Item 8.01 Other Information.
On January 18, 2023, Deciphera Pharmaceuticals, Inc. (the "Company") filed a
preliminary prospectus supplement with the Securities and Exchange Commission
under its effective shelf registration statement on Form S-3 (Registration
No. 333-266523) (the "Preliminary Prospectus Supplement") in connection with a
proposed registered underwritten public offering of common stock.
The Preliminary Prospectus Supplement contains information relating to recent
developments concerning the Company's business and includes the following
disclosure:
Recent Developments
Preliminary Unaudited Financial Update
On January 3, 2023, the Company disclosed that it had a preliminary unaudited
amount of total revenue of approximately $36 million for the fourth quarter
ended December 31, 2022 and approximately $134 million for the year ended
December 31, 2022. QINLOCK® (ripretinib) net product revenue is estimated to be
approximately $33 million, including approximately $26 million in U.S. QINLOCK
net product revenue and approximately $7 million in international QINLOCK net
product revenue, in addition to approximately $3 million in collaboration
revenue, for the fourth quarter ended December 31, 2022. The Company's U.S.
QINLOCK net product revenue increased an estimated 20% over 2022. Approximately
half of that growth was due to increased demand volume with the remainder from
net price growth and a lower percentage of patients receiving free drug under
the Company's patient assistance program. The increased demand observed in 2022
was driven principally by an increasing average duration of therapy.
The Company also disclosed that it had a preliminary unaudited amount of cash,
cash equivalents, and marketable securities of approximately $339 million as of
December 31, 2022. As of December 31, 2022, the Company had 67,637,351 and
8,855,963 shares of common stock and pre-funded warrants outstanding,
respectively. These amounts are preliminary and are subject to completion of
financial closing procedures. As a result, these amounts may differ materially
from the amounts that will be reflected in the Company's consolidated financial
statements for the year ended December 31, 2022.
The preliminary financial data included in this Current Report on Form 8-K has
been prepared by, and is the responsibility of, the Company's management.
PricewaterhouseCoopers LLP has not audited, reviewed, examined, compiled, nor
applied agreed-upon procedures with respect to the preliminary financial data.
Accordingly, PricewaterhouseCoopers LLP does not express an opinion or any other
form of assurance with respect thereto.
Exploratory Efficacy Analysis using ctDNA in INTRIGUE Study
Background
On January 3, 2023, the Company announced findings of an exploratory analysis
using circulating tumor DNA (ctDNA) from its INTRIGUE Phase 3 clinical study of
QINLOCK. The INTRIGUE Phase 3 clinical study is a randomized, global,
multicenter, open-label study to evaluate the efficacy and safety of QINLOCK
compared to sunitinib in patients with gastrointestinal stromal tumor (GIST)
previously treated with imatinib. As previously reported, the INTRIGUE study did
not achieve the primary efficacy endpoint of progression-free survival (PFS) as
determined by independent radiologic review using modified Response Evaluation
Criteria in Solid Tumors (mRECIST) 1.1 criteria. The statistical analysis plan
included a hierarchical testing sequence that included testing patients with a
KIT exon 11 primary mutation and then in the all patient intent-to-treat (AP)
population. In patients with a KIT exon 11 primary mutation (n=327), QINLOCK
demonstrated a mPFS of 8.3 months compared to 7.0 months for the sunitinib arm
(hazard ratio [HR] 0.88, p=0.360). Although not formally tested due to the rules
of the hierarchical testing sequence, in the AP population QINLOCK demonstrated
a mPFS of 8.0 months compared to 8.3 months for the sunitinib arm (HR 1.05,
nominal p=0.715). QINLOCK was generally well tolerated. Fewer patients in the
QINLOCK arm experienced Grade 3-4 treatment-emergent adverse events compared to
sunitinib (41.3% vs 65.6%).
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An exploratory objective in the INTRIGUE Phase 3 study in GIST patients
previously treated with imatinib was to evaluate anti-tumor efficacy of QINLOCK
according to baseline KIT primary and secondary mutation status. Baseline
peripheral whole blood was analyzed by Guardant360, a 74-gene ctDNA
next-generation sequencing liquid biopsy assay.
Of the 453 patients in the overall intent-to-treat population (ITT), baseline
ctDNA was analyzed in 362 patients for whom evaluable samples were available.
ctDNA was detected in 280 samples and KIT mutations were detected in 213
patients. Primary mutations in KIT were detected in exon 11 in 157 patients and
in exon 9 in 36 patients. Common resistance mutations in KIT were detected in
exons 17/18 in 89 patients and in exons 13/14 in 81 patients. In patients with a
KIT exon 11 primary mutation, 52 patients had mutations in exon 17/18 only, 41
patients had mutations in exon 13/14 only, and 22 patients had mutations in both
exon 13/14 and exon 17/18. The figure below summarizes the KIT primary and
secondary mutations that were detected in the 213 patients in which KIT
mutations were detected.
[[Image Removed: LOGO]]
Findings
Patients with mutations in KIT exon 11 and exon 17/18 only had substantially
improved PFS, objective response rate (ORR), and overall survival (OS) with
QINLOCK versus sunitinib. The table below summarizes these efficacy results.
Efficacy results in patients with detectable ctDNA in KIT exon 11 and in the ITT
populations were consistent with the primary analysis of the INTRIGUE study
based on tumor data used for randomization. The subgroup safety profiles were
consistent with the primary analysis.
INTRIGUE Efficacy Results of ctDNA Analysis for Patients with Mutations in KIT
Exon 11 and 17/18 Only
Hazard Ratio/Response
Ripretinib Sunitinib Difference
(n=27) (n=25) (95% CI)
Median Progression-Free Survival (1) 0.22 (0.11, 0.44),
14.2 months 1.5 months nominal p value <0.0001
Objective Response Rate (1) 44.4% (23.0%, 62.7%),
44.4% 0% nominal p value = 0.0001
Overall Survival (2) 0.34 (0.15, 0.76),
Not Estimable 17.5 months nominal p value = 0.0061
(1) Data cut off date of September 1, 2021; (2) Data cut off date of September 1,
2022.
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The figures below depict the ORR, PFS and OS for QINLOCK compared with sunitinib
in the subgroup analysis.
Objective Response Rate for QINLOCK and sunitinib in KIT Exon 11+17/18 Only
Patients1,2
[[Image Removed: LOGO]]
(1) Data cut off date of September 1, 2021; (2) for 2 patients in the sunitinib
arm and 1 patient in the ripretinib arm, no postbaseline disease assessment
was available; (3) ORR was confirmed with follow-up imaging; (4) determined
using mRECIST 1.1 criteria; (5) response difference=44.4%, 95% CI (23.0,
62.7), nominal p value 0.0001.
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Progression Free Survival for QINLOCK and sunitinib in KIT Exon 11+17/18 Only
Patients1
[[Image Removed: LOGO]]
(median PFS of 14.2 months vs. 1.5 months; HR=0.22, 95% CI [0.11-0.44], nominal
p value <0.0001)
(1) Data cut off date of September 1, 2021.
Overall Survival for QINLOCK and sunitinib in KIT Exon 11+17/18 Only Patients1
[[Image Removed: LOGO]]
(median OS of NE months vs. 17.5 months; HR=0.34, 95% CI [0.15-0.76], nominal p
value = 0.0061)
(1) Data cut off date of September 1, 2022.
Planned INSIGHT Study
Based on the results of the ctDNA analysis and discussions with the U.S. Food
and Drug Administration (the FDA), the Company plans to initiate the INSIGHT
pivotal Phase 3 clinical study of QINLOCK versus sunitinib in second-line GIST
patients with mutations in KIT exon 11 and 17/18 only. The planned INSIGHT Phase
3 clinical study will be a randomized, global, multicenter, open-label study to
evaluate the efficacy and safety of QINLOCK compared to sunitinib in patients
with GIST previously treated with imatinib with mutations in KIT exon 11 and 17
and/or 18 only (excluding patients with mutations in KIT exons 9, 13, or 14). In
the planned study, 54 patients will be randomized 2:1 to either QINLOCK 150 mg
once daily or sunitinib 50 mg once daily for four weeks followed by two weeks
without sunitinib. The primary endpoint will be PFS as determined by independent
radiologic review using mRECIST 1.1 criteria. Secondary endpoints include ORR as
determined by independent radiologic review using mRECIST 1.1 criteria and OS.
Patients randomized to the sunitinib arm may crossover to the QINLOCK arm after
progressive disease. The Company expects to initiate the INSIGHT study in the
second half of 2023.
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Potential U.S. Market Opportunity
As previously disclosed, the Company estimates that the annual new
treatment-eligible second-line GIST patients in the U.S. are approximately
2,000. This estimate, which is based on the Company's analyses of U.S. claims
data, is inherently uncertain. Based on a literature review as well as the
Company's ctDNA analysis from INTRIGUE described above, the Company estimates
that approximately 14% of second-line GIST patients will harbor mutations in
exon 11 and exon 17/18 only.
U.S. QINLOCK net product revenue grew year-over-year based on increased demand,
higher monthly price and a lower percentage of patients receiving free drug.
Increased demand in 2022 compared to 2021 was driven principally by an increase
in average duration of therapy to approximately 7 months, based upon the
Company's estimates through the first three quarters of 2022. The Company
anticipates this average duration of therapy for QINLOCK in fourth-line GIST
will continue to increase modestly from approximately 7 months to approximately
8 to 8.5 months at peak. This is based upon the Company's commercial data
trends, data from QINLOCK clinical trials, and published data covering a broad
set of approved oncology therapeutics that compared average to median survival
endpoints (e.g., PFS and OS) and demonstrated that the average commonly exceeds
the median by up to 1.4 times or more. The mPFS observed in the Company's
pivotal INVICTUS study for the treatment of fourth-line GIST was 6.3 months.
Second-line GIST patients receiving QINLOCK in the Company's INTRIGUE study and
in the sub-group analysis described above had a mPFS greater than that observed
in the Company's fourth-line GIST patients, including an mPFS of 14.2 months for
the patients with mutations in KIT exon 11 and 17/18 only. The Company similarly
assumes that the average duration of therapy for QINLOCK in this second-line
GIST patient subpopulation will increase beyond the mPFS of 14.2 months that the
Company observed. The Company estimates that INSIGHT, if successful, together
with continued sales growth in fourth-line GIST has the potential to grow the
Company's peak U.S. QINLOCK revenue to $350 million to $400 million per year,
based on the assumptions above as well as the Company's estimates of net price
growth over time, adoption of ctDNA testing for GIST patients, estimates of
on-label adoption, the potential for unpromoted off-label usage and the
potential impact of the Inflation Reduction Act of 2022, or the IRA, among
others. Estimates are inherently uncertain and are subject to a wide variety of
assumptions, risks and uncertainties that can cause actual results to differ
materially.
Planned 2023 Corporate Milestones
In January 2023, the Company also announced the following planned 2023 corporate
milestones:
QINLOCK® (ripretinib)
• Present additional data from the INTRIGUE Phase 3 exploratory ctDNA
analysis at a medical meeting in January 2023.
• Initiate the INSIGHT pivotal Phase 3 clinical study of QINLOCK versus
sunitinib in second-line GIST patients with mutations in KIT exon 11 and
17/18 only in the second half of 2023.
• Continue European geographic expansion of QINLOCK in 2023, with planned
commercial launches following conclusion of pricing and reimbursement
negotiations in key European markets.
Vimseltinib
• Complete enrollment for the pivotal Phase 3 MOTION study of vimseltinib,
an investigational, orally administered, potent, and highly selective
switch-control kinase inhibitor of CSF1R for the potential treatment of
tenosynovial giant cell tumor (TGCT), in the first half of 2023 and
announce top-line results from the study in the fourth quarter of 2023.
• Present updated data from the Phase 1/2 study of vimseltinib in the
second half of 2023.
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DCC-3116
• Present updated data from the single agent dose escalation phase and
initial data from the combination dose escalation cohorts of the Phase
1/2 study of DCC-3116, an investigational switch-control kinase inhibitor
of ULK1/2 designed to inhibit autophagy, in the second half of 2023.
• Initiate one or more expansion cohorts in the ongoing Phase 1/2 study of
DCC-3116 in the second half of 2023 in combination with the MEK
inhibitors trametinib or binimetinib, or the KRASG12C inhibitor
sotorasib.
• Announced a clinical trial collaboration and supply agreement with
Pfizer, Inc., and plan to initiate a new dose escalation combination
study evaluating DCC-3116 in combination with encorafenib and cetuximab
in patients with colorectal cancer in the second half of 2023. Under the
terms of the clinical trial collaboration and supply agreement with
Pfizer, Inc., the Company will sponsor the trial and Pfizer will supply
encorafenib at no cost.
• Present preclinical data on new clinical combinations with DCC-3116 in
the first half of 2023.
DCC-3084
• Submit an investigational new drug (IND) application with the FDA for
DCC-3084, a potential best-in-class pan-RAF inhibitor, in the second half
of 2023.
• Present in vitro and in vivo data demonstrating a preclinical profile as
a potent and selective inhibitor of BRAF/CRAF kinases, with optimized
pharmaceutical properties for development in both single-agent and
combination opportunities, in the first half of 2023.
Kinase Switch-Control Research Engine
• Nominate a new development candidate from the Company's proprietary
discovery engine of novel switch-control inhibitors in the first half of
2023.
• Present new preclinical data from research programs at medical meetings
in 2023.
Termination of ATM Prospectus
On January 18, 2023, in connection with commencing this offering, the Company
delivered written notice to Jefferies LLC, or the Agent, that the Company was
suspending and terminating the prospectus related to the Company's common stock,
or the ATM Prospectus, issuable pursuant to the terms of the Open Market Sale
AgreementSM, dated August 10, 2022, or the Open Market Sales Agreement, by and
between us and the Agent. As a result, the Company will not make any sales of
the Company's securities pursuant to the Open Market Sales Agreement, unless and
until a new prospectus, prospectus supplement or a new registration statement is
filed. Other than the termination of the ATM Prospectus, the Open Market Sales
Agreement remains in full force and effect.
Cautionary Note Regarding Forward-Looking Statements
This Current Report on Form 8-K contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995, as amended,
including, without limitation, statements regarding the Company's preliminary
unaudited total revenue for the fourth quarter and the year ended December 31,
2022 and preliminary unaudited cash, cash equivalents, and marketable securities
for the year ended December 31, 2022, the Company's expectations and timing
regarding its planned Phase 3 INSIGHT study of QINLOCK versus sunitinib in
second-line GIST patients with mutations in KIT exon 11 and 17/18 only, the
potential peak U.S. revenue for QINLOCK, and the Company's expectations
regarding upcoming corporate milestones, including but not limited to planned
regulatory submissions, plans related to the commercialization of QINLOCK and
the timing of its clinical studies. The words "may," "will," "could," "would,"
"should," "expect," "plan," "anticipate," "intend," "believe," "estimate,"
"predict," "project," "potential," "continue," "seek," "target" and similar
expressions are intended to identify forward-looking statements, although not
all forward-looking statements contain these identifying words. Forward-looking
statements are based on current expectations of management and upon what
management believes to be reasonable assumptions based on information currently
available to it, and are subject to risks and uncertainties. Such risks and
uncertainties may cause actual results to differ materially from the
expectations set forth in the forward-looking statements. Such risks and
uncertainties include, but are not limited to, risks related to preliminary
financial results, including the risks that the preliminary financial results
reported herein reflect information available to the Company only at this time
and may differ materially from actual results, including in connection with the
Company's completion of financial closing procedures, as well as other risks
detailed in the Company's recent filings on Forms 10-K and 10-Q with the
Securities and Exchange Commission. The Company undertakes no obligation to
update any forward-looking statements to reflect new information, events or
circumstances, or to reflect the occurrence of unanticipated events.
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