Slide 1: APG777 Phase 1 Data March 2024
APG777 PHASE 1 DATA March 2024
Slide 2: Disclaimers and Forward-looking statements
© Apogee Therapeutics, Inc. 2 Disclaimers and Forward-looking statements This presentation contains certain "forward-looking statements" within the meaning of applicable securities laws. Other than statements of historical facts, all statements included in this presentation are forward-looking state
Slide 3: Introduction & Executive Summary Agenda
© Apogee Therapeutics, Inc. 3 Introduction & Executive Summary Michael Henderson, MD Chief Executive Officer APG777 Phase 1 Interim Results Carl Dambkowski, MD Chief Medical Officer APG777 Phase 2 Trial in Atopic Dermatitis Kristine Nograles, MD SVP, Clinical Development Building a Leading I&I Compa
Slide 4: People living with these diseases deserve the best possible treatment
© Apogee Therapeutics, Inc. 4 People living with these diseases deserve the best possible treatment Significant unmet need continues Apogee plans to reshape the current standard of care for inflammatory and immune diseases Focus on developing differentiated biologics with known biologic drivers Refu
Slide 5: 1Q24 Update reflects significant progress
© Apogee Therapeutics, Inc. 5 1Q24 Update reflects significant progress Expect to initiate Phase 1 in healthy volunteers in 1H’24 (ahead of schedule) APG777 APG808 Phase 1 interim data accelerated to 2H 2024 (from 2025) Phase 1 initial data has exceeded all trial objectives Planned, integrated Phase
Slide 6: APG777 leverages lebrikizumab's mechanism to deliver a potentially best-in-class antibody
© Apogee Therapeutics, Inc. 6 APG777 leverages lebrikizumab's mechanism to deliver a potentially best-in-class, pipeline in a product antibody 0.6 1.4 0.5 0.6 STAT6 TARC 1.4 13.4 IC90 (nM) APG777 Concentration Lebrikizumab Time 28 vs 18 days APG777 Lebri DUPIXENT Overlapping region Human IL-13 APG77
Slide 7: APG777 Phase 1 initial data has exceeded all trial objectives
© Apogee Therapeutics, Inc. 7 APG777 Phase 1 initial data has exceeded all trial objectives NOTE: PK = Pharmacokinetic 1 Exposure target based on Ctrough in maintenance, the minimal concentration of APG777 to hav e similar exposures to lebrikizumab Phase 1 Establish safety & PK profile Well-tolerate
Slide 8: APG777 Phase 1 in Healthy Volunteers
APG777 Phase 1 in Healthy Volunteers
Slide 9: APG777 interim data from ongoing Phase 1 trial in healthy volunteers
© Apogee Therapeutics, Inc. 9 APG777 interim data from ongoing Phase 1 trial in healthy volunteers ` ` Single ascendingdose Multiple ascending dose Double-blind, placebo-controlled, first-in-human trial Single ascending dose component with a nested multiple ascending dose component N = 40 8 per coho
Slide 10: Baseline characteristics are in line with our expectations
© Apogee Therapeutics, Inc. 10 Baseline characteristics are in line with our expectations Single dose Multiple dose Placebo N=6 Cohort 1 300 mg N=6 Cohort 2 600 mg N=6 Cohort 3 1,200 mg N=6 Placebo N=4 Cohort 1 300 mg at Day 1, 300 mg at Day 29 N=6 Cohort 2 300 mg at Day 1, 300 mg at Day 15 N=6 Age
Slide 11: APG777 was well-tolerated with a favorable safety profile
© Apogee Therapeutics, Inc. 11 APG777 was well-tolerated with a favorable safety profile Single dose Multiple dose Overall trial Placebo N=6 Cohort 1 300 mg N=6 Cohort 2 600 mg N=6 Cohort 3 1,200 mg N=6 Placebo N=4 Cohort 1 300 mg at Day 1, 300 mg at Day 29 N=6 Cohort 2 300 mg at Day 1, 300 mg at Da
Slide 12: APG777 exhibited a potentially best-in-class PK profile with half-life of ~75 days
© Apogee Therapeutics, Inc. 12 APG777 exhibited a potentially best-in-class PK profile with a half-life of ~75 days • Slow clearance, resulting in half-life of ~75 days • Dose-proportional increases in both Cmax and AUC PK demonstrated dose-proportionality and half-life of ~75 days (approximately 3x
Slide 13: pSTAT6 and TARC are biomarkers of IL-13 target engagement and AD severity
© Apogee Therapeutics, Inc. 13 pSTAT6 and TARC are biomarkers of IL-13 target engagement and AD severity 1. pSTAT6 is one of the earliest markers of IL-13 receptor activation APG777 Phase 1 biomarkers Taken together, APG777’s reduction of these biomarkers confirms inhibition of IL-13 signaling and a
Slide 14: Head-to-head NHP study: '777 tool compound inhibited pSTAT6 longer than lebrikizumab
© Apogee Therapeutics, Inc. 14 0 25 50 75 100 50 100 0 Days Post-Dose % pSTAT6 ‘777 Tool Compound Lebrikizumab In a head-to-head NHP study, ‘777 tool compound inhibited pSTAT6 significantly longer than lebrikizumab Head-to-head PK data in NHP Head-to-head PD data in NHP 777 tool compound had ~60% lo
Slide 15: Single dose APG777 showed near complete pSTAT6 inhibition for ~3 months
© Apogee Therapeutics, Inc. 15 Single dose APG777 showed near complete pSTAT6 inhibition for ~3 months (limit of available follow-up) 0 1 2 3 4 5 6 7 8 9 10 11 12 0 50 100 Weeks % pSTAT6 300 mg (N=1) 600 mg (N=6) 1200 mg (N=6) Placebo (N=4) 100% pSTAT6 inhibition was demonstrated for approximately 3
Slide 16: Single dose of APG777 led to deep, sustained TARC inhibition for ~3 months
© Apogee Therapeutics, Inc. 16 Single dose of APG777 led to deep + sustained TARC inhibition for ~3 months (limit of available follow-up) • 300 mg APG777 showed similar maximum PD marker changes as DUPIXENT • APG777 sustained TARC inhibition demonstrates the potential for better durability • All dos
Slide 17: APG777 positive PK readout is a key risk-reducing milestone
© Apogee Therapeutics, Inc. 17 APG777 positive PK readout is a key risk-reducing milestone that validates program and pipeline Phase 1 Antibody attributes Clinical profile Equivalent or better potency vs. 1st generation mAbs across relevant pre-clinical assays Epitope overlaps with lebrikizumab epit
Slide 18: APG777 Phase 2 in Atopic Dermatitis
APG777 Phase 2 in Atopic Dermatitis
Slide 19: APG777 Phase 2 in atopic dermatitis expected to begin 1H 2024
© Apogee Therapeutics, Inc. 19 APG777 Phase 2 in atopic dermatitis expected to begin 1H 2024 with 16-week efficacy data in 2H 2025 AD Phase 2 APG777 180 mg/mL formulation enables 44% greater dose than lebrikizumab in the same volume HIGHER DOSES ENABLED Planned to combine Ph2a and Ph2b elements into
Slide 20: Integrated Phase 2 design has potential for significant timeline acceleration
© Apogee Therapeutics, Inc. 20 Integrated Phase 2 design has potential for significant timeline acceleration • Combines Ph2a and Ph2b elements into a single protocol; All Part A sites are Part B sites (avoiding site startup delays between parts) Planned integrated Phase 2 expected to have 16- week t
Slide 21: APG777 Phase 2 exposures designed to exceed lebrikizumab in induction and equal in maintenance
© Apogee Therapeutics, Inc. 21 APG777 Phase 2 exposures are designed to exceed lebrikizumab in induction and equal in maintenance Modeled induction and maintenance dosing for APG7771 and lebrikizumab Induction exposure goal: EXCEED Maintenance exposure goal: EQUAL AD Phase 2 • Lebrikizumab data sugg
Slide 22: Lebrikizumab Ph3 appears to show an E-R relationship for efficacy in induction
© Apogee Therapeutics, Inc. 22 Exposure Induction Lebrikizumab Ph3 appears to show an E-R relationship for efficacy in induction that has not been maximized SOURCE: Lebrikizumab European Public Assessment Report NOTE: Lebrikizumab exposures and efficacy are for the Phase 3 dose (500 mg Loading Dose
Slide 23: Lebrikizumab Ph3 appears to show an E-R relationship for efficacy in induction
© Apogee Therapeutics, Inc. 23 Exposure Induction Lebrikizumab Ph3 appears to show an E-R relationship for efficacy in induction that has not been maximized SOURCE: Lebrikizumab European Public Assessment Report NOTE: Lebrikizumab exposures and efficacy are for the Phase 3 dose (500 mg Loading Dose
Slide 24: Modeled induction dosing for APG777 and lebrikizumab
© Apogee Therapeutics, Inc. 24 Modeled induction dosing for APG777 and lebrikizumab Modeled Phase 2 induction exposures exceed those of lebrikizumab by ~30-40% ~30-40% increase in exposures APG777 Lebrikizumab Injections x2 x2 x2 x2 Induction NOTE: Planned APG777 induction regimen is 720 mg in w eek
Slide 25: Modeled Q3M maintenance exposures equal those of lebrikizumab
© Apogee Therapeutics, Inc. 25 Modeled Phase 2 Q3M maintenance exposures equal those of lebrikizumab AD Phase 2 Maintenance APG777 Q3M Aiming for annual maintenance injections: 4 vs 13-26 for lebrikizumab/ DUPIXENT Modeled concentration in maintenance Induction Maintenance APG777 Median 95% PI Lebri
Slide 26: Modeled Q6M maintenance exposures equal those of lebrikizumab
© Apogee Therapeutics, Inc. 26 Modeled Phase 2 Q6M maintenance exposures equal those of lebrikizumab AD Phase 2 Maintenance APG777 Q6M Aiming for annual maintenance injections: 2 vs 13-26 for lebrikizumab/ DUPIXENT Modeled concentration in maintenance Induction Maintenance 95% PI Median Low dose Med
Slide 27: Building a Leading I&I Company
Building a Leading I&I Company
Slide 28: APG777's potential to be a leading product in the expected $50B+ AD market
© Apogee Therapeutics, Inc. 28 APG777’s best-in-class Phase 1 PK profile shows potential to be a leading product in the expected $50B+ AD market1 Favorable product characteristics and COGS • As few as 2-4 doses per year in maintenance • Expected improved formulation, manufacturability and viscosity
Slide 29: AD is the largest of the major I&I markets and projected to grow significantly
© Apogee Therapeutics, Inc. 29 AD is the largest of the major I&I markets and projected to grow significantly in the next decade Estimated population size, MM Moderate or severe in 7 Major Markets1 25.1M AD 1.4M IBD 2.9M RA 15.2M Asthma 9.4M COPD 9.2M PsO • Psoriasis expected to be a $30B+ market; a
Slide 30: In psoriasis, Skyrizi has taken the lead with quarterly dosing
© Apogee Therapeutics, Inc. 30 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 14 16 18 20 22 24 Dosing Interval (weeks) Efficacy (PASI -75, %) In psoriasis, an analog to AD, Skyrizi has taken the lead with quarterly dosing Note: Year denotes US launch y ear f or adults with moderate to sev ere pla
Slide 31: Significant whitespace in the landscape of biologics for AD
© Apogee Therapeutics, Inc. 31 0 2 4 6 8 10 12 14 16 18 20 22 24 0 30 35 40 45 50 55 60 65 70 75 80 95 90 100 85 Dosing Interval (weeks) Lebrikizumab CBP-201 Nemolizumab Rocatinlimab Amlitelimab Dupilumab Tralokinumab There is significant whitespace in the landscape of approved and in-development bi
Slide 32: Apogee plans to advance APG777 into Phase 2 with 3- or 6-month maintenance dosing
© Apogee Therapeutics, Inc. 32 0 2 4 6 8 10 12 14 16 18 20 22 24 0 30 35 40 45 50 55 60 65 70 75 80 95 90 100 85 Dosing Interval (weeks) Lebrikizumab CBP-201 Nemolizumab Rocatinlimab Amlitelimab Dupilumab Tralokinumab Apogee plans to advance APG777 into a Phase 2 trial with 3- or 6-month maintenance
Slide 33: Dermatologists view every 3- or 6-month dosing as highly differentiated
© Apogee Therapeutics, Inc. 33 Dermatologists view every 3- or 6-month dosing as highly differentiated Source: In 2023, Apogee conducted a single-blinded market research surv ey of 25 practicing dermatologists in 14 states in the United States, with the assistance of an expert search network Note: F
Slide 34: Apogee plans to become a leader in I&I therapeutics
© Apogee Therapeutics, Inc. 34 APG777 (IL-13) ✓ Positive Phase 1 PK & safety in HVs 1H: Phase 2 initiation in AD 2H: 16-week PoC data in AD Phase 2 initiation in asthma Disclose additional indication ✓ Phase 1 initiated in HVs ✓ 6-month chronic toxicology completed Candidate nomination Phase 1 initi
Slide 35: Q&A Backup
Q&A Backup
Slide 36: APG777 was well-tolerated (TEAEs ≥5% across all cohorts)
© Apogee Therapeutics, Inc. 36 APG777 was well-tolerated with a favorable safety profile (TEAEs ≥5% across all cohorts, all grades) Single dose Multiple dose Overall trial Placebo N=6 Cohort 1 300 mg N=6 Cohort 2 600 mg N=6 Cohort 3 1,200 mg N=6 Placebo N=4 Cohort 1 300 mg at Day 1, 300 mg at Day 29
Slide 37: Single dose APG777 showed near complete pSTAT6 inhibition for ~3 months
© Apogee Therapeutics, Inc. 37 Single dose APG777 showed near complete pSTAT6 inhibition for ~3 months (limit of available follow-up) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 0 50 100 Weeks % pSTAT6 300 mg (N=1) 600 mg (N=6) 1200 mg (N=6) Placebo (N=4) 100% pSTAT6 inhibition was demonstrated for approximatel
Slide 38: Company Overview
Company Overview
Slide 39: Engineering antibodies with potential best-in-class profiles in largest I&I indications
© Apogee Therapeutics, Inc. 39 Engineering antibodies with potential best-in-class profiles in largest I&I indications with highly differentiated dosing Four programs leveraging well-established mechanisms and addressing I&I indications with multi-billion-dollar potential Technology approach proven
Slide 40: Apogee mAbs are engineered for best-in-class properties, including half-life extension
© Apogee Therapeutics, Inc. 40 Apogee mAbs are engineered for best-in-class properties, including half-life extension Potential for PK that: • Optimizes exposures • Decreases variability • Increases half-life • Designed to maximize antibody recycling • Drug exists at higher levels for longer effect
Slide 41: APG777
APG777
Slide 42: AD represents a larger opportunity than psoriasis
© Apogee Therapeutics, Inc. 42 AD represents a larger opportunity than psoriasis; AD biologics penetration mirrors early years of psoriasis 1 The 7 Major Markets are US, Japan, Germany , France, Italy , Spain, and UK. 2 $30B+ projected market size in 2028 and bey ond, including both biologics and sm
Slide 43: APG777 is designed to disrupt Th2 signaling
© Apogee Therapeutics, Inc. 43 APG777 is designed to disrupt Th2 signaling by preventing formation of IL-13Rα1 / IL-4Rα heterodimer • IL-13 signaling begins with binding of IL-13 to IL-13Rα1 • This forms an inactive complex that then binds to IL-4Rα to create a complete, active heterodimer • Active
Slide 44: APG777's epitope overlaps with lebrikizumab
© Apogee Therapeutics, Inc. 44 APG777's epitope overlaps with lebrikizumab, differentiating from other approaches to target IL-13 Note: IL-4Ra binding site deriv ed f rom PDB 3BPO. Lebrikizumab epitope deriv ed f rom PDB 4I77. ADBRY epitope deriv ed f rom PDB 5L6Y . APG777’s mechanism of action disr
Slide 45: Lebrikizumab and DUPIXENT have similar efficacy across key AD endpoints
© Apogee Therapeutics, Inc. 45 Lebrikizumab and DUPIXENT have similar efficacy across key AD endpoints Source: 1 Lebrikizumab 250mg Q2W Ph3 Av g. Silv erberg JI et al AAD 2022. 2 DUPIXENT 300 mg Q2W mono Ph3 Av g. DUPIXENT USPI. 3 ADBRY 300 mg Q2W mono Ph3 Av g. ADBRY USPI 4 In the 16- week inductio
Slide 46: Lebrikizumab showed greater efficacy with higher doses in Ph2b
© Apogee Therapeutics, Inc. 46 Lebrikizumab showed greater efficacy with higher doses in Ph2b with no dose-dependent increases in AE rates Placebo 125mg Q4W 250mg Q4W 250mg Q2W 0.0% 1.4% 3.8% 2.7% Conjunctivitis rates by dose level in lebrikizumab Ph2b Response at 16 weeks (placebo-adjusted), % by d
Slide 47: APG777 is as potent as lebrikizumab and DUPIXENT in key preclinical assays
© Apogee Therapeutics, Inc. 47 APG777 is as potent as lebrikizumab and DUPIXENT in key preclinical assays More potent Less potent Assay Affinity to human IL-13 by SPR Inhibition of STAT-6 phosphorylation Inhibition of TARC secretion Measurement KD (pM) IC90 (nM) IC90 (nM) APG777 78 0.56 1.40 ADBRY 1
Slide 48: APG777 NHP half-life is significantly longer than lebrikizumab
© Apogee Therapeutics, Inc. 48 APG777 NHP half-life is significantly longer than lebrikizumab *Note: N = 3 per group. 2 of 3 animals in the lebrikizumab. SQ arm dev eloped ADAs by day 40 and those timepoints associated with ADAs are excluded. 1APG777 and lebrikizumab. half -liv es were 27.6 day s an
Slide 49: Strong correlation between Phase 2 and 3 results in AD
© Apogee Therapeutics, Inc. 49 Strong correlation between Phase 2 and 3 results in AD for validated endpoints EASI-75 and IGA 0/1 Strong historical correlation between Phase 2 and 3 data makes APG777 16-week AD data a key catalyst Source: Ph3 data f or DUPIXENT, Rinv oq, Cibinqo, Adbry is f rom USPI
Slide 50: APG777 could substantially decrease annual maintenance injections
© Apogee Therapeutics, Inc. 50 APG777 could substantially decrease annual maintenance injections for patients Lebrikizumab 13 INJECTIONS ONE INJECTION EVERY 4 WEEKS DUPIXENT 26 INJECTIONS ONE INJECTION EVERY OTHER WEEK APG777* 2-4 INJECTIONS ONE INJECTION EVERY 3- or 6- MONTHS NOTE: *Positioning of
Slide 51: APG808
APG808
Slide 52: APG808 targets the same mechanism as DUPIXENT, validated in COPD
© Apogee Therapeutics, Inc. 52 APG808 targets the same mechanism as DUPIXENT, which has been validated in COPD COPD represents area of high unmet and a promising opportunity given recent positive DUPIXENT data 10% of the global population >40 yrs 3rd Leading cause of death in the US in 2019 150K+ Pe
Slide 53: Treatments for moderate-severe COPD are limited
© Apogee Therapeutics, Inc. 53 Treatments for moderate-severe COPD are limited NOTE: *Positioning of Apogee program is illustrativ e and not based on clinical trial data. Dupixent is not approv ed f or the treatment of COPD SOURCE: 1Bhatt SP et al NEJM 2023; 2Sanofi press release November 26, 2023,
Slide 54: Asthma shows how biologics can be rapidly adopted
© Apogee Therapeutics, Inc. 54 Asthma, an analog for COPD, shows how biologics can be rapidly adopted when they address unmet needs 0 5 10 15 20 2002 2004 2006 2008 2010 2012 2014 2016 2018 2020 2022 2024 Biologic penetration in severe asthma (%) Approved in 2018 $20B+ est. peak revenue1 Xolair was
Slide 55: APG808 Phase 1 expected to initiate in 1H 2024
© Apogee Therapeutics, Inc. 55 APG808 Phase 1 expected to initiate in 1H 2024 (ahead of schedule) with planned readout in 2H 2024 1 SAD dose ascension will ultimately be determined by the SRC (Scientif ic Rev iew Committee) based on av ailable data. 2Design f or the expansion portion of the study in
Slide 56: APG808 is as potent as DUPIXENT in key preclinical assays
© Apogee Therapeutics, Inc. 56 APG808 is as potent as DUPIXENT in key preclinical assays APG808 APG808 vs DUPIXENT on key potency assay Additional in vitro assays support APG808 potency Assay Affinity to human IL-4R⍺ 1,2 Inhibition of STAT-6 phosphorylation Inhibition of TARC secretion Measurement K
Slide 57: APG808 NHP half-life is significantly longer than DUPIXENT
© Apogee Therapeutics, Inc. 57 APG808 NHP half-life is significantly longer than DUPIXENT APG808 APG808 has advantages over DUPIXENT in our NHP NHP PK, SQ administration head-to-head studies NHP average half-life1 APG808: ~26 days DUPIXENT: ~12 days APG808 showed extended half-life in NHPs *NOTE: N
Slide 58: APG808 predicted human half-life vs. observed NHP half-life
© Apogee Therapeutics, Inc. 58 APG808 (YTE)* 27 APG808 predicted human half-life vs. observed NHP half-life, days comparators, days 22 14 13 Dupixent CDX-0159 (YTE) (c-KIT/CD117) VRDN-002 (YTE) (IGF-1R) VRDN-003 (YTE) (IGF-1R) 11 15 32 (~1.5X) 30-43 (~1.5-3X) 40-50 (~3-4X) Non-YTE mAb Indication / Y
Slide 59: APG990/APG222
APG990/APG222
Slide 60: APG990 blocks OX40L and potentially rebalances the immune system
© Apogee Therapeutics, Inc. 60 APG990 blocks OX40L and potentially rebalances the immune system OX40L blockade targets Th2, Th17, and Th22 pathways, which have been implicated in numerous I&I conditions Upcoming clinical trial readouts could provide PoC for OX40L beyond AD including asthma, hidraden
Slide 61: OX40L and OX40 inhibition have similar efficacy, but OX40L has safety advantage
© Apogee Therapeutics, Inc. 61 OX40L and OX40 inhibition have shown similar efficacy, but OX40L has a clear advantage on safety 22 17 IGA 0/1 response at Week 16 Amlitelimab (OX40L)1 Rocatinlimab (OX40)2 40 42 EASI-75 at Week 16 APG990 • In Phase 2b, rocatinlimab (OX40) was associated with pyrexia (
Slide 62: APG222 combines two validated mechanisms
© Apogee Therapeutics, Inc. 62 • OX40L treatment reduces circulating IL-13 levels supporting the potential for synergy with IL-13 blocker • Combination potentially enables wider subset of patients to achieve deeper clinical responses and durable remission in AD and other I&I indications Given strong
Slide 63: Corporate
Corporate
Slide 64: Experienced team with proven history of clinical development
© Apogee Therapeutics, Inc. 64 Michael Henderson, MD Chief Executive Officer, Director Carl Dambkowski, MD Chief Medical Officer Jane Pritchett Henderson Chief Financial Officer Rebecca Dabora, PhD Chief Technical Officer Matt Batters, JD General Counsel Wendy Aspden-Curran SVP of Clinical Operation
Slide 65: Board of Directors with industry-leading expertise
© Apogee Therapeutics, Inc. 65 Michael Henderson, MD CEO, Apogee Therapeutics BJ Jones CCO, NewAmsterdam Pharma Mark McKenna Chairman Peter Harwin Managing Member, Fairmount Jennifer Fox CFO & CBO, Zenas BioPharma Andrew Gottesdiener, MD Venrock Tomas Kiselak Managing Member, Fairmount Nimish Shah V
Slide 66: Our programs have broad potential to disrupt the I&I space
© Apogee Therapeutics, Inc. 66 Dermatology AD AA PN Pulmonology / Immunology Asthma1 COPD1 CSU CRSwNP Gastroenterology EoE UC1 EGID Planned Apogee Ph2 based on well-established mechanism 3 rd party clinical data supporting one or more Apogee targets Ongoing 3rd party clinical trials which could vali
Slide 67: Apogee definition
Apogee /ˈapəjē/ noun The highest point in the development of something; a climax or culmination