements” within
the meaning of the Private Securities Litigation Reform Act of
1995, as amended, relating to our business, operations, and
financial conditions, including, but not limited to, current
beliefs, expectations and assumptions regarding the future of our
business, future plans and strategies, our development plans, our
preclinical and clinical results, as well as relating to other
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“plan,” “would,” “should” and “could,” and similar expressions or
words, identify forward-looking statements. New risks and
uncertainties may emerge from time to time, and it is not possible
to predict all risks and uncertainties. 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, risks relating to: (i) the success
and timing of our product development activities, including the
initiation and completion of SpringWorks’ clinical trials, (ii) the
fact that topline or interim data from a clinical study may not be
predictive of the final or more detailed results of such study, or
the results of other ongoing or future studies, (iii) the success
and timing of our collaboration partners’ ongoing and planned
clinical trials, (iv) the timing of our planned regulatory
submissions and interactions, including the timing and outcome of
decisions made by the U.S. Food and Drug Administration (FDA) and
other regulatory authorities, investigational review boards at
clinical trial sites and publication review bodies; (v) whether FDA
or other regulatory authorities will require additional information
or further studies, or may fail or refuse to approve or may delay
approval of our drug candidates, (vi) our ability to obtain and
maintain regulatory approval of any of our product candidates,
(vii) our plans to research, discover and develop additional
product candidates, (viii) our ability to maintain adequate patent
protection and successfully enforce patent claims against third
parties, (ix) our ability to enter into collaborations for the
development of new product candidates, (x) our ability to establish
manufacturing capabilities, and our and our collaboration partners’
abilities to manufacture our product candidates and scale
production, (xi) our ability to meet any specific milestones set
forth herein, and (xii) uncertainties and assumptions regarding the
impact of the COVID-19 pandemic on SpringWorks’ business,
operations, clinical trials, supply chain, strategy, goals and
anticipated timelines.
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. Although we believe the expectations
reflected in such forward-looking statements are reasonable, we can
give no assurance that such expectations will prove to be correct.
Accordingly, readers are cautioned not to place undue reliance on
these forward-looking statements.
For further information regarding the risks, uncertainties and
other factors that may cause differences between SpringWorks’
expectations and actual results, you should review the “Risk
Factors” in Item 1A of Part II of SpringWorks’ Quarterly Report on
Form 10-Q for the quarter ended March 31, 2023, as well as
discussions of potential risks, uncertainties and other important
factors in SpringWorks’ subsequent filings.
Contacts:
Kim DiamondVice President, Communications and Investor
RelationsPhone: 203-561-1646 Email: kdiamond@springworkstx.com
Samantha Hilson SandlerSenior Director, Investor RelationsPhone:
203-461-5501Email:
samantha.sandler@springworkstx.com
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