- Strong balance sheet of ~$368
million cash, cash equivalents and marketable securities as
of December 31, 2021 is anticipated
to fund planned operations into 2025
- Enrolling into IDE397 Cohort 6 with no observed drug-related
serious adverse events and without observing maximum tolerated dose
through Cohort 5
- Observed robust dose-proportional pharmacokinetic exposures
and exposure-dependent pharmacodynamic modulation of S-adenosyl
methionine (SAM) in plasma and of symmetric dimethyl arginine
(SDMA) in tumor biopsy samples from Phase 1 dose escalation
cohorts
- Targeting IDE397 monotherapy cohort expansion and initiation
of combination cohorts mid-year 2022, the timing of which may be
influenced by observing the MTD
- Darovasertib and crizotinib clinical combination data
presented in December 2021 showed
robust clinical activity with manageable side effect profile,
including 100% DCR (n=16)
- Targeting additional darovasertib and crizotinib clinical
combination data mid-year 2022, the timing of which may be
influenced by data maturity, including observation of median
duration of response (DOR) and/or median progression free survival
(mPFS)
- Expanded relationship with Pfizer under a clinical
collaboration and supply agreement to support clinical evaluation
of darovasertib and crizotinib combination therapy in a potential
registration-enabling clinical trial in MUM, subject to FDA
guidance on trial design, and in additional cMET-driven tumors such
as NSCLC and/or HCC, subject to preclinical validation
SOUTH SAN FRANCISCO, Calif.,
March 15, 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 year ended
December 31, 2021.
![(PRNewsfoto/IDEAYA Biosciences, Inc.) (PRNewsfoto/IDEAYA Biosciences, Inc.)](https://mma.prnewswire.com/media/820568/IDEAYA_Logo.jpg)
"We are encouraged by the early clinical activity and the
tolerability profile in our clinical-stage programs, including our
Phase 1 MAT2A inhibitor, IDE397, in MTAP-deletion patients, and our
Phase 2 PKC inhibitor, darovasertib, in MUM and other GNAQ/11
patients. As these data mature, we are evaluating multiple
expansion opportunities for these clinical programs, including
various combination therapies. We are also aggressively
advancing our preclinical programs toward the clinic – including
our potential first-in-class PARG inhibitor, IDE161, for which are
targeting an IND in Q4 2022, and our potential first-in-class Pol
Theta helicase inhibitor, for which we are collaborating with GSK
with IND-enabling studies in H1 2022," said Yujiro S. Hata, Chief Executive Officer and
President of IDEAYA Biosciences.
Program Updates
Key highlights for IDEAYA's pipeline
programs include:
IDE397 (MAT2A)
IDEAYA is 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 leading early clinical development of IDE397. Subject to
exercise of its option, GlaxoSmithKline (GSK) will lead later stage
global clinical development. Highlights:
- Actively enrolling patients into Cohort 6 of the Phase 1
clinical trial IDE397-001 (NCT04794699)
- Patients are being identified by next generation sequencing
(NGS) or by MTAP immunohistochemistry (IHC) assay with confirmatory
NGS
- Evaluating IDE397 in patients with MTAP deletion across
multiple solid tumor types, including non-small cell lung cancer,
pancreatic cancer, thymic cancer, adenoid cystic carcinoma,
esophagogastric cancer and bladder cancer
- IDE397 has been generally well tolerated, with no observed
drug-related serious adverse events, no observed dose limiting
toxicities and without observing the maximum tolerated dose through
Cohort 5
- Observed dose-proportional pharmacokinetic exposures across
dose ranges of Cohort 1 through Cohort 5 of the Phase 1 dose
escalation; achieved active exposure targets established from
preclinical models at doses of Cohort 4 and Cohort 5
- Observed exposure-dependent pharmacodynamic modulation of
S-adenosyl methionine (SAM) in evaluable plasma samples across dose
ranges of Cohort 1 through Cohort 5
- Observed exposure-dependent pharmacodynamic modulation of
symmetric dimethyl arginine (SDMA) in evaluable tumor biopsies from
Cohort 4 and Cohort 5
- Observed preliminary signals of clinical activity in
MTAP-deletion patients in early dose escalation cohorts, including
pharmacodynamic modulation and tumor shrinkage
- Submitted a clinical protocol amendment to the FDA to support
monotherapy cohort expansion in NSCLC, esophagogastric cancer, as
well as one or more basket cohorts, and to support potential
combinations, including taxane and other combination agents
- Targeting IDE397 monotherapy cohort expansion and initiation of
combination cohorts mid-year 2022, with an aggregate of 150 or more
patients across expansion cohorts; the timing of the monotherapy
expansion cohorts and combination cohorts may be influenced by the
timing of when a MTD is observed
- Targeting delivery of IDE397 option data package to GSK
mid-year 2022, subject to initiation of expansion cohorts or
establishing the MTD; the option data package will trigger an
evaluation period for GSK to make an opt-in decision; subject to
GSK election to opt-in and HSR clearance, the company is entitled
to receive a $50 million opt-in
payment from GSK, ongoing development costs will be shared as 80%
GSK / 20% IDEAYA, and IDEAYA is entitled to potential development
and regulatory milestones aggregate up to $465 million; upon commercialization, IDEAYA is
entitled to 50% of U.S. net profits and tiered royalties on global
non-U.S. net sales ranging from high single digit to sub-teen
double digit percentages, as well as certain commercial milestones
of up to $475 million
- Demonstrated robust preclinical PK / PD in in vivo
models, with sustained target inhibition and biological impact, as
evidenced for example, by modulation of alterations to pre-mRNA
splicing profile
- Observed preclinical in vivo efficacy of IDE397 in
combination with standard of care agents, including with taxanes
showing enhanced TGI in pancreatic cancer PDX models, and with
novel combination agents; evaluating additional IDE397 combination
strategies
PARG
IDEAYA is advancing preclinical research for an inhibitor of poly
(ADP-ribose) glycohydrolase (PARG) in patients having tumors with a
defined biomarker based on genetic mutations and/or molecular
signature. 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:
- Ongoing IND-enabling studies for IDE161, 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 genetic
alterations
- Targeting IND for IDE161 in the fourth quarter of 2022
- Exercised option for an exclusive worldwide license from Cancer
Research Technology Ltd., also known as Cancer Research UK (CRUK),
and University of Manchester;
following the option exercise, IDEAYA holds an exclusive worldwide
license to patent rights covering a broad class of PARG
inhibitors
- Demonstrated preclinical in vivo efficacy as monotherapy,
including dose-dependent efficacy with tumor regression or stasis
in ovarian, gastric and breast cancer CDX models, and tumor
regressions in multiple breast cancer PDX models with defined
genetic and subtyping profiles
- Observed in vivo efficacy with enhanced TGI or tumor
regressions relative to niraparib, a PARPi, in multiple CDX models,
including in a niraparib-resistant CDX model, as well as in
niraparib resistant breast cancer PDX models
- Showed pharmacological inhibition of PARG in a panel of
homologous recombination deficient cell lines and in CDX and PDX
models; study data reported at AACR 2021
Pol Theta
IDEAYA's DNA Polymerase Theta, (Pol Theta) program targets tumors
with BRCA or other homologous recombination deficiency, or HRD,
mutations. IDEAYA and GSK are collaborating on ongoing
preclinical research, including small molecules and protein
degraders, and GSK will lead clinical development for the Pol Theta
program. Highlights:
- Demonstrated in vivo efficacy with tumor regression in
BRCA2 -/- xenograft model with IDEAYA Pol Theta Helicase inhibitor
in combination with niraparib, a GSK PARP inhibitor
- Targeting IND-enabling studies for a Pol Theta helicase
inhibitor in the first half of 2022 in collaboration with GSK
- Potential for up to $20 million
in aggregate milestone payments from GSK for advancing a Pol Theta
Helicase inhibitor from preclinical to early Phase 1 clinical
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:
- Observed dose-dependent cellular viability effect and
dose-dependent cellular PD response in multiple endogenous MSI high
cell lines
- Demonstrated efficacy and PD response in relevant MSI high
in vivo models
- Targeting selection of a Werner Helicase development candidate
in 2023
- Potential for up to $20 million
in aggregate milestone payments from GlaxoSmithKline 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.
Darovasertib (IDE196)
IDEAYA continues to execute on its clinical trial strategy to
evaluate darovasertib (IDE196), a potent and selective PKC
inhibitor.
IDEAYA is evaluating darovasertib in combination with
crizotinib, a cMET inhibitor, in metastatic uveal melanoma
(MUM). The company is also clinically evaluating darovasertib
as a combination with crizotinib in GNAQ/11 mutant skin melanoma in
an ongoing arm of the current clinical trial, and in adjuvant
primary uveal melanoma (UM) as monotherapy through an investigator
sponsor clinical trial (IST). IDEAYA is also evaluating other
potential darovasertib expansion opportunities, including in cMET
driven tumors and in KRAS-mutation tumors.
Darovasertib / Crizotinib Combination Therapy
IDEAYA
is continuing patient enrollment into the darovasertib / crizotinib
combination arm of the Phase 1/2 clinical trial under clinical
trial collaboration and supply agreements with Pfizer.
Highlights:
- As of March 1, 2022, the company
has enrolled 53 MUM patients into the darovasertib/crizotinib
combination arm, and is continuing patient enrollment in the dose
expansion cohort of this combination arm
- IDEAYA presented darovasertib and crizotinib clinical
combination data in December 2021. As of data and analyses
cutoff on November 25, 2021, twenty-two heavily pre-treated
MUM patients (91% with prior therapies, and 59% with 2 or more
prior therapies) had enrolled in the darovasertib and crizotinib
combination arm at the expansion dose, with sixteen evaluable
patients who had received one or more tumor scans and six patients
who were awaiting their 1st tumor scan. Thirteen
patients had received two or more tumor scans for evaluation of
potential response. The reported preliminary data,
based on an unlocked database, showed robust clinical activity with
manageable side effect profile:
-
- 100% Disease Control Rate (DCR): 16 of 16 evaluable patients
with >1 post-baseline scan showed tumor shrinkage as determined
by target lesion size reduction
- 31% Overall Response Rate (ORR): 4 of 13 patients with > 2
post-baseline scans had a confirmed partial response (PR) as
determined by RECIST 1.1 based on investigator or central review;
and no patients have come off-treatment prior to the 2nd
scan
- 46% of patients (6 of 13) with > 2 post-baseline scans
observed >30% tumor reduction, including one patient with an
unconfirmed PR as determined by RECIST 1.1 is awaiting follow-on
tumor scan
- Observed side effect profile in MUM patients (n=22) showed a
low rate of drug-related serious adverse events (SAE's) and
predominantly Grade 1 or 2 drug-related adverse events; eighteen
patients experienced a drug-related AE, of which six patients
observed Grade 3, and no patients observed Grade 4 or Grade
5
- These data provide clinical proof-of-concept for the
darovasertib and crizotinib synthetic lethal combination treatment,
and are consistent with the company's translational research
discovery that Phase 1 clinical response to darovasertib
monotherapy associated with low cMET activity, as measured by gene
signature score
- The company is targeting a clinical data update for
darovasertib and crizotinib combination in mid-2022, including
tolerability and clinical efficacy. IDEAYA is also
planning to seek FDA regulatory guidance for potential
registration-enabling trial design to evaluate darovasertib and
crizotinib combination in MUM in mid-2022. The timing of the
clinical data and FDA regulatory guidance may be influenced by data
maturity, including observation of median duration of response
(DOR) or median progression free survival (mPFS).
- Expanded relationship with Pfizer under a clinical
collaboration and supply agreement to support clinical evaluation
of darovasertib and crizotinib combination in a potential
registration-enabling clinical trial in MUM, subject to FDA
feedback and guidance
- Associated cMET expression and activation to observed clinical
response based on a retrospective analysis of human clinical
biopsies from the Novartis darovasertib Phase 1 clinical trial,
supporting cMET expression / activation as potential combination
agent
- Observed preclinical synergies between darovasertib and
crizotinib in relevant cellular models under conditions simulating
a tumor microenvironment in the liver, the site of approximately
90% of uveal melanoma metastases; study data reported at AACR
2021
Darovasertib Monotherapy
IDEAYA has completed
enrollment into its ongoing Phase 1/2 clinical trial evaluating
darovasertib as monotherapy in MUM patients.
IDEAYA is planning to initiate an Investigator Sponsored Trial,
with St. Vincent's Hospital Sydney Limited to evaluate IDE196 as
monotherapy in a neo-adjuvant / adjuvant setting in
(non-metastatic) uveal melanoma (UM) patients. Data from this
clinical trial may offer proof of concept on its hypothesis that
earlier treatment of UM patients with IDE196, prior to tumor
metastasis, may lead to improved patient outcomes.
Darovasertib – Other Potential Indications
IDEAYA is
evaluating the potential for darovasertib in other oncology
indications, including in cMET-driven tumors and in KRAS-mutation
tumors. The company is also evaluating darovasertib for
potential treatment of GNAQ mutation-mediated rare diseases,
including Sturge-Weber Syndrome (SWS) and Port Wine Stains (PWS),
neurocutaneous disorders characterized by capillary malformations
and associated with mutations in GNAQ. Highlights:
- Expanded its relationship with Pfizer under a clinical
collaboration and supply agreement for clinical evaluation of
darovasertib and crizotinib combination therapy in cMET-driven
tumors, such as NSCLC or HCC, subject to preclinical validation
studies
- Evaluating darovasertib in combination with a KRAS inhibitor in
preclinical studies in KRAS-driven solid tumors
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 losses were $49.8
million and $34.5 million for
the years ended December 31, 2021 and
December 31, 2020, respectively. As
of December 31, 2021, the company had
an accumulated deficit of $176.7
million.
As of December 31, 2021, IDEAYA
had cash, cash equivalents and marketable securities of
$368.1 million. IDEAYA believes that
its cash, cash equivalents and marketable securities will be
sufficient to fund its planned operations into 2025. 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 December 31, 2021, IDEAYA
had cash, cash equivalents and short-term and long-term marketable
securities totaling $368.1 million.
This compared to cash, cash equivalents and short-term and
long-term marketable securities of $283.6
million at December 31,
2020. The increase was primarily due to $86.0 million in net proceeds received from
issuance of common stock in an underwritten public offering on
July 12, 2021 and $57.3 million in net proceeds under the ATM
Program received through December 31,
2021, offset by cash used in operations and purchases of
property and equipment.
Collaboration revenue for the three months ended December 31, 2021 totaled $3.0 million compared to $10.6 million for the same period in 2020.
Collaboration revenue was recognized for the performance
obligations satisfied through December 31,
2021 under the GSK Collaboration Agreement.
Research and development (R&D) expenses for the three months
ended December 31, 2021 totaled
$16.1 million compared to
$12.1 million for the same
period in 2020. The increase was primarily due to higher
personnel-related expenses, laboratory supplies expenses and
consulting fees.
General and administrative (G&A) expenses for the three
months ended December 31, 2021
totaled $5.2 million compared to
$3.8 million for the same period
in 2020. The increase was primarily due to higher personnel-related
expenses, software expenses and consulting fees.
The net loss for the three months ended December 31, 2021
was $18.2 million compared to $5.1 million for
the same period in 2020. Total stock compensation expense for the
three months ended December 31, 2021
was $2.1 million compared
to $1.0 million for the same period in 2020.
The net loss for the year ended December
31, 2021 was $49.8 million
compared to $34.5 million for the
same period in 2020. Total stock compensation expense for the year
ended December 31, 2021 was
$8.2 million compared to $3.6 million for the same period in 2020.
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. IDEAYAs 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 monotherapy cohort expansion and combination cohort
initiation in the IDE397 Phase 1 clinical trial, (iii) the timing
and content of an additional clinical data update for the
darovasertib and crizotinib combination, (iv) the timing of
submitting an IND for PARG inhibitor, IDE161, (v) the timing of
initiating IND-enabling studies for a Pol Theta inhibitor, (vi) the
timing of the delivery of the GSK option data package, (vii) the
potential receipt of GSK milestone payments, (viii) the timing of
identification of a development candidate for a Werner Helicase
inhibitor, (ix) the timing of obtaining FDA guidance for potential
registration-enabling trial design to evaluate the darovasertib and
crizotinib combination, (x) the initiation of an IST to evaluate
ID196 in a neo-adjuvant / adjuvant setting, al pathway, (xi) the
initiation of a Phase 1 clinical trial to evaluate darovasertib in
SWS and PWS, and (xii) 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, 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
Quarterly Report on Form 10Q filed on November 15, 2021 and any current and periodic
reports filed with the U.S. Securities and Exchange Commission.
IDEAYA
Biosciences, Inc. Condensed Statements of
Operations and Comprehensive Loss (in
thousands, except share and per share amounts)
|
|
|
|
Three Months
Ended
December
31,
|
|
|
Year
Ended
December
31,
|
|
|
|
2021
|
|
|
2020
|
|
|
2021
|
|
|
2020
|
|
|
|
(Unaudited)
|
|
|
(Unaudited)
|
|
|
|
|
Collaboration
revenue
|
|
$
|
2,963
|
|
|
$
|
10,571
|
|
|
$
|
27,941
|
|
|
$
|
19,538
|
|
Operating
expenses
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Research and
development
|
|
|
16,109
|
|
|
|
12,051
|
|
|
|
58,158
|
|
|
|
39,698
|
|
General and
administrative
|
|
|
5,223
|
|
|
|
3,800
|
|
|
|
20,051
|
|
|
|
15,184
|
|
Total operating
expenses
|
|
|
21,332
|
|
|
|
15,851
|
|
|
|
78,209
|
|
|
|
54,882
|
|
Loss from
operations
|
|
|
(18,369)
|
|
|
|
(5,280)
|
|
|
|
(50,268)
|
|
|
|
(35,344)
|
|
Interest income and
other income, net
|
|
|
157
|
|
|
|
145
|
|
|
|
506
|
|
|
|
849
|
|
Net loss
|
|
$
|
(18,212)
|
|
|
$
|
(5,135)
|
|
|
$
|
(49,762)
|
|
|
$
|
(34,495)
|
|
Unrealized losses on
marketable securities
|
|
|
(662)
|
|
|
|
(28)
|
|
|
|
(719)
|
|
|
|
(58)
|
|
Comprehensive
loss
|
|
$
|
(18,874)
|
|
|
$
|
(5,163)
|
|
|
$
|
(50,481)
|
|
|
$
|
(34,553)
|
|
Net loss per share
attributable to common stockholders, basic and diluted
|
|
$
|
(0.47)
|
|
|
$
|
(0.18)
|
|
|
$
|
(1.41)
|
|
|
$
|
(1.40)
|
|
Weighted average
number of shares outstanding,
basic and diluted
|
|
|
38,501,335
|
|
|
|
29,149,106
|
|
|
|
35,252,443
|
|
|
|
24,721,775
|
|
IDEAYA
Biosciences, Inc. Condensed Balance
Sheet Data (in thousands)
|
|
|
|
December
31,
|
|
|
December
31,
|
|
|
|
2021
|
|
|
2020
|
|
|
|
(Unaudited)
|
|
|
|
|
Cash and cash
equivalents and short-term and long-term marketable securities
|
|
$
|
368,063
|
|
|
$
|
283,585
|
|
Total
assets
|
|
|
381,347
|
|
|
|
298,269
|
|
Total
liabilities
|
|
|
79,833
|
|
|
|
99,995
|
|
Total liabilities and
stockholders' equity
|
|
|
381,347
|
|
|
|
298,269
|
|
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SOURCE IDEAYA Biosciences, Inc.