SOUTH SAN FRANCISCO, Calif.,
May 10, 2021 /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 first quarter ended
March 31, 2021.
"We are excited to advance IDE397, a potential best-in-class
MAT2A inhibitor, in the Phase 1 dose escalation for evaluation in
patients with MTAP deletion tumors, including in non-small cell
lung cancer (NSCLC). We are also continuing to invest in our
preclinical synthetic lethality programs, including our PARG and
Pol Theta programs for patients with HRD tumors, where we are
targeting a development candidate for both programs in 2021," said
Yujiro S. Hata, Chief Executive
Officer and President of IDEAYA Biosciences.
"We are excited by the preliminary darovasertib monotherapy
overall survival data in MUM and look forward to receiving FDA
regulatory guidance based on the data in the second half of
2021. We are also executing on our darovasertib clinical
combination strategy and are encouraged by the early partial
responses observed in the combination arms, including now in the
crizotinib combination. Importantly, the 54% tumor reduction
by RECIST 1.1 observed in a patient treated with the darovasertib
and crizotinib combination is the deepest partial response we have
seen to date in the darovasertib Phase 1/2 clinical trial," said
Matthew Maurer, M.D., Vice
President, Head of Clinical Oncology and Medical Affairs, 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:
- Initiated a Phase 1 clinical trial designated as IDE397-001
(ClinicalTrials.gov Identifier: NCT04794699) to evaluate IDE397
under an investigational new drug application
- Completed enrollment into an initial dose escalation cohort of
the Phase 1 clinical trial
- Clinical development plans for IDE397 include a dose escalation
portion of the Phase 1 clinical trial in which IDEAYA is enrolling
patients having solid tumors with MTAP gene deletion.
Patients are being identified by next generation sequencing (NGS)
or by MTAP immunohistochemistry (IHC) assay with confirmatory
NGS
- Subject to satisfactory completion of the dose escalation
portion of the Phase 1 clinical trial, IDEAYA plans to enroll MTAP
deletion patients into expansion arms in NSCLC and potentially in
other solid tumor indications such as esophageal, gastric, bladder,
head and neck, or pancreatic cancers
- Planning to obtain patient biopsies from the dose escalation
and expansion portions of the clinical trial for translational
research, including evaluation of certain pharmacodynamic, or PD,
biomarkers, such as peripheral S-adenosyl methionine (SAM), tumor
SAM and tumor symmetric dimethylarginine (SDMA)
- Program objective is to obtain preliminary clinical PD data
from the dose-escalation portion of the IDE397 monotherapy Phase 1
clinical trial in the second half of 2021
- Demonstrated preclinical efficacy of monotherapy IDE397 in a
study of over forty solid tumor patient derived xenograft (PDX)
models with homozygous MTAP deletions across a range of solid tumor
types, including NSCLC, esophageal, gastric, bladder, head and
neck, and pancreatic cancers; study data was reported at AACR 2021
and showed:
-
- tumor regressions, with >100% tumor growth inhibition, or
TGI, in multiple PDX models across multiple solid tumor types,
including in NSCLC as well as in bladder and gastric cancer
models
- >75% TGI in approximately 50% of models and across major
solid tumor types
- >60% TGI in approximately 75% of models and across major
solid tumor types
- dose-dependent modulation of PD biomarkers, including SDMA and
SAM
- Observed single-agent IDE397 preclinical activity in NSCLC PDX
models, demonstrating >60% TGI in 11 independent PDX models out
of 13 models evaluated in the MTAP-deletion PDX panel study,
including in 7 of 9 NSCLC adenocarcinoma PDX models, and in 4 of 4
NSCLC squamous carcinoma PDX models evaluated, and demonstrating
tumor regressions in 2 of 4 NSCLC squamous PDX models, including
one complete response
- Showed correlation of in vivo efficacy with PD
modulation of tumor SDMA and tumor SAM in a study evaluating IDE397
in an MTAP-deletion NSCLC CDX model
- Reported preclinical analyses of genomic and metabolic effects
of pharmacological inhibition of MAT2A in an isogenic cell pair and
of proliferation effects in a panel of MTAP wild type and
MTAP-deleted cell lines at AACR 2021
- Observed in vivo efficacy of IDE397 in combination with a
taxane, showing enhanced TGI in a pancreatic cancer PDX model, and
separately in combination with a PRMT inhibitor, showing enhanced
TGI in an HCT116 MTAP-null CDX model
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:
- Identified a novel and proprietary HRD biomarker to guide
patient selection, with validation in vitro and in vivo in CDX
models across multiple solid tumor indications
- Demonstrated PARGi dose-dependent in vivo efficacy as
monotherapy with tumor regression or stasis in ovarian, gastric and
breast cancer CDX models
- 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
- Showed tumor regressions in multiple breast cancer PDX models
with defined genetic and subtyping profiles
- Reported preclinical data at AACR 2021, including
pharmacological inhibition of PARG in a panel of homologous
recombination deficient cell lines and in CDX and PDX models
- Subject to further preclinical studies, IDEAYA is targeting to
identify a PARG inhibitor development candidate in 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 inhibitor in
combination with niraparib, a GSK PARP inhibitor; and
- Subject to further preclinical studies, IDEAYA is targeting
selection of a Pol Theta inhibitor development candidate in
2021
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 in vivo efficacy and PD response in relevant MSI
high models
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 distinct DNA Damage Targets for
patients with solid tumors characterized by a proprietary biomarker
or a gene signature.
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 metastatic uveal melanoma
(MUM) as monotherapy and in combination therapies, including
combinations of darovasertib / binimetinib and independently,
darovasertib / crizotinib. The company is continuing to enroll
MUM patients into each of these combination arms of the Phase 1/2
clinical trial, and it targeting to provide a clinical data update
for the darovasertib combination(s) in the second half of 2021.
Based on preliminary monotherapy clinical data in MUM and its
mechanism of action, we anticipate darovasertib clinical activity
independent of Human Leukocyte Antigen (HLA) status in
GNAQ/11-mutation cancers.
The company is also evaluating darovasertib as monotherapy
outside of MUM, with a focus in GNAQ/11-mutation skin
melanoma.
Darovasertib Monotherapy
IDEAYA has completed
enrollment into its ongoing Phase 1/2 clinical trial evaluating
darovasertib as monotherapy in MUM patients. IDEAYA is
targeting to receive FDA guidance in H2 2021 on potential
regulatory path, based on the preliminary darovasertib monotherapy
overall survival data in MUM. The company is continuing enrollment
into its ongoing basket trial evaluating darovasertib as
monotherapy in patients having non-MUM tumors harboring GNAQ or
GNA11 activating mutations. The company's development
strategy in the monotherapy non-MUM GNAQ/11 arm of the clinical
trial is focused on skin melanoma. Highlights:
- Reported interim clinical data from Phase 1/2 clinical trial
arm evaluating monotherapy darovasertib in predominantly second and
third line (2L/3L) and heavily pre-treated out to seventh or eighth
line (7L/8L) MUM patients. As of data and analyses cutoff on
April 13, 2021 based on preliminary
data from an unlocked database:
-
- Enrolled an aggregate of 81 darovasertib monotherapy BID MUM
patients across the IDEAYA and Novartis Phase 1/2 clinical trials,
with 81 patients evaluable for safety and 75 patients evaluable for
efficacy pursuant to RECIST 1.1 guidelines
- Observed 57% 1-year overall survival (OS) with 95% confidence
interval (44%, 69%), in predominantly 2L/3L and heavily pretreated
to 7L/8L patients
- Observed median OS of 13.2 months with 95% confidence interval
(10.7 months, not reached), in predominantly 2L/3L and heavily
pretreated to 7L/8L patients
- Historical 37% 1-year OS and median OS of ~7 months have been
reported in similar 2L/3L+ MUM patient population (Rantala
2019)
- Observed tumor reduction in 61% (n=46) of 75 evaluable MUM
patients pursuant to RECIST 1.1 guidelines, including 15 patients
(20%) with >30% target lesion reduction, and one confirmed
complete response
- Reported preliminary clinical data from Phase 1/2 clinical
basket trial arm evaluating monotherapy darovasertib in skin
melanoma patients. As of data and analyses cutoff of April 13, 2021 based on preliminary data from an
unlocked database:
-
- Enrolled 7 darovasertib monotherapy BID skin melanoma patients
in the IDEAYA Phase 1/2 clinical trial, with 7 patients evaluable
for safety and 5 patients evaluable for efficacy pursuant to RECIST
1.1 guidelines
- Observed tumor reduction in 80% (n=4) of 5 evaluable skin
melanoma patients pursuant to RECIST1.1 guidelines, including one
confirmed PR
- An aggregate of 88 patients were evaluable for safety across
Phase 1/2 arms evaluating darovasertib in MUM and skin melanoma
patients. As of the April 13,
2021 data and analyses cutoff, and based on preliminary data
from an unlocked database, the overall safety profile of
darovasertib monotherapy is consistent with prior experience and
includes primarily common low grade but manageable GI and skin
toxicities
- Preliminary clinical data from darovsertib monotherapy arm
shows that darovasertib activity is independent of HLA status
Darovasertib / Binimetinib Combination Therapy
IDEAYA
is continuing patient enrollment into the darovasertib /
binimetinib combination arm of the Phase 1/2 clinical trial under
the clinical trial collaboration and supply agreement with
Pfizer. Highlights:
- Initiated dose expansion evaluating the darovasertib /
binimetinib combination in MUM based on early clinical
activity
- Amended the clinical trial collaboration and supply agreement
with Pfizer to support target enrollment of approximately 40
patients in the darovasertib and binimetinib clinical combination
arm
- Reported preliminary clinical data from Phase 1/2 clinical
trial arm evaluating the darovasertib / binimetinib combination in
MUM patients, predominantly as second line, third line (2L / 3L) or
later lines of treatment. As of data and analyses cutoff of
April 13, 2021 based on preliminary
data from an unlocked database:
-
- 24 MUM patients have enrolled in the darovasertib and
binimetinib combination study and 14 of these patients were
evaluable, including eight patients dosed in the Phase 1/2 dose
expansion cohort of the combination study
- Observed 22% (n=2) partial responses (PR), including one
confirmed PR and on unconfirmed PR awaiting a confirmatory scan, of
nine evaluable MUM patients with at least two post-baseline scans
pursuant to RECIST 1.1 guidelines
- Observed tumor reduction in 79% (n=11) of 14 evaluable MUM
patients with at least one post-baseline scan pursuant to RECIST1.1
guidelines
- Drug-related adverse events observed in the darovasertib and
binimetinib combination arm in MUM, as of April 13, 2021 data and analyses cutoff based on
preliminary data from an unlocked database, primarily include:
serious adverse events of liver toxicity, nausea and vomiting, and
syncope; and adverse events that occurred in greater than 10% of
patients of nausea, vomiting, diarrhea, rash, edema,
aminotransaminase, or AST increase, alanine aminotransferase, or
ALT, increase and creatine phosphokinase increase
Darovasertib / Crizotinib Combination Therapy
IDEAYA
is continuing patient enrollment into the darovasertib / crizotinib
combination arm of the Phase 1/2 clinical trial under the
clinical trial collaboration and supply agreement with
Pfizer. Highlights:
- 6 MUM patients have enrolled in the darovasertib and crizotinib
combination study and 2 of these patients were evaluable for
response with one post-baseline scan
- Observed early clinical efficacy of the darovasertib and
crizotinib combination in MUM. As of data and analyses cutoff
on May 5, 2021 based on preliminary
data from an unlocked database, these data showed:
-
- tumor reduction in 2 of 2 evaluable patients in a first
cohort
- one unconfirmed partial response in a 3rd-line patient, with a
54% tumor reduction, which is the deepest response, as reflected by
the largest percentage reduction in tumor size, reported in the
darovasertib clinical trial to date; this patient is awaiting a
confirmatory scan
- Drug-related adverse events observed in the darovasertib and
crizotinib combination arm in MUM as of May
5, 2021, based on preliminary data from an unlocked
database, primarily include: serious adverse events of syncope and
hypotension, each of which resolved with patients continuing
dosing; and adverse events that occurred in at least two of the six
treated patients of nausea, diarrhea, vomiting, edema, decreased
appetite, and syncope.
- Initiated dose expansion for a cohort of the Phase 1/2
darovasertib / crizotinib combination arm, with additional dose
exploration ongoing
- 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, as reported at AACR
2021
- Correlated 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
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
$9.0 million and $5.1 million for the three months ended
March 31, 2021 and December 31, 2020, respectively. As of
March 31, 2021, the company had an
accumulated deficit of $136.0
million.
As of March 31, 2021, IDEAYA had
cash, cash equivalents and marketable securities of $310.4 million. IDEAYA supplemented its
first-quarter-end cash, cash equivalents and marketable securities
with an additional $14.6 million in
aggregate gross proceeds received subsequent to quarter end from
the sale and issuance of common stock at a weighted average sale
price of $22.99 per share under an
at-the-market offering pursuant to the January 2021 Sales Agreement with Jefferies as
sales agent.
IDEAYA believes that its cash, cash equivalents and marketable
securities will be sufficient to fund our planned operations into
2024. 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 March
31, 2021, IDEAYA had cash, cash equivalents and short-term
marketable securities totaling $310.4 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 $41.8 million in net
proceeds received through March 31,
2021 from issuance of common stock under at-the-market
offerings pursuant to the August 2020
Sales Agreement and January 2021
Sales Agreement with Jefferies as sales agent offset by cash used
in operations and purchases of property and equipment.
Collaboration revenue for the three months ended March 31, 2021 totaled $7.2 million compared to $10.6M for the three months ended December 31, 2020. Collaboration revenue was
recognized for the performance obligations satisfied through
March 31, 2021 under the GSK
Collaboration Agreement.
Research and development (R&D) expenses for the three months
ended March 31, 2021 totaled
$11.6 million compared to
$12.1 million for the three
months ended December 31, 2020. The
decrease was primarily due to a decrease in external clinical
development expenses for IDE397 and darovasertib and a decrease in
fees to CROs, CMOs and external consultants related to our lead
product candidates, offset by an increase in R&D headcount
costs.
General and administrative (G&A) expenses for the three
months ended March 31, 2021 totaled
$4.8 million compared to
$3.8 million for the three
months ended December 31, 2020. The
increase was primarily due to an increase in G&A headcount
costs, an increase in legal patent expense, and an increase in
costs related to the filing of our shelf registration statement on
Form S-3 during the quarter.
The net loss for the three months ended March 31, 2021
was $9.0 million compared to $5.1 million for
the three months ended December 31,
2020. Total stock compensation expense for the three months
ended March 31, 2021 was $1.9 million compared
to $1.0 million for the three months ended
December 31, 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. 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 timing of obtaining FDA guidance for
potential darovasertib registrational pathway, (ii) the enrollment
into expansion arms of the IDE397 clinical trial, (iii) the timing
of obtaining preliminary clinical PD data from the dose-escalation
portion of the IDE397 monotherapy Phase 1 clinical trial (iv) the
timing of identification of a development candidate for a PARG in
inhibitor, (v) the timing of identification of a development
candidate for a Pol Theta inhibitor, (vi) darovasertib clinical
activity independent of HLA status, (vii) the impact of COVID-19,
and (viii) the extent to which IDEAYA's existing cash, cash
equivalents, and marketable securities will fund its planned
operations. 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 recent Quarterly Report on Form 10-Q filed on May 10, 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
|
|
|
|
March 31,
2021
|
|
|
December 31,
2020
|
|
Collaboration
revenue
|
|
$
|
7,247
|
|
|
$
|
10,571
|
|
Operating
expenses
|
|
|
|
|
|
|
|
|
Research and
development
|
|
|
11,566
|
|
|
|
12,051
|
|
General and
administrative
|
|
|
4,816
|
|
|
|
3,800
|
|
Total operating expenses
|
|
|
16,382
|
|
|
|
15,851
|
|
Loss from
operations
|
|
|
(9,135)
|
|
|
|
(5,280)
|
|
Interest income and other
income (expense), net
|
|
|
114
|
|
|
|
145
|
|
Net loss
|
|
$
|
(9,021)
|
|
|
$
|
(5,135)
|
|
Change in unrealized gains
(losses) on
marketable securities
|
|
|
(7)
|
|
|
|
(28)
|
|
Comprehensive
loss
|
|
$
|
(9,028)
|
|
|
$
|
(5,163)
|
|
Net loss per share
attributable to common stockholders,
basic and diluted
|
|
$
|
(0.28)
|
|
|
$
|
(0.18)
|
|
Weighted average
number of shares outstanding,
basic and diluted
|
|
|
31,761,207
|
|
|
|
29,149,106
|
|
IDEAYA
Biosciences, Inc.
Condensed Balance Sheet Data
(in thousands)
|
|
|
|
|
March
31,
|
|
|
December
31,
|
|
|
|
2021
|
|
|
2020
|
|
Cash and cash
equivalents and short-term and long-term
marketable securities
|
|
$
|
310,401
|
|
|
$
|
283,585
|
|
Total
assets
|
|
|
326,097
|
|
|
|
298,269
|
|
Total
liabilities
|
|
|
92,971
|
|
|
|
99,995
|
|
Total liabilities and
stockholders' equity
|
|
|
326,097
|
|
|
|
298,269
|
|
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SOURCE IDEAYA Biosciences, Inc.