amsulostat (SNT-5505) / Syntara - LARVOL DELTA

Lysyl oxidases directly control cell surface abundance of platelet-derived growth factor receptors and signaling in osteoblasts (ASH 2025) - P1/2 | "Such oxidationsenhance overall cell surface expression after PDGF stimulation, leading to a prolonged response andaugmented signaling. Importantly, these effects are blocked by amsulostat, suggesting a powerful modeof action beyond the extracellular inhibition of cross-linking"

Fibrosis • Hematological Malignancies • Immunology • Myeloproliferative Neoplasm • Sarcoma • Solid Tumor • EGFR • LOX

A phase 1/2a trial of amsulostat, a novel pan-lysyl oxidase inhibitor, in patients with advanced myelofibrosis as an add-on to ruxolitinib treatment for up to 52 weeks (ASH 2025) - P1/2 | "In addition to mediating extracellularstructural effects, amsulostat also reduces intracellular proto-oncogene growth factor signaling.PXS5505-MF-101 (NCT04676529) is a multi-center Phase 1/2a study of amsulostat in MF patients (pts). The majority oftreatment emergent AEs were mild, 63/84 (75%) ≤ Grade 2 (data cut-off 5th May 2025).Efficacy and safety from the completed 52-week study will be presented at the conference.ConclusionThe complete data from the AOP will provide insight into the safety profile of amsulostat in combinationwith RUX and also whether longer durations of amsulostat provide additional efficacy benefits. Thisevidence will be used to plan a randomized controlled confirmatory trial of amsulostat in the treatmentof MF."

Clinical • Metastases • P1/2 data • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Thrombocytopenia • LOX

Amsulostat data to be presented at 67th American Society of Hematology Annual Meeting (Syntara Press Release) - "One poster presentation, titled 'A Phase 1/2a Trial of Amsulostat, a Novel Pan-Lysyl Oxidase Inhibitor, in Patients with Advanced Myelofibrosis as an Add-On to Ruxolitinib Treatment for Up to 52 Weeks', will be featured in the session 'Myeloproliferative Syndromes: Clinical and Epidemiological' on Saturday 6 December (EST). In a concurrent 'Bone Marrow Microenvironment' session, Syntara will also present preclinical research highlighting amsulostat-sensitive, lysyl oxidase-mediated modulation of growth factor signaling..."

P1/2 data • Preclinical • Myelofibrosis • Myeloproliferative Neoplasm

Initiation of amsulostat Phase 2 MESSAGE trial in transfusion-dependent MDS (Syntara Press Release) - "The multi-centre study will open at 10 hospitals across Australia with up to 30 patients to be recruited for treatment. It aims to reduce the reliance on fortnightly blood transfusions typically required by MDS patients, improving the survival outcomes and lessening the treatment burden....The commencement of this trial follows...the initiation of AZALOX, a Phase 1b/2 multi-centre study in Germany evaluating amsulostat in combination with 5-Azacitidine for the treatment of high-risk Myelodysplastic Neoplasms (MDS) and Chronic Myelomonocytic Leukemia (CMML). Updates on recruitment and interim safety and efficacy data are anticipated as both studies progress in 2026."

Clinical data • Trial status • Chronic Myelomonocytic Leukemia • Myelodysplastic Syndrome

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 (ASH 2024) - P1/2 | "PXS5505-MF-101 is an ongoing phase 1/2a study in patients (pts) with intermediate or high-risk MF (NCT04676529). Updated efficacy and safety data will be presented at the conference including 12-week data from all pts. Conclusion : The results from this trial using a novel combination of PXS-5505 and RUX will add to the existing safety profile of PXS-5505 and provide preliminary indicators of efficacy to help inform future investigations of PXS-5505 in pts with MF."

Clinical • P1/2 data • Tumor mutational burden • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytopenia • Thrombocytosis • ASXL1 • IDH1 • IDH2 • SRSF2 • TMB • U2AF1

PXS5505-MF-101: A Phase 1/2a Study to Evaluate Safety, Pharmacokinetics and Pharmacodynamics of Pxs-5505 in Patients with Primary, Post-Polycythemia Vera or Post-Essential Thrombocythemia Myelofibrosis (ASH 2023) - P1/2 | "Background: Myelofibrosis (MF) is characterized by a progressive increase in extracellular matrix in the bone marrow (BM) associated with decreased production of hematopoietic cells. PXS-5505 has been well tolerated with no dose limiting toxicity or serious TRAEs. PD results indicate excellent LOX inhibition at the 200mg BID level. Further, there are preliminary indications of disease modification characterized by stable/improved blood counts and an improvement in collagen fibrosis."

Clinical • P1/2 data • PK/PD data • Anemia • Cardiovascular • Dermatology • Febrile Neutropenia • Fibrosis • Hematological Disorders • Immunology • Infectious Disease • Myelofibrosis • Myeloproliferative Neoplasm • Myocardial Infarction • Neutropenia • Septic Shock • Thrombocytopenia • Thrombocytosis • Urticaria • LOX

Syntara Limited…has received a positive opinion on the submission of Orphan Drug Designation (ODD) from the European Medicines Agency (EMA) for its advanced clinical asset amsulostat (SNT-5505) for the treatment of myelofibrosis (MF) (Syntara Press Release) - "Syntara recently announced positive top-line Phase 2a data for amsulostat in MF, with patients sub optimally controlled on ruxolitinib with 73% achieving at least a 50% reduction in total symptom score, and nearly half showing meaningful spleen volume reduction after a year of treatment."

European regulatory • Myelofibrosis

AZALOX: A Phase Ib/II Study of Azacitidine in Combination with the Pan-Lysyl Oxidase Inhibitor PXS-5505 in Patients with Higher-Risk Myelodysplastic Neoplasms (MDS) and Chronic Myelomonocytic Leukemia (CMML) (DGHO 2025) - "This study will enroll approximately n=40 patients ≥18 years with a confirmed diagnosis of MDS (intermediate, high or very high-risk per IPSS-R) or myelodysplastic CMML with ≥10% blasts, and no prior treatment of the combination with azacitidine and venetoclax. Exploratory analyses include assessment of erythroid maturation, fibrotic markers, and molecular predictors of response or resistance. Enrollment has begun and will include Mannheim, Hannover, München, Düsseldorf, Dresden, Göttingen, Lübeck, Mainz and Bonn."

Clinical • Combination therapy • P1/2 data • Anemia • Chronic Myelomonocytic Leukemia • Fibrosis • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome

Positive top-line Phase 2a data confirms amsulostat’s competitive profile in myelofibrosis (Syntara Press Release) - "Improvements of 50% or more in total symptom score (TSS50) were observed quickly (as early as 12 weeks) and were sustained, with 73% (8/11) of patients achieving TSS50 at Week 24 or beyond. The 2 patients that reached 52 weeks (in addition to the 5 reported at EHA) achieved a complete (100%) resolution of symptoms from baseline. Meaningful spleen volume reductions (SVR) were observed at 24 weeks and maintained thereafter, with 44% (4/9) of patients chieving SVR25 at Week 24 or beyond."

P2a data • Myelofibrosis

PXS5505-MF-101: Study to Evaluate Safety, Pharmacokinetic and Pharmacodynamic Dose Escalation and Expansion Study of PXS-5505 in Patients With Primary, Post-polycythemia Vera or Post-essential Thrombocythemia Myelofibrosis (clinicaltrials.gov) - P1/2 | N=43 | Completed | Sponsor: Syntara | Active, not recruiting ➔ Completed

Trial completion • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • Thrombocytosis

Syntara receives guidance from FDA on next stages of amsulostat clinical progression (Syntara Press Release) - "During a Type C meeting, the FDA reviewed a comprehensive data package that included interim data (as presented at the European Hematology Association congress in June 2025) from the ongoing open label trial (MF-101) of amsulostat in combination with ruxolitinib, as well as a proposal for a pivotal registrational study. The FDA has provided guidance that a Phase 2 trial with a control arm be undertaken to acquire additional safety and efficacy data, focusing on improvements in symptoms and spleen volume reductions in order to optimise the design and efficiency of a subsequent pivotal Phase 3 trial."

FDA event • Myelofibrosis

Amsulostat: "73% (8/11) of evaluable patients achieved TSS50 at 24 weeks of treatment or beyond"; Myelofibrosis (Syntara) - SNT-5505 Interim Data Update

P2a data • Hematological Malignancies • Myelofibrosis • Oncology

Quarterly Shareholder Report | June 2025 (Syntara Press Release) - "Phase 2 study of amsulostat in MF:...The ongoing trial has enrolled a total of 16 patients, of which 11 reached the standard 24-week assessment mark. Of these, 8 continued to 38 weeks, and 5 have completed the full 52 weeks, with three remaining patients expected to conclude treatment in Q3 2025. Final results will be published subsequently....Syntara intends to engage with the FDA in Q3 2025 to discuss the findings to date and the design for a pivotal Phase 2c/3 trial."

FDA event • Trial status • Myelofibrosis

Quarterly Shareholder Report | June 2025 (Syntara Press Release) - "The net cash outflows in operating activities during the quarter was $3.74 million, compared with $3.49 million for the previous quarter to 31 March 2025. R&D ($2.49 million) and staff costs ($1.35 million) totalling $3.84 million represented 93% of the Company’s total net operating cash outflows. Of the $2.49 million direct R&D expenditure the majority was represented by expenditure on the company’s ongoing major clinical programs: the Phase 2 clinical trial in MF;..."

Commercial • Myelofibrosis

Initiation of Phase 1b/2 AZALOX clinical trial of amsulostat in second blood cancer indication (Syntara Press Release) - "Syntara Limited...is pleased to report initiation of AZALOX, a Phase 1b/2 multi-centre study evaluating amsulostat (SNT-5505) in combination with 5-Azacitidine for the treatment of high-risk Myelodysplastic Neoplasms (MDS) and Chronic Myelomonocytic Leukemia (CMML). The study commenced at University Medicine Mannheim (UMM), Germany, the first of nine planned centres expected to enrol patients under the German MDS Study Group."

Trial status • Chronic Myelomonocytic Leukemia • Myelodysplastic Syndrome

WHO grants official INN for Syntara’s clinical development asset SNT-5505: amsulostat (Syntara Press Release) - "Syntara Limited...announces that the World Health Organization (WHO) has formally granted the International Non-Proprietary Name (INN) of amsulostat to its advanced clinical development asset SNT-5505...Amsulostat is an innovative oral therapy currently in clinical development for myelofibrosis (MF)..."

Regulatory • Myelofibrosis

A PHASE 1/2A TRIAL OF PXS-5505, A NOVEL PAN-LYSYL OXIDASE INHIBITOR, IN PATIENTS WITH ADVANCED MYELOFIBROSIS (EHA 2025) - P1/2 | "PXS-5505 is a novel pan-lysyl oxidase inhibitor designed to exert an anti-fibrotic mode of action by preventing the cross-linking of collagen and elastin.PXS5505-MF-101 (NCT04676529) is a multi-center phase 1/2a study of PXS-5505 in MF patients (pts) which included a dose escalation phase (DEP), a cohort expansion phase (CEP) and an Add-on phase (AOP)...In the ongoing AOP, PXS-5505 200 mg BID is given in addition to ruxolitinib (RUX) over 52 weeks to assess safety and tolerability and determine the impact of PXS-5505 on disease-related parameters... Data from this current AOP using a combination of PXS-5505 and RUX in advanced MF will provide insight into the existing safety profile of PXS-5505 and help identify further indicators of efficacy, including when used in addition to RUX. This evidence will be used to inform clinical and regulatory discussions on the further development of PXS-5505 in MF."

Clinical • Metastases • P1/2 data • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Thrombocytopenia • ASXL1 • IDH1 • IDH2 • JAK2 • LOX • SRSF2 • U2AF1

New positive interim data in Phase 2 study of SNT-5505 in myelofibrosis (Syntara Press Release) - P1/2a | N=43 | NCT04676529 | Sponsor: Syntara | "This data will be presented at the European Hematology Association (EHA) Conference on Sunday 15 June 2025....73% (8/11) of evaluable patients achieved TSS50 at 24 weeks of treatment or beyond. 44% (4/9) of evaluable patients achieved a spleen volume reduction (SVR) of 25% at Week 24 or beyond. Notably there were no increases in dosage of concomitant RUX that might otherwise explain the impact of SNT-5505 on spleen volume. The continued improvement in patient symptoms and spleen volume is a novel finding that differentiates SNT-5505 from MF drugs on market and in later stages of development. It highlights the potential of SNT-5505 to be used in combination with JAK inhibitors to change the long-term outcomes for MF patients....SNT-5505, in combination with a stable dose of RUX, was safe and well tolerated with no treatment related serious adverse events (SAEs) attributed to SNT-5505."

P2a data • Myelofibrosis

SNT-5505 awarded US FDA Fast Track designation (Syntara Press Release) - "Syntara Limited...announces that its lead candidate, SNT-5505, has been granted Fast Track designation by the US Food and Drug Administration (FDA) for the treatment of myelofibrosis in patients with an inadequate response to JAK inhibitor therapy....With the published and peer reviewed pre-clinical and clinical data, as well as presentations at preeminent hematology meetings, there is a growing body of evidence supporting SNT-5505....Syntara continues to advance SNT-5505 through its Phase 2 clinical trial, with additional interim data to be presented at the European Hematology Association meeting on Saturday 14 June 2025 (Sunday 15 June AEST)."

Fast track • P2 data • Myelofibrosis

Updated data from SNT-5505 myelofibrosis Phase 2 study to be presented at EHA2025 (Syntara Press Release) - "Syntara Limited...is pleased to announce that its abstract has been selected for a poster presentation at the European Hematology Association 2025 Congress (EHA2025). The presentation will contain the next data update from the ongoing Phase 2 trial evaluating SNT-5505 in combination with ruxolitinib to treat the bone marrow cancer myelofibrosis. Syntara’s abstract, titled ‘A PHASE 1/2A TRIAL OF PXS-5505, A NOVEL PAN-LYSYL OXIDASE INHIBITOR, IN PATIENTS WITH ADVANCED MYELOFIBROSIS’, will be presented in Poster Session 2 at 18:30 – 19:30 CEST, Saturday 14 June (02:30 – 03:30 AEST, Sunday 15 June)."

P1/2 data • Myelofibrosis

A phase I / IIa trial of PXS-5505, a novel pan-lysyl oxidase inhibitor, in advanced myelofibrosis. (PubMed, Haematologica) - "PXS5505-MF-101 is a multi-center phase 1/2a study of PXS-5505 in MF patients which included a dose escalation phase (DEP) and a cohort expansion phase (CEP). Over the 24-week treatment period preliminary indications of clinical efficacy, including a reduction in BM collagen, were evident. Overall, these data support continued investigation of PXS-5505."

Journal • P1/2 data • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Thrombocytopenia • LOX

Quarterly Shareholder Report | December 2024 (Syntara Press Release) - "Positive interim data in Phase 2 study of SNT-5505 in myelofibrosis:...Syntara plans to release additional interim data in the first half of 2025 and finalise results in the second half of the year. The company aims to discuss the design of a pivotal Phase 2c/3 study with the FDA after receiving 52-week data from a subset of patients in March 2025."

FDA event • P2 data • Myelofibrosis

SNT-5505: “SNT-5505 has been well tolerated with no treatment related SAEs”; Myelofibrosis (Syntara) - Phase 2 study of SNT-5505 in myelofibrosis – ASH 2024: “Improvements seen in TSS from Baseline to week 12”

P2 data • Hematological Malignancies • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

Syntara announces positive interim data in Phase 2 study of SNT-5505 in myelofibrosis (Syntara Press Release) - P1/2a | N=43 | NCT04676529 | Sponsor: Syntara | "Syntara Limited...is pleased to announce positive interim data from its ongoing Phase 2 clinical trial evaluating SNT-5505 (200 mg BID) in combination with ruxolitinib (RUX) for the treatment of myelofibrosis (MF)...Further interim data will be released in 1H 2025 and final data in 2H 2025...After receiving data from a subset of patients reaching 52 weeks of treatment by March 2025, the company intends to discuss with the FDA the trial design for a pivotal Phase 2c/3 study...At Week 12 – 46% (6/13) of evaluable patients achieved a ≥50% reduction in Myelofibrosis Symptom Assessment Form Total Symptom Score (TSS50), a benchmark for clinical response recognised by regulatory authorities such as the FDA...82% (9/11) of evaluable patients experienced stable or reduced spleen volume with no dosage adjustments in RUX...Professor Claire....will discuss the interim data as part of a webinar, which is being held at 2pm AEDT today..."

Clinical protocol • New P2/3 trial • P2 data • Hematological Malignancies • Myelofibrosis • Oncology

Syntara completes strongly supported placement to raise A$15m (Syntara Press Release) - "Syntara receives firm commitments to raise approximately A$15.0 million via two-tranche placement at A$0.06 per share. The funds raised will fund myelofibrosis (MF) combination clinical trials, iRBD/Parkinson’s and scar trials, MDS clinical trials, drug development, employee research costs, general working capital and capital raising costs. The Placement follows positive interim results from the Company’s Phase 2 study of SNT-5505 in MF."

Financing • Myelodysplastic Syndrome • Myelofibrosis