Kymera Therapeutics, Inc. (NASDAQ: KYMR), a clinical-stage
biopharmaceutical company advancing targeted protein degradation
(TPD) to deliver novel small molecule protein degrader medicines,
today reported business highlights and financial results for the
fourth quarter and full year ended December 31, 2022.
“2022 was a significant year for Kymera, with our clinical data
validating critical aspects of our approach to drug discovery and
development, moving us forward toward becoming a fully integrated
global biopharmaceutical company. Our lead program, KT-474,
demonstrated the first clinical impact of a degrader outside of
oncology in complex inflammatory diseases, and also showed the
superior clinical potential of an IRAK4 degrader compared to a
small molecule inhibitor, confirming our platform and target
selection strategy. In addition, we are excited that programs from
our oncology pipeline continue to show fidelity of translation of
PK, PD and tolerability from preclinical models to human patients,
validating our proprietary molecular design and translational
capabilities,” said Nello Mainolfi, PhD, Co-Founder, President and
CEO. “Looking ahead, we plan to share important data from our
oncology programs this year, including clinical data evaluating
anti-tumor activity with our STAT3 (KT-333) and IRAKIMiD (KT-413)
programs. With four clinical stage programs, a proprietary
discovery engine designed to enable us to add one new program to
our clinical pipeline each year, and a strong financial position
that will enable us to continue to invest in our platform and
pipeline, we are well-positioned to deliver on our goals and
improve patients’ lives with a new generation of medicines.”
Recent Business Highlights and Developments
- In December, Kymera announced positive results from the Phase 1
clinical trial evaluating KT-474 (SAR444656) in patients with
hidradenitis suppurativa (HS) and atopic dermatitis (AD),
demonstrating clinical activity, impact on inflammatory biomarkers,
and an encouraging safety profile. In addition, the Company shared
Sanofi’s decision to advance this program into Phase 2 clinical
trials. Kymera also provided initial data from the dose escalation
phase of the ongoing KT-413 and KT-333 clinical trials, which
demonstrated target degradation without dose limiting toxicities
and fidelity of PK/PD translation from preclinical models to human
patients. During the update, the Company also announced the IND
cleared for KT-253 and its plan to initiate the Phase 1 trial in
early 2023.
- At the American Society of Hematology (ASH) Annual Meeting,
Kymera presented preclinical data demonstrating KT-253, a selective
MDM2 degrader, inhibited tumor growth as a single agent and in
combination with widely used treatments in Acute Myeloid Leukemia
(AML) models. In addition, preclinical data from the Company’s
collaborations was shared demonstrating the therapeutic potential
of STAT3 degraders in cutaneous T-cell lymphoma (CTCL), as well as
the potential of IRAKIMiD degraders combined with BCL-2 inhibitors
as a therapeutic approach for the treatment of MYD88-mutant diffuse
large B-cell lymphoma.
- In January, Kymera announced the appointment of Ellen Chiniara,
J.D., as Chief Legal Officer and Corporate Secretary. Ms. Chiniara
joined Kymera with extensive experience overseeing legal activities
at biopharmaceutical companies ranging from the discovery phase
through commercialization, and most recently served as Executive
Vice President, Chief Legal Officer and Corporate Secretary of
Alexion Pharmaceuticals through its acquisition by AstraZeneca. She
graduated magna cum laude from Bryn Mawr College and earned her
Juris Doctor from Stanford University School of Law.
- Kymera has appointed Rebecca Mosher, MD, as Senior Vice
President, Translational Medicine. Dr. Mosher joins the Company
from Mersana Therapeutics where she was Vice President,
Translational Medicine. Prior to Mersana, Dr. Mosher held positions
of increasing responsibility in translational medicine,
translational research and molecular pathology at Novartis, Vertex,
and Millennium. Dr. Mosher graduated magna cum laude from Harvard
College and received her MD from Columbia University.
- Kymera has appointed Juliet Williams, PhD, as Head of Research.
Dr. Williams was previously Kymera’s Head of Biology and has more
than 20 years of drug development experience, including leadership
positions at Novartis, Sanofi, Millennium, and Curis. Dr. Williams
holds a degree in Natural Sciences (Biochemistry) from the
University of Cambridge and a PhD in Developmental Biology from
University College London.
Kymera’s 2023 Objectives
The Company’s recent data, generated in healthy volunteers and
patients with HS, AD, hematological malignancies and solid tumors,
demonstrated its industry leading, proprietary know-how in TPD and
its progress in developing medicines in areas of significant
patient and commercial opportunity. In January, the Company
outlined its strategic objectives for 2023:
- Collaborate with Sanofi to initiate KT-474 Phase 2 clinical
trial
- Publish results of KT-474 Phase 1 trial including patient
cohorts
- Demonstrate clinical anti-tumor activity in target patient
populations for KT-333 and KT-413
- Initiate KT-253 Phase 1 trial in solid and hematological tumors
and demonstrate clinical proof-of-mechanism in patients
- Deliver at least 2 new development candidates
(DC)/Investigational New Drugs (IND) from the preclinical pipeline
in areas of large clinical and commercial opportunity and pathways
where TPD has potential to provide either the only or the
best-in-class solution
- Further expand the capabilities of Kymera’s Pegasus™ platform
and continue to leverage Kymera’s E3 Ligase Whole-Body Atlas of
over 600 unique E3 ligases, with a focus on tissue restricted E3
ligases
- Expand novel molecular glue franchise in areas of unmet medical
need, exploiting a newly identified degron motif
- Advance existing collaborations, or execute additional
strategic partnerships, that support the company’s evolution into a
fully integrated, global biopharmaceutical company
Program Background Information
IRAK4 Degrader Program (KT-474/SAR444656)
KT-474 is a potent, highly selective, orally bioavailable IRAK4
degrader, in development for the treatment of IL-1R/TLR-driven
complex inflammatory diseases where there is an opportunity to
significantly advance the standard of care in a broad variety of
diseases. In 2021, Kymera completed dose escalation in the single
ascending dose (SAD) and multiple ascending dose (MAD) portions of
its KT-474 Phase 1 trial, with the data demonstrating near complete
IRAK4 degradation in peripheral blood mononuclear cells (PBMC) and
skin that was generally well tolerated, as well as robust
inhibition of multiple ex vivo-stimulated disease-relevant
cytokines.
In the recently completed patient cohort of the Phase 1 trial,
KT-474 showed evidence of robust IRAK4 degradation in the blood and
active skin lesions of HS and AD patients and was generally well
tolerated. Treatment with KT-474 was associated with a systemic
anti-inflammatory response and meaningful improvement in skin
lesions and symptoms in both HS and AD patients, with internal
consistency between the effect on inflammatory biomarkers and
impact on clinical endpoints. KT-474 was generally safe and
well-tolerated, with no serious adverse events, no drug-related
infections, and no dose interruptions or discontinuations due to
adverse events. Sanofi, which is collaborating with Kymera on the
development of KT-474 (SAR444656) outside of the oncology and
immune-oncology fields, will advance KT-474 into Phase 2 clinical
studies in HS and AD, with the first study initiating in 2023.
STAT3 Degrader Program (KT-333)
KT-333 is designed as a potent degrader of STAT3, a
transcriptional regulator that has been linked to numerous cancers
and inflammatory and autoimmune diseases. KT-333 is being developed
for the treatment of STAT3-dependent hematological malignancies and
solid tumors. The Phase 1 clinical trial of KT-333 is designed to
evaluate the safety, tolerability, PK/PD and clinical activity of
KT-333 dosed weekly in adult patients with relapsed and/or
refractory lymphomas, leukemias and solid tumors.
The Phase 1a dose escalation portion of the trial is ongoing. In
December 2022 Kymera announced that Dose Level (DL) 1 had been
completed with a total of 4 patients enrolled. All patients were
heavily pretreated with multiple prior regimens and included 3 with
solid tumors and 1 with cutaneous T-cell lymphoma. Plasma PK and PD
translated as expected in humans, with mean maximum STAT3
degradation in PBMC following the first 2 doses averaging 66%, with
maximum STAT3 knockdown of up to 86% as measured by mass
spectrometry. There were no dose-limiting toxicities or
treatment-related serious adverse events reported at this dose.
KT-333 has been granted orphan drug designation by the U.S. Food
and Drug Administration for both the treatment of cutaneous T-cell
lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL).
More information on the Phase 1 study can be found at
www.clinicaltrials.gov, identifier NCT05225584.
IRAKIMiD Degrader Program (KT-413)
KT-413 is a novel heterobifunctional degrader targeting both
IRAK4 and the IMiD substrates Ikaros and Aiolos. Designed to
address both the IL-1R/TLR and Type 1 IFN pathways synergistically
with a single molecule, KT-413 is in development for the treatment
of MYD88-mutant B cell malignancies. The Phase 1 clinical trial of
KT-413 is designed to evaluate the safety, tolerability, PK/PD and
clinical activity of KT-413 administered as an IV infusion once
every 3 weeks to adult patients with relapsed and/or refractory
B-cell non-Hodgkin's lymphomas.
The Phase 1a dose escalation portion of the trial is ongoing. In
December 2022, Kymera announced that the first two dose levels had
been completed. Patients were heavily pretreated with multiple
prior regimens and included follicular lymphoma and DLBCL, which
were both wild-type for MYD88. Plasma PK and PD translated as
expected in humans with both dose levels showing dose-dependent
degradation of IRAK4, Ikaros and Aiolos in PBMC, with up to 95/100%
knockdown of Ikaros/Aiolos and 40% knockdown of IRAK4 at the second
dose level. Serial tumor biopsies at Cycle 3/Day 4 in the patient
treated at DL1 showed comparable knockdown of Ikaros/Aiolos and
IRAK4 as in plasma. There were no dose-limiting toxicities or
treatment-related serious adverse events and no neutropenia
observed in the two patient cohorts.
More information on the Phase 1 study can be found at
www.clinicaltrials.gov, identifier NCT05233033.
MDM2 Degrader Program (KT-253)
The FDA has cleared the IND for KT-253, an investigational
degrader that targets MDM2, the crucial regulator of the most
common tumor suppressor, p53, which remains intact (Wild Type) in
close to 50% of cancers. Unlike small molecule inhibitors, KT-253
has been shown preclinically to have the ability to overcome the
MDM2 feedback loop and rapidly induce apoptosis, even with brief
exposures. Kymera plans to commence the KT-253 Phase 1a dose
escalation study in early 2023, with IV doses of KT-253
administered every 3 weeks to patients with solid tumors and
hematological malignancies, including AML.
Platform and Discovery Programs
Kymera is leveraging the Company’s proprietary E3 Ligase
Whole-Body Atlas, including the differential expression profile of
known E3 ligases, to pursue targets and indications that may
benefit from tissue-restricted or -selective degradation. Kymera
has also expanded the Company’s platform to develop a new
generation of molecular glue degraders for high value undrugged and
non-ligandable targets. Multiple programs are approaching
development stage in 2023.
Conference Call
To access the conference call via phone, please dial +1 (833)
630-2127 (U.S.) or +1 (412) 317-1846 (International) and ask to
join the Kymera Therapeutics call. A live webcast of the event will
be available under “Events and Presentations” in the Investors
section of the Company’s website at www.kymeratx.com. A replay of
the webcast will be archived and available following the event.
Fourth Quarter 2022 Financial Results
Collaboration Revenues: Collaboration revenues
were $16.1 million for the fourth quarter of 2022 and $46.8 million
for the year ended December 31, 2022 compared to $15.3 million and
$72.8 million, respectively, for the same periods of 2021.
Collaboration revenues include revenue from the Company’s Sanofi
and Vertex collaborations.
Research and Development Expenses: Research and
development expenses were $43.1 million for the fourth quarter of
2022 and $164.2 million for the year ended December 31, 2022,
compared to $37.5 million and $137.0 million, respectively, for the
same periods of 2021. This increase was primarily due to increased
expenses related to the investment in our MDM2 program, platform
and discovery programs, as well as an increase in occupancy and
related costs due to continued growth in the research and
development organization. Stock based compensation expenses
included in R&D were $4.5 million for the fourth quarter of
2022 and $18.0 million for the year ended December 31, 2022,
compared to $3.7 million and $11.7 million, respectively, for the
same periods in 2021.
General and Administrative Expenses: General
and administrative expenses were $11.6 million for the fourth
quarter of 2022 and $43.8 million for the year ended December 31,
2022, compared to $11.7 million and $36.3 million, respectively,
for the same periods of 2021. The increase in annual expense was
primarily due to increase in legal and professional service fees in
support of the Company’s growth and an increase in personnel,
facility, occupancy, and other expenses from an increase in
headcount to support growth as a public company. Stock based
compensation expenses included in G&A were $4.4 million for the
fourth quarter of 2022 and $17.5 million for the year ended
December 31, 2022, compared to $5.0 million and $13.2 million,
respectively, for the same periods in 2021.
Net Loss: Net loss was $34.9 million for the
fourth quarter of 2022 and $154.8 million for the year ended
December 31, 2022 compared to a net loss of $33.9 million and
$100.2 million, respectively, for the same periods of 2021.
Cash and Cash Equivalents: As of December 31,
2022, Kymera had approximately $559.5 million in cash, cash
equivalents, and investments. Kymera expects that its cash and cash
equivalents will provide the company with an anticipated cash
runway into the second half of 2025 that is expected to take the
company past the proof-of-concept Phase 2 data for KT-474, as well
as early proof-of-concept data for KT-413, KT-333 and KT-253, while
Kymera continues to identify opportunities to accelerate growth and
expand its pipeline, technologies, and clinical indications.
About Kymera TherapeuticsKymera is a
biopharmaceutical company pioneering the field of targeted protein
degradation, a transformative approach to address disease targets
and pathways inaccessible with conventional therapeutics. Kymera’s
Pegasus platform is a powerful drug discovery engine, advancing
novel small molecule programs designed to harness the body’s innate
protein recycling machinery to degrade dysregulated,
disease-causing proteins. With a focus on undrugged nodes in
validated pathways, Kymera is advancing a pipeline of novel
therapeutic candidates designed to address the most promising
targets and provide patients with more effective treatments.
Kymera’s initial programs target IRAK4, IRAKIMiD, and STAT3 within
the IL-1R/TLR or JAK/STAT pathways, and the MDM2 oncoprotein,
providing the opportunity to treat patients with a broad range of
immune-inflammatory diseases, hematologic malignancies, and solid
tumors. For more information, visit www.kymeratx.com.
Founded in 2016, Kymera is headquartered in Watertown, Mass.
Kymera has been named a “Fierce 15” company by Fierce Biotech and
has been recognized by both the Boston Globe and the Boston
Business Journal as one of Boston’s top workplaces. For more
information about our people, science, and pipeline, please visit
www.kymeratx.com or follow us on Twitter or LinkedIn.
About Kymera’s Pegasus™ PlatformKymera’s
Pegasus platform is a powerful drug discovery engine that enables
the discovery of novel small molecule protein degrader medicines
designed to target and disrupt specific protein complexes and full
signaling cascades in disease, placing once elusive disease targets
within reach. The key components of the platform combine Kymera’s
broad understanding of the localization and expression levels of
the hundreds of E3 ligases in the human body with the Company’s
proprietary E3 Ligase Binders Toolbox, and advanced chemistry,
biology, and computational capabilities to develop protein
degraders that address significant, unmet medical needs.
Cautionary Note Regarding Forward-Looking
StatementsThis press release contains forward-looking
statements within the meaning of the Private Securities Litigation
Reform Act of 1995, as amended, including, without limitation,
implied and express statements by Kymera Therapeutics regarding
its: strategy, business plans and objectives for the IRAK4,
IRAKIMiD, STAT3 and MDM2 degrader programs; plans and timelines for
the preclinical and clinical development of its product candidates,
including the therapeutic potential, clinical benefits and safety
thereof; expectations regarding timing, success and data
announcements of current ongoing preclinical and clinical trials;
the ability to initiate new clinical programs; and Kymera’s
financial condition and expected cash runway into the second half
of 2025. The words "may," “might,” "will," "could," "would,"
"should," "expect," "plan," "anticipate," "intend," "believe,"
“expect,” "estimate," “seek,” "predict," “future,” "project,"
"potential," "continue," "target" and similar words or expressions
are intended to identify forward-looking statements, although not
all forward-looking statements contain these identifying words. Any
forward-looking statements in this press release are based on
management's current expectations and beliefs and are subject to a
number of risks, uncertainties and important factors that may cause
actual events or results to differ materially from those expressed
or implied by any forward-looking statements contained in this
press release, including, without limitation, risks associated
with: the impact of COVID-19 on countries or regions in which we
have operations or do business, as well as on the timing and
anticipated results of our current and future preclinical studies
and clinical trials, supply chain, strategy and future operations;
the delay of any current and future preclinical studies or clinical
trials or the development of Kymera Therapeutics' drug candidates;
the risk that the results of current preclinical studies and
clinical trials may not be predictive of future results in
connection with current or future preclinical and clinical trials,
including those for KT-474, KT-333, KT-413 and KT-253; Kymera
Therapeutics' ability to successfully demonstrate the safety and
efficacy of its drug candidates; the timing and outcome of the
Kymera Therapeutics' planned interactions with regulatory
authorities; obtaining, maintaining and protecting its intellectual
property; and Kymera Therapeutics' relationships with its existing
and future collaboration partners. These and other risks and
uncertainties are described in greater detail in the section
entitled "Risk Factors" in the Annual Report on Form 10-K for the
year ended December 31, 2022 filed on February 23, 2023, as well as
discussions of potential risks, uncertainties, and other important
factors in Kymera Therapeutics' subsequent filings with the
Securities and Exchange Commission. In addition, any
forward-looking statements represent Kymera Therapeutics' views
only as of today and should not be relied upon as representing its
views as of any subsequent date. Kymera Therapeutics explicitly
disclaims any obligation to update any forward-looking statements.
No representations or warranties (expressed or implied) are made
about the accuracy of any such forward-looking statements.
KYMERA THERAPEUTICS, INC. |
Consolidated Balance Sheets |
(In thousands, except share and per share
amounts) |
(Unaudited) |
|
|
|
|
|
|
|
|
|
|
|
|
December 31,2022 |
|
December 31,2021 |
Assets |
|
|
|
|
Cash, cash equivalents and
marketable securities |
|
$ |
559,494 |
|
$ |
567,605 |
Property and equipment,
net |
|
|
13,334 |
|
|
11,881 |
Other assets |
|
|
30,306 |
|
|
26,419 |
Total assets |
|
$ |
603,134 |
|
$ |
605,905 |
Liabilities and
Stockholders’ Equity |
|
|
|
|
Deferred revenue |
|
$ |
63,260 |
|
$ |
101,034 |
Other liabilities |
|
|
49,723 |
|
|
45,233 |
Total liabilities |
|
|
112,983 |
|
|
146,267 |
Total stockholders’
equity |
|
|
490,151 |
|
|
459,638 |
Total liabilities and
stockholders’ equity |
|
$ |
603,134 |
|
$ |
605,905 |
KYMERA THERAPEUTICS, INC. |
Consolidated Statements of Operations and Comprehensive
Loss |
(In thousands, except share and per share
amounts) |
(Unaudited) |
|
|
|
|
|
|
|
|
|
Three Months Ended December
31, |
|
Year EndedDecember 31, |
|
|
2022 |
|
|
2021 |
|
|
2022 |
|
|
2021 |
Collaboration Revenue—from
related parties |
$ |
16,139 |
|
$ |
15,275 |
|
$ |
46,826 |
|
$ |
72,832 |
|
|
|
|
|
|
|
|
Operating expenses: |
|
|
|
|
|
|
|
Research and development |
$ |
43,133 |
|
$ |
37,530 |
|
$ |
164,248 |
|
$ |
137,017 |
General and administrative |
|
11,637 |
|
|
11,740 |
|
|
43,834 |
|
|
36,345 |
Total operating expenses |
|
54,770 |
|
|
49,270 |
|
|
208,082 |
|
|
173,362 |
Loss from operations |
|
(38,631) |
|
|
(33,995) |
|
|
(161,256) |
|
|
(100,530) |
Other income (expense): |
|
|
|
|
|
|
|
Interest and other income |
|
3,824 |
|
|
144 |
|
|
6,624 |
|
|
488 |
Interest and other expense |
|
(58) |
|
|
(50) |
|
|
(176) |
|
|
(175) |
Total other income |
|
3,766 |
|
|
94 |
|
|
6,448 |
|
|
313 |
Net loss attributable to common
stockholders |
$ |
(34,865) |
|
$ |
(33,901) |
|
$ |
(154,808) |
|
$ |
(100,217) |
Net loss per share attributable
to common stockholders, basic and diluted |
$ |
(0.60) |
|
$ |
(0.66) |
|
$ |
(2.87) |
|
$ |
(2.09) |
Weighted average common stocks
outstanding, basic and diluted |
|
57,889,273 |
|
|
51,394,065 |
|
|
53,933,229 |
|
|
47,989,023 |
Investor
Contact: Bruce Jacobs Chief Financial
Officer investors@kymeratx.com 857-285-5300 Chris
Brinzey Managing Director,
Westwicke chris.brinzey@westwicke.com 339-970-2843 |
Media
Contact: Todd Cooper Senior Vice President,
Corporate Affairs media@kymeratx.com 857-285-5300 |
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