amsulostat (SNT-5505) / Syntara - LARVOL DELTA

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

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

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

Extracellular matrix remodelling is a targetable feature of invasive lobular carcinoma (ILC) (SABCS 2024) - "These data demonstrate that ECM remodelling is a targetable feature of ILC and suggest that the LOXi PXS-5505, a well tolerated drug provides additional benefit to standard of care endocrine therapy. Changes in fibrillar collagen and matrix-associated proteins result in decreased MYC activity, which may serve as an endpoint in a prospective window trial."

Breast Cancer • Oncology

Syntara Gains $4.56 Million to Boost Drug Development (MSN News) - "Syntara Limited has secured a substantial R&D tax incentive of $4.56 million from the Australian Government to bolster its clinical development initiatives, including the promising SNT-5505 drug for myelofibrosis. This financial boost is expected to advance Syntara’s pipeline of innovative treatments targeting various cancers..."

Financing • Myelofibrosis

Syntara Limited to Host Investor Webinar on Drug Development Progress (Business Insider) - "Syntara Limited...is set to update investors in an upcoming webinar, highlighting its promising pipeline including the lead candidate SNT-5505 for myelofibrosis."

Clinical • Myelofibrosis

Phase 2 blood cancer trial fully recruited – interim results due December 2024 (Syntara Press Release) - "Clinical stage drug development company Syntara Limited...is pleased to announce that it has completed full recruitment in its Phase 2 trial evaluating SNT-5055, in combination with ruxolitinib, treating the bone marrow cancer myelofibrosis...Syntara has reached the milestone with the 15th patient dosed yesterday and has already exceeded the minimum threshold of one month treatment for 12 patients proposed in FDA discussions for safety evaluation...Syntara expects to report interim results from the trial in late 2024, in conjunction with the American Society of Hematology (ASH) Annual Meeting. In line with the excellent safety profile observed in earlier phase 1 and phase 2 studies, no drug related dropouts nor any serious adverse reactions have been observed to date...Syntara to engage with and discuss pivotal study design with the FDA in Q1 2025, with the full 12- month data set to be available in Q3 2025."

P1/2 data • Trial status • 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 | Active, not recruiting | Sponsor: Syntara | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • Thrombocytosis

Pan-lysyl oxidase inhibition disrupts fibroinflammatory tumor stroma, rendering cholangiocarcinoma susceptible to chemotherapy. (PubMed, Hepatol Commun) - "CCA upregulates all 5 lysyl oxidase isoforms, and pan-LOX inhibition reverses tumor-induced mechanical forces associated with chemotherapy resistance to improve chemotherapeutic efficacy and reprogram antitumor immune responses. Thus, combination therapy with pan-LOX inhibition represents an innovative therapeutic strategy in CCA."

Journal • Stroma • Biliary Cancer • Cholangiocarcinoma • Fibrosis • Gastrointestinal Cancer • Oncology • Solid Tumor • LOX

New indication for Syntara lead asset SNT-5505 as German MDS study group awarded A$2.5m grant to conduct phase 2 blood cancer trial (Syntara Press Release) - "Researchers at Heidelberg University to take SNT-5505 into the clinic for the blood cancers myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) with A$2.5m funding from Deutsche Krebshilfe (German Cancer Aid). The phase 1b/2 study (AZALOX) in patients with high risk MDS and CMML will commence Q1 2025, running in parallel with the previously announced Australian phase 1c/2 study in low/intermediate risk MDS patients. 7 German specialist centres have agreed to join the study, which has been prioritised by the German MDS Study Group. The grant will cover the cost of the study and Syntara will provide SNT-5505."

Financing • New P1/2 trial • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Syntara doses first patient in bone cancer Phase 2 trial assessing SNT-5505 in combination with ruxolitinib (Investing.com) - "Syntara Ltd...has dosed the first patient in a phase two clinical trial assessing its pan-LOX inhibitor SNT-5505 in combination with kinase inhibitor ruxolitinib in patients with bone marrow cancer myelofibrosis....The company expects to complete recruitment for this cohort of patients in the first half of 2024."

Trial status • Hematological Malignancies • Myelofibrosis • Oncology