Tyra Biosciences, Inc. · NASDAQ:TYRA

Tyra Biosciences — ENA Symposium (Abstract 500 LBA)

23 slides from Tyra Biosciences's conference presentation

  1. Slide 1: Preliminary safety and anti-tumor activity of TYRA-300 in advanced solid tumors (SURF301)

    Preliminary safety and anti-tumor activity of TYRA-300, a highly selective FGFR3 inhibitor, in participants with advanced solid tumors with activating FGFR3 mutations/fusions (SURF301) Ben Tran1, A. Zhang2, A. Hansen3, V. Boni4, C. Mantia5, E. Yu6, A. Weickhardt7, M. Robert8, S. Gupta9, A. Necchi10,

  2. Slide 2: Disclosures: Conflict of Interest

    DISCLOSURES Conflict of Interest I have the following potential conflicts of interest to report: Research Funding Amgen, Astellas, AstraZeneca, Bayer, BMS, Genentech, Ipsen, Janssen, Pfizer, Movember, MSD Honoraria Amgen, Astellas, AstraZeneca, Bayer, BMS, Ipsen, Janssen, Merck, MSD, Pfizer, Sanofi,

  3. Slide 3: FGFR3 activating alterations occur in 10-20% of mUC

    FGFR3 activating alterations occur in 10−20% of mUC1 FGFR3 Erdafitinib2 Other FGFRi Cysteine Mutations Pan-FGFR inhibitor The FGFR1/2/3 approved for locally inhibitors pemigatinib Available FGFRi S249C R248C advanced or mUC with and infigratinib were are associated CC Y373C susceptible FGFR3 previou

  4. Slide 4: Pan FGFR inhibition is associated with key on-target toxicities

    Pan FGFR inhibition is associated with key on-target toxicities Grade 1−2 ≥Grade 3 Adverse reactions in ≥15% of patients who received erdafitinib (n=135)1,# FGFR2 Nail disorders RELATED2,3 Stomatitis Dry mouth PPE Dry eye Central serous retinopathy 0 20 40 60 80 FGFR1 Hyperphosphatemia RELATED 3,4 0

  5. Slide 5: Adverse reactions requiring dosage modifications of erdafitinib

    Adverse reactions requiring dosage modifications of erdafitinib Adverse reactions resulting in dose adjustments in patients who received erdafitinib (n=135)1,# INTERRUPTION REDUCTION DISCONTINUATION 72% 69% 14% Nail disorders 22 Nail disorders 27 Stomatitis 19 Stomatitis 19 Eye disorders 16 Eye diso

  6. Slide 6: TYRA-300 is a first-in-class, highly selective FGFR3 inhibitor

    TYRA-300 is a first-in-class, highly selective FGFR3 inhibitor Selectivity observed for TYRA-300 vs. other FGFR inhibitors: in vitro Ba/F3 Cellular IC50 (nM)1 E erdafitinib F futibatinib P pemigatinib I infigratinib T TYRA-300 63x FGFR1 FE P I 19x T FGFR2 FE P I T FGFR3 FT E PI 55x FGFR4 F E T P I 0

  7. Slide 7: SURF301: FIH study of TYRA-300 in mUC and other solid tumors

    SURF301: FIH study of TYRA-300 in mUC and other solid tumors Dose Escalation Dose Expansions Endpoints Phase 1 Part A i3+3 design Phase 1 Part B Primary • Advanced solid tumors (must have • Advanced solid tumors with activating • Incidence of DLTs / AEs exhausted all standard therapies) FGFR3 altera

  8. Slide 8: Part A & B QD data from ongoing Phase 1 portion

    Part A & B QD data from ongoing Phase 1 portion Dose Escalation Dose Expansions Endpoints Phase 1 Part A i3+3 design Phase 1 Part B Primary • Advanced solid tumors (must have • Advanced solid tumors with activating • Incidence of DLTs / AEs exhausted all standard therapies) FGFR3 alterations; focus

  9. Slide 9: Baseline demographics and disease history characteristics

    Baseline demographics and disease history characteristics n=41 n (%) MEDIAN AGE (range 34−84) 66 (yrs) TUMOR TYPE mUC 25 (61) Lung 3 (7) n (%) Head and Neck 4 (10) Other 9 (22) SEX AT BIRTH Male 30 (73) PRIOR LINES 0 5 (12) ECOG PS 0 14 (34) OF THERAPY 1 7 (17) 1 27 (66) 2 11 (27) ≥3 18 (44) FGFR3 M

  10. Slide 10: Preliminary data suggest TYRA-300 is generally well tolerated

    Preliminary data suggest TYRA-300 is generally well tolerated n=41 Any Grade ≥ Grade 3 Any TRAEs, n (%) 32 (78) 8 (20) 1 DLT 90 mg QD, Gr. 3 diarrhea* TRAEs in >10% of participants, n(%) Drug-related ALT increase# 10 (24) 2 (5) 1 discontinuation 90 mg QD, Gr. 3 ALT elevation# Diarrhea* 9 (22) 1 (2)

  11. Slide 11: No phosphorus elevation >7.0 mg/dL across all doses

    There was no phosphorus elevation >7.0 mg/dL across all doses C1D15 Phosphate C2D1 Phosphate 7.0 Phosphate binder was used to 2.0 6.0 manage treatment-related hyperphosphatemia in one mmol/L mg/dL 5.0 patient (90 mg QD). 1.5 4.0 1.0 3.0 2.0 0.5 40 60 90 120 40 60 90 120 Dose (mg) Dose (mg)

  12. Slide 12: Exposure at ≥90 mg exceeded FGFR3 IC90 target coverage

    Exposure at ≥90 mg exceeded FGFR3 IC90 target coverage 10,000 FGFR1 (IC50) Dose N AUC FGFR4 (IC50) (mg) (C1D15) (ng*h/mL) TYRA-300 Concentration (ng/ml) FGFR2 (IC50) 120 3 23,578 1,000 120 mg 2.5x 90 mg 90 13 10,300 FGFR3 (IC90) 2.4x 60 mg 60 8 4,360 100 40 mg 2.5x 20 mg 40 10 2,270 20 1 1,830 10 10

  13. Slide 13: 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 Tumor Volume (mm3) AUClast (ng/mL) Vehicle Murine 18 mg/kg Erda (12.5 mg/kg BID) TYRA-300 (18 mg/kg QD) Days Dose Group (mg QD) Data on File.

  14. Slide 14: Radiographic response assessment in all evaluable patients

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

  15. Slide 15: Anti-tumor activity observed in all FGFR3+ mUC ≥90 mg QD

    Anti-tumor activity observed in all FGFR3+ mUC ≥90 mg QD Efficacy-evaluable population (n=36) Best Percent Change from Baseline NE# FGFR3+ mUC 120 mg FGFR3+ mUC 90 mg FGFR3+ mUC <90 mg Others Abbreviations: BOR, best overall response; NE, non- mUC                       evaluabl

  16. Slide 16: Anti-tumor activity observed in all FGFR3+ mUC ≥90 mg QD

    Anti-tumor activity observed in all FGFR3+ mUC ≥90 mg QD Investigator-assessed radiographic FGFR3+ mUC ≥90 mg QD BOR by RECIST v1.1 (n=11) Best Percent Change from Baseline 6 confirmed PRs at ≥90 mg QD (n=11) • 5 confirmed PRs at 90 mg QD (n=10) • 1 confirmed PR at 120 mg QD (n=1) 100% Disease Contr

  17. Slide 17: Overview: time on treatment for target population, FGFR3+ mUC

    Overview: time on treatment for target population, FGFR3+ mUC Prior lines 40 mg 4 6 5 16.6 months 3 1 3 60 mg 4 Confirmed Partial Response (PR) 4 Unconfirmed Partial Response 8 3 Progressive Disease (PD) 4 Remains on study drug 3 Death 3 1−8 No. of prior lines of therapy 90 mg 2 4 2 4 2 2 3 1 3 1 AE

  18. Slide 18: FGFR2- or FGFR1-associated TRAEs at 90 mg QD

    FGFR2- or FGFR1-associated TRAEs at 90 mg QD TYRA-300 (%, n=15) Grade 1−2 ≥Grade 3 FGFR2 Nail disorders n=1 (7%) Stomatitis n=1 (7%) RELATED 1,2 Dry mouth n=6 (40%) PPEs n=2 (13%) Dry eye Central serous retinopathy n=1 (7%) 0 20 40 60 80 FGFR1 Hyperphosphatemia n=2 (13%) RELATED 2,3 0 20 40 60 80 Di

  19. Slide 19: Radiographic regression seen at first imaging

    Radiographic regression seen at first imaging FGFR3+ mUC Patients at 90-120 mg QD (n=11) % Change from Baseline in Target Lesions 50 25 0 -25 -50 Mutation: S249C -75 Fusion: FGFR3-JAKMIPI 1 57 113 169 225 281 337 Days Based on Investigator Assessment; RECIST v1.1

  20. Slide 20: Case study: mUC with an activating FGFR3 S249C mutation

    Case study: mUC with an activating FGFR3S249C mutation LUNG TARGET LESION SEPT 25, 2023 4mo JAN 15, 2024 Age/sex: 84-year-old female # prior lines tx: 4 Target lesions: Lung NTL: Lung, bone BOR: -64% (cPR) Treatment: 90 mg QD, 11 mo.* Baseline Confirmed PR * Treatment ongoing at time of data cut BOR

  21. Slide 21: Case study: mUC with an activating FGFR3-JAKMIPI fusion

    Case study: mUC with an activating FGFR3-JAKMIPI fusion LUNG TARGET LESION SEPT 27, 2023 4mo FEB 2, 2024 Age/sex: 64-year-old male # prior lines tx: 2 Target lesions: Lung (x2), LN (x2) NTL: Lung (x2) and LN (x2) BOR: -75% (cPR) Treatment: 90 mg QD, 11 mo.* Baseline Confirmed PR * Treatment ongoing

  22. Slide 22: Preliminary data are encouraging as SURF301 continues

    Preliminary data are encouraging as SURF301 continues Preliminary data from SURF301 suggest TYRA-300 to 1 be generally well tolerated, with infrequent FGFR2- Phase 1 is ongoing and and FGFR1-associated toxicities. the MTD was not reached; TYRA-300 plasma concentrations indicate adequate the optimal

  23. Slide 23: Acknowledgements

    Acknowledgements The authors would like to thank all patients, caregivers, all the SURF301 investigators, and study personnel at study sites. The authors would like to acknowledge Jennifer Davis, Alexandra Balcer, Ben Suttle, PhD (qPharmetra), Alexander Wyatt, PhD, and Gillian Vandekerkhove, PhD (Un

Tyra Biosciences — ENA Symposium (Abstract 500 LBA) on 6ix