Tyra Biosciences, Inc. · NASDAQ:TYRA

Tyra Biosciences — Corporate Update (October 2024)

38 slides from Tyra Biosciences's corporate update, Oct 25, 2024

  1. Slide 1: Interim clinical proof-of-concept with TYRA-300 in mUC (SURF301)

    Interim clinical proof-of-concept with TYRA-300 in mUC (SURF301) October 25, 2024 Exhibit 99.1

  2. Slide 2: Today's participants and agenda

    Today’s participants and agenda AGENDA Introduction Todd Interim SURF301 TYRA-300 results Doug Q&A: Perspective of a leading Urologist Gary Todd Harris, PhD Doug Warner, MD Gary Steinberg, MD CEO, TYRA CMO, TYRA Professor of Urology, Dept. of Urology, Rush University Medical Center

  3. Slide 3: Disclaimers

    Disclaimers We caution you that this presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, including statements regarding our business strategy, research and development plans, the anticipated timing and phase of de

  4. Slide 4: Our expertise in FGFR biology creates a differentiated pipeline

    Our expertise in FGFR biology creates a differentiated pipeline Discovery IND-Enabling 1 2 3 Phase Estimated Annual US Addressable1 GENETIC CONDITIONS FGFR3ACH: TYRA-300 ~3K Potentially leading to additional skeletal dysplasias, including FGFR3-related conditions (HCH, SHOX), and pediatric short sta

  5. Slide 5: TYRA-300 safety, activity and PK/PD summary

    SAFETY ACTIVITY PK/PD On par with erdafitinib label in FGFR3+ mUC patients at active dose levels TYRA-300 is the world’s first oral, selective FGFR3 inhibitor with the potential to deliver benefit to cancer patients with a tolerable safety profile BENCHMARK1 READOUT 54.5% (6/11) confirmed PRs vs. 35

  6. Slide 6: TYRA-300 safety, activity and PK/PD summary

    SAFETY ACTIVITY PK/PD On par with erdafitinib label in FGFR3+ mUC patients at active dose levels Dose-dependent activity TYRA-300 is the world’s first oral, selective FGFR3 inhibitor with the potential to deliver benefit to cancer patients with a tolerable safety profile Anti-tumor activity observed

  7. Slide 7: TYRA-300 safety, activity and PK/PD summary

    SAFETY ACTIVITY PK/PD On par with erdafitinib label in FGFR3+ mUC patients at active dose levels Dose-dependent activity Safety profile with improved tolerability in FGFR1/2/4-driven toxicities compared to pan-FGFRis TYRA-300 is the world’s first oral, selective FGFR3 inhibitor with the potential to

  8. Slide 8: Interim Phase 1 results

    INTERIM PHASE 1 RESULTS ENA 2024

  9. Slide 9: FGFR3 oncogenic alterations are common in bladder cancer

    Cysteine Mutations CC S249C R248C Y373C G370C P P Fusions TACC3 (example) FGFR3 oncogenic alterations are common in bladder cancer Abbreviations: IR, Intermediate Risk; HR, High Risk 1. Weickhardt 2022 2. Mayr, 2022; Kacew, 2020; Knowles, 2020 3. BALVERSA® (erdafitinib) prescribing information 01/20

  10. Slide 10: FGFR3 oncogenic alterations are common in bladder cancer

    Cysteine Mutations CC S249C R248C Y373C G370C P P Fusions TACC3 (example) FGFR3 oncogenic alterations are common in bladder cancer Abbreviations: IR, Intermediate Risk; HR, High Risk 1. Weickhardt 2022 2. Mayr, 2022; Kacew, 2020; Knowles, 2020 3. BALVERSA® (erdafitinib) prescribing information 01/20

  11. Slide 11: FGFR3 oncogenic alterations are common in bladder cancer

    Cysteine Mutations CC S249C R248C Y373C G370C P P Fusions TACC3 (example) FGFR3 oncogenic alterations are common in bladder cancer Abbreviations: IR, Intermediate Risk; HR, High Risk 1. Weickhardt 2022 2. Mayr, 2022; Kacew, 2020; Knowles, 2020 3. BALVERSA® (erdafitinib) prescribing information 01/20

  12. Slide 12: Pan FGFR inhibition is associated with key on-target toxicities

    Pan FGFR inhibition is associated with key on-target toxicities Nail disorders Stomatitis Dry mouth PPE Dry eye Central serous retinopathy Diarrhea ALT increase AST increase Dry skin Hyperphosphatemia Adverse reactions in ≥15% of patients who received erdafitinib (n=135)1,# FGFR2 RELATED FGFR1 RELAT

  13. Slide 13: Adverse reactions have required dosage modifications of erdafitinib

    Adverse reactions have occurred requiring dosage modifications of erdafitinib 1. BALVERSA (erdafitinib) prescribing information 01/2024, BLC3001 Cohort 1 data. Adverse reactions leading to dosage interruptions or reductions of erdafitinib in >4% of patients. Nail disorders 22 Stomatitis 19 Eye disor

  14. Slide 14: TYRA-300 is a potential first-in-class, highly selective FGFR3 inhibitor

    TYRA-300 is a potential first-in-class, highly selective FGFR3 inhibitor All experiments conducted under identical conditions, tested in duplicate. 0 20 40 60 80 120 Selectivity observed for TYRA-300 vs. approved or late-stage clinical compounds: in vitro Ba/F3 Cellular IC50 (nM) FGFR1 FGFR2 FGFR3 F

  15. Slide 15: Our Phase 1 explored QD dose escalation and expansion

    Our Phase 1 explored QD* dose escalation and expansion Dose QD* Illustrative Dose QD PART A (all comers) PART B (FGFR3+ only) Dose Escalation Dose Expansion *1x daily All solid tumor types1 FGFR+/- Solid tumors with focus on mUC1 FGFR3+ only 1. Previously treated patients, including FGFRi, allowed

  16. Slide 16: We dose escalated to 120mg QD and then expanded up to 90mg

    We dose escalated to 120mg QD and then expanded up to 90mg Dose QD* 10mg 20mg 40mg 60mg Illustrative Dose QD 40mg 60mg PART A (all comers) PART B (FGFR3+only) 90mg RP2D Dose Escalation Dose Expansion 120mg 1 1 3 3 7 7 10 5 4 90mg N= N= *1x daily

  17. Slide 17: The study population was older and heavily pre-treated mUC

    The study population was older and heavily pre-treated mUC 25 (61) Lung 3 (7) Head and Neck 4 (10) Other 9 (22) Mutation 17 (41) Fusion 15 (37) None 10 (24) 0 5 (12) 1 7 (17) 2 11 (27) ≥3 18 (44) TUMOR TYPE FGFR3 ALTERATION PRIOR LINES OF THERAPY n=41 (range 34−84) 66 (yrs) MEDIAN AGE SEX AT BIRTH E

  18. Slide 18: The study population was older and heavily pre-treated mUC

    The study population was older and heavily pre-treated mUC 25 (61) Lung 3 (7) Head and Neck 4 (10) Other 9 (22) Mutation 17 (41) Fusion 15 (37) None 10 (24) 0 5 (12) 1 7 (17) 2 11 (27) ≥3 18 (44) TUMOR TYPE FGFR3 ALTERATION PRIOR LINES OF THERAPY n=41 (range 34−84) 66 (yrs) MEDIAN AGE SEX AT BIRTH E

  19. Slide 19: Preliminary data suggests TYRA-300 is generally well tolerated

    Preliminary data suggests TYRA-300 is generally well tolerated Any Grade ≥ Grade 3 Any TRAEs, n (%) 32 (78) 8 (20) TRAEs in >10% of participants, n(%) ALT increase# 10 (24) 2 (5) Diarrhea* 9 (22) 1 (2) Dry mouth 9 (22) AST increase 8 (20) 1 (2) Dry skin 6 (15) Fatigue 5 (12) #Drug-related discontinu

  20. Slide 20: Minimal changes in phosphate at ≤90 mg QD observed

    Minimal changes in phosphate at ≤90 mg QD observed Minimal impact in phosphate at ≤ 90 mg QD. Dashed lines denote 5.5 and 7 mg/dL used by Loriot et al. where 5.5- 6.9 mg/dL was defined as Grade 1 and 7.0-8.9 mg/dL as Grade 2. C1D15 Phosphate C2D1 Phosphate 2.0 1.5 1.0 0.5 40 60 90 120 40 60 90 120 m

  21. Slide 21: Exposure at doses ≥90 mg exceeded FGFR3 IC90 target coverage

    Exposure at doses ≥90 mg exceeded FGFR3 IC90 target coverage 10,000 1,000 TYRA300 Concentration (ng/ml) 100 10 1 10 mg 20 mg 40 mg 60 mg 90 mg 120 mg 0 6 12 18 24 Time (hr) FGFR1 (IC50) FGFR4 (IC50) FGFR3 (IC90) FGFR2 (IC50) 2.5x 2.4x 2.5x Dose (mg) N (C1D15) AUC (ng*h/mL) 120 3 23,578 90 13 10,300

  22. Slide 22: Predicted exposure was achieved in human doses ≥90 mg QD

    Predicted exposure was achieved in human doses ≥90 mg QD FGFR3+ UM-UC-14 Xenograft Individual Steady State AUCs in Patients Murine 18 mg/kg Vehicle Erda (12.5 mg/kg BID) TYRA-300 (18 mg/kg QD) Days Dose Group (mg QD) AUClast (ng/mL) Tumor Volume (mm3) Data on File.

  23. Slide 23: Radiographic tumor response assessment in all evaluable patients

    Radiographic tumor response assessment in all evaluable patients Best Percent Change from Baseline Efficacy-evaluable population (n=36) FGFR3 Mutation FGFR3 Fusion mUC NE# FGFR3+ mUC Others Abbreviations: BOR, best overall response; NE, non-evaluable; PR, partial response; SD, stable disease; PD, pr

  24. Slide 24: Anti-tumor activity observed in all FGFR3+ mUC ≥90 mg QD

    Anti-tumor activity observed in all FGFR3+ mUC ≥90 mg QD Best Percent Change from Baseline l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l 40 90 60 90 40 60 90 10 40 40 120 40 120 90 40 40 60 60 20 60 60 40 60 90 90 90 90 90 90 40* 90 120 90 90 90

  25. Slide 25: Anti-tumor activity observed in all FGFR3+ mUC ≥90 mg QD

    Anti-tumor activity observed in all FGFR3+ mUC ≥90 mg QD Abbreviations: BOR, best overall response; CR, complete response; PR, partial response; SD, stable disease. Only confirmed PRs reported. Disease Control Rate: CR+PR+SD Best Percent Change from Baseline Investigator-assessed radiographic BOR by

  26. Slide 26: Time on treatment for target population, FGFR3+ mUC

    Time on treatment for target population, FGFR3+ mUC Death unrelated to study drug (Respiratory Syncytial Virus) 2. AE refers to adverse event Time on treatment (months) Confirmed Partial Response (PR) Unconfirmed Partial Response Progressive Disease (PD) Remains on study drug Death No. of prior line

  27. Slide 27: At 90mg QD, improved tolerability observed compared to erdafitinib

    Nail disorders Stomatitis Dry mouth PPEs Dry eye Central serous retinopathy Diarrhea ALT increase AST increase Dry skin Hyperphosphatemia erdafitinib %, n=1354,# TYRA-300 (%, n=15) FGFR2 DRIVERS FGFR1 DRIVER UNKNOWN DRIVERS ≥Grade 3 Grade 1−2 At 90mg QD, improved tolerability observed compared to er

  28. Slide 28: Radiographic regression seen at first imaging

    Radiographic regression seen at first imaging Fusion: JAKMIPI Mutation: S249C FGFR3+ mUC Patients at 90-120 mg QD (n=11) 1 % Change from Baseline in Target Lesions 57 113 169 225 281 337 -100 -75 -50 -25 0 25 50 Days Based on Investigator Assessment; RECIST v 1.1

  29. Slide 29: Case study: mUC with activating FGFR3 S249C mutation

    84-year-old female FGFR3 S249C 4 prior lines Lung Lung, bone -64% (cPR) 90 mg QD, 11 mo.* Age/sex: Alteration: Prior tx: Target lesions: NTL: BOR: Treatment: Case study: mUC with activating FGFR3S249C mutation Mutation * Treatment ongoing at time of data cut BOR: Best Overall Response; cPR: Confirme

  30. Slide 30: Case study: mUC with activating FGFR3-JAKMIPI fusion

    Case study: mUC with activating FGFR3-JAKMIPI fusion 64-year-old male FGFR3 JAKMIPI 2 prior lines lung (x2), LN (x2) lung (x2) and LN (x2) -75% (cPR) 90 mg QD, 11 mo.* Age/sex: Alteration: Prior tx: Target lesions: NTL: BOR: Treatment: Fusion SEPT 27, 2023 FEB 2, 2024 Baseline Confirmed PR LUNG TARG

  31. Slide 31: Interim clinical proof-of-concept established with TYRA-300 in mUC

    Interim clinical proof-of-concept established with TYRA-300 in mUC TYRA-300 plasma concentrations indicate adequate target coverage at ≥90 mg QD; further pharmacokinetic characterization is ongoing. Preliminary anti-tumor activity of TYRA-300 in heavily pre-treated patients is encouraging, especiall

  32. Slide 32: Looking ahead: TYRA-300

    LOOKING AHEAD: TYRA-300 mUC Improved toxicity profile NMIBC Patient-friendly oral ACH Differentiated efficacy

  33. Slide 33: Attractive market opportunities for TYRA-300

    Attractive market opportunities for TYRA-300 2L+ mUC NMIBC ACH Total addressable (incident and recurrent) FGFR3+ Market Size US: ~3.4K IR US: ~22−41K US: ~3K Global: ~20K Unmet Needs Less FGFR1/2/4-related and other toxicities Reduction in recurrence Oral administration vs TURBT + chemotherapy Diffe

  34. Slide 34: High FGFR3+ rate drives an outsized opportunity in IR NMIBC

    41 High FGFR3+ rate drives an outsized opportunity in IR NMIBC 75 25 0 FGFR3+ proportion of total addressable US market HR NMIBC 2L+ mUC 175 50 100 125 150 34 44 22.8 10−20% ~40% 60−80% Incidence and recurrence with alteration (patient ’000s) 3.4 All FGFR3 / Urothelial 163 66−721 22 18 63 60−80% IR

  35. Slide 35: Erdafitinib demonstrated efficacy but also toxicity at a lower dose

    Erdafitinib demonstrated efficacy… but also toxicity at a lower dose SG (spell out) Erdafitinib 6mg (vs. 8 or 9mg in mUC trial) THOR-2 TRIAL IR NMIBC Cohort 3 n=18 CR Rate: DOR: Tx duration: 83% (15 of 18) 12.7 months (median) 7.1 months (median) Hyperphosphatemia 100 Dry mouth 72.2 Diarrhea 61.1 Dy

  36. Slide 36: Safety readthrough at lower doses: FGFR-related toxicities were infrequent

    Safety readthrough at lower doses: FGFR-related toxicities were infrequent ≤60 mg (n=22) 90 mg (n=15) 120 mg (n=4) All (n=41) Gr. 1-2 ≥Gr. 3 Gr. 1-2 ≥Gr. 3 Gr. 1-2 ≥Gr. 3 Gr. 1-2 ≥Gr. 3 ALT increase 1 (5) — 5 (33) 2 (13) 2 (50) — 8 (20) 2 (5) Diarrhea 3 (14) — 2 (13) 1 (7) 4 (100) — 9 (22) 1 (2) Dry

  37. Slide 37: Our goals for TYRA-300 in mUC, NMIBC and ACH

    ACH mUC NMIBC Improved tolerability profile for 2L+ mUC in larger Phase 2 study A patient-friendly oral alternative to IVE therapies for NMIBC AHV changes leading to differentiated final adult height and functional improvements Our goals for TYRA-300 in mUC, NMIBC and ACH Further dose optimization S

  38. Slide 38: Q&A

    Q&A

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