Full Press Release Details
Agenda Introduction Justine Koenigsberg Vice President, Investor
Relations Revolutionizing Immunology with Oral Medicines Nello Mainolfi, PhD Founder, President and Chief Executive Officer KT-621 BroADen Phase 1b Data Jared Gollob, MD Chief Medical Officer Closing Remarks Nello Mainolfi, PhD Founder, President
and Chief Executive Officer Question and Answer Session 2
Forward Looking Statements This presentation contains forward-looking
statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. These statements include, but are not limited to, implied and express statements about our strategy, business plans and
objectives for our programs; plans and timelines for the preclinical and clinical development of our product candidates, including the therapeutic potential, clinical benefits and safety profiles of such product candidates; expectations regarding
timing, success and data announcements of ongoing preclinical studies and clinical trials; our ability to initiate new clinical programs, including plans to submit investigational new drug (IND) applications; our ability to deliver additional
investigational drugs into the clinic; 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; our expectations regarding strategy, business plans and objectives on the
development of KT-621, including the therapeutic potential, clinical benefits and safety thereof, the initiation of the Phase 2b study of KT-621 in patients with asthma in the first quarter of 2026, the effect of initial parallel development of
Phase 2b studies in AD and asthma patients on acceleration of late parallel development and dose selection across multiple indications, Phase 2b data readout of KT-621 in patients with moderate to severe AD expected by mid-2027; and the preliminary
cross-study assessments comparing non-head-to-head clinical data of KT-621 to published data for dupilumab, and our financial condition and expected cash runway into the second half of 2028. All statements other than statements of historical facts
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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 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 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-621; the risk that cross-trial comparisons my not be reliable as no head-to-head trials have been completed KT-621 to dupilumab, and Phase 1 clinical data for KT-621 may not be directly comparable to dupilumab's
clinical data due to differences in molecule composition, trial protocols, dosing regiments, and patient populations and characteristics. our ability to successfully demonstrate the safety and efficacy of our drug candidates; the timing and outcome
of any interactions with regulatory authorities; obtaining, maintaining and protecting our intellectual property; our relationships with existing and future collaboration partners; the impacts of current macroeconomic and geopolitical events. In
addition, any forward-looking statements represent Kymera's views only as of today and should not be relied upon as representing its views as of any subsequent date. Kymera explicitly disclaims any obligation to update any forward-looking
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presentation relating to or based on such internal estimates and research. This presentation contains trademarks, trade names and service marks of other companies, which are the property of their respective owners. 3
Revolutionizing Immunology with Oral Medicines Nello Mainolfi, PhD
Founder, President and CEO 4
Kymera: Revolutionizing Immunology with Oral Medicines Leader in
Targeted Protein Degradation (TPD) Unique target selection strategy pursuing traditionally undrugged targets in highly validated pathways Best-in-industry capabilities in hit finding and optimization of oral degraders Strategically
focused on immunology and delivering disruptive oral therapies with biologics-like profiles to transform treatment paradigms 5
Immunology Remains a Large Underserved Market Millions of Patients Do
Not Have Access to Advanced Systemic Therapies Untreated ~62M (39%) Advanced Therapies >$100B ~160M IN ANNUAL SALES ~5M (3%) PATIENTS FOR ADVANCED DIAGNOSED WITH 2 THERAPIES IMMUNOLOGICAL 1 DISEASES Non-Advanced Therapies ~90M (58%) 6
Advanced Systemic Therapies Are Mostly Injectable Biologics Biologics
Have Numerous Limitations, Making Orals Preferred by Most Patients >90% Inconvenient, burdensome, and often painful for patients WOULD SWITCH TO AN ORAL Immunogenicity risks 1 OPTION In-office injection training costs HCPs
valuable time and resources Expensive to manufacture; cold chain delivery/storage 7
Small Molecule Oral Degraders Can Transform Treatment of Diseases Oral
Drugs with Biologics-like Activity Unlike Traditional Small Molecule Inhibitors (SMI), Degraders Allow for Continuous, Complete Pathway Blockade PD OF DEGRADERS VS SMI TYPICAL PK OF ORAL DRUGS SMI Suppression (follows exposure) Drug Target/Pathway
Exposure Suppression Degrader Suppression 100% SMI pharmacology (PD) is correlated to drug exposure (PK); Degraders PD is not correlated to PK and can lead to complete 1 continuous degradation with its catalytic mechanism Unlocks target
classes unreachable by other modalities Achieves full pathway blockade, matching biologics-like depth of immune modulation High selectivity, strong potency, and catalytic mechanism enable full and constant target suppression with low
Potential to deliver the power of biologics in an oral form doses/concentrations 8
STAT6 Transcription Factor, Highly Validated but Undrugged Target STAT6
STAT6 is the specific transcription factor in TR A N S C R I P TI O N FA C TO R the IL-4/IL-13 pathway Dupilumab Dupilumab IL-4 IL-4 IL-13 IL-4/IL-13 pathway is clinically validated by dupilumab across multiple Type 2 allergic
IL-4R C IL-4R IL-13R 1 and atopic diseases: AD, asthma, COPD, EoE, CRSwNP, BP, PN, CSU STAT6 is genetically validated by human GoF and heterozygous LoF alleles STAT6 KT-621 While several therapies
target the upstream IL-4/IL-13 receptors, there are no known drugs that selectively target this pathway Allergic Type 2 Inflammation within the cell with oral delivery potential 9
STAT6 Opportunity to Serve Millions of Patients with Type 2
Inflammation 1 PA T I E N T S DERMATOLOGY AD 43M CSU 4.4M PN 305K BP 166K <2M >140M GASTROENTEROLOGY TREATED WITH TOTAL EoE 1.6M SYSTEMIC ADVANCED POTENTIAL RESPIRATORY 2 1 THERAPIES PATIENT IMPACT Asthma 55M COPD 34M CRSwNP 2.8M An oral STAT6
degrader has the potential to transform the treatment paradigm for Type 2 diseases and tap into large underserved markets 10
KT-621: Compelling Preclinical Profile Preclinical Package Suggests
Potential for Dupilumab-like Activity in a Pill Full Inhibition of IL-4/IL-13 Excellent Preclinical Robust Degradation Exquisite Pathways, More Potent Activity Comparable or in Relevant Cell Types Selectivity than Dupilumab Superior to Dupilumab
Lung Remodeling STAT6 Degradation in IL-4 Induced TARC Release in Goblet Cell Metaplasia Immune Cells Human PBMC 1 in HDM Model 4 2 0 -2 0 2 Log2(Fold-Change) Favorable safety profile: well-tolerated in multiple preclinical species and safety
studies at concentrations 40-fold above efficacious dose with up to 4 months of dosing 11 -Log10(p-Value)
KT-621: Compelling Clinical Profile KT-621 Phase 1 Healthy Volunteer
Data Suggests Potential for Dupilumab-like Activity in a Pill Reductions in Multiple Disease-Relevant Robust STAT6 Degradation in Blood and Type 2 Biomarkers Skin Following Low Daily Oral Doses 1 2 Serum TARC with Serum Eotaxin-3 with 100 Blood
14-Day KT-621 Dosing 14-Day KT-621 Dosing Skin Placebo n=18 50 mg QD n=8 Placebo n=18 50 mg QD n=8 1.5 mg QD n=9 100 mg QD n=9 1.5 mg QD n=9 100 mg QD n=8 50 12.5 mg QD n=7 200 mg QD n=9 12.5 mg QD n=7 200 mg QD n=9 25 mg QD n=8 25 mg QD n=8 20 20 0
0 0 -20 -50 -20 -40 -60 -40 -100 Placebo 1.5mg QD 12.5mg QD 25mg QD 50mg QD 100mg QD 200mg QD -80 1 4 7 14 28 1 4 7 14 28 18 9 7 9 9 9 9 Blood N ON TREATMENT ON TREATMENT 17 7 7 8 9 9 9 Skin N 3 3 Time (Day) Time (Day) Favorable safety profile:
well-tolerated across all dose levels with safety profile undifferentiated from placebo 12 STAT6 % Change from Baseline Mean (SE( ) TARC % Change from Baseline Median Eotaxin-3 % Change from Baseline Median
KT-621 Development Plan Enables Efficient Path to Registration Across
All Type 2 Diseases Ph3 Ph3: AD (Initial), Ph2b AD Dose Dose Ranging EoE, CSU, PN, BP Ongoing Data expected by Mid-2027 Ph1 HV Ph1b AD SAD-MAD Single Arm, Open Label Today's Release Complete Ph3 Dose Ph3: Asthma (Initial),
Ph2b Asthma Dose Ranging COPD, CRSwNP Anticipated Start 1Q26 Initial parallel Phase 2b trials in moderate to severe AD and asthma have the potential to support subsequent Phase 3 trials across multiple dermatology, GI, and respiratory indications
BroADen KT-621 Phase 1b AD Study Surpassed Objectives Effects on All
Type 2 Biomarkers and Clinical Endpoints Were in Line with or in Some Cases Numerically Exceeded Published Data for Dupilumab at Week 4 BroADen Endpoints Phase 1b Results Highlights Strong fidelity of translation from Phase 1a healthy
volunteer study to AD patients STAT6 Degradation with deep STAT6 degradation in blood and skin Type 2 Biomarkers Robust reductions in Type 2 biomarkers in blood, skin lesions and lung (FeNO) Meaningful improvements of clinical
endpoints and patient-reported outcomes in AD, Clinical Endpoints comorbid asthma and allergic rhinitis Well-tolerated and favorable safety profile similar to Phase 1a healthy volunteer Safety study Clinical data continue to support a
potential dupilumab-like profile in AD and other Type 2 diseases with a once daily, oral drug 14
KT-621: Phase 1b Atopic Dermatitis Trial Results Jared Gollob, MD Chief
Agenda Atopic Dermatitis Overview Trial Design
Demographics/Baseline Characteristics STAT6 Degradation Type 2 Inflammation Biomarkers Clinical Endpoints Safety 16
Atopic Dermatitis: Intensely Pruritic, Chronic and Underserved Disease
Opportunity Exists to Transform the Treatment Paradigm Chronic inflammatory disease that causes inflamed and irritated skin, making it itchy and painful Majority of patients have disease onset as children and carry the disease burden
into adulthood Can significantly impact a patient's quality of life through sleep loss, depression, missed work/school, interference with social activities Common comorbidities include asthma and allergic rhinitis Many
options only address symptoms, not underlying Type 2 inflammation 1 Estimated 43 million adults in US/EU5/JP Significant unmet need with less than 1 million patients currently on 2 dupilumab - Eric Simpson, MD, MCR,
"There remains a clear need for new oral therapies that can address the underlying Frances J. Storrs Medical Dermatology Professor and Director of CLEAR Eczema biology of the disease while potentially offering patients greater
convenience." Center, Oregon Health & Science University 17
Design Single arm, open label 22 patients Oral,
once daily dose for 28 days Phase 1b in Moderate to Severe Atopic Dermatitis Patients 14-day follow-up after dosing completed Baseline entry criteria: Dosing Adult, moderate to severe AD patients Two sequential dose cohorts
EASI 16 100 mg (10 patients) vIGA-AD 3 200 mg (12 patients) PPNRS 4 BSA 10% Documented TCS (Topical Corticosteroid) Endpoints failure for AD Safety Prior biologics allowed, after
washout, if Pharmacokinetics patient has responded to treatment STAT6 degradation Type 2 biomarkers in blood, skin lesions and lung Concurrent medications for AD not permitted Clinical activity (EASI, PPNRS,
vIGA-AD, patient- reported outcomes) 18
BroADen Phase 1b Demographics Generally Well-Balanced Across Treatment
Cohorts 100 mg 200 mg Overall (n=10) (n=12) (n=22) Gender, n (%) Female 6 (60) 7 (58.3) 13 (59.1) Male 4 (40) 5 (41.7) 9 (40.9) 30.1 (8.5) 33.0 (11.4) 31.7 (10.1) Age, years, mean (SD) 2 32.8 (11.5) 30.8 (9.2) 31.7 (10.1) BMI, kg/m , mean (SD)
Ethnicity, n (%) Hispanic or Latino 3 (30) 2 (16.7) 5 (22.7) Non Hispanic or Latino 7 (70) 10 (83.3) 17 (77.3) Race, n (%) 4 (40) 3 (25) 7 (31.8) White Black or African American 5 (50) 7 (58.3) 12 (54.5) Asian 0 1 (8.3) 1 (4.5) Mixed/Other 1 (10) 1
BroADen Phase 1b Baseline Disease Characteristics Generally
Well-Balanced Across Treatment Cohorts 100 mg 200 mg Overall (n=10) (n=12) (n=22) vIGA-AD, n (%) Moderate (3) 6 (60) 6 (50) 12 (54.5) Severe (4) 4 (40) 6 (50) 10 (45.5) EASI Score, mean (SD) 23.5 (7.5) 26.1 (9) 24.9 (8.3) Other Disease
Characteristics, Mean (SD) Peak Pruritus NRS 7.4 (1.2) 7.6 (0.9) 7.5 (1) SCORAD 55.7 (15.6) 63.8 (13.4) 60.1 (14.7) BSA (%) 29.1 (9.8) 30.0 (15.1) 29.6 (12.7) Comorbid Type 2 Diseases, n (%) 3 Asthma 1 (10) 3 (25) 4 (18.2) Allergic Rhinitis 2 (20) 7
(58.3) 9 (40.9) 1 2 Prior Systemic Therapy for AD, n (%) 1 (10) 4 (33.3) 5 (22.7) 20
STAT6 Degradation 21
KT-621 Achieved Deep STAT6 Degradation in Blood Degradation Maintained
for 28 Days Across Both Dose Cohorts Median % Change from Baseline in STAT6 Method: Flow Cytometry Median STAT6 degradation of 98% in KT-621 100 mg QD (n = 8) blood in both dose groups after 4 KT-621 200 mg QD (n = 10) weeks of treatment
Deep degradation maintained throughout dosing period Plasma PK profile at 100 and 200 mg similar to healthy volunteer study ON TREATMENT Strong translation from healthy Time (Day) volunteer study Median % Change from Baseline
Dose at D29 100 mg -98% 200 mg -98% 22 % STAT6 Change from Baseline Median (Q1, Q3)
KT-621 Achieved Deep STAT6 Degradation in Skin Median % Change from
Baseline in STAT6 Method: Targeted Mass Spec Median STAT6 degradation of 94% in skin in both dose groups after 4 weeks of treatment using targeted Mass Spec Deep skin degradation with multiple patients' STAT6 levels below the
LLOQ (lower limit of quantification) Strong translation from healthy volunteer study KT-621 100 mg QD KT-621 200 mg QD (n = 11) (n = 9) Median % Change from Baseline Dose at D29 100 mg -94% 200 mg -94% 23 % STAT6 Change from Baseline Median