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Kymera Therapeutics Shares Key 2023 Goals to Support its Evolution into a Fully Integrated Degrader Medicines Company

Key Takeaway: Kymera Therapeutics outlined its strategic goals for 2023, focusing on its advancement in targeted protein degradation therapies. The company reported successful Phase 1 trial results for its lead program KT-474, and plans to advance several other candidates in its oncology pipeline. With approximately $560 million in cash, Kymera expects to fund operations through 2025, facilitating the development of innovative therapies for inflammatory diseases and cancer. Key objectives for the year include progressing KT-474 into Phase 2 trials and expanding its discovery pipeline.

Market Sentiment Analysis

POSITIVE FACTORS

  • Demonstrated encouraging safety profile and clinical impact of KT-474.
  • Significant cash runway into the second half of 2025 for further development.
  • Advancing multiple clinical programs with potential for best-in-class therapies.
  • Collaboration with Sanofi for KT-474 indicates strong industry support.

Full Press Release Details

Kymera Therapeutics Shares Key 2023 Goals to Support its Evolution
into a Fully Integrated Degrader Medicines Company
WATERTOWN, Mass., January 10, 2023 Kymera Therapeutics, Inc. (NASDAQ: KYMR), a clinical-stage biopharmaceutical company advancing targeted
protein degradation (TPD) to deliver novel small molecule protein degrader medicines, today announced its research, development and corporate goals for 2023.
2022 was a pivotal year for Kymera, as the Phase 1 trial of our lead program, KT-474 (SAR444656), demonstrated
fidelity of translation from healthy volunteers to patients, an encouraging safety profile, and clinical impact in complex inflammatory diseases such as hidradenitis suppurativa (HS) and atopic dermatitis (AD), highlighting the superior clinical
potential of an IRAK4 degrader over a small molecule inhibitor and validating our platform, molecule design and target selection capabilities and strategies, said Nello Mainolfi, PhD, Founder, President and CEO. With our oncology
pipeline advancing through dose escalation, we look forward to sharing data on the clinical activity of our STAT3 (KT-333) and IRAKIMiD (KT-413) programs in their target
patient populations later this year, as well as initial proof-of-mechanism data on our MDM2 degrader (KT-253). More broadly, we
have demonstrated the ability to effectively translate pharmacokinetic (PK), pharmacodynamic (PD) and safety from preclinical models into patients, as well as validation of our target selection strategy, allowing us to leverage and extend these
learnings as we continue to expand our pipeline with differentiated and potentially best-in-class programs in large immunology and oncology franchises.
Kymera ended 2022 with a cash balance of approximately $560 million, providing the company with an anticipated cash runway into the second half of
2025 that is expected to take us 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. Continued Dr. Mainolfi. In addition, we are well-positioned to advance our wholly-owned clinical programs while continuing significant investments in our platform and robust discovery
pipeline, additional details about which we look forward to sharing in 2023.
Kymera s 2023 Objectives
Kymera is a leader in the discovery and development of novel small molecule therapeutics designed to selectively degrade disease-causing proteins by harnessing
the body s natural protein degradation system. The company s data, generated in healthy volunteers and patients with HS, AD, hematological malignancies and solid tumors, has provided industry leading, proprietary know-how in TPD and enabled Kymera to focus on applications in areas with significant patient need and large commercial opportunities, including immunology and oncology.
Key objectives include:
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, robust inhibition of multiple ex vivo-stimulated disease-relevant cytokines, and was generally well tolerated.
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, has notified Kymera of its commitment to advance KT-474 into Phase 2 clinical studies. Initial Phase 2 clinical trials of
KT-474 will investigate its potential in HS and AD, with the first study initiating in 2023.
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-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.
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 suppress 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 the first quarter of 2023, with IV doses of KT-253 administered every 3 weeks to patients with solid tumors and hematological malignancies, including acute myeloid leukemia (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.
J.P. Morgan Healthcare Conference
present at the virtual 41st Annual J.P. Morgan Healthcare Conference at 9:00 a.m. PT (12:00 p.m. ET) on Tuesday, January 10, 2023. Nello Mainolfi, PhD, Co-Founder, President and CEO of Kymera, will
provide an overview of the Company s progress and 2023 goals.
A live webcast of the presentation can be accessed under Events and
Presentations in the Investors section of the Company s website at www.kymeratx.com. An archived webcast recording of the presentation will be available on the website for approximately 30 days.
An updated corporate overview presentation is available on the Investors section of the Company s website at https://investors.kymeratx.com/events-and-presentations.
About Kymera Therapeutics
Kymera 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
Cautionary Note Regarding Forward-Looking Statements
This 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 and KT-413; 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, 2021 and our Quarterly Report on Form 10-Q for the quarter ended September 30, 2022, 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

Frequently Asked Questions

What is Kymera Therapeutics focusing on in 2023?

Kymera is advancing its research and development in targeted protein degradation and aims to expand its pipeline in oncology and immunology.

What trials are planned for KT-474 in 2023?

Phase 2 clinical trials for KT-474 will focus on its effectiveness in treating hidradenitis suppurativa and atopic dermatitis.

What is the goal of the KT-333 program?

KT-333 aims to treat STAT3-dependent hematological malignancies and solid tumors through its Phase 1 clinical trial.

What new program is Kymera starting for KT-253?

Kymera plans to begin the Phase 1a dose escalation study for KT-253, targeting MDM2 in hematological malignancies.

How is Kymera using its E3 Ligase Atlas?

Kymera uses its E3 Ligase Whole-Body Atlas to identify targets for tissue-restricted or selective protein degradation therapies.

Last updated: Jan 10, 2023