- Strong balance sheet of $393.9
million cash, cash equivalents and marketable securities as
of September 30, 2022 is anticipated
to fund planned operations into 2026
- Reported Phase 2 interim clinical data for darovasertib and
crizotinib combination in MUM; subject to FDA guidance, targeting
initiation of potential registrational trial for Daro + Crizo in
MUM in Q1 2023
- Reported preliminary clinical proof-of-concept supporting
potential darovasertib use in (neo)adjuvant uveal melanoma;
targeting initiation of company-sponsored trial for Daro in
neoadjuvant UM in Q4 2022
- Initiated IDE397 Phase 2 monotherapy expansion cohorts and
Phase 1 combination dose escalation cohorts with pemetrexed and
taxanes in MTAP-null tumors
- Targeting IND filing in Q4 2022 for PARG development candidate
IDE161
- Targeting First-in-Human Phase 1 study initiation in H1 2023
for Pol Theta Helicase inhibitor development candidate, in
collaboration with GSK, for solid tumors with HRD
- Hosting IDEAYA Investor R&D Day on Monday, December 12, 2022 at 8:00 am ET
SOUTH
SAN FRANCISCO, Calif., Nov. 8, 2022
/PRNewswire/ -- IDEAYA Biosciences, Inc. (Nasdaq:IDYA), a synthetic
lethality focused precision medicine oncology company committed to
the discovery and development of targeted therapeutics, provided a
business update and announced financial results for the third
quarter ended September 30, 2022.
"Our clinical portfolio is maturing, with four potential
first-in-class clinical-stage programs anticipated in the first
half of 2023 – darovasertib (PKC), IDE397 (MAT2A), IDE161 (PARG)
and our Pol Theta Helicase inhibitor development candidate. This
broad pipeline of precision medicine therapeutics reflects our
commitment to develop transformative therapies with the potential
to improve patient lives," said Yujiro S.
Hata, President and Chief Executive Officer, IDEAYA
Biosciences. "We have built a unique platform in synthetic
lethality and an organization with the capabilities to effectively
discover and advance our growing preclinical and clinical precision
medicine oncology pipeline. Importantly, we own or control all
development and commercial rights and interests in our three most
advanced programs," continued Mr. Hata.
IDEAYA's most advance clinical program is darovasertib, a
potential first-in-class small molecule oral protein kinase C (PKC)
inhibitor for patients having tumors with GNAQ/11 mutations. The
company reported positive Phase 2 interim clinical data for
darovasertib and crizotinib synthetic lethal combination in
metastatic uveal melanoma (MUM) in September
2022 and is targeting initiation of a potential
registrational trial in MUM in the first quarter of 2023. IDEAYA
also reported preliminary clinical proof-of-concept for a potential
expansion opportunity in (neo)adjuvant uveal melanoma (UM) and is
targeting initiation of company-sponsored trial for darovasertib
monotherapy in neoadjuvant UM in the fourth quarter of 2022.
IDEAYA's clinical pipeline also includes IDE397, a potential
first-in-class Phase 2 MAT2A inhibitor, for patients having tumors
with MTAP deletion, which represents approximately 15% of all solid
tumors. Clinical data from Phase 1 monotherapy dose escalation
reflects robust target engagement and an observed therapeutic
window, positioning IDE397 to evaluate clinical efficacy – as
monotherapy and multiple combination therapies. IDEAYA's clinical
development plan includes an emphasis on combination strategies,
based on observed in vivo efficacy in preclinical studies.
The company believes that IDE397 combination therapies could
potentially enhance clinical efficacy in patients having tumors
with MTAP deletion.
The company's preclinical pipeline includes several potential
first-in-class synthetic lethal therapeutics advancing toward the
clinic. IDEAYA is targeting an IND in the fourth quarter of 2022
for IDE161, its PARG inhibitor, for patients having tumors with
HRD. In collaboration with GSK, the company is targeting
first-in-human clinical evaluation in the first half of 2023 for
its Pol Theta Helicase inhibitor development candidate in
combination with niraparib for patients having tumors with HRD. Its
Werner Helicase program continues in collaboration with GSK toward
development candidate nomination in 2023.
Program Updates
Key highlights for IDEAYA's pipeline
programs include:
Darovasertib (PKC)
IDEAYA continues to advance its Phase 1/2 clinical trial evaluating
darovasertib (IDE196), a potent and selective PKC inhibitor, in
combination with crizotinib, a cMET inhibitor, in metastatic uveal
melanoma (MUM). The company is also clinically evaluating
darovasertib in (neo)adjuvant uveal melanoma (UM) as monotherapy
through an investigator sponsor clinical trial (IST).
IDEAYA is planning to initiate a company-sponsored clinical
trial to evaluate darovasertib in (neo)adjuvant uveal
melanoma. The company is also evaluating other potential
darovasertib expansion opportunities, including in cMET driven
tumors and in KRAS-mutation tumors.
Darovasertib / Crizotinib Combination Therapy in Metastatic
Uveal Melanoma (MUM)
IDEAYA is continuing patient enrollment
into the darovasertib / crizotinib combination arm of the Phase 1/2
clinical trial in MUM under clinical trial collaboration and supply
agreements with Pfizer, with continued emphasis on enrollment of
first-line MUM patients. Highlights:
- IDEAYA presented interim Phase 2 darovasertib and crizotinib
clinical combination data in September
2022. The reported data, based on an unlocked database with
a data analyses cutoff date of June 26,
2022, showed robust clinical activity. These
investigator-reviewed data by RECIST 1.1 include, as of the data
analysis cutoff date:
-
- 89% of patients show tumor shrinkage in Any-Line MUM: 31 of 35
evaluable patients showed tumor shrinkage as determined by target
lesion size reduction;
- 83% Disease Control Rate (DCR) in Any-Line MUM: 29 of 35
evaluable patients showed stable disease or better as determined by
target lesion size reduction;
- 50% Overall Response Rate (ORR) in First-Line MUM: 4 of 8
evaluable patients had a confirmed partial response;
- 31% Overall Response Rate (ORR) in Any-Line MUM: 11 of 35
evaluable patients had a confirmed partial response;
- 43% of patients with >30% Tumor Reduction in Any-Line MUM:
15 of 35 evaluable patients observed partial responses with >30%
tumor reduction, including 11 confirmed and 4 unconfirmed partial
responses;
- Median Study Follow-Up of 6.5 months for First-Line MUM
patients and 7.8 months for Any-Line MUM patients;
- Median Duration of Response (DOR) in evaluable First-Line MUM
patients has not yet been reached and 4 of 4 patients with
confirmed PR's in First-Line MUM remain in response; median DOR in
evaluable Any-Line MUM patients has not yet been reached and 7 of
11 patients with confirmed PR's in Any-Line MUM remain in
response;
- Median Progression Free Survival (PFS) in First-Line MUM
patients has not yet been reached and is >5 months in evaluable
First-Line MUM patients; median PFS for evaluable Any-Line MUM
patients is ~5 months; and
- The darovasertib and crizotinib combination therapy has
indicated a manageable adverse event profile in MUM patients (n=37)
at the combination expansion doses, with a low rate of drug-related
serious adverse events (SAEs) and with no Grade 4 or Grade 5
drug-related adverse events observed as of the data analysis cutoff
date of June 26, 2022;
- Targeting initiation of a potential registration-enabling trial
for the darovasertib and crizotinib combination in MUM in Q1 2023,
subject to FDA feedback and guidance, in collaboration with Pfizer
under a clinical collaboration and supply agreement
- In April 2022, the U.S. FDA
designated darovasertib as an Orphan Drug in Uveal Melanoma,
including MUM
Darovasertib – (Neo)Adjuvant Uveal Melanoma
(UM)
IDEAYA is evaluating the potential for darovasertib in
neoadjuvant and/or adjuvant uveal melanoma. Highlights:
- (Neo)adjuvant UM represents a significant expansion opportunity
– with a potential annual incidence of approximately 8,700 patients
aggregate in US and Europe
- Initiated an Investigator Sponsored Trial in coordination with
St. Vincent's Hospital Sydney Limited to evaluate darovasertib
monotherapy in (neo)adjuvant UM patients
- Reported preliminary clinical proof-of-concept data in
September 2022, with observed
clinical activity supporting potential darovasertib use in the
(neo)adjuvant uveal melanoma setting. As of a data cut-off date of
August 19, 2022, these data include
observed tumor shrinkage by investigator review of primary ocular
lesions in 5 of 5 (100%) UM or MUM patients treated as monotherapy
or in combination with crizotinib and observed improvement in
visual symptoms in the affected eye in two MUM patients having
intact primary tumors
- Targeting initiation of an IDEAYA-sponsored clinical trial in
Q4 2022 to further evaluate darovasertib monotherapy in neoadjuvant
UM patients, including potential clinical endpoints such as vision
and organ preservation which would be temporally proximal to
primary interventional treatments
Darovasertib – Other Potential Indications
IDEAYA is
evaluating the potential for darovasertib in other oncology
indications, including in cMET-driven tumors and RAS-mutation
tumors. Highlights:
- Evaluating darovasertib in combination with crizotinib, an
investigational cMET inhibitor, in preclinical studies in
cMET-driven tumors, such as NSCLC or HCC. Subject to preclinical
evaluation and portfolio priorities, we may evaluate this
combination in a Phase 1/2 clinical trial in collaboration with
Pfizer under a clinical collaboration and supply agreement
- Evaluating darovasertib in combination with a KRAS inhibitor in
preclinical studies in KRAS-driven solid tumors
IDE397 (MAT2A)
IDEAYA is clinically evaluating IDE397, a potent and selective
small molecule inhibitor targeting methionine adenosyltransferase
2a (MAT2A), in patients having solid tumors with
methylthioadenosine phosphorylase (MTAP) deletion, a patient
population estimated to represent approximately 15% of solid
tumors. IDEAYA is continuing clinical development of IDE397 in its
Phase 1/2 clinical trial, IDE397-001 (NCT04794699). Highlights:
- Patients are being identified by next generation sequencing
(NGS) or by MTAP immunohistochemistry (IHC) assay with confirmatory
NGS
- Initiated and actively enrolling patients into monotherapy
expansion cohorts, with a focus on squamous cell NSCLC and
esophagogastric cancer, consistent with preclinical efficacy and
translational data
- Initiated combination dose escalation cohorts with enrollment
open for combinations of IDE397 with pemetrexed and taxanes, each
of which are standard-of-care agents used as early-line therapies
in NSCLC, mesothelioma and other solid tumor indications. The
combination of IDE397 with pemetrexed is a novel and potential
first-in-class combination of a MAT2A inhibitor with an antifolate
agent.
- Entered into Clinical Trial Collaboration and Supply Agreement
with Amgen to clinically evaluate IDE397 MAT2A inhibitor in
combination with AMG 193, Amgen's investigational small molecule
MTA-cooperative inhibitor of PRMT5, in MTAP-null solid
tumors. The combination of IDE397 with AMG 193 is a novel and
potential first-in-class synthetic lethality combination which
targets two distinct and mechanistically complementary nodes of the
MTAP methylation pathway – MAT2A and PRMT5, providing a
complementary approach for targeting MTAP-deletion
tumors.
- IDEAYA owns all right, title and interest in and to IDE397 and
the MAT2A program, including all worldwide commercial rights
thereto, following GSK waiver in August
2022 of its right to exercise its option to obtain an
exclusive license to further develop and commercialize IDE397, as
well as other IDEAYA compounds, if any, directly targeting
MAT2A
- Demonstrated IDE397 clinical tumor pharmacodynamic modulation
based on ctDNA Molecular Responses observed in thirteen evaluable
patients with liquid biopsy samples available at baseline and after
first treatment cycle, including:
-
- 31% (n=4 of 13) of evaluable patients treated with IDE397
across all dose escalation Cohorts 1 thru 6 observed ctDNA
molecular responses
- 75% (n=3 of 5) of evaluable patients treated with IDE397 at
higher doses in Cohorts 5 and 6 observed ctDNA molecular
responses
- 100% (n=2 of 2) of evaluable NSCLC patients observed ctDNA
molecular responses
PARG
IDEAYA is advancing its poly (ADP-ribose) glycohydrolase (PARG)
inhibitor development candidate, IDE161, in patients having tumors
with a defined biomarker based on genetic mutations and/or
molecular signature. IDE161 is a potential first-in-class
PARG inhibitor development candidate for patients having tumors
with homologous recombination deficiencies (HRD), including BRCA1
and BRCA2, and potentially other alterations, in solid tumors such
as breast cancer or ovarian cancer. PARG is a novel target in the
same clinically validated biological pathway as poly (ADP-ribose)
polymerase (PARP). IDEAYA owns or controls all commercial rights in
its PARG program. Highlights:
- Targeting IND for IDE161 in the fourth quarter of 2022
- Considering potential development approaches based on observed
activity of IDE161 in PARPi resistant and/or platinum-resistant
tumors, differentiated sensitivity relative to PARP inhibitors, and
improved preliminary safety profile relative to PARP
inhibitors
Pol Theta
IDEAYA's DNA Polymerase Theta, (Pol Theta) program targets tumors
with BRCA or other homologous recombination (HR) mutations or
homologous recombination deficiency (HRD). IDEAYA and GSK are
collaborating on ongoing preclinical research and GSK will lead
clinical development for the Pol Theta program.
Highlights:
- Selected a potential first-in-class Pol Theta Helicase
inhibitor development candidate (DC) in collaboration with GSK
- Observed tumor regressions in preclinical combination studies
of Pol Theta Helicase DC with niraparib in multiple in vivo PDX and
CDX HRD models
- Targeting first-in-human clinical evaluation of Pol Theta
Helicase inhibitor DC combination with niraparib in H1 2023 for
patients having tumors with HRD
- IDEAYA achieved the first preclinical development milestone in
connection with ongoing IND-enabling studies to support evaluation
of Pol Theta Helicase Inhibitor DC
- IDEAYA is eligible to receive total development and regulatory
milestones of up to $485 million
aggregate from GSK, with up to $20
million in aggregate for advancing a Pol Theta Helicase
inhibitor from preclinical to early Phase 1 clinical, including up
to $10 million aggregate through IND
effectiveness
Werner Helicase
IDEAYA is advancing preclinical research for an inhibitor targeting
Werner Helicase for tumors with high microsatellite instability
(MSI). IDEAYA and GSK are collaborating on ongoing preclinical
research, and GSK will lead clinical development for the Werner
Helicase program. Highlights:
- Targeting selection of a Werner Helicase development candidate
in 2023
- IDEAYA is eligible to receive future development and regulatory
milestones of up to $485 million
aggregate from GSK, with potential for up to $20 million in aggregate for advancing a Werner
Helicase inhibitor from preclinical to early Phase 1 clinical
Other Synthetic Lethality Pipeline Programs
IDEAYA is advancing additional preclinical research programs to
identify small molecule inhibitors for an MTAP-synthetic lethality
target, as well as for multiple potential first-in-class synthetic
lethality programs for patients with solid tumors characterized by
proprietary biomarkers or gene signatures.
General
IDEAYA continues to monitor Covid-19 and its
potential impact on clinical trials and timing of clinical data
results. Initiation of clinical trial sites, patient enrollment and
ongoing monitoring of enrolled patients, including obtaining
patient computed tomography (CT) scans, may be impacted for IDEAYA
clinical trials evaluating IDE397 and darovasertib; the specific
impacts are currently uncertain.
Corporate Updates
IDEAYA's net income was $1.6 million for the three months ended
September 30, 2022 and its net loss
was $22.1 million for the three
months ended June 30, 2022. As of
September 30, 2022, the company had
an accumulated deficit of $211.2
million.
As of September 30, 2022, IDEAYA
had cash, cash equivalents and marketable securities of
$393.9 million. IDEAYA believes
that its cash, cash equivalents and marketable securities will be
sufficient to fund its planned operations into 2026. These funds
will support the company's efforts through potential achievement of
multiple preclinical and clinical milestones across multiple
programs.
Our updated corporate presentation is available on our website,
at our Investor Relations page:
https://ir.ideayabio.com/.
Financial Results
As of September 30, 2022, IDEAYA had cash, cash
equivalents and short-term marketable securities totaling
$393.9 million. This compared to
cash, cash equivalents and short-term and long-term marketable
securities of $323.8 million at
June 30, 2022. The increase was
attributable to receipt of aggregate net proceeds of $86.1 million from the sale of shares of IDEAYA
common stock in an underwritten public financing in September 2022 and net proceeds of $8.9 million from the sale of shares of IDEAYA
common stock under an at-the-market offering program during the
three months ended September 30,
2022, partially offset by cash used in operations.
Collaboration revenue for the three months ended September 30, 2022 totaled $29.7 million compared to $5.9 million for the three months ended
June 30, 2022. Collaboration revenue
was recognized for the performance obligations satisfied through
September 30, 2022 under the GSK
Collaboration Agreement. The increase was primarily driven by
non-recurring revenue recognized upon achievement of the Pol Theta
preclinical development milestone, GSK's waiver of its option
related to MAT2A program and an increase in collaboration revenue
for R&D services performed related to the Pol Theta and Werner
Helicase programs. Generally, revenue recognition related to the
GSK Collaboration Agreement, including as related to the previously
received upfront payment or to certain development milestone
payments, may vary considerably by period and certain components
thereof may generally decrease year-over-year as we satisfy
remaining performance obligations, for example, relating to the Pol
Theta and WRN R&D Services.
Research and development (R&D) expenses for the three months
ended September 30, 2022 totaled
$22.4 million compared to
$22.8 million for the three months
ended June 30, 2022. The decrease was
primarily due to lower clinical trial and external research
expenses, partially offset by higher consulting expenses.
General and administrative (G&A) expenses for the three
months ended September 30, 2022
totaled $6.7 million compared to
$5.6 million for the three months
ended June 30, 2022. The increase was
primarily due to higher operational, consulting and
personnel-related expenses.
The net income for the three months ended September 30, 2022 was $1.6 million compared to the net loss of
$22.1 million for the three months
ended June 30, 2022. Total stock
compensation expense for the three months ended September 30, 2022 was $3.0 million compared to $3.0 million for the three months ended
June 30, 2022.
About IDEAYA Biosciences
IDEAYA is a synthetic
lethality focused precision medicine oncology company committed to
the discovery and development of targeted therapeutics for patient
populations selected using molecular diagnostics. IDEAYA's approach
integrates capabilities in identifying and validating translational
biomarkers with drug discovery to select patient populations most
likely to benefit from its targeted therapies. IDEAYA is applying
its research and drug discovery capabilities to synthetic lethality
– which represents an emerging class of precision medicine
targets.
Forward-Looking Statements
This press release contains
forward-looking statements, including, but not limited to,
statements related to (i) the extent to which IDEAYA's
existing cash, cash equivalents, and marketable securities will
fund its planned operations, (ii) the timing of initiation of a
potential registrational trial for the darovasertib and crizotinib
combination, (iii) the timing of initiation of a company-sponsored
trial for darovasertib in a neoadjuvant setting (iv) the timing of
submitting an IND for PARG inhibitor, IDE161, (v) the timing of
initiation of first-in-human clinical evaluation of Pol Theta
inhibitor with niraparib, (vi) the timing and occurrence of the
Investor R&D Day, (vii) the timing of identification of a
development candidate for a Werner Helicase inhibitor, (viii) the
receipt of development and regulatory milestones, and (ix) the
impact of COVID-19. Such forward-looking statements involve
substantial risks and uncertainties that could cause IDEAYA's
preclinical and clinical development programs, future results,
performance or achievements to differ significantly from those
expressed or implied by the forward-looking statements. Such risks
and uncertainties include, among others, the uncertainties inherent
in the drug development process, including IDEAYA's programs' early
stage of development, the process of designing and conducting
preclinical and clinical trials, the regulatory approval processes,
the timing of regulatory filings, the challenges associated with
manufacturing drug products, IDEAYA's ability to successfully
establish, protect and defend its intellectual property, the
effects on IDEAYA's business of the worldwide COVID-19 pandemic,
the ongoing military conflict between Russia and Ukraine, and other matters that could affect
the sufficiency of existing cash to fund operations. IDEAYA
undertakes no obligation to update or revise any forward-looking
statements. For a further description of the risks and
uncertainties that could cause actual results to differ from those
expressed in these forward-looking statements, as well as risks
relating to the business of IDEAYA in general, see IDEAYA's recent
Quarterly Report on Form 10-Q filed on November 8, 2022 and any current and periodic
reports filed with the U.S. Securities and Exchange Commission.
Investor and Media Contact
IDEAYA Biosciences
Paul Stone
Senior Vice President and Chief Financial Officer
investor@ideayabio.com
IDEAYA Biosciences,
Inc. Condensed Statements of Operations and Comprehensive
Loss (in thousands, except share and per share
amounts) (Unaudited)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Three Months
Ended
|
|
|
Nine Months
Ended
|
|
|
|
September 30,
|
|
|
June
30,
|
|
|
September 30,
|
|
|
September 30,
|
|
|
|
2022
|
|
|
2022
|
|
|
2022
|
|
|
2021
|
|
Collaboration
revenue
|
|
$
|
29,699
|
|
|
$
|
5,851
|
|
|
$
|
46,909
|
|
|
$
|
24,979
|
|
Operating
expenses:
|
|
|
|
|
|
|
|
|
|
|
|
|
Research and
development
|
|
|
22,372
|
|
|
|
22,796
|
|
|
|
64,823
|
|
|
|
42,048
|
|
General and
administrative
|
|
|
6,667
|
|
|
|
5,554
|
|
|
|
18,145
|
|
|
|
14,830
|
|
Total operating
expenses
|
|
|
29,039
|
|
|
|
28,350
|
|
|
|
82,968
|
|
|
|
56,878
|
|
Income (loss) from
operations
|
|
|
660
|
|
|
|
(22,499)
|
|
|
|
(36,059)
|
|
|
|
(31,899)
|
|
Interest income and
other income, net
|
|
|
955
|
|
|
|
443
|
|
|
|
1,604
|
|
|
|
349
|
|
Net income
(loss)
|
|
|
1,615
|
|
|
|
(22,056)
|
|
|
|
(34,455)
|
|
|
|
(31,550)
|
|
Unrealized loss on
marketable securities
|
|
|
(373)
|
|
|
|
(825)
|
|
|
|
(3,289)
|
|
|
|
(57)
|
|
Comprehensive income
(loss)
|
|
$
|
1,242
|
|
|
$
|
(22,881)
|
|
|
$
|
(37,744)
|
|
|
$
|
(31,607)
|
|
Net income (loss) per
share
attributable to common
stockholders, basic
|
|
$
|
0.04
|
|
|
$
|
(0.57)
|
|
|
$
|
(0.88)
|
|
|
$
|
(0.92)
|
|
Weighted-average number
of shares
outstanding, basic
|
|
|
40,301,568
|
|
|
|
38,660,971
|
|
|
|
39,191,098
|
|
|
|
34,157,578
|
|
Net income (loss) per
share
attributable to common
stockholders, diluted
|
|
$
|
0.04
|
|
|
$
|
(0.57)
|
|
|
$
|
(0.88)
|
|
|
$
|
(0.92)
|
|
Weighted-average number
of shares
outstanding, diluted
|
|
|
41,109,571
|
|
|
|
38,660,971
|
|
|
|
39,191,098
|
|
|
|
34,157,578
|
|
IDEAYA Biosciences,
Inc. Condensed Balance Sheet Data (in
thousands)
|
|
|
|
September 30,
|
|
|
December 31,
|
|
|
|
2022
|
|
|
2021
|
|
|
|
(Unaudited)
|
|
|
|
|
Cash and cash
equivalents and short-term and
long-term marketable securities
|
|
$
|
393,935
|
|
|
$
|
368,063
|
|
Total assets
|
|
|
410,907
|
|
|
|
381,347
|
|
Total
liabilities
|
|
|
42,138
|
|
|
|
79,833
|
|
Total liabilities and
stockholders' equity
|
|
|
410,907
|
|
|
|
381,347
|
|
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SOURCE IDEAYA Biosciences, Inc.