EX-99.2 3 d161011dex992.htm EX-99.2 EX-99.2

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WITH TARGETED PROTEIN DEGRADATION June 28, 2021 INVENTING NEW MEDICINES KT-474 Phase 1 Clinical Trial Update Exhibit 99.2

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Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 (PSLRA) and other federal securities laws. These statements include information about our current and future prospects and our operations and financial results, which are based on currently available information. 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 terminology such as ‘‘aim,’’ ‘‘anticipate,’’ ‘‘assume,’’ ‘‘believe,’’ ‘‘contemplate,’’ ‘‘continue,’’ ‘‘could,’’ ‘‘design,’’ ‘‘due,’’ ‘‘estimate,’’ ‘‘expect,’’ ‘‘goal,’’ ‘‘intend,’’ ‘‘may,’’ ‘‘objective,’’ ‘‘plan,’’ ‘‘predict,’’ ‘‘positioned,’’ ‘‘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. These forward-looking statements include statements about the initiation, timing, progress and results of our future clinical trials and current and future preclinical studies of our product candidates and of our research and development programs; our plans to develop and commercialize our current product candidates and any future product candidates and the implementation of our business model and strategic plans for our business, current product candidates and any future product candidates. 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. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. We undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, the occurrence of certain events or otherwise. As a result of these risks and others, including those set forth in our most recent and future filings with the Securities and Exchange Commission, actual results could vary significantly from those anticipated in this presentation, and our financial condition and results of operations could be materially adversely affected. This presentation contains trademarks, trade names and service marks of other companies, which are the property of their respective owners. Certain information contained in this presentation and statements made orally during this presentation relate to or is based on studies, publications, surveys and other data obtained from third-party sources and the Company’s own internal estimates and research. While the Company believes these third-party studies, publications, surveys and other data to be reliable as of the date of the presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent sources has evaluated the reasonableness or accuracy of the Company’s internal estimates or research and no reliance should be made on any information or statements made in this presentation relating to or based on such internal estimates and research.

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Kymera: A Leading TPD Company VISION KEY PARTNERSHIPS INITIAL FOCUS FIRST-IN-CLASS Fully integrated, disease agnostic protein degrader medicine company Immune inflammation (I/I) and oncology CLINICAL PIPELINE PROOF-OF-BIOLOGY WELL-POSITIONED First to show placebo-controlled degrader proof-of-mechanism 2 additional INDs and clinical initiations expected by end of 2021 To be established in humans in 2021 $435M cash balance at Q1 2021

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Discovery Pre-Clinical Phases 1-3 JAK/STAT STAT3 Liquid & Solid Tumors Ph1: 4Q21 STAT3 Autoimmune & Fibrotic Diseases IL-1R/TLR IRAK4 Atopic Dermatitis, Hidradenitis Suppurativa, Rheumatoid Arthritis, others Rights1 Next Milestone POB: 4Q21 Indication(s) Program Pathway IRAKIMiD (IRAK4, Ikaros, Aiolos) MYD88MT DLBCL Ph1: 2H21 Kymera’s Pipeline of Novel Protein Degraders 1. Option to participate equally in the development and commercialization of Sanofi-partnered programs in the US. 2. Sanofi collaboration to develop IRAK4 degrader candidates, including KT-474 (SAR444656), outside of oncology and immuno-oncology fields. = Oncology = Immunology-Inflammation Discovery Pipeline Several Discovery Programs 1 Undisclosed Program 6 Undisclosed Programs 6 targets in 5 disease areas outside of immunology-inflammation and oncology Multiple programs in immune-inflammatory and genetically-defined oncology indications Research and development of degraders against a second undisclosed target with Sanofi KT-4742 Discovery Preclinical Phases 2/3 Phase 1 Next Gen.2 KT-413 KT-333

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Near-Term Milestones Provide Significant Opportunity Liquid & Solid Tumors IRAK4 AD, HS, RA, others Indication(s) Program IRAKIMiD (IRAK4, Ikaros, Aiolos) MYD88MT DLBCL Discovery Programs & Platform Expected Upcoming Milestones Initiated SAD portion of Phase 1 trial in healthy volunteers (Feb 2021) Established degrader proof-of-mechanism in healthy volunteer SAD portion of Phase 1 trial (June 2021) Initiate enrollment in MAD portion of Phase 1 trial (July 2021) Present data from atopic dermatitis cohort in non-interventional study (2H21) Establish Phase 1 proof-of-biology in healthy volunteers (4Q21) and in patient cohort (1H22) Continue pipeline expansion by advancing early-stage discovery programs toward IND-enabling studies Further expand Pegasus platform to generate novel degrader product candidates Leverage Whole-Body Atlas to unlock new opportunities across broad therapeutic applications Presentation of preclinical data updates at AACR, ICML meetings (2Q21) Submit IND to initiate Phase 1 clinical trial in r/r B cell lymphomas (2H21) Present additional KT-413 preclinical data and potential expansion strategies (2H21) Establish Phase 1 proof-of-biology in patients (2022) Establish Phase 1 initial clinical proof-of-concept in patients (2022) Nominated development candidate for liquid & solid tumor indications (1Q21)  Present additional preclinical data in liquid & solid tumor indications (2H21) Submit IND to initiate Phase 1 clinical trial in liquid and solid tumors (4Q21) Establish Phase 1 proof-of-biology in patients (2022) Establish Phase 1 initial clinical proof-of-concept in patients (2022) = Oncology = Immunology-Inflammation STAT3 KT-474 KT-413 KT-333 Compound ✔ ✔ ✔ ✔

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IRAK4 Degrader KT-474

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IRAK4 Targeting: Clinical Validation, Human Genetics De-risking and Degrader Advantage IL-1R/TLR Pathway IL1-Ra/IL-1β : Rheumatologic Diseases IL-1a: Atopic Dermatitis IL-1β: CANTOS Data, Atherosclerosis, Lung Cancer IL-18: Macrophage Activation Syndrome IL-36: Generalized Pustular Psoriasis IRAK4 SMI: Rheumatoid Arthritis Unmet Medical Need Validated Biology Undrugged Node Precision Medicine Approach Clinical Pathway Validation IRAK4 is a key component of the myddosome protein complex involved in innate immunity that mediates signals through IL-1R and TLRs Several commercial and clinical stage drugs have validated this pathway in multiple diseases Degrading IRAK4, and fully blocking IL-1R/TLR signaling, is expected to be superior to antibody-based therapies that block only single cytokines, with convenience of a daily oral therapy IRAK4 degradation can block pathway fully vs kinase inhibitors that partially block signaling Human genetics de-risk safety: adults that lack IRAK4 are healthy

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Atopic Dermatitis (AD) Rheumatoid Arthritis (RA) Hidradenitis Suppurativa (HS) Additional Opportunities KT-474 Opportunity Immune-inflammatory disorders collectively impacting millions of patients in the U.S. Total Prevalence (U.S.) >1.3M >16.0M >325K Chronic, pruritic inflammatory skin disease Large unmet need for safe and effective oral agents for patients with AD Chronic, systemic autoimmune disease that can cause irreversible joint damage Multiple therapies targeting the IL-1R/TLR pathway are approved Chronic and debilitating inflammatory skin disease ~25% of patients with moderate-to-severe disease4 Adalimumab is approved, which provides some benefit to ~50% of patients with moderate-to-severe disease5 Immune-inflammatory diseases impacted by IL-1R/TLR pathway 1 2 3 1. Chiesa Fuxench et al. J Invest Dermatol. 2019 Mar;139(3):583-590. 2. Hunter et al. Rheumatol Int . 2017 Sep;37(9):1551-1557. 3. Garg et al. JAMA Dermatol. 2017;153(8):760-764. 4. Calao et al. PLoS One. 2018; 13(7): e0200683. 5. Kyriakou et al. Dermatol Reports. 2018 Oct 1; 10(2): 7859.

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KT-474: Potent and Specific IRAK4 Degradation Superior to Kinase Inhibition KT-474 DC50 = 2.1 nM in human immune cells KT-474 only degraded IRAK4 in human immune cells at concentration 10-fold above the DC90 KT-474 better able to inhibit IL-6 under both LPS and LPS + IL-1B than clinically active IRAK4 SM kinase inhibitor PF-06550833 Degradation and Selectivity Superiority over SM kinase Inhibitor LPS + IL-1B à IL-6 Log[Compound] (nM) pval=0.05 Protein Level Fold Change (log2) Pvalue (–log 10) 10xDC90 24hr 0 0.5 1 1.5 2 2.5 3 -2 -1 0 0.5 -0.5 1 2 -1.5 1.5 IRAK4 Legend Compound IL-6 IC50 (nM) IRAK4 Degrader 0.8 Negative control 450 IRAK4 SMI (PF-06550833) N/A

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85% IRAK4 Degradation Sufficient for Maximal In Vivo Efficacy in Preclinical Models Ability to inhibit topical skin thickening induced by imiquimod was measured in a mouse model of psoriasis Orally dosed KT-474 inhibited thickening, a reflection of local and systemic inflammation, comparable to a topic corticosteroid after 2 or 4 days of dosing Full efficacy at doses achieving at 65-80% IRAK4 reduction in skin and spleen. In other models KT-474 has demonstrated full efficacy with 85% degradation Skin Spleen

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Dog Single Ascending Dose (SAD) IRAK4 Knockdown at Day 1 Dog Multiple Ascending Dose (MAD) IRAK4 Knockdown at Day 7 KT-474 in Dog: Multi-dosing Required to Achieve Target Degradation Orally-administered KT-474 achieves >85% knockdown of IRAK4 at Day 7 with repeat dosing in MAD study Multiple doses (MAD) lead to optimal degradation profile vs SAD upon reaching steady-state Consistency of IRAK4 knockdown observed across peripheral blood mononuclear cells (PBMC) and skin tissue * = Below Limit of Quantitation

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KT-474 Interim Phase 1 SAD Results

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KT-474 Phase 1 Trial Design Double-blind, Placebo-controlled, Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) trial 1 SAD Portion Healthy Volunteers 2 MAD Portion Healthy Volunteers 3 MAD Portion Patient Cohort Safety & tolerability 5 cohorts (up to 60 adult healthy subjects) 12 per cohort (9:3 randomization) 14x daily doses (starting dose 25 mg) 1 cohort (up to 20 AD and HS patients) Open-label 14x daily doses Three-part Phase 1 Design Endpoints Primary 7 cohorts (up to 56 adult healthy subjects) 8 per cohort (6:2 randomization) Single dosing (starting dose 25 mg) Secondary/Exploratory Pharmacokinetic measures (half-life, bioavailability) IRAK4 knockdown in PBMC IRAK4 knockdown in skin biopsies Proinflammatory cytokine and chemokine levels in skin biopsies C-reactive protein and cytokine levels in plasma Ex vivo response of whole blood to TLR agonists and IL-1b Exploratory MAD only SAD & MAD

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KT-474 Phase 1 Trial Goals Establishing proof-of-mechanism and proof-of-biology Oral Bioavailability and Proof-of-Mechanism Efficacious plasma exposures that are safe and well-tolerated Proof-of-mechanism with IRAK4 knockdown following single KT-474 dose Predictable PK/PD supporting oral daily dosing regimen Optimal IRAK4 Reduction and Proof-of-Biology ≥85% IRAK4 knockdown in skin and blood with daily dosing x 14 days that is safe and well-tolerated Proof-of-biology with systemic anti-inflammatory effect: reduction in plasma hsCRP and inhibition of whole blood ex vivo response to TLR agonists and IL-1b Establishment of maximum effective dose Establish Proof-of-Biology in Patients ≥85% IRAK4 degradation in diseased skin and blood Anti-inflammatory effect in diseased skin and reduction of plasma cytokines and hsCRP Confirmation of dose for subsequent Phase 2 studies 1 SAD Portion Healthy Volunteers 2 MAD Portion Healthy Volunteers 3 MAD Portion Patient Cohort De-risking Milestones

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KT-474 Interim Phase 1 Healthy Volunteer SAD Overview Interim Results (Cohorts 1-4) Dosing Pharmacokinetic (PK) Features Safety & Tolerability 32 subjects randomized 24 subjects administered KT-474 8 subjects administered placebo Single dose administration of oral KT-474 tablet Dose levels (mg): 25 75 150 300 PK profile consistent with oral daily dosing Predictable, dose-dependent plasma exposures after single oral dose of KT-474 Half-life: 25-32 hours No treatment-related adverse events No Serious Adverse Events

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KT-474 Achieved Profound IRAK4 Degradation after Single Oral Dose that Lasted for at Least 6 Days   Measured by mass spectrometry in circulating PBMC IRAK4 levels nadired at 48-72 hours IRAK4 reduction lasted for at least 144h (6 days post-dose) in all dose groups Absolute IRAK4 Levels Mean % Reduction of IRAK4 * BLQ BLQ = Below Limit of Quantitation * * SAD4 144/312 h PD timepoints pending

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Percent IRAK4 Reduction in PBMC at 48 Hours Post-Dose using Mass Spectrometry   Placebo (n=8) Cohort 1 (n=6) Cohort 2 (n=6) Cohort 3 (n=6) Cohort 4 (n=6) KT-474 dose - 25 mg 75 mg 150 mg 300 mg Mean IRAK4 Change +3% -38% -71% -78% -84% Median IRAK4 Change +16% -41% -71% -78% -90% p value* 0.0057 <0.0001 <0.0001 <0.0001 * p-values relative to placebo IRAK4 Degradation >85% Achieved Following Single KT-474 Dose

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Interim Results from Phase 1 Healthy Volunteer SAD Summary and Next Steps KT-474 interim Phase 1 results demonstrate degrader proof-of-mechanism, first time for TPD in a placebo-controlled study Median IRAK4 reduction of 90% (p<0.0001 vs placebo) and maximum reduction of 94% at 48 hours following single dose of 300 mg, with sustained degradation that lasted for at least 6 days at all dose levels Based on potency, PK and PD profiles with deep and sustained multiday degradation, expect to achieve biologically relevant (85%) level of degradation with repeat dosing at lower doses; selected MAD starting dose of 25 mg Demonstrated predictable, dose-dependent and biologically active plasma exposures, and half-life that supports oral daily dosing No treatment-related adverse events or serious adverse events observed to date Demonstrating Phase 1 target degradation of >85% de-risks KT-474 ability to reach clinically relevant biological effects in future development as a potential best-in-class anti-inflammatory oral drug FDA lifted partial clinical hold following review of interim healthy volunteer SAD results Dose escalation in SAD portion of Phase 1 to continue, including assessment of food-effect In July, plan to initiate MAD portion of Phase 1 in healthy volunteers assessing daily dosing of KT-474 for 14 days Expect to present updated results from healthy volunteer SAD/MAD portions in Q4’21 Data to include IRAK4 degradation in skin and PBMC and effects on inflammatory biomarkers after repeat dosing Optimal dose from MAD healthy volunteer portion to be evaluated in an open label cohort of patients with atopic dermatitis and hidradenitis suppurativa

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2020 2021 2022 2023 KT-474 Development Plan . 1. Estimated clinical development timeline. Non-Interventional Study Phase 1 HV SAD Phase 2 Trials (Sanofi-sponsored)1 Interim Data Updated Results HV POB Patient POB IND Final Results Interim Results HV MAD Patient Cohort SAD dosing initiated 1Q21 SAD/MAD studies: healthy volunteers (HV) and AD/HS patients Endpoints: primary - Safety; secondary - Proof-of-Biology Data updates: Interim SAD proof-of-mechanism: June 2021 HV proof-of-biology: 4Q21 Patient proof-of-biology: 1H22 40 patients (HS n=30; AD n=10) Biomarker endpoints in blood and skin: IRAK4, cytokines, acute phase reactants Data updates: Interim: Oct 2020 Updated HS: May 2021 Final AD: 2H21 Non-Interventional Phase 1 Randomized, placebo-controlled trials in patients in potential indications such as AD, HS, RA, others Phase 2

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