KYMR 8-K
Kymera Therapeutics, Inc. (KYMR)
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM
CURRENT REPORT
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| Item 2.02 | Results of Operations and Financial Condition. |
On January 14, 2025, Kymera Therapeutics, Inc. (the “Company”) issued a press release announcing its preliminary cash balance as of December 31, 2024, a business update and further details on its 2025 key objectives and outlook. A copy of this press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K.
Although it has not finalized its full financial results for the fourth quarter and fiscal year ended December 31, 2024, the Company announced on January 14, 2025, that it estimates it had approximately $850 million of cash, cash equivalents and marketable securities as of December 31, 2024.
The information contained in Item 2.02 of this Current Report on Form 8-K and Exhibit 99.1 attached hereto is unaudited and preliminary and does not present all information necessary for an understanding of the Company’s financial condition as of December 31, 2024 and its results of operations for the three months and year ended December 31, 2024. The audit of the Company’s consolidated financial statements for the year ended December 31, 2024 is ongoing and could result in changes to the information set forth above.
The information contained in Item 2.02 of this Current Report on Form 8-K and Exhibit 99.1 attached hereto is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended (the “Securities Act”), or the Exchange Act, except as expressly set forth by specific reference in such filing.
| Item 7.01 | Regulation FD Disclosure. |
On January 14, 2025, the Company issued a press release outlining its key 2025 objectives and strategy to advance its leading portfolio of immunology programs. A copy of the press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K.
The Company will be conducting meetings with participants attending the 43rd Annual J.P. Morgan Healthcare Conference (the “Conference”) during the week of January 13, 2025. A copy of the slides to be presented by the Company at the Conference is furnished as Exhibit 99.2 to this Current Report on Form 8-K. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.2.
The information contained in Item 7.01 of this Current Report on Form 8-K and Exhibit 99.1 and Exhibit 99.2 is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act or the Exchange Act, except as expressly set forth by specific reference in such a filing.
| Item 8.01 | Other Events. |
On January 14, 2025, the Company announced that the Phase 1 clinical trial of KT-621 in healthy volunteers is ongoing, with data expected in the second quarter of 2025. The Company also announced plans to advance KT-621, the Company’s investigational oral degrader of STAT6, into a Phase 1b clinical trial in atopic dermatitis (AD) patients in the second quarter of 2025 with data expected in the fourth quarter of 2025 and plans to initiate parallel Phase 2b clinical trials of KT-621 in AD and asthma in late 2025 and early 2026, respectively. Additionally, the Company announced a novel oral immunology program with a first-in-class development candidate will be disclosed in the first half of 2025.
The disclosure under this Item 8.01 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 about the Company’s expectations regarding strategy, business plans and objectives for clinical development of its clinical and preclinical pipeline including the therapeutic potential, clinical benefits and safety thereof, the Phase 1 data readout of KT-621 in the first half of 2025 and plans to initiate a Phase 1b trial in atopic dermatitis (AD) patients in the second quarter of
2025 with data in the fourth quarter of 2025 and plans to initiate parallel Phase 2b trials in AD and asthma in late 2025 and early 2026, respectively. The words “expect,” “plan,” and “will” 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 Item 8.01 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 any forward-looking statements contained in this Item 8.01, including, without limitation, risks associated with: uncertainties inherent in the initiation, timing and design of future clinical trials, the availability and timing of data from ongoing and future clinical trials and the results of such trials, whether preliminary results of early clinical trials will be indicative of the results of later clinical trials, the ability to successfully demonstrate the safety and efficacy of drug candidates, the timing and outcome of planned interactions with regulatory authorities, the availability of funding sufficient for the Company’s operating expenses and capital expenditure requirements and other factors. These risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in the most recent Quarterly Report on Form 10-Q and in subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent the Company’s views only as of today and should not be relied upon as representing the Company’s views as of any subsequent date. The Company explicitly disclaim 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.
| Item 9.01. | Exhibits |
(d) Exhibits
| Exhibit No. |
Description | |
| 99.1 | Press release issued by Kymera Therapeutics, Inc. on January 14, 2025, furnished herewith. | |
| 99.2 | Corporate Presentation, furnished herewith. | |
| 104 | Cover Page Interactive Data (embedded within the Inline XBRL document). | |
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Kymera Therapeutics, Inc. | ||||||
| Date: January 14, 2025 | By: | /s/ Nello Mainolfi | ||||
| Nello Mainolfi, Ph.D. | ||||||
| President and Chief Executive Officer | ||||||
Exhibit 99.1
Kymera Therapeutics Outlines Key 2025 Objectives and Strategy to Advance
Industry Leading Portfolio of Oral Immunology Programs
KT-621 (STAT6) Phase 1 healthy volunteer trial ongoing, with data expected in 2Q25
Kymera plans to initiate a KT-621 Phase 1b trial in atopic dermatitis (AD) patients in 2Q25 with data in
4Q25 and plans to initiate parallel Phase 2b trials in AD and asthma in late 2025 and early 2026, respectively
KT-295 (TYK2) to advance into Phase 1 testing in 2Q25 with data expected in late 2025
KT-474/SAR444656 (IRAK4) Phase 2b dose-ranging studies in hidradenitis suppurativa (HS) and AD
ongoing, with completion expected in 1H26 and mid-2026, respectively
Novel oral immunology program with a first-in-class development candidate to be disclosed in 1H25
Well-capitalized with $8501 million in cash and runway into mid-2027
Kymera to present its 2025 outlook at J.P. Morgan Annual Healthcare Conference on
Tuesday, January 14, 2025, at 9:00 a.m. PT/12:00 p.m. ET
Watertown, Mass. (January 14, 2025) – Kymera Therapeutics, Inc. (NASDAQ: KYMR), a clinical-stage biopharmaceutical company advancing a new class of oral small molecule degrader medicines with biologics-like activity for immunological diseases, today announced its corporate goals for 2025, including anticipated progress on its clinical pipeline of immunology programs.
“We expect 2025 to be another year of significant progress and accomplishments, and likely our busiest year to date. After unveiling our broader immunology strategy and new pipeline last year, we are poised to demonstrate the clinical potential of our first-in-class, wholly owned STAT6 and TYK2 oral degrader programs,” said Nello Mainolfi, PhD, Founder, President and CEO, Kymera Therapeutics. “Our vision is to leverage the power of targeted protein degradation to deliver, for the first time in industry, oral drugs with biologics-like activity that have the potential to revolutionize the treatment of many inflammatory diseases with significant unmet needs. We are rapidly progressing the development of our first-in-industry oral STAT6 degrader, KT-621, and will have Phase 1 healthy volunteer data, Phase 1b atopic dermatitis data, as well as initiate the first Phase 2b study, all in 2025.”
Dr. Mainolfi continued, “In addition to the significant progress we expect with our disclosed immunology programs, we look forward to expanding our immunology pipeline with a new program disclosure in the first half of 2025, continuing to build what we believe is the best oral immunology portfolio in industry.”
Additional details around Kymera’s pipeline, including its development plans for KT-621, will be presented today at the J.P. Morgan Healthcare Conference.
Program updates on the company’s disclosed programs and platform include:
STAT6 Degrader Program
KT-621 is an investigational, first-in-class, once daily, oral degrader of STAT6, the specific transcription factor responsible for IL-4/IL-13 signaling and the central driver of Th2 inflammation. Currently in Phase 1 testing, KT-621 has demonstrated dupilumab-like activity and very good safety data in preclinical models. Recruiting for the KT-621 Phase 1 heathy volunteer trial is ongoing, with multiple single ascending dose (SAD) and multiple ascending dose (MAD) cohorts completed. KT-621 has the potential to address numerous Th2 diseases including AD, asthma, chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis with nasal polyps (CRSwNP), eosinophilic esophagitis (EoE), chronic spontaneous urticaria (CSU) and prurigo nodularis (PN), among others. Kymera intends to develop KT-621, an oral drug with potential for biologics-like efficacy, with the goal of transforming the treatment paradigm for the more than 130 million patients (children and adults) in the world suffering from Th2 diseases.
Key upcoming KT-621 milestones:
| • | Complete KT-621 Phase 1 healthy volunteer clinical trial and report data in the second quarter of 2025. |
| • | Advance KT-621 into a Phase 1b clinical trial in AD patients in the second quarter of 2025 and report data in the fourth quarter of 2025. |
| • | Initiate KT-621 Phase 2b clinical trial in AD in the fourth quarter of 2025, followed by a Phase 2b clinical trial in asthma in early 2026. |
TYK2 Degrader Program
KT-295 is an investigational, first-in-class, once daily, oral degrader of TYK2, a member of the Janus kinase (JAK) family required for Type I IFN, IL-12 and IL-23 signaling. Given KT-295’s ability, observed in preclinical studies, to replicate the human genetic loss of function profile of TYK2, and to block the pathway to the level of upstream biologics (e.g., anti-IL-23), KT-295 has the potential to be the first oral therapy to deliver biologics-like activity in diseases such as IBD, psoriasis and others.
Key upcoming KT-295 milestones:
| • | File KT-295 IND and initiate dosing in the Phase 1 healthy volunteer clinical trial in the second quarter of 2025, with Phase 1 data expected in the fourth quarter of 2025. |
IRAK4 Degrader Program
KT-474 (SAR444656) is an investigational, first-in-class, once daily, oral degrader of IRAK4, a key protein involved in TLR/IL-1R-driven inflammation. Given IRAK4’s ability to block IL-1 family cytokine and TLR signaling, KT-474 holds promise to be superior to individual upstream cytokines blockers (e.g., anti-IL-1, anti-IL-33) as an oral drug. Initial Phase 2b clinical trials for HS and AD, in collaboration with Sanofi, are currently ongoing with potential in the future to expand beyond these two indications.
Key upcoming KT-474 milestones:
| • | Collaborate with Sanofi to advance the KT-474/SAR444656 (IRAK4) Phase 2b dose-ranging clinical trials in HS and AD, with primary completion expected in the first half of 2026 for HS and mid-2026 for AD. |
Research Platform
Leveraging its proven small molecule discovery capabilities, deep expertise, and unique target selection strategy, Kymera is building an industry leading portfolio of innovative oral immunology medicines addressing high value undrugged or poorly-drugged targets for areas of significant need.
Key upcoming pipeline disclosures:
| • | Kymera plans to announce the next immunology program, a first-in-class development candidate addressing an undrugged transcription factor, in the first half of 2025, and initiate clinical testing in early 2026. |
For more information on Kymera’s pipeline visit our website.
J.P. Morgan Healthcare Conference Webcast
Kymera will present its 2025 outlook at the 43rd Annual J.P. Morgan Healthcare Conference on Tuesday, January 14, at 9:00 a.m. PT (12:00 p.m. ET). A live webcast of the presentation and Q&A session will be available under “News and Events” in the Investors section of the Company’s website at www.kymeratx.com. A replay of the webcast and the presentation will be archived on Kymera’s website following the event.
1Unaudited, estimated cash as of December 31, 2024.
About Kymera Therapeutics
Kymera is a clinical-stage biotechnology company pioneering the field of targeted protein degradation (TPD) to develop medicines that address critical health problems and have the potential to dramatically improve patients’ lives. Kymera is deploying TPD to address disease targets and pathways inaccessible with conventional therapeutics. Having advanced the first degrader into the clinic for immunological diseases, Kymera is focused on building an industry-leading pipeline of oral small molecule degraders to provide a new generation of convenient, highly effective therapies for patients with these conditions. Founded in 2016, Kymera has been recognized as one of Boston’s top workplaces for the past several years. For more information about our science, pipeline and people, please visit www.kymeratx.com or follow us on X or LinkedIn.
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 about our expectations regarding strategy, business plans and objectives on the clinical development of clinical and preclinical pipeline, including the therapeutic potential, clinical benefits and safety thereof, Sanofi’s expansion of the Phase 2 clinical trials of KT-474/SAR444656, the Phase 1 data readout of KT-
621 in the first half of 2025, the advancement of KT-295 into Phase 1 clinical testing, the declaration of its next clinical candidate and filing of an IND in second half of 2025, and Kymera’s financial condition and expected cash runway into mid-2027. The words “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “expect,” “estimate,” “seek,” “predict,” “future,” “project,” “potential,” “continue,” “target,” “upcoming” 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 any forward-looking statements contained in this press release, including, without limitation, risks associated with: uncertainties inherent in the initiation, timing and design of future clinical trials, the availability and timing of data from ongoing and future clinical trials and the results of such trials, whether preliminary results of early clinical trials will be indicative of the results of later clinical trials, the ability to successfully demonstrate the safety and efficacy of drug candidates, the timing and outcome of planned interactions with regulatory authorities, the availability of funding sufficient for our operating expenses and capital expenditure requirements and other factors. These risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in the most recent Quarterly Report on Form 10-Q and in subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. We explicitly disclaim 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.
Investor and Media Contact:
Justine Koenigsberg
Vice President, Investor Relations
857-285-5300
Exhibit 99.2
Nello Mainolfi, Ph.D., Founder, President and CEO J.P. Morgan Healthcare Conference January 2025
Forward Looking Statements This presentation contains forward-looking statements within the meaning of the Securities Litigation Reform Act of 1995 and other federal securities laws. These statements include, but are not limited to, implied and express statements about strategy, business plans and objectives for our programs; plans and timelines for the preclinical and clinical development of our product candidates, including the potential, clinical benefits and safety profiles of such product candidates; expectations regarding timing, success and data announcements of ongoing preclinical studies clinical trials; our ability to initiate new clinical programs, including plans to submitinvestigational new drug (IND) applications; our ability to deliver additional investigational drugs into the clinic by 2026; the initiation, timing, progress and results of our current and future preclinical studies and clinical trials of our current and prospective product candidates; our plans to develop and commercialize our current and any future product candidates and the implementation of our business model and strategic plans for our business, current; any future product candidates; and our financial condition and expected cash runway into mid-2027. All statements other than statements of historical facts contained in this presentation, including express or implied statements regarding our strategy, future financial condition, future operations, projected costs, prospects, plans objectives of management and expected market growth, are forward-looking statements. In some cases, you can identify forward-looking statements by such as ‘‘anticipate,’’ “upcoming,” ‘‘assume,’’ ‘‘believe,’’ ‘‘could,’’ ‘‘estimate,’’ ‘‘expect,’’ ‘‘goal,’’ ‘‘intend,’’ ‘‘may,’’ “milestones,” ‘‘objective,’’ ‘‘plan,’’ ‘‘predict,’’ ‘‘potential,’’ ‘‘seek,’’ ‘‘should,’’ ‘‘target,’’ ‘‘will,’’ ‘‘would’’ and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. You should not rely upon forward-looking statements as predictions of future events and actual results or events could differ materially from the plans, intentions and expectations disclosed herein. Any forward-looking statements 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 including, without limitation, risks associated with: the timing and anticipated results of our current and future preclinical studies clinical trials, supply chain, strategy and future operations; the delay of any current and future preclinical studies or clinical trials or the development of our drug candidates; the risk that the results of prior preclinical studies and clinical trials may not be predictive of future results in connection with current or future preclinical studies and clinical trials, including those for KT-474/SAR-444656, KT-621 and KT-295; our ability tosuccessfully demonstrate the safety and efficacy of our drug candidates; the timing and outcome of any interactions with regulatory authorities; obtaining, maintaining protecting our intellectual property; our relationships with existing and future partners; the impacts of current macroeconomic and geopolitical events. In addition, any forward-looking statements represent Kymera’s views only as of today should not be relied upon as representing its views as of any subsequent date. Kymera explicitly disclaims any obligation to update any forward-looking statements, except required by law. No representations or warranties (expressed or implied) are made about the accuracy of any such d-looking statements. As a result of these risks and others, including those set forth in our gs with the SEC, actual results could vary significantly from those anticipated in this ion, and our financial condition and results of operations could be materially adversely cted. Certain information contained in this presentation and ements made orally during this presentation relate to or is based on studies, publications, and other data obtained from third-party sources and the Company’s own internal stimates and research. While the Company believes these third-party studies, publications, urveys and other data to be reliable as of the date of the presentation, it has not ndependently verified, and makes no representation as to the adequacy, fairness, accuracy completeness of, any information obtained from third-party sources. In addition, no t sources have evaluated the reasonableness or accuracy of the Company’sinternal estimates or research, and no reliance should be made on any information or ements made in this presentation relating to or based on such internal estimates andresearch. This presentation contains trademarks, trade names and service marks of companies, which are the property of their respective owners.
3 Revolutionizing Immunology: Oral Drugs with Biologics-Like Efficacy •Targeted Protein Degradation (TPD) leader Best-in-industry capabilities in hit finding and optimization of oral degraders •Unique target selection strategy pursuing traditionally undrugged targets •Portfolio poised to disrupt conventional treatment paradigms By combining the “right target” with the disruptive potential of TPD, Kymera is delivering oral therapies with biologics-like profiles for the first time in industry with the potential to expand access to millions of patients around the world Science-driven clinical stage organizationwith industry-leading oral immunology pipeline
4 Clear Vision and History of Strong Execution •Delivered 5 new investigational degrader drugs into the clinic since 2020, and on path to deliver a total of 10 by 2026 •Dosed over 300 healthy volunteers/patients to date across clinical pipeline, demonstrating: •>90% target degradation in all programs •Desired safety and efficacy profiles VISION EXECUTION IMPACT •Reinventing the treatment of human disease as a fully integrated commercial global biotech •Building a world-class immunology development team to execute on large Phase 2/3 trials •Raised $1.7B to date, with $850M1 of cash on hand, providing a runway to mid-2027
Targeted Protein Degradation: New Modality Expanding the Range of Treatable Disease Targeted Protein Degradation Existing modalities have limitations that restrict their application leaving millions Traditional Small Molecule Yet 80% of disease-causing can unlock the undrugged proteome Drugged proteins remain Proteome out of reach to existing • Small molecule-based modality with gene silencing Antibody An technologies power • Not limited by delivery, target or tissue/organ type; disease agnostic • Oral delivery Cell/Gen • Efficient development/manufacturing Therapy • Validated across multiple FDA-approved drugs with >$17 billion in combined peak WW sales1 5
Immunology: A Large, Underserved Market Oral Degraders with ~160M Total Patients Across Key Immunologic Diseases1 Biologics-Like Advanced Therapies: ~5M (3%) Profiles Can Disrupt >$100B >$500B the Immunology • â^¼5M patients (3% of Non-Advanced ? total diagnosed) are Therapies: • â^¼ 97% of the on systemic advanced ~90M (58%) diseased therapies with >$100B population does not in annual sales for key have access to • Displace injectable I/I indications2 advanced therapies biologics • 2/3 of those • Enormous • Offer a convenient therapies are untapped market highly effective injectable biologics Untreated potential advanced therapy to ~62M (39%) the 97% unserved and underserved patients 6
Small Molecule Oral Degraders Can Transform Immunology Potentially Superior Profile to Injectable Biologics and Traditional Small Molecule Inhibitors Biologics have several limitations: Orals preferred by most patients: • Expensive, challenging to • In multiple surveys1, prescribe/reimburse • Immunogenicity 75% of patients would switch from injectable • Cold storage biologics to oral with similar profile • Inconvenient and/or painful 75% route of administration for patients Oral degraders have unique potential to provide Traditional small molecule inhibitors (SMI) insufficiently block pathways, limiting efficacy: comparable pathway • Traditional small 80 molecule inhibitors inhibition to biologics, with 70 • Anti IL-23 biologic the convenience of oral 60 do not allow (%)* dramatically more 16 50 continuous and dosing, and potentially 90 40 75% effective than Wk 30 complete pathway access broader patient TYK2 SMI in 20 32% blockade PASI PsO2 10 populations Oral Degrader 0 Risankizumab Deucravacitinib (IL-23 mAb) (TYK2 SMI) 7
Unique Target Selection Strategy Drives Best-In-Class Pipeline Undrugged or STAT6 Clear path to inadequately early clinical drugged differentiation targets TYK2 IRAK4 Strong e clinical/ genetic/c mercial validatio ortunities FO C U S O N F I RS T—A N D B E S T—I N- C L A S S O P P O RT U NIT IE S 8
Industry L eader at Developing Oral Degrader Drugs Hit Finding, Structural Biology and Chemistry C omprehens ive Proprietary Tec hnolog ies to B es t-in-Indus try S truc tural B iolog y Identify Novel L ig ands to Undrug g ed C apabilities Ac ros s all Prog rams Proteins Frag ment- Cys teine E xample: Cereblon-(K T-474)-IR AK 4 Virtual DEL Bas ed Cov alent HT S A SMS Screen Screen Screening IRAK 4 KT-474 • Transcription Factors • E 3 Ligases ernary complex • Scaffolding P roteins • Others ryo-E M structures nable design of Leading to: ighly specific and >8 development c andidates , including >4 potent degraders targeting undrug g ed trans c ription fac tors Highly potent degraders (sub-nanomolar) with refined drug-like properties (orally bioavailable World-C las s C hemis try:with systemic distribution to all target tissues), and comprehensive understanding of P K/P D, resulting in impeccable translation of our pipeline into the clinic across programs 9
Building the Best-In-Industry Oral Immunology P ipeline P otential IND-E nabling P has e 1 P has e 2 OP P ORTUNITY Indications Kymera Wholly-Owned AD, Asthma, C OP D, Dupilumab-like activity STAT6 P N, C R S wNP, EoE , KT-621 in a pill BP, others P soriasis, IBD , P sA, TY K 2-L O F profile to deliver TYK2 KT-295 biologics (i.e., anti IL -23)-like Lupus , others activity in a pill Transcriptio Lupus , S jogren’s, R A, Drugging a genetically Undrugged target to be disclosed in 1H25 validated target with an oral n Factor IBD , others degrader P artnered with S anofi (Kym era 50/50 US Opt-In P otential) 1 C ombined activity of upstream HS , AD, R A, Asthma, KT-474—HS IRAK4 2 biologics IBD , others KT-474—AD (anti IL -1/18/33/36) in a pill Value P ropos ition: Combining the convenience of oral drugs and the efficacy of biologics to expand access to advanced therapies for millions of patients around the world 10
Oral Degraders in Immunology With S ignificant Market Potential First-In-Industry: Orals with Biologics -Like P rofiles Could Change the Commercial Landscape S T A T 6 T Y K 2 I R A K 4 T R A N S C R I P T I O N F A C T O R S C A F F O L D I N G K I N A S E S C A F F O L D I N G K I N A S E Key Indications : AD, Asthma, Key Indications : Ps O , PsA, SLE , Key Indications 3: HS , AD, Asthma, CO P D, CR S wNP, EoE , CS U, PN UC, CD, MS CO P D, RA, SL E , UC, CD >140M2 Diag nos ed >130M1 Diag nos ed P atients >20M2 Diag nos ed P atients P atients Systemic Advanced Systemic Advanced Systemic Advanced Therapies 1% Therapies 11% Therapies 3% 10B 1 65B 2 55B 2 Untreated/Other Therapies Untreated/Other Therapies Untreated/Other Therapies 99% 89% 97% 11
T Y K 2: R eplicating Human Genetics to Deliver Biologics (i.e., IL -23)-L ike E fficacy with an Oral P ill T Y K 2 Cytokine Pathway IL-23 Type I IFN IL-12 IL-10 S C A F F O L D I N G Only a deg rader W T TY K 2 K I N A S E can eliminate all ++++ ++++ ++++ ++++ scaffolding and C omplete deficiency Type I + + + +++ IL-23 IL-12 TY K 2 -/- interferons catalytic functions TY K 2 K inas e dead + ++++ ++++ ++++ P 1104A/P 1104A TYK2 JAK1 TYK2 JAK2 TYK2 JAK2 K T-295: Hig hly S elec tive, Pic omolar, Orally Ac tive TYK 2 Deg rader S caffolding TY K 2 Degradation in NHP Blood Post 7-day QD KT-295 Oral Dosing for KT-295 Genetic Validation 0 • Loss of function (LO F ) variant is protective in Baseline immunological diseases and generally normal Clinic al Validation (All Biolog ics ) from -50 • A pprov ed: IL-12/23 biologics (P sO, P sA, IBD); T Y K2 S MI (P sO) Change Insufficiently Drug g ed Targ et (Ideal for % TPD) 2 -100 • P ossesses both kinase and scaffold function; K TY cannot be fully addressed by S MIs 0.3 mg/kg 1 mg/kg 3 mg/kg Larg e Patient Impact Potential: • P sO, P sA, S LE , IBD , MS , others S tatus : IND-enabling studies ongoing Next Miles tones : Phase 1 healthy volunteer start 2Q 2025 12
IR AK 4: C ombined Activity of Upstream Biologics (IL -1/18/33/36) in an Oral P ill LP S + IL-1bïƒ IL-6 I R A K 4 S C A F F O L D I N G Only a deg rader K I N A S E can fully block (Control) 6 IL1/T L R signaling—TLR s IL-1R %IL MyD88 Log[C ompound] (nM) IRAK 4 KT-474 IRAK 1/2 K T-474 Ph1 S tudy: Robus t Deg radation and Early POC in HS and AD TRAF6 C atalytic S caffolding Th1/Th2/Th17 Inflammation >95% IRAK 4 Degradation in Humans Robust Reduction of AN Counts in HS Patients 0 Genetic Validation • IR A K4 null adults are healthy 4 -10 Clinic al Validation (All Biolog ics ) IRAK -20 Baseline • A pprov ed: IL-1R (C AP S , R P ), IL-36 (G P P ) % Mean) -27.4 ) Change • Phas e 3: IL-1a/b (HS ), IL-33 (C OP D) -30 from % of • Phas e 2: IL-18 (HS , AD, C D), IL-33 (Asthma) (±SE -40 Mean (±SE -45.4 Insufficiently Drug g ed Targ et -50 -49.6 (Ideal for TPD) Mean Change -50.7 • P ossesses both kinase and scaffold function; -60 0 7 14 21 28 35 42 cannot be fully addressed by S MIs Day Larg e Patient Impact Potential: • HS , AD, R A, C OP D , Asthma, IBD , others S tatus : Phas e 2b trials in HS and AD ongoing Next Miles tones : Phase 2b completion: 1H 2026 (HS ) and mid-2026 (AD) 13
KT-621: First-In-Industry S TAT6 Degrader A Paradigm S hift in Immunology 14
S TAT 6 Degrader: Dupilumab-L ike Activity in a P ill B es t-in-P athway Mechanis m S T A T 6 T R A N S C R I P T I O N • Dupilumab (IL -4Rα mAb) approved F A C T O R for multiple indications IL -4/13 Pathway • Gain of function variants cause Clinical and g enetic Type I IL-4 Type II IL-4 severe allergic diseases Receptor Receptor pathway validation • K O phenotype (mouse) normal IL-4 IL-4 IL-13 • S TAT6 loss-of-function, healthy, and IL-4R α γc IL-4R α IL-13R α1 protects from Th2-driven asthma Undrug g ed/ • Historically undrugged transcription factor; TP D only small molecule inadequately drug g ed Cytoplasm by other technolog ies technology that can fully block target/pathway STAT STAT KT-621 6 6 Clear path to early • S TAT6 degradation and Th2 clinical de-ris king biomarkers Allergic Th2 Inflammation STAT6 is the only specific • Dupilumab indications (AD, Asthma, transcription factor responsible Acc es s larg e patient COP D, CRS wNP, E oE , P N, others), for IL -4/13 signaling populations mega-blockbuster potential 15
KT-621: A Highly S elective and P otent Oral S TAT 6 Degrader Only S TAT 6 is Deg raded in Human Cells Even at Hig h Full S TAT 6 Deg radation in All Relevant Human Cell Concentrations (100 x DC90) Types at P icomolar Concentrations (DC50) T cell = 36 pM S TAT 6 S TAT6 Monocyte = 60 pM Other S TATS B Cell = 86 pM 100 K eratinocyte = 22 pM 4 S mall Airway Epithelial Cell = 35 pM O Bronchial S mooth Muscle Cell = 25 pM Value) DMS S ensory Neuron = 22 pM—to Log10(p 2 50—Percentage 0 0 100 101 102 103 104 105 -2 0 2 Concentration (pM) Log2(Fold-Change) 16
KT-621: An Oral S TAT 6 Degrader with P otency S imilar or S uperior to Dupilumab in Human Cells KT-621 Fully B loc ks IL -4/13 Pathway in Human Th2 Func tional As s ays with IC50’s L ower than Dupilumab IL-4 Induced P erios tin Releas e in Human IL-13 Induced TAC1 Expres s ion in iP S C B ronchial S mooth Mus cle Cell Derived Human S ens ory Neuron IC50 IC 50 KT-621 24 pM K T-621 89 pM 7 pM 7 pM O O DMS 100 DMS 100 to to ercentage rcentage e P P 100 101 102 103 104 105 100 101 102 103 104 105 Concentration (pM) Concentration (pM) 17
KT-621: An Oral S TAT 6 Degrader with P otency S imilar or S uperior to Dupilumab in In Vivo P reclinical Models KT-621 B loc ks Th2 Inflammation In Vivo Equally/B etter than a S aturating Dos e of Dupilumab in Mous e HDM As thma Model TARC (CCL17) Reduction in Lung s Reduction in Lung Goblet Cell Metaplas ia 104 2.5 KT-621 dos ed QD 2.0 orally for 31 days 103 Score 1.5 2/8/32 mpk doses (pg/ml) 102 Cell showed 72/85/91% C 1.0 S TAT6 TAR 101 Goblet deg radation 0.5 respectively in mouse spleen 100 0.0 18
KT-621 Compelling P reclinical P K/P D and S afety Holds P romise for P ositive Human Translation KT-621 Potently Deg rades S TAT6 to Depletion with L ow Oral Dos es Ac ros s Multiple Prec linic al S pec ies and in Multiple Tis s ues S TAT 6 Deg radation in Dog B lood P os t 7 S TAT 6 Deg radation in NHP Tis s ues P os t 14 Days of KT-621 QD Oral Dos ing Days of KT-621 10 mpk QD Oral Dos ing 0 0 aseline B Baseline fromfrom Change -50 Change -50 % % TAT6 TAT6 S S -100 -100 No advers e safety finding s in any doses of GL P tox studies 19
Kymera’s Goal is to Build a S TAT 6 Franchise T hat Will S erve AL L P atients with T h2 Inflammation >130 million diag nos ed mild and 46.5% moderate/s evere patients acros s the s even major markets 1 Mild 1% Treated with S ystemic Advanced 52.5% Therapy Moderate/Severe (>$10B market1) Kymera is the leader in the STAT6 target space (with multiple molecules as needed) poised to deliver transformative treatments for ALL patients with Th2 diseases: AD, Asthma, COP D, CRS wNP, CSU, EoE , BP, PN, others 20
Opportunity to Transform Treatment P aradigm in T h2 Inflammation Examples: Atopic Dermatitis and Asthma Atopic Non-Rx. Management Topicals Therapy Systemic Advanced Therapy Dermatitis1 (Emollients, salt baths, (Corticosteroids, Calcineurin, trigger avoidance) PDE 4, JAK inhibitors) (Biologic: IL-4/13, IL-13, S MI: JA K ) KT-621 Inhaled Corticos teroids (ICS) ICS ± LA B A ± ICS + LA B A + LAMA ± Biolog ic Asthma2 (As needed ïƒ Maintenance) LAMA ± LTRA (Biologic: IgE, IL-5, T S LP, IL-4/13) 21
KT-621: First S TAT 6 Agent to Enter Clinical Evaluation Phase 1 Trial: Double-blind, Placebo-controlled SAD and MAD in Healthy Volunteers • Safety & tolerability of 2Q 2025 Part A Primary escalating single and S ing le As c ending Dos e multiple doses of KT-621 Phas e 1 Healthy (S A D) Volunteer Data Secondary • Pharmacokinetic measures Key trial aim is to show that KT-621 c an Part B robus tly deg rade Multiple As c ending Dos e • S TAT 6 protein levels in S TAT6 in blood and (MAD) Exploratory blood and skin (MAD) s kin at doses that are • Th2 biomarkers 14x daily doses safe and well-tolerated Phase 1 trial status update: Recruitment ong oing with multiple S A D/MAD cohorts completed 22
KT-621 on Track for Full Development Across at L east Eight Dupilumab Established Indications Initial Parallel Development in Moderate/S evere Atopic Dermatitis (AD ) and As thma is Expec ted to Enable Ac c elerated L ate Parallel Development Ac ros s All Other Dermatolog y/GI and Res piratory indic ations D E R M A T O L O G Y R E S P I R A T O R Y AD Asthma Near-Term Planned Trials CSU COP D • Phase 1b in AD (2Q25) PN CRS wNP • Parallel Phase 2b in AD BP (4Q25) and Asthma (1Q26) G A S T R O E N T E R O L O G Y EoE Total Potential Patient Impact: >130M patients 1 23
P ipeline with Clear L ine of S ight to L arge Value Creation Potential Upc oming 2025 1H 2026 Indic ations Miles tones Immunolog y – Oral QD Small Molecule Degraders AD, Asthma, P h1 HV Data: 2Q25 Ph1 HV Ph1b AD Ph2b AD STAT6 COP D, P N, P h1b AD Data: 4Q25 CRS wNP, E oE , S afety, S TAT 6 Biomarkers in KT-621 Ph2b As thma P h2b S tarts: 4Q25/1Q26 degradation in blood & blood & skin, BP, others skin 28-day efficacy P soriasis, P h1 HV S tart: 2Q25 TY K 2 IBD, P sA, IND Enabling Ph1 HV Patient Studies P h1 HV Data: 4Q25 KT-295 Safety, STAT6 L upus, degradation in blood & skin S afety, T YK 2 degradation IND in blood & skin others L upus, Trans cription IND Enabling Ph1 FIH: E arly 2026 S jogren’s, RA, Factor IBD, others P rogram & IND S afety, degradation data disclosure in blood & skin P artnered with S anofi / Kym era Opt-In P otential HS , AD, RA, Ph2b HS IRAK 4 Asthma, P h2b Completion: 1 HS : 1H26 KT-474 IBD, others2 Ph2b AD AD: Mid-2026 24
Thank You NAS DAQ: KY MR For additional information contact: w w w . k y m e r a t x . c o m [email protected] @ K y m e r a T X [email protected] [email protected] KYMERA THERA PE UTICS 500 North Beacon S treet, 4th Floor Watertown, MA 02472
Abbreviations Ab Antibody FIH First-in-Human JAK Janus K inase AD Atopic Dermatitis GLP Good Laboratory Practice JP Japan AS MS Affinity S election Mass S pectrometry GOF Gain of Function KO K nockout AN Count Abscess and Inflammatory Nodule Count GPP Generalized Pustular Psoriasis LA B A Long-A cting Beta Agonist BP Bullous Pemphigoid HD High Dose LAMA Long-A cting Muscarinic Antagonist CAPS Cryopyrin-A ssociated Periodic S yndrome HDM House Dust Mite LD Low Dose CD Crohn’s Disease HS Hidradenitis S uppurativa LOF Loss of Function COPD Chronic Obstructive Pulmonary Disease HTS High Throughput S creening LP S Lipopolysaccharide S olution CRSwNP Chronic Rhinosinusitis with Nasal Polyps HV Healthy Volunteers LTRA Leukotriene Receptor Antagonist Cryo-EM Cryo-Electron Microscopy I&I Immunology and Inflammation MAD Multiple Ascending Dose S tudy Ctrl Control IBD Inflammatory Bowel Disease MS Multiple S clerosis CSU Chronic S pontaneous Urticaria IC Inhibitory Concentration # NHP Nonhuman Primate DC# Degradation Concentration ICS Inhaled Corticosteroid nM Nanomolar DEL DNA -E ncoded Library IFN Interferon PAS I Psoriasis Area and S everity Index DMSO Dimethyl S ulfoxide IgE Immunoglobulin E Pbo Placebo EoE Eosinophilic Esophagitis IL Interleukin Ph Phase EU European Union IND Investigational New Drug Application PK /PD Pharmacokinetics/Pharmacodynamics FDA Food and Drug Administration IRAK4 Interleukin 1 Receptor Associated K inase 4 pM Picomolar PN Prurigo Nodularis 26
Abbreviations PsA Psoriatic Arthritis UC Ulcerative Colitis PsO Psoriasis US United S tates QD Once a day WW Worldwide R&D Research and Development RA Rheumatoid Arthritis ROW Rest of World RP Recurrent Pericarditis SA D S ingle Ascending Dose study SL E S ystemic Lupus Erythematosus SMI S mall Molecule Inhibitor STA T S ignal Transducer and Activator of Transcription STA T6 S ignal Transducer and Activator of Transcription 6 TARC Thymus and Activation-R egulated Chemokine Th1 Type 1 Th2 Type 2 Th17 Type 17 TLR Toll-like Receptors TPD Targeted Protein Degradation TYK2 Tyrosine K inase 2 27