amsulostat (SNT-5505) / Syntara - LARVOL DELTA

Syntara Limited has secured an A$4.7 million Research and Development Tax Incentive refund from the Australian Government for eligible activities undertaken in the 2026 financial year (TipRanks) - "The incentive, which returns a significant proportion of qualifying R&D expenditure, provides a non-dilutive capital injection that helps sustain the company’s clinical programs without issuing new equity. The funding strengthens Syntara’s capacity to progress its pipeline of drug candidates...including the further development of amsulostat for myelofibrosis and myelodysplastic syndrome."

Financing • Myelodysplastic Syndrome • Myelofibrosis

Structure-guided computational identification of novel competitive inhibitors targeting the human LOXL2 active site | Poster Board #1318 (ACS-Fall 2026) - "A series of novel inhibitors was developed using the scaffolds of SNT-5382, PXS-5505, and PAT-1251 as structural baselines. Superior binding affinities and Induced Fit Scores, relative to existing benchmarks, were demonstrated through computational validation of specific scaffold modifications. A translational path for the development of high-affinity inhibitors designed to attenuate fibrosis across varying disease severities is provided by these findings."

Fibrosis • Immunology

Structure-guided computational identification of novel competitive inhibitors targeting the human LOXL2 active site | Poster Board #1738 (ACS-Fall 2026) - "A series of novel inhibitors was developed using the scaffolds of SNT-5382, PXS-5505, and PAT-1251 as structural baselines. Superior binding affinities and Induced Fit Scores, relative to existing benchmarks, were demonstrated through computational validation of specific scaffold modifications. A translational path for the development of high-affinity inhibitors designed to attenuate fibrosis across varying disease severities is provided by these findings."

Fibrosis • Immunology

Syntara Limited…is pleased to announce completion of the first dose-escalation cohort in the Phase 1b component of the AZALOX clinical trial evaluating amsulostat, in combination with the hypomethylating agent 5-Azacitidine (5-AZA) in patients with high-risk Myelodysplastic Neoplasms (MDS) and Chronic Myelomonocytic Leukaemia (CMML) (Syntara Press Release) - "Following review of the safety data from the first cohort, the independent Drug Safety Monitoring Board (DSMB) has approved escalation to the final Phase 1b dose cohort, in which patients will receive amsulostat at 200 mg twice daily in combination with 5-AZA.The initial cohort evaluated amsulostat at 150 mg twice daily in combination with 5-AZA. No dose-limiting toxicities were observed and no new adverse events attributable to amsulostat were reported....Preliminary results from the completed Phase 1b dose-escalation component are expected during Q4 CY26. All 10 participating clinical sites in Germany have now been initiated and are open for recruitment."

P1 data • Trial status • Chronic Myelomonocytic Leukemia • Myelodysplastic Syndrome

Amsulostat in pancreatic cancer Phase 1/2 clinical trial in collaboration with the Garyan funded by MREF (Syntara Press Release) - "In January, the Garvan Institute of Medical Research was awarded a $3 million grant under the Australian Government's Medical Research Future Fund (MRFF) to conduct two multicentre clinical studies in advanced pancreatic cancer. One of these studies will evaluate Syntara's investigational anti-fibrotic LOX inhibitor amsulostat in combination with standard-of-care chemotherapy....Recruitment is expected to commence in 2H 2026 across leading NSW cancer centres."

Financing • New trial • Pancreatic Cancer

Syntara Limited…is pleased to announce that it has received positive feedback from the U.S. Food and Drug Administration (FDA) following a constructive in person Type C meeting regarding the planned Phase 2b clinical trial of its lead candidate, amsulostat, for the treatment of patients with myelofibrosis (MF) who have had an inadequate response to standard of care. (Syntara Press Release) - "Following a review of amsulostat’s development to date, the FDA supported the proposed Phase 2b study design and provided guidance on the detail of the study and overall development pathway for amsulostat....The Phase 2b study will be a double blind, placebo-controlled study of amsulostat added to standard of care (JAK inhibition) for patients who have had an inadequate response....Subject to final protocol review, the number of patients to be studied is expected to be approximately 100."

FDA event • Myelofibrosis

Matrix structure and microenvironment dynamics correlate with chemotherapy response in ovarian cancer. (PubMed, iScience) - "Carboplatin/paclitaxel treatment triggered dynamic transcriptional changes in immune and ECM-related pathways, and analyses of the ECM structure revealed modifications in the chemo-sensitive tumors. Moreover, treatment with PXS-5505 before chemotherapy enhanced the therapeutic response. We conclude that pretreatment with ECM targeting agents may improve chemotherapy efficacy by altering ECM structure and immune responses."

Journal • Platinum sensitive • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor

LOX Inhibition Disrupts a Collagen-Integrin-MYC Axis to Suppress Progression of Invasive Lobular Carcinoma. (PubMed, Cancer Res) - "Collagen fiber density/alignment and MYC/AP-1 gene signatures served as pharmacodynamic readouts of drug activity. These data uncover a tractable ECM-integrin-MYC axis in ILC and nominate PXS-5505, alone or with endocrine therapy, for window of opportunity trials in this understudied breast cancer subtype."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CDH1 • ITGB5 • LOX

Amsulostat in pancreatic cancer Phase 1/2 clinical trial in collaboration with the Garvan, funded by MRFF (Syntara Press Release) - "The Garvan Institute of Medical Research secures $3 million MRFF grant funding for two multicentre studies in advanced pancreatic cancer, including one testing Syntara’s amsulostat (SNT-5505) with standard-ofcare chemotherapy....Under the collaboration, Syntara will supply the drug in addition to scientific and clinical expertise to support the program....The MRFF-funded studies are expected to commence recruitment in mid-2026, enrolling patients with advanced pancreatic cancer across leading cancer centres in New South Wale....Amsulostat studies in MDS...due to report data later this year."

Clinical data • Financing • New trial • Myelodysplastic Syndrome • Pancreatic Cancer

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