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Title text 2 March 3rd 2025 APG990 Phase 1 Interim Results
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2© Apogee Therapeutics, Inc 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 statements, including statements about our plans for our current and future product candidates and programs, our plans for current and future clinical trials, including a Phase 1b trial of APG279 in atopic dermatitis, Phase 2 trial of APG777 in atopic dermatitis, Phase1b and 2b trials of APG777 in asthma and a trial of APG777 in eosinophilic esophagitis, a Phase 1b trial of APG808 in asthma, and a Phase 1 trial for APG333; our plans for clinical trial design; the anticipated timing of the initiation of and results from our clinical trials, including data from our Phase 2 trial of APG77and our Phase 1b trial of APG279; the potential clinical benefit, half-life and dosing regimen of APG777, APG808, APG990, APG333 and any other potential programs, including APG279, and the combination of APG777 and APG333; our expected timing for future pipeline updates; and estimates of market size. In some cases, you can identify forward-looking statements by terms such as “anticipate,” “believe,” “can,” “could,” “design,” “estimate,” “expect,” “intend,” “likely,” “may,” “might,” “plan,” “potential,” “predict,” “suggest,” “target,” “will,” “would,” or the negative of these terms, and similar expressions intended to identify forward-looking statements. The forward-looking statements are based on our beliefs, assumptions and expectations of future performance, taking into account the information currently available to us. These statements are only predictions based upon our current expectations and projections about future events. Forward-looking statements are subject to known and unknown risks, uncertainties and other factors that may cause our actual results, level of activity, performance or achievements to be materially different from those expressed or implied by such forward-looking statements, including those risks described in “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in our Annual Report on Form 10-K for the year ended December 31, 2024, filed with the SEC on March 3, 2025 and subsequent disclosure documents we may file with the U.S. Securities and Exchange Commission. Although we have attempted to identify important factors that could cause actual results to differ materially from those contained in forward-looking statements, there may be other factors that cause results not to be as anticipated, estimated or intended. This presentation concerns drug candidates that are under clinical investigation, and which have not yet been approved by the U.S. Food and Drug Administration. These are currently limited by federal law to investigational use, and no representation is made as to their safety or effectiveness for the purposes for which they are being investigated. The assumptions used in the preparation of this presentation, although considered reasonable by us at the time of preparation, may prove to be incorrect. You are cautioned that the information is based on assumptions as to many factors and that actual results may vary from the results projected and such variations may be material. Accordingly, you should not place undue reliance on any forward-looking statements contained herein or rely on them as predictions of future events. All forward-looking statements in this presentation apply only as of the date made and are expressly qualified by the cautionary statements included in this presentation. We do not undertake to update any forward-looking statements, except in accordance with applicable securities laws. The trademarks, trade names and service marks appearing in this presentation are the property of their respective owners. Certain information contained in this presentation relate to or are based on studies, publications and other data obtained from third-party sources as well as our own internal estimates and research. While we believe these third-party sources to be reliable as of the date of this 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. Disclaimers and Forward-looking statements
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3© Apogee Therapeutics, Inc Introduction Michael Henderson, MD Chief Executive Officer APG279 Scientific Rationale and APG990 Phase 1 Interim Results Carl Dambkowski, MD Chief Medical Officer APG279 Development Program Kristine Nograles, MD SVP, Clinical Development Building a Leading I&I Company Michael Henderson, MD Chief Executive Officer Analyst Q&A Michael Henderson, MD, CEO Carl Dambkowski, MD, CMO Jane Pritchett Henderson, CFO Agenda
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Introduction Michael Henderson, MD Chief Executive Officer
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5 © Apogee Therapeutics, Inc 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 360 40 42 44 46 48 0 30 40 50 60 70 38 Rocatinlimab Amlitelimab Atopic dermatitis is a future $50B market and Apogee has multiple shots to transform the treatment paradigm Efficacy (EASI-75, %) Dosing Interval (weeks) All programs enabled for every 3-months or longer maintenance dosing intervals with a single 2 mL subcutaneous injection Ph2 Part A mid-20251 Ph2 Part B 2H 2026 2 Three opportunities to demonstrate best-in-class potential in AD with planned readouts before end of 2026 NOTE: *Positioning of Apogee programs is illustrative and based on Phase 1 results for APG777 and APG990 only and illustrates what we believe we can potentially achieve. Only DUPIXENT, ADBRY, EBGLYSS , and NEMLUVIO are approved in the US. Efficacy data are derived from different clinical trials conducted at different times, with differenc es in trial design and patient populations. As a result, cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted. Future $50B AD market size based on EvaluatePharma and company projections. SOURCE: 1 EBGLYSS 250mg Q2W Ph3 avg. Silverberg JI et al. AAD 2022. 2 DUPIXENT 300 mg Q2W mono Ph3 avg. DUPIXENT USPI. 3 ADBRY 300 mg Q2W mono Ph3 avg. ADBRY USPI. 4 NEMLUVIO 30 mg Q4W Ph3 avg. Silverberg J et al EADV 2023. 5 Rocatinlimab 150mg Q4W Ph2b Guttman-Yassky E et al Lancet 2023. 6 Amlitelimab 250mg Q4W Ph2b Weidinger S et al EADV oral presentation 2023. APG279* APG777* Maximizing monotherapy potential (become the backbone of AD therapy) Maximize efficacy with potential first- / best-in-class combo 3 Ph1b vs Dupixent 2H 2026 100
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6© Apogee Therapeutics, Inc APG777APG990 HUMAN IL -13 Overlapping region (vs. EBGLYSS) OVERLAPPING EPITOPE Overlapping region (vs. amlitelimab) HUMAN OX40L APG279 combines APG777 and APG990 – two antibodies targeting validated mechanisms for potentially best-in-class efficacy and dosing in AD APG279 OPTIMIZED PK AND FORMULATION 77-day half -life 3x lebrikizumab ~60 -day half -life ~2.5 -3x amlitelimab Coformulated at ≥180 mg/mL for potential 2 mL commercial presentation APG279 IL-22 Type 3 TARC Type 2 Dupilumab 3 16 17 389 76APG279 3 Type 1 IFNγ 123 45 Ex vivo human ALR assay1 BROAD & ROBUST INHIBITION IL-4Rα OX40LIL-13 + Untreated Cytokine level (% of untreated) 2 100 50 25 75 10050250 75 125+ NOTE: 1 The ALR was performed using TSLP-primed mDCs paired with allogeneic CD4 cells for 5 days. 2 Cytokine levels for dupilumab and APG279 are reported as the mean percent of isotype control across four donor pairs. 3 Dupilumab and APG279 (tested as coadministered APG777+APG990) were tested at 45 µg/mL that is comparable to DUPIXENT steady -state trough concentrations for the approved dose (300mg Q2W) in atopic dermatitis.
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APG279 Scientific Rationale Carl Dambkowski, MD Chief Medical Officer
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8 © Apogee Therapeutics, Inc Targeting all inflammatory types may provide greater efficacy Efficacy of advanced systemics in AD (Week 16, placebo-adjusted) APG279 inhibits Type 1, 2, and 3 inflammation with the potential for better efficacy or tolerability than available treatments • JAKs address AD heterogeneity by targeting Type 1-3 inflammation but carry a black box warning and require lab monitoring • Current biologics are well tolerated, but less efficacious than JAKs NOTE: In EBGLYSS Ph2b and Ph3 there has been no dose -AE or exposure-AE relationship. EBGLYSS exposures and efficacy are for the Phase 3 dose (500 mg Loading Dose at Weeks 0 and 2, 250 mg Q2W Weeks 4 to 16). Efficacy data are derived from different clinical trials conducted at different points in time, with differences in trial des ign and patient populations. As a result, cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted. SOURCE: EBGLYSS European Public Assessment Report. DUPIXENT USPI. RINVOQ USPI. Weindinger, S. Oral Presentation. AAD (2024). . Amlitelimab, Ph2b (250mg Q4W +LD) DUPIXENT Ph3 EBGLYSS Ph3, all patients Responders, % EBGLYSS Ph3, <60 kg subgroup (N = 180) RINVOQ Ph3, 30mg 29 34 38 49 62APG279 potential EASI-75 APG777 potential APG279
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9 © Apogee Therapeutics, Inc Preclinical data demonstrate the robust Type 1, 2, and 3 inhibitory effect of APG279 Type 1 IL-22 Type 3 TARC Type 2 Dosing IL-13 Lebrikizumab 3 IL-4Rα Dupilumab 3 25 16 69 17 154 389 53 76 Untreated = 100% 100 50 25 0 Cytokine level (% of untreated) 2 75 100 50 25 0 75 125+ JAK Upadacitinib 4 DAILY 10 30 NOTE: 1 The ALR was performed using TSLP-primed mDCs paired with allogeneic CD4 cells for 5 days. 2 Cytokine levels for lebrikizumab, dupilumab, amlitelimab, and APG279 are reported as the mean percent of isotype control across four donor pairs; upadacitinib reported as mean percent of DMSO control across four donor pairs. 3 Lebrikizumab, dupilumab, amlitelimab, and APG279 (tested as co-administered APG777+APG990) were tested at 45 µg/mL that is comparable to DUPIXENT steady -state trough concentrations for the approved dose ( 300mg Q2W) in atopic dermatitis. 4 Upadacitinib was tested at the Cmax concentration for RINVOQ 15mg (31 ng/mL), reflecting maximum inhibition achieved briefly after dosing. Ex vivo human allogeneic lymphocyte reaction (ALR) assay1 1 2 3 Q2W - Q4W Q2W Q4W+ APG279 3 Q3M - Q6MOX40LIL-13 OX40L Amlitelimab 3 • APG777 targets IL-13 for deep inhibition of Type 2 inflammation • APG990 targets OX40L for broader inhibition across Type 1, 2, and 3 inflammation • Targeting all inflammatory types may provide greater efficacy vs. “Type 2 only” inhibitors (e.g., DUPIXENT), similar to JAK- inhibitor upadacitinib IFNγ 121 123 46 45 8 APG279 +
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10© Apogee Therapeutics, Inc NOTE: MACE: Major Adverse Cardiovascular Event; CBC: Complete Blood Count. 1 Non-human primate, dog, or murine model. 2 APG279 (APG777+APG990) was co-administered for NHP preclinical toxicity studies; coformulation planned for future clinical studies and commercialization. 3 Red symbols indicate adverse findings within published preclinical toxicology studies. SOURCE: Package inserts for upadacitin ib, abrocitinib. Preclinical Toxicology1Clinical Black Box Warning Cytopenia Decreased Spleen, Thymus Weight Increased Thymomas Tachycardia Hypotension Potential infection risk Potential malignancy risk Potential risk of MACE APG279 2 OX40LIL-13 N/A (not marketed product) None None None None None JAK Upadacitinib 3 Black Box Warning Infection Risk, Malignancy, Thrombosis None JAK Abrocitinib 3 Black Box Warning Infection Risk, Malignancy MACE, Thrombosis None JAKs require labs (CBC, lipid profile) at baseline, after 4 – 12 weeks, and necessitate physician monitoring for infections, MACE, thrombosis, and malignancies APG279 showed no signs of preclinical safety signals evident with JAK inhibitors Lymphocytes, neutrophils Lymphocytes Combination toxicology study of APG279 in non-human primates showed no toxicity at any tested dose, in contrast to JAK inhibitors APG279 +
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11 © Apogee Therapeutics, Inc APG279 could be dosed as a single 2 mL injection two or four times per year in maintenance NOTE: 1Potential APG279 injections per year based on preliminary PK data and PK simulations. Injections per year in maintenance afte r an induction regimen. Stability Stable at high concentrations (i.e., ≥180 mg/mL) Injectability Expected injection time comparable to DUPIXENT Potency Potency equivalent to each component tested individually APG279 pre-filled syringe APG279 APG279 2-4 Injections per year One 2 mL injection every 3- and 6- months in maintenance1
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APG990 Phase 1 Interim Results Carl Dambkowski, MD Chief Medical Officer
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13© Apogee Therapeutics, Inc NOTE: 1 Based on Apogee modeled exposures for amlitelimab Q12W maintenance dosing ( Ctrough,ss = ~5 µg/mL). Sanofi has also published a 4 µg/mL PD threshold for amlitelimab (Weidinger et al. AAD 2024). APG990 PHASE 1 INTERIM DATA SUMMARY APG990 PHASE 1 Interim APG990 Phase 1 data met or exceeded all trial objectives G O A L Confirm tolerable safety profile to enable future combination trials All tested doses well- tolerated, supporting continued development R E S U L T G O A L Determine dosing regimens to sustain exposures similar to amlitelimab Every 3-month (50 mg) and 6-month (200 mg) dosing modeled to maintain comparable exposures to amlitelimab1 R E S U L T G O A L Establish optimized PK profile with a half-life of at least 21 days Approximately 60-day half-life R E S U L T A C H I E V E D E X C E E D E DE X C E E D E D
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14© Apogee Therapeutics, Inc `` Double-blind, placebo-controlled, first-in-human trial Single ascending dose in healthy volunteers N = 40 8 per cohort (6:2 active:placebo) Key inclusion criteria: healthy adult volunteers Primary endpoint: safety Secondary endpoints: PK, ADA 1,200 mg (SQ) ×1 dose 600 mg (SQ) ×1 dose 300 mg (SQ) ×1 dose 150 mg (SQ) ×1 dose 75 mg (SQ) ×1 dose Single ascending doseTrial design elements APG990 PHASE 1 APG990 Phase 1 trial in healthy volunteers is fully enrolled with interim data from all cohorts Interim data from all cohorts
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15© Apogee Therapeutics, Inc NOTE: Seven participants were randomized to Cohort 5 but only six participants were dosed. Therefore, total randomized analys is population was 41 participants and total safety analysis population was 40 participants. Single dose Placebo N=10 Cohort 1 75 mg N=6 Cohort 2 150 mg N=6 Cohort 3 300 mg N=6 Cohort 4 600 mg N=6 Cohort 5 1,200 mg N=7 Age (yrs), mean (SD) 34.7 (13.3) 27.5 (7.9) 40.2 (13.8) 40.3 (15.5) 31.8 (10.7) 33.4 (8.9) Female 60.0% 50.0% 33.3% 66.7% 50.0% 42.9% Caucasian 40.0% 83.3% 50.0% 83.3% 16.7% 42.9% Weight (kg), mean (SD) 69.1 (17.6) 67.9 (8.7) 74.9 (8.3) 78.2 (20.9) 63.7 (8.7) 73.1 (14.0) Demographics were generally well balanced across cohorts APG990 PHASE 1 Baseline characteristics in the APG990 Phase 1 study were in line with our expectations
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16© Apogee Therapeutics, Inc NOTE: TEAE = Treatment-Emergent Adverse Event. TE -SAE = Treatment-Emergent-Serious Adverse Event. Interim data includes AEs repo rted as of 06 February 2025 data cut. The trial is ongoing. 1 Incidence of dysmenorrhea deemed unrelated to drug in patient with history of chronic dysmenorrhea. Patient presented to the emergency department for lower abdominal pain, was treated with morphine, and discharged. Single dose Overall trial Placebo N=10 Cohort 1 75 mg N=6 Cohort 2 150 mg N=6 Cohort 3 300 mg N=6 Cohort 4 600 mg N=6 Cohort 5 1,200 mg N=6 Placebo N=10 APG990 N=30 ≥1 TEAE 5 (50.0%) 4 (66.7%) 5 (83.3%) 3 (50.0%) 3 (50.0%) 1 (16.7%) 5 (50.0%) 16 (53.3%) ≥1 serious TEAE 0 0 0 0 0 0 0 0 ≥1 drug-related TEAE 2 (20.0%) 1 (16.7%) 2 (33.3%) 2 (33.3%) 1 (16.7%) 0 2 (20.0%) 6 (20.0%) ≥1 Grade 3 TEAE 0 0 1 (16.7%)1 0 0 0 0 1 (3.3%) 1 Discontinued study due to TEAE 0 0 0 0 0 0 0 0 N (%) No reported TEAE of pyrexia/chills Favorable safety profile of APG990 is supportive of continued development in combination studies APG990 PHASE 1 APG990 was well-tolerated and exhibited a profile consistent with assets targeting OX40L
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17© Apogee Therapeutics, Inc NOTE: Linear PK observed across doses, up to 20 weeks, suggesting saturation of target -mediated drug disposition (TMDD). 1 Mean (SD) profiles. 2 Range based on amlitelimab half-life reported for relevant MAD cohorts and geometric mean terminal half -life; Saghari, Mahdi et al. “OX40L Inhibition Suppresses KLH -driven Immune Responses in Healthy Volunteers: A Randomized Controlled Trial Demonstrating Proof -of-Pharmacology for KY1005.” Clinical pharmacology and therapeutics vol. 111,5 (2022): 1121 -1132. APG990 PHASE 1 PK demonstrated a half-life of ~60 days with dose proportionality and low variability APG990 exhibited potentially best-in-class PK with a half-life of ~60 days ~20-24 days 2 ~60 days Amlitelimab APG990 ~2.5-3x longer half-life APG990 half-life was ~2.5-3x longer than amlitelimabSingle-dose concentration-time profile1 Nominal Time Post Dose, Weeks Serum Concentration, µg/mL (N=6)150 mg (N=6)300 mg (N=6)600 mg (N=6)75 mg (N=6)1200 mg
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18© Apogee Therapeutics, Inc 1 Solid blue line represents population PK (PPK) model predicted median concentrations of APG990 for Q3M or Q6M dosing regimen, shaded blue area represents 90% prediction interval (PI). 2 Based on Apogee modeled exposures for amlitelimab Q12W maintenance dosing ( Ctrough,ss = ~5 µg/mL). Sanofi has also published a 4 µg/mL PD threshold for amlitelimab (Weidinger et al. AAD 2024). NOTE: The above graph is illustrative only with respect to plans for dosing of APG990 and does not present comparative data. APG990 PHASE 1 APG990 modeled exposures are comparable to amlitelimab and enable potential every 3- and 6-month dosing for APG279 Modeled concentration based on APG990 Phase 1 PK1 Potential for APG279 every 3- and 6-month dosing in a single 2mL injection (AI or PFS) in maintenance enabled by APG990 PK and high concentration coformulation (≥180 mg/mL) 0 10 20 Amlitelimab threshold2 Months3 APG990 (50 mg) Every 3 monthsMedian and 90% PI 3 3 3 3 3 Concentration, μg/mL APG990 (200 mg) Every 6 months 0 10 20 30 40 Median and 90% PI Amlitelimab threshold2 Months6 6 6 Concentration, μg/mL
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APG279 Development Program Kristine Nograles, MD SVP, Clinical Development
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20© Apogee Therapeutics, Inc NOTE: R = Randomization. 1 APG279 (APG777+APG990) will be co-administered in the proof-of-concept Phase 1b trial; coformulation planned for future clinical studies and commercialization. Trial design elements Phase 1b trial in moderate-to-severe AD Randomized assessor-blinded, active comparator trial N ~50-75 Key inclusion criteria: biologic naïve, moderate- to-severe AD at screening and baseline (EASI ≥16, IGA ≥3, BSA ≥10) Primary endpoint: safety/tolerability Secondary endpoints: efficacy (EASI75, IGA0/1), PK, biomarkers R APG279 (APG777+APG990)1 DUPIXENT 16-week efficacy readout Phase 1b readout against DUPIXENT in 2H 2026 could demonstrate potential for transformational efficacy and dosing Phase 1b of APG279 against DUPIXENT planned to initiate this year APG279 24-week efficacy readout
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21© Apogee Therapeutics, Inc Safety PD biomarkers Efficacy Objectives Confirm tolerable safety profile to enable additional combination trials Demonstrate broader pharmacodynamic effect on biomarkers of Type 1, 2, and 3 inflammation compared with standard of care Proportion of patients achieving key endpoints (e.g., EASI75, IGA0/1) at higher rates than with standard of care APG279 Phase 1b clinical trial objectives APG279
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Building a Leading I&I Company Michael Henderson, MD Chief Executive Officer
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APG777 in AD: Best-in-class monotherapy • Potential megablockbuster in the future $50B+ AD market • Accelerated mid-2025 Ph2 POC readout testing higher induction exposures for potentially better efficacy • Potential for transformational every 3- or 6-month dosing Best-in-class combinations Our vision for building a next-gen biotech • Rapidly advancing with potential to break through the monotherapy efficacy ceiling – APG279 (777+990): Ph1b against DUPIXENT initiation expected in 2025; readout expected in 2H 2026 – APG279 coformulation can potentially be dosed as a single 2 mL injection every 3-months or longer in maintenance © Apogee Therapeutics, Inc APG777: Pipeline-in-a-product • Path to leadership in 10+ potential expansion indications starting with asthma and EoE
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24© Apogee Therapeutics, Inc • 1H: Initial Phase 1 PK & safety in HVs✓ KEY READOUT 2025 2026 Potential best-in-class monotherapy in AD Potential first- or best-in-class combination approaches Potential best-in-class mAbs for combinations • 2H: Initial Phase 1 PK & safety in HVs NOTE: As of December 31st, 2024, Apogee had cash, cash equivalents and marketable securities of $731M IL-13 APG777 • AD Phase 1b PoC trial initiation (against DUPIXENT) IL-13 TSLP APG777 + APG333 IL-13 OX40L APG279 • 1H: Asthma Phase 1b readout TSLP APG333 OX40L APG990 IL-4Rα APG808 • 1H: AD Phase 2 Part A 52-week readout • 2H: AD Phase 2 Part B 16-week readout • Asthma Phase 1b readout • EoE Phase 2 initiation • 2H: AD Phase 1b PoC readout (against DUPIXENT) • Additional clinical plan announced $731M in cash with runway into Q1 2028 • Mid-2025: AD Phase 2 16-week PoC readout (fully enrolled) • 1H: Asthma Phase 1b initiation • 2H: Asthma Phase 2b initiation Over the next 2 years, 7 clinical trial readouts expected across our pipeline CORPORATE + +
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Appendix
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© Apogee Therapeutics, Inc APG990 was well-tolerated with a favorable safety profile (TEAEs ≥5% across all cohorts, all grades) NOTE: TEAE = Treatment-Emergent Adverse Event. TE -SAE = Treatment-Emergent-Serious Adverse Event. Interim data includes AEs repo rted as of 06 February 2025 data cut. The trial is ongoing. APG990 PHASE 1 Phase 1 Single Ascending Dose: By Cohort Overall N (%) Placebo N=10 Cohort 1 75 mg N=6 Cohort 2 150 mg N=6 Cohort 3 300 mg N=6 Cohort 4 600 mg N=6 Cohort 5 1,200 mg N=6 Placebo N=10 APG990 N=30 Headache 1 (10.0%) 1 (16.7%) 3 (50.0%) 1 (16.7%) 0 0 1 (10.0%) 5 (16.7%) Diarrhea 1 (10.0%) 2 (33.3%) 0 0 0 0 1 (10.0%) 2 (6.7%) Arthropod bite 1 (10.0%) 0 0 0 1 (16.7%) 0 1 (10.0%) 1 (3.3%) Injection site erythema 0 1 (16.7%) 0 1 (16.7%) 0 0 0 2 (6.7%) Upper respiratory tract infection 0 1 (16.7%) 0 1 (16.7%) 0 0 0 2 (6.7%) Viral upper respiratory tract infection 1 (10.0%) 1 (16.7%) 0 0 0 0 1 (10.0%) 1 (3.3%)