BOULDER, Colo., May 10, 2017 /PRNewswire/ --
- COLUMBUS / BRAF-mutant melanoma Part 2 demonstrates positive
results and New Drug Application (NDA) filing on track for June or
July 2017
- New Binimetinib / KEYTRUDA® collaboration initiated
with Merck
- BEACON CRC Phase 3 enrollment underway based on an attractive
safety profile and with early encouraging activity from safety
lead-in
- Cash, Cash Equivalents and Marketable Securities as of
March 31, 2017 were $207 million
Array BioPharma Inc. (Nasdaq: ARRY), a biopharmaceutical company
focused on the discovery, development and commercialization of
targeted small molecule cancer therapies, today reported results
for its third quarter of fiscal 2017 and provided an update on the
progress of its key clinical development programs.
COLUMBUS PHASE 3 TRIAL: Positive Part 2 Results
Announced
On May 9, 2017,
Array announced top-line results from Part 2 of the Phase 3
COLUMBUS study evaluating binimetinib, a MEK inhibitor, and
encorafenib, a BRAF inhibitor, in patients with BRAF-mutant
advanced, unresectable or metastatic melanoma. The primary
analysis of Part 2 compared progression free survival (PFS) in
patients treated with binimetinib 45mg twice daily plus encorafenib
300mg daily (COMBO300) to patients treated with encorafenib 300mg
daily as a single agent. The median PFS (mPFS) for patients
treated with COMBO300 was 12.9 months compared to 9.2 months for
patients treated with single agent encorafenib, with a HR of 0.77
[95% CI 0.61-0.97, p=0.029]. COMBO300 was generally well-tolerated
and reported dose intensity and adverse events were consistent with
binimetinib (45mg twice daily) plus encorafenib 450mg daily
(COMBO450) results from Part 1 of the COLUMBUS trial. Part 2 of
COLUMBUS was designed specifically to assess the contribution of
binimetinib to the combination of binimetinib and encorafenib by
reducing the dose of encorafenib to 300mg in the combination arm to
allow for a comparison of equal doses across arms. Further
results from Part 2 will be presented at a medical meeting during
the second half of 2017.
"The robust PFS benefit and tolerability observed with
binimetinib plus encorafenib in COLUMBUS suggest the combination
represents a potential important addition to the MEK/BRAF treatment
landscape for patients with BRAF-mutant melanoma," said Ron
Squarer, Chief Executive Officer, Array BioPharma.
Based on the strength of data from Part 1 and Part 2, Array is
on track to file an NDA for COLUMBUS in June or July 2017. The primary endpoint for the COLUMBUS
trial is a PFS comparison of COMBO450 versus vemurafenib in Part 1.
Array's European partner, Pierre
Fabre, remains on track to file the Marketing Authorization
Application during the summer.
Melanoma is the fifth most common cancer among men and the sixth
most common cancer among women in the
United States, with more than 87,000 new cases and over
9,700 deaths from the disease expected in 2017. Novel therapies
that target the RAS-RAF-MEK-ERK pathway have a strong scientific
rationale for activity in this disease, as up to 50 percent of
patients with metastatic melanoma have activating BRAF mutations,
the most common gene mutation in this patient population. Currently
marketed MEK/BRAF combination agents have a run rate approaching
$1 billion in annual worldwide
sales.
MERCK COLLABORATION: Binimetinib and KEYTRUDA combination
trial announced in MSS colorectal cancer patients
Array
entered into a clinical trial collaboration agreement with Merck to
investigate the safety and efficacy of binimetinib with Merck's
anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in metastatic
colorectal cancer patients with microsatellite stable tumors (MSS
CRC). The companies entered into this collaboration based on the
growing body of preclinical and clinical evidence that the immune
activity of an anti-PD-1 therapy, such as KEYTRUDA, can be enhanced
when combined with a MEK inhibitor, such as binimetinib.
Under the agreement, Array and Merck will collaborate on a
clinical trial to investigate the safety and efficacy of the
combination of binimetinib with KEYTRUDA, in MSS CRC patients. The
trial is expected to establish a recommended dose regimen of
binimetinib and KEYTRUDA, as well as explore the preliminary
anti-tumor activity of several novel regimens. The study is
expected to begin in the second half of 2017. Results from this
first study will be used to determine optimal approaches to further
clinical development of these combinations.
Merck will act as the sponsor of this clinical trial, and Array
will supply Merck with binimetinib for use in the trial. This
agreement does not include a non-competition provision that
generally prohibits Merck or Array from entering into agreements
with third parties to perform other clinical studies.
BEACON CRC PHASE 3 TRIAL: Randomized portion of trial now
enrolling; patients receiving treatment
Array is advancing
BEACON CRC, a global Phase 3 trial of encorafenib and Erbitux®
(cetuximab), with or without binimetinib, versus standard of care
in patients with BRAF-mutant CRC who have previously received
first- or second-line systemic therapy. Based on an attractive
safety profile and with early encouraging clinical activity
observed in the safety lead-in, the randomized portion of the trial
is now enrolling and patients are receiving treatment. Array
expects to present early data from the safety lead-in later this
year.
BEACON CRC was initiated based on results from a Phase 2 study
including the combination of encorafenib and cetuximab in patients
with advanced BRAF-mutant CRC, which were presented at the 2016
ASCO annual meeting. In this study median Overall Survival for
these patients exceeded one year, which is more than double several
historical published benchmarks for this population.
Colorectal cancer is the second most common cancer among men and
third most common cancer among women in the United States, with more than 135,000 new
cases and more than 50,000 deaths from the disease projected in
2017. In the United States, BRAF
mutations occur in 8 to 15 percent of patients with colorectal
cancer and represent a poor prognosis for these patients.
ARRY-382 + KEYTRUDA PHASE 1/2 TRIAL: Phase 1b/2 expansions
to begin shortly
Array is advancing a Phase 1/2 dose
escalation immuno-oncology trial of ARRY-382 in combination with
KEYTRUDA, in patients with advanced solid tumors. ARRY-382 is a
wholly-owned, highly selective and potent, small molecule inhibitor
of CSF-1R kinase activity. Planned expansions include patients with
melanoma and non-small cell lung cancer.
FINANCIAL HIGHLIGHTS
Novartis continues to
substantially fund all ongoing trials with binimetinib and
encorafenib that were active or planned as of the close of the
Novartis Agreements in 2015, including the NEMO and COLUMBUS Phase
3 trials. Reimbursement revenue from Novartis was approximately
$119 million for the previous 12
months, of which $26 million was
recorded over the quarter ending March 31,
2017.
Third Quarter of Fiscal 2017 Compared to Second Quarter of
Fiscal 2017 (Sequential Quarters Comparison)
- Revenue for the third quarter of fiscal 2017 was
$33.3 million, compared to
$44.5 million for the prior
sequential quarter. The decrease was primarily due to non-recurring
milestones received in the prior quarter.
- Cost of partnered programs for the third quarter of
fiscal 2017 was $7.4 million,
compared to $9.0 million for the
prior quarter.
- Research and development expense was $46.1 million, compared to $46.5 million in the prior quarter.
- Loss from Operations for the quarter was $31.9 million, which includes $2.9 million of stock-based compensation and
$0.5 million of depreciation
expense. This compares to a loss from operations of
$20.0 million in the previous
quarter, which included $2.1 million
of stock-based compensation and $0.5
million of depreciation expense.
- Net loss for the third quarter was $35.3 million, or ($0.21) per share, compared to $23.3 million, or ($0.14) per share, in the prior quarter.
The increase in net loss was primarily due to non-recurring
milestones received in the prior quarter.
- Cash, Cash Equivalents and Marketable Securities as of
March 31, 2017 were $207 million.
Third Quarter of Fiscal 2017 Compared to Third Quarter of
Fiscal 2016 (Prior Year Comparison)
- Revenue for the third quarter of fiscal 2017 decreased
$9.8 million compared to the same
quarter of fiscal 2016. The decrease was primarily due to decreased
reimbursement revenue for the Novartis transitioned studies.
- Cost of partnered programs increased $1.6 million compared to the third quarter of
fiscal 2016. The increase was primarily due to higher costs
incurred for the BEACON CRC trial.
- Research and development expense decreased $2.7 million, compared to the third quarter of
fiscal 2016. The decrease was due to greater expenses associated
with the Novartis transitioned binimetinib and encorafenib
studies.
- Net loss for the third quarter of fiscal 2017 was
$35.3 million, or ($0.21) per share, compared to $22.7 million, or ($0.16) per share, for the same quarter in
fiscal 2016.
LEADERSHIP
Array announced that Shalini Sharp, Chief Financial Officer and
Executive Vice President of Ultragenyx Pharmaceutical Inc., joined
the company's Board of Directors, effective April 27, 2017. Ms. Sharp has been appointed to
the Audit Committee of the Board.
CONFERENCE CALL INFORMATION
Array will hold a
conference call on Wednesday, May 10,
2017 at 9:00 a.m. Eastern Time
to discuss these results and provide an update on the progress of
its key clinical development programs. Ron Squarer, Chief Executive
Officer, will lead the call.
Date:
|
Wednesday, May 10,
2017
|
Time:
|
9:00 a.m. Eastern
Time
|
Toll-Free:
|
(844)
464-3927
|
Toll:
|
(765)
507-2598
|
Pass
Code:
|
92608803
|
Webcast, including Replay and Conference Call Slides:
http://edge.media-server.com/m/p/hgm92o9w
About the Phase 3 COLUMBUS Study
The COLUMBUS trial,
(NCT01909453), is a two-part, international, randomized, open label
Phase 3 study evaluating the efficacy and safety of the combination
of binimetinib plus encorafenib to vemurafenib and encorafenib
monotherapy in 921 patients with locally advanced, unresectable or
metastatic melanoma with BRAF V600 mutation. Prior
immunotherapy treatment was allowed. Over 200 sites across
North America, Europe, South
America, Africa,
Asia and Australia participated in the study. Patients
were randomized into two parts:
•
|
In COLUMBUS Part 1,
577 patients were randomized 1:1:1 to receive 45mg binimetinib plus
450mg encorafenib (COMBO450), 300mg encorafenib alone, or 960mg
vemurafenib alone. The dose of encorafenib in the combination arm
is 50% higher than the single agent maximum tolerated dose of
300mg. A higher dose of encorafenib was possible due to
improved tolerability when combined with binimetinib. The
primary endpoint for the COLUMBUS trial was a PFS comparison of
COMBO450 versus vemurafenib. PFS is determined based on tumor
assessment (RECIST version 1.1 criteria) by a Blinded Independent
Central Review (BICR). Secondary endpoints include a comparison of
the PFS of encorafenib monotherapy to that of COMBO450 and a
comparison of overall survival (OS) for COMBO450 to that of
vemurafenib alone.
|
|
|
|
In November 2016,
results from Part 1 were presented at the Society for Melanoma
Research Annual Congress. The study met its primary endpoint, with
COMBO450 significantly improving PFS compared with vemurafenib
alone. In the analysis of the primary endpoint, the mPFS for
patients treated with COMBO450 was 14.9 months versus 7.3 months
for patients treated with vemurafenib; hazard ratio (HR) 0.54, (95%
CI 0.41-0.71, P<0.001). As part of the trial design, the primary
analysis was based on a BICR of patient scans, while results by
local review at the investigative site were also analyzed. The
chart below outlines the mPFS results, as determined by both
assessments, for COMBO450 versus vemurafenib, COMBO450 versus
encorafenib, and encorafenib versus vemurafenib:
|
|
|
|
|
mPFS
BICR
|
|
mPFS Local
Review
|
COMBO450
vs.
Vemurafenib
|
|
COMBO450
|
Vemurafenib
|
|
COMBO450
|
Vemurafenib
|
|
14.9
months
|
7.3 months
|
|
14.8
months
|
7.3 months
|
|
HR (95% CI): 0.54
(0.41-0.71); P<0.001
|
|
HR (95% CI): 0.49
(0.37-0.64); P<0.001
|
|
COMBO450
vs.
Encorafenib
|
|
COMBO450
|
Encorafenib
|
|
COMBO450
|
Encorafenib
|
|
14.9
months
|
9.6 months
|
|
14.8
months
|
9.2 months
|
|
HR (95% CI): 0.75
(0.56-1.00); P=0.051
|
|
HR (95% CI): 0.68
(0.52-0.90); P=0.006
|
|
Encorafenib
vs.
Vemurafenib
|
|
Encorafenib
|
Vemurafenib
|
|
Encorafenib
|
Vemurafenib
|
|
9.6 months
|
7.3 months
|
|
9.2 months
|
7.3 months
|
|
HR (95% CI): 0.68
(0.52-0.90); P=0.007
|
|
HR (95% CI): 0.70
(0.54-0.91); P=0.008
|
|
|
|
|
COMBO450 was
generally well-tolerated and reported adverse events (AEs) were
overall consistent with previous bini/enco combination clinical
trial results in BRAF-mutant melanoma patients. Grade 3/4 AEs which
occurred in more than 5 percent of patients receiving COMBO450
included increased gamma-glutamyltransferase (GGT), increased blood
creatine phosphokinase (CK), and hypertension. The incidence of AEs
of special interest (toxicities commonly associated with
commercially available MEK+BRAF-inhibitor treatments), for patients
receiving COMBO450 included: rash (23 percent), pyrexia (18
percent), retinal pigment epithelial detachment (13 percent) and
photosensitivity (5 percent).
|
|
|
|
|
•
|
In COLUMBUS Part 2,
344 patients were randomized 3:1 to receive 45mg binimetinib plus
300mg encorafenib or 300mg encorafenib alone. Part 2 was designed
to provide additional data to help evaluate the contribution of
binimetinib to the combination of binimetinib and encorafenib. As
the comparison of COMBO450 to encorafenib in Part 1 did not achieve
statistical significance, the statistical analysis conducted in
Part 2 is descriptive.
|
|
About Array BioPharma
Array BioPharma Inc. is a
biopharmaceutical company focused on the discovery, development and
commercialization of targeted small molecule drugs to treat
patients afflicted with cancer. Seven registration studies are
currently advancing related to seven drugs: binimetinib (MEK162),
encorafenib (LGX818), selumetinib (partnered with AstraZeneca),
danoprevir (partnered with Roche), larotrectinib (partnered with
Loxo Oncology), tucatinib (partnered with Cascadian Therapeutics)
and ipatasertib (partnered with Genentech).
Forward-Looking Statement
This press release contains
forward-looking statements within the meaning of the Private
Securities Litigation Reform Act of 1995, including statements
about the timing of the announcement of the results of clinical
trials for our proprietary and our partnered programs, the timing
of the completion or initiation of further development of our
wholly-owned and our partnered programs, including the timing of
regulatory filings for binimetinib/encorafenib, expectations that
events will occur that will result in greater value for Array, the
potential for the results of ongoing preclinical and clinical
trials to support regulatory approval or the marketing success of a
drug candidate, our ability to partner our proprietary drug
candidates for up-front fees, milestone and/or royalty payments,
our future plans to progress and develop our proprietary programs,
our future capital requirements and the plans of our collaborators
to progress and develop programs we have licensed to them, and our
plans to build a late-stage development company. These statements
involve significant risks and uncertainties, including those
discussed in our most recent annual report filed on Form 10-K, in
our quarterly reports filed on Form 10-Q, and in other reports
filed by Array with the Securities and Exchange Commission. Because
these statements reflect our current expectations concerning future
events, our actual results could differ materially from those
anticipated in these forward-looking statements as a result of many
factors. These factors include, but are not limited to, our ability
to continue to fund and successfully progress internal research and
development efforts and to create effective, commercially-viable
drugs; risks relating to the regulatory approval process for our
drug candidates, which may not result in approval for our drug
candidates, cause delays in development or require that we expend
more resources to obtain approval than expected; risks associated
with our dependence on our collaborators for the clinical
development and commercialization of our out-licensed drug
candidates; the ability of our collaborators and of Array to meet
objectives tied to milestones and royalties; our ability to
effectively and timely conduct clinical trials in light of
increasing costs and difficulties in locating appropriate trial
sites and in enrolling patients who meet the criteria for certain
clinical trials; risks associated with our dependence on
third-party service providers to successfully conduct clinical
trials within and outside the United
States; our ability to achieve and maintain profitability
and maintain sufficient cash resources; the extent to which the
pharmaceutical and biotechnology industries are willing to
in-license drug candidates for their product pipelines and to
collaborate with and fund third parties on their drug discovery
activities; our ability to out-license our proprietary candidates
on favorable terms; and our ability to attract and retain
experienced scientists and management. We are providing this
information as of May 10, 2017. We
undertake no duty to update any forward-looking statements to
reflect the occurrence of events or circumstances after the date of
such statements or of anticipated or unanticipated events that
alter any assumptions underlying such statements.
Array BioPharma
Inc.
|
Condensed
Statements of Operations
|
(Unaudited)
|
(in thousands, except
per share amounts)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Three Months
Ended
March 31,
|
|
Nine Months
Ended
March 31,
|
|
|
|
|
|
|
2017
|
|
2016
|
|
2017
|
|
2016
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Revenue
|
|
|
|
|
|
|
|
|
|
|
Reimbursement revenue
- Novartis
|
|
|
$
26,085
|
|
$
36,941
|
|
$
85,354
|
|
$
73,912
|
|
Collaboration
revenue
|
|
|
5,530
|
|
5,249
|
|
17,849
|
|
18,800
|
|
License and milestone
revenue
|
|
|
1,665
|
|
857
|
|
13,871
|
|
1,962
|
|
|
Total
revenue
|
|
|
33,280
|
|
43,047
|
|
117,074
|
|
94,674
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Operating
expenses
|
|
|
|
|
|
|
|
|
|
|
Cost of partnered
programs
|
|
|
7,432
|
|
5,847
|
|
25,303
|
|
17,722
|
|
Research and
development for proprietary programs
|
|
|
46,069
|
|
48,802
|
|
139,101
|
|
111,151
|
|
General and
administrative
|
|
|
11,714
|
|
8,406
|
|
28,410
|
|
25,702
|
|
|
Total operating
expenses
|
|
|
65,215
|
|
63,055
|
|
192,814
|
|
154,575
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Loss from
operations
|
|
|
(31,935)
|
|
(20,008)
|
|
(75,740)
|
|
(59,901)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Other income
(expense)
|
|
|
|
|
|
|
|
|
|
|
Impairment loss
related to cost method investment
|
|
|
-
|
|
-
|
|
(1,500)
|
|
-
|
|
Realized gain on
investments and other
|
|
|
785
|
|
-
|
|
785
|
|
-
|
|
Change in fair value
of notes payable
|
|
|
(1,300)
|
|
-
|
|
(2,100)
|
|
-
|
|
Interest
income
|
|
|
228
|
|
76
|
|
510
|
|
167
|
|
Interest
expense
|
|
|
(3,095)
|
|
(2,743)
|
|
(9,181)
|
|
(8,092)
|
|
|
Total other expense,
net
|
|
|
(3,382)
|
|
(2,667)
|
|
(11,486)
|
|
(7,925)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Net
loss
|
|
|
$
(35,317)
|
|
$
(22,675)
|
|
$
(87,226)
|
|
$
(67,826)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Net loss per share
- basic
|
|
|
$
(0.21)
|
|
$
(0.16)
|
|
$
(0.54)
|
|
$
(0.47)
|
Net loss per share
- diluted
|
|
|
$
(0.21)
|
|
$
(0.16)
|
|
$
(0.54)
|
|
$
(0.47)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Weighted average
shares outstanding - basic
|
|
|
169,020
|
|
143,338
|
|
160,689
|
|
142,792
|
Weighted average
shares outstanding - diluted
|
|
|
169,020
|
|
143,338
|
|
160,689
|
|
142,792
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Summary Balance
Sheet Data
|
(in
thousands)
|
|
|
|
|
|
|
March
31,
|
|
June
30,
|
|
|
|
|
|
|
|
2017
|
|
2016
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Cash, cash
equivalents and marketable securities
|
|
|
|
$
207,392
|
|
$
110,538
|
|
|
|
Working
capital
|
|
|
|
$
175,701
|
|
$
102,867
|
|
|
|
Total
assets
|
|
|
|
$
256,202
|
|
$
168,900
|
|
|
|
Long-term debt,
net
|
|
|
|
$
119,394
|
|
$
113,655
|
|
|
|
Stockholders'
equity
|
|
|
|
$
27,714
|
|
$
(37,932)
|
|
CONTACT:
|
Tricia
Haugeto
|
|
(303)
386-1193
|
|
thaugeto@arraybiopharma.com
|
To view the original version on PR Newswire,
visit:http://www.prnewswire.com/news-releases/array-biopharma-reports-financial-results-for-the-third-quarter-of-fiscal-2017-300454928.html
SOURCE Array BioPharma