Slide 1: Multicenter, Open-Label Phase 1/2a Study of PXS-5505 and Ruxolitinib in Myelofibrosis
Multicenter, Open-Label Phase 1/2a Study of PXS-5505 and Ruxolitinib in Patients With Primary, Post-Polycythemia Vera (PV) or Post- Essential Thrombocythemia (ET) Myelofibrosis (NCT04676529) Contributing Investigators: Peter Tan1, Ross Baker2, Sung-Eun Lee3, Anne-Marie Watson4, Stanley Cheung5, Shan
Slide 2: Acknowledgements
Acknowledgements 2024 We would like to sincerely thank all of the investigators, site staff, patients, families and caregivers who are participating in this study. This study is funded by Syntara Limited, Sydney, Australia 2 PXS5505-MF-101: Presenter: Peter Tan, MD; One Clinical Research Pty Ltd,
Slide 3: The role of lysyl oxidases in myelofibrosis
The role of lysyl oxidases in myelofibrosis 2024 PXS-5505 designed to improve the bone marrow microenvironment Lysyl oxidase gene family upregulated in the bone marrow (BM) of myelofibrosis patients1 Increased lysyl oxidase activity1: Catalyzes the formation of stabilizing crosslinks leading t
Slide 4: Elevated LOX in MF targeted by PXS-5505
Elevated LOX in MF targeted by PXS-5505 2024 PXS-5505 demonstrates >90% target inhibition1 LOX and LOXL2 are upregulated Very consistent PXS-5505 High target engagement in MF patients (plasma) plasma levels across patients even at trough (pre-dose) ✱ ✱✱✱✱ Plasma concentration [ng/mL] 10000 100 LOX a
Slide 5: Aims/Methods
Aims/Methods 2024 PXS-5505-MF-101 Add-on to RUX (study in progress) This add-on phase aims to further evaluate the safety and efficacy of PXS-5505 (200 mg BID) in patients with MF on stable background regimens of ruxolitinib (RUX) over a 52-week period STUDY POPULATION DESIGN ENDPOINTS PRIMARY Pha
Slide 6: Baseline characteristics
Baseline characteristics 2024 Heterogenous population with a high disease burden Study is ongoing – data extracted 14 Characteristic N=16 Nov 2024 Age, median (range), years 71 (46-82) Sex, male, n (%) 7 (44) 13 patients (pts) reached 12 week visit Time since MF diagnosis, median (range), 60 (7–
Slide 7: Safety
Safety 2024 PXS-5505 has been well tolerated with no treatment related SAEs Pts with Grade 3/4 AEs Regardless of Causality# Majority of AEs were mild, 44/61 (72%) ≤ Grade 2 Grade 3 Grade 4 Adverse Event 82% of AEs considered not related N=16 N=16 to treatment Anemia 4 11 possibly related AEs*
Slide 8: Total symptom score
Total symptom score 2024 Improvements in TSS from Baseline to Week 12 6/13 pts (46%) achieved TSS50 100 Median absolute change 10 was -10 50 TSS Change from Baseline (%) 11 Median % change was -41 Baseline TSS 37 52 51 45 22 16 18 32 19 23 10 0 -50 TSS50 -100 8 PXS5505-MF-101: Presenter: Peter
Slide 9: Total symptom score over time
Total symptom score over time 2024 Substantial reduction in TSS observed in the majority of patients 8/13 pts (62%) reached TSS50 up 100 to Week 38 Week 12 Week 24 Improvement in TSS continue Week 38 over time 50 TSS Change from Baseline (%) 11 TSS improvement despite a prior RUX duration of 2
Slide 10: Spleen volume over time
Spleen volume over time 2024 Additional reductions seen with longer treatment 11/13 pts had spleen volumes at 50 45 baseline > 450 cm3 40 Week 12 * Week 24 35 Week 38 9/11 pts (82%) had either stable or 30 * reduced spleen volume 25 Spleen Volume Change % 20 15 Additional improvements at 10 13
Slide 11: Hematology parameters
Hematology parameters 2024 Stable with some observed decreases in transfusion burden Of the 13 pts with ≥3 months treatment, at baseline: 2 transfusion dependent 4 receiving transfusions 7 not receiving transfusions 1/2 transfusion dependent pts had over 50% reduction in RBC transfusions
Slide 12: Efficacy outcomes at Week 38
Efficacy outcomes at Week 38 2024 Longer duration of therapy leads to additional improvements Baseline TSS Baseline Spleen Volume (cm3) 10 52 22 45 18 23 0 5 602 478 3832 3050 2153 Pt # 1 Pt # 2 Pt # 3 Pt # 4 Pt # 5 0 Pt # 4 Pt # 2 Pt # 5 Pt # 1 Pt # 3 Spleen Volume Change (%) -5 -10 SVR10 TSS Chang
Slide 13: Safety and efficacy
Safety and efficacy 2024 Summary of outcomes to date PXS-5505 200 mg BID in addition to TSS Change Over 38 Weeks stable background dose of RUX: Safe and well tolerated 0 No changes in dose of concomitant RUX TSS Change (%) Symptom improvement observed over time with majority of patients achi
Slide 14: Conclusions
Conclusions 2024 PXS-5505 warrants further development in MF 41 pts have now been treated with PXS-5505 200 mg BID, median duration of 6 months (range 0.5 – 11) Consistent with monotherapy data1, PXS-5505 is safe and well tolerated in combination with RUX in a broad population with high disease