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C o m p a n y W e b c a s t December 14, 2022
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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,
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current and future preclinical studies or clinical trials or the development of our 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 clinical trials, including those for KT-474, KT-333 and KT-413; Our ability to successfully demonstrate the safety and efficacy of our drug candidates; the timing and outcome of our planned interactions with regulatory authorities; obtaining,
maintaining and protecting our intellectual property; and our relationships with its existing and future collaboration partners. 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, except as required by law. 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
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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. 2022 KYMERA THERAPEUTICS, INC. PAGE 2
1. Welcome 2. Oncology Update 15' IRAKIMiD (KT-413)
STAT3 (KT-333) 3. IRAK4 Update 35' KT-474 HS and AD Patient Cohort 4. Q&A 40' P R E S E N TAT I O N A G E N D A
Introduction to Kymera Key accomplishments to date: Kymera is a leader
in Targeted Protein Since 2016 founding, advanced 4 clinical stage programs and Degradation (TPD) developed a deep pipeline positioned to deliver 1 IND/year Building a fully-integrated, Unique target selection strategy based
on using TPD to unlock high value, undrugged targets global biotech company First to advance degraders (KT-474) in healthy volunteers and Initial focus in Immunology/ patients with HS and AD, demonstrating degrader vs. small Inflammation and
Oncology, molecule inhibitors (SMI) biological differentiation, and potential but already a disease- best in class profile in I/I agnostic platform Demonstrated fidelity of translation of PK, PD and safety across Accelerating forward three
clinical programs in I/I and oncology patients integration through key strategic partnerships Well capitalized with $596 million of cash as of 9/30/22 positioning Kymera to accelerate and expand clinical impact in areas with large clinical
and commercial opportunities 2022 KYMERA THERAPEUTICS, INC. PAGE 4
Kymera's Pipeline of Novel Protein Degraders Pathway Program
Indication(s) Discovery IND Enabling Phase 1 Rights* Phase 2 Next Milestones Phase 2 Start Immuno-inflammatory KT-474 IRAK4 Diseases: HS, AD, RA, others Multiple molecules staged as potential back ups if needed 2023 IL-1R/TLR IRAKIMiD Clinical
Activity MT MYD88 Tumors KT-413 (IRAK4, Ikaros, Aiolos) 2023 Clinical Activity STAT3 Liquid & Solid Tumors KT-333 2023 JAK/STAT Autoimmune & STAT3 Fibrotic Diseases Phase 1 Start MDM2 Liquid & Solid Tumors KT-253 p53 2023 Confidential
Confidential Collaboration Discovery Multiple programs in immune-inflammatory and 1 DC Several Discovery Programs oncology indications anticipated to deliver 1 IND/year Annually Pipeline 6 targets in 5 disease areas outside of
Collaboration 6 Undisclosed Programs immunology-inflammation and oncology *Option to participate equally in the development and commercialization of Sanofi-partnered programs in the US. = Oncology = Immunology-Inflammation RA: Rheumatoid arthritis,
AD: Atopic Dermatitis, HS: Hidradenitis suppurativa 2022 KYMERA THERAPEUTICS, INC. PAGE 5
Presentation Summary Oncology KT-333 and KT-413 Phase 1 trials
in dose escalation phase Both molecules demonstrating PK/PD consistent with pre-clinical models No dose-limiting toxicities observed to date KT-253 IND cleared; Phase 1 trial expected to commence in early 2023 KT-474
Part C cohort complete: data supportive of promising clinical and market opportunities in HS and AD PK/PD in patients in line with healthy volunteers with broad impact on disease relevant cytokines in blood and skin of HS and AD patients
KT-474 generally well-tolerated; QTc spontaneously returned to normal baseline during the dosing period Clinical endpoints suggest promising potential in both HS and AD, supporting targeting IRAK4 and clear differentiation of
degrader versus small molecule inhibitors Sanofi officially committed to advance KT-474 into Phase 2 clinical trials, initially in HS and AD 2022 KYMERA THERAPEUTICS, INC. PAGE 6
STAT3 Degraders In Oncology: KT-333 U.S. R.O.W. Prevalence Incidence
Prevalence Incidence High degree of validation of JAK-STAT pathway in oncology Peripheral T-cell ~13k ~6.5k ~27k ~15k lymphoma (PTCL) and immuno-oncology supported by >25k publications Cutaneous T-cell ~30k ~2.6k ~67k ~6k lymphoma (CTCL)
Traditionally undrugged target Large granular lymphocyte ~4.5k <1k ~24k ~3k leukemia (LGL-L) First-in-class opportunity to address STAT3 driven pathology Solid Tumors, PD-1 Combo across large and diverse indications ~30k ~5k ~78k
~20k (e.g. Stage IV MSI-H CRC) Source: Bionest, SEER. GlobalData; ROW includes EU, UK, Japan and China. STAT3 Has Unique Tumor Cell Intrinsic Cytokine Growth Factor Receptor Adrenergic Receptor Receptor and Extrinsic Mechanisms Intrinsic:
Hyperactivation of STAT3 Extrinsic: STAT3 promotes the via either receptor signaling, or differentiation and activity of hotspot mutations promotes gene immunosuppressive and endothelial JAK JAK SRC expression programs involved with cells,
resulting in an P survival, proliferation, stemness and immunosuppressive tumor STAT3 metastasis of tumor cells microenvironment P P STAT3 STAT3 Opportunities in STAT3-dep. Opportunities in multiple heme and malignancies (e.g., T
cell maligs., solid tumor indications that are not DLBCL, AML) and drug resistant responsive to immune checkpoint P P tumors (e.g., TKI res. oncogene- inhibitors STAT3 STAT3 driven solids) 2022 KYMERA THERAPEUTICS, INC. PAGE 8
KT-333 Highly Active on Intermittent Dosing Regimens Complete Tumor
Regressions Associated with Robust STAT3 KD for 48h in Preclinical Models SU-DHL-1 Preclinical PK/PD Weekly Dosing Dose- and degradation-dependent tumor growth inhibition observed with once-weekly dosing in ALK+ Based on
preclinical model (STAT3 dependent ALK+ ALCL ALCL), target PD >90% STAT3 KD for ~48 hours to achieve robust anti-tumor activity 10 mg/kg sufficient to drive full tumor regression in SU-DHL- 1 that was durable for multiple weeks after the
last dose (on day 14) 2022 KYMERA THERAPEUTICS, INC. PAGE 9
KT-333: Phase 1, Multicenter, Dose-Escalation and Expansion Trial to
Evaluate KT-333 in Adult Patients with PTCL, CTCL, LGL-L, and Solid Tumors Phase 1a (n up to 40) Phase 1b (n=40) R/R Lymphoma/Leukemia or Solid Tumors Cohort 1: PTCL Regimen: mg/kg IV Infusion weekly n=20 Cohort 2: CTCL Dec. 2022: Currently n=20
MTD/RP2D enrolling DLX Expansion* 0.40 Cohort 3: LGL-L 0.20 n=20 0.10 Predicted clinically 0.05 Cohort 4: Solid Tumors efficacious doses n=20 Key Objectives Phase 1a Phase 1b Safety/Tolerability at RP2D in Patients with Primary
Safety/Tolerability and MTD and RP2D Lymphoma/Leukemia and Solid Tumors PK Parameters of KT-333 Preliminary Clinical Activity (ORR, DoR, PFS, DCR, OS) Secondary Preliminary Estimates of Activity PK Parameters of KT-333
Exploratory PD Effects of KT-333 PD Effects of KT-333 MTD: Maximum Tolerated Dose. RP2D: Recommended Phase 2 Dose. ORR: Overall Response Rate 2022 KYMERA THERAPEUTICS, INC. PAGE 10
Interim Safety Data Summary Dose Level 1 4 patients at Dose
Level 1 (DL1, 0.05 mg/kg) Dose Level 3 All 4 patients heavily pretreated ( 3 prior lines) 0.51 mg/kg 3 solid tumor Dose leve4 cleared by SRC, open 1 CTCL for enrollment No DLTs, no treatment-related SAEs, no AEs
leading to discontinuation 2022 KYMERA THERAPEUTICS, INC. PAGE 11
Summary of PK Data From 4 Patients Enrolled in DL1 Week 1 DL1
0.05 mg/kg PK Parameter Week 1 (n = 4) C (ng/mL) 306 (30.9%) max AUC (ng.h/mL) 1550 (66.4%) Vd (L/kg) 0.278 (17.5%) CL (L/h/kg) 0.0450 (62.5%) t (h) 6.25 (78.8%) 1/2 2022 KYMERA THERAPEUTICS, INC. PAGE 12
STAT3 Degradation in Blood at Dose Level 1 (DL1: 0.05 mpk) Consistent
with Prediction from Preclinical Modeling Clinical PD in PBMC by MS Mean Max Degradation* Subject ID Method: Targeted MS Post-doses 1&2 (Range) n = 4 subjects DL1-1 -79.8 % (-75.6 % to -84.1 %) DL1-2 -67.8 % (-73.5 % to -62.0 %) DL1-3
-50.0 % (-47.4 % to -52.6 %) DL1-4 -66.7 % (-47.7 % to -85.8 %) Cohort -66.0 % Average KT-333 KT-333 *Max degradation as measured across timepoints sampled 0.05 mpk 0.05 mpk Observed STAT3 degradation of 50-80% in PBMCs at Dose Level 1 is
consistent with the range predicted for tumor based on preclinical modeling of SUDHL1 xenograft PK-PD data Maximal degradation in DL1 patients is observed between 24-96 hours post infusion in Cycle 1 weeks 1 & 2, with recovery of STAT3
levels between doses, as seen in preclinical models 2022 KYMERA THERAPEUTICS, INC. PAGE 13
Demonstration of Initial Proof-of-Mechanism (POM) for KT-333
Accrual to first dose level completed STAT3 degradation in blood at first dose level consistent with preclinical predictions, with mean maximum degradation following first 2 doses of Cycle 1 averaging 66%, with maximum knockdown of up to 86%
At least 48h of target degradation observed that in preclinical species led to robust antitumor activity in STAT3 sensitive preclinical models DL1 level generally well-tolerated with no DLTs or treatment-related SAEs DL2
currently enrolling patients DL3-4 expected to be clinically active doses 2022 KYMERA THERAPEUTICS, INC. PAGE 14
IRAKIMiDs are Potent Degraders of IRAK4 and IMiD Substrates MT
Targeting Redundant Pro-survival Pathways in MYD88 DLBCL Autoantigens Single-agent therapies targeting activated NF B TLRs B Cell IL-1R signaling in DLBCL show limited activity Receptor IFNAR1/2 Redundant NF B pathway
activation and MT downregulation of Type 1 IFN common in MYD88 lymphoma Simultaneous degradation of IRAK4 and IMiD CD79A/B * substrates Ikaros and Aiolos shows synergistic activity BTK MYD88MYD88 MT * in MYD88 models IRAK4 IRAK4 CARD11 *
Ikaros P MALT1 P IRAK1 IRAK1 U.S. R.O.W. * BCL10 Aiolos Prevalence Incidence Prevalence Incidence Aiolos 2.8 / 1.2 / IKK IFN MYD88 MT DLBCL A20* ~8k ~10k JNK 100k 100k IKK IKK MYD88 MT 0.3 / 0.7 / * IFN AP1 NF B
Waldenstr m's ~9k ~26k IRF4 IRF7 100k 100k Pathway Pathway Pathway Macroglobulinemia MYD88 MT PCNS 0.6 / 0.6 / ~2k ~10k PROLIFERATION & Lymphoma 100k 100k IFITs SURVIVAL Source: Bionest and Global Data. ROW includes E.U., U.K. and
Japan. * Pathway-activating alterations in DLBCL Adapted from Yang et al. (2012) Cancer Cell 21, 6, pp723-737 2022 KYMERA THERAPEUTICS, INC. PAGE 16 TRAF6 TRAF6
KT-413 Highly Active on Intermittent Dosing in Preclinical Models
Complete Tumor Regressions Associated with Robust IRAK4 and Ikaros/Aiolos Degradation for 72h T/C% Drug (Day 33) CR PR SD PD (REG%) Single 10 mg/kg dose showed extended tumor CC-220 9 0 0 0 7 exposure and strong degradation of both
IRAK4 and KT-413 10 mg/kg (94) 5 2 0 0 IMiD substrates that was maintained for least 72hr in preclinical models MT In the OCI-LY10 MYD88 xenograft model, intermittent dosing of KT-413 induced strong Target PD 80-90% Ikaros KD and
50-70% IRAK4 KD antitumor activity, including complete regressions. in tumor for 72 hrs to achieve robust anti-tumor Superior activity compared to IMiD CC-220 alone activity 2022 KYMERA THERAPEUTICS, INC. PAGE 17
KT-413: Phase 1, Multicenter, Dose-Escalation and Expansion Trials to
Evaluate KT-413 in Patients with R/R DLBCL Phase 1a (n up to 40) Phase 1b (n=40) R/R B-cell NHL R/R DLBCL Regimen: mg/kg IV Infusion q 3 weeks Dec. 2022: MT Cohort 1: MYD88 Currently n=20 enrolling MTD/RP2D Expansion* WT DLX Cohort 2: MYD88 0.82
n=20 0.51 *Additional 3-6 0.32 pts for a total of 9 patients dosed 0.16 at MTD Predicted clinically efficacious doses Key Objectives Phase 1a Phase 1b Primary Safety/Tolerability and MTD and RP2D Safety/Tolerability at RP2D in Patients
with DLBCL PK Parameters of KT-413 Preliminary Clinical Activity (ORR, DoR, PFS, DCR, OS) Secondary Preliminary Estimates of Activity PK Parameters of KT-413 Exploratory PD Effects of KT-413 PD Effects of
KT-413 MTD: Maximum Tolerated Dose. RP2D: Recommended Phase 2 Dose. ORR: Overall Response Rate 2022 KYMERA THERAPEUTICS, INC. PAGE 18
Interim Safety Data Summary Dose Levels 1-2 All patients with
heavily pretreated B-cell lymphoma (up to 3 prior lines of therapy) Follicular lymphoma, DLBCL (all wild-type MYD88) No DLTs, no treatment-related SAEs or AEs leading to discontinuation, no neutropenia in first two dose levels
2022 KYMERA THERAPEUTICS, INC. PAGE 19
Plasma PK Showing Dose-Proportional Increase in Exposure 0.16 0.32
Cycle 1 Plasma PK mg/kg mg/kg PK (DL1) (DL2) Parameter Cycle 1 Cycle 1 C max 140 493 (ng/mL) AUC inf 1360 3490 (ng.h/mL) Vd (L/kg) 10.1 3.99 CL (L/h/kg) 0.118 0.092 t (h) 59.3 30.2 1/2 2022 KYMERA THERAPEUTICS, INC. PAGE 20
Degradation Profile of IRAK4, Ikaros and Aiolos in DL1/DL2 Consistent
with Preclinical Models in Blood and Tumor At least 72h of Target Degradation Observed with Once Every Three-week Dosing DL2 DL1 Target Degradation in PBMC by FLOW 0.16mg/kg 0.32mg/kg Cycle 1 Cycle 2 Dose IRAK4 Cycle 1 Cycle 2 Level Target Knockdown
in Tumor by Targeted MS DL1 -16% 0 Percent Change from Baseline at C3D4 DL2 -27% -40% 104-002: 0.16mg/kg Ikaros Dose Cycle 1 Cycle 2 Level DL1 -84% -88% -27% DL2 -92% -95% -41% -66% Dose Aiolos Cycle 1 Cycle 2 Level *Mean is from 2-3 peptides
measured for each analyte DL1 -93% - 91% DL2 -100% -100% Up to 40% KD of IRAK4 and 95/100% KD of Ikaros and Aiolos in PBMC at DL1-2 2022 KYMERA THERAPEUTICS, INC. PAGE 21
Demonstration of Initial POM for KT-413 First two dose levels