SNT-5505 / Syntara - LARVOL DELTA

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

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

Syntara Announces Two-Tranche Placement to Raise A$5m (Syntara) - "Clinical stage drug development company Syntara Ltd...today announces that it has received firm commitments from institutional and high net worth investors to raise approximately A$5.0m by way of a two-tranche institutional placement comprising: The issue of approximately 96.4 million fully paid ordinary shares at A$0.028 per share, to raise approximately A$2.7 million via a placement (Tranche 1); and The issue of approximately 82.1 million fully paid ordinary shares at A$0.028 per share, to raise another approximately A$2.3 million....The funds raised from the Placement will provide certainty of funding towards the Phase 2 clinical study of Syntara’s lead drug asset SNT-5505 in MF in combination with standard of care (ruxolitinib), further Phase 2 clinical studies in MDS, skin scarring and iRBD/Parkinson’s disease, in addition to general working capital purposes and capital raising costs."

Financing • Myelofibrosis

Syntara CEO to Present at Life Sciences Webinar (Nasdaq) - "Syntara Limited has announced its CEO, Mr Gary Phillips, will present at the ‘Hidden Gems in Life Sciences’ Webinar, inviting shareholders and interested parties to the virtual event scheduled for June 13. The presentation will focus on the company’s advancements, including their lead drug candidate SNT-5505 for myelofibrosis, which has received FDA Orphan Drug Designation."

Clinical • Hematological Malignancies • Myelofibrosis • Oncology

Syntara reaches 50% patient recruitment for lead asset SNT-5505 Phase 2 trial; interim results expected in December (Proactiveinvestors) - "Syntara...has hit another milestone in the clinical development of its lead asset SNT-5505, achieving 50% recruitment of patients for a Phase 2 trial evaluating SNT-5505, in combination with JAK inhibitor ruxolitinib, treating the bone marrow cancer myelofibrosis. The eighth patient in the 15-patient trial was dosed earlier this week, in keeping with the company’s schedule with recruitment expected to be complete by the end of the first half of the year. Syntara expects to report its six-month interim results at the American Society of Hematology (ASH) Annual Meeting and Exposition in December, which will inform study design with the FDA moving forward - the full 12-month data set will be available in mid-2025."

Enrollment status • P2a data • Myelofibrosis

Syntara adds new blood cancer indication to SNT-5505 development plan following government grant (Investing.com) - "Syntara Ltd...will undertake a new Phase 2 trial evaluating the combination treatment of SNT-5505 and chemotherapy in patients with low and intermediate risk myelodysplastic syndromes (MDS), a group of blood cancer which affect blood cell production in bone marrow. The trial will begin later this year, headed by the University of Newcastle’s Associate Professor Anoop Enjeti under the clinical framework of the Australasian Leukaemia and Lymphoma Group (ALLG)."

New P2 trial • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

A novel first-in-class anti-fibrotic blunts tumour desmoplasia, rewires stromal signalling and augments gemcitabine response and survival in pancreatic cancer (LCC 2024) - "The lysyl oxidase family represents a promising target in stromal targeting of solid tumours due to the importance of this family in crosslinking and stabilizing fibrillar collagens and its known role in tumour desmoplasia. PXS-5505 is orally bioavailable, safe and effective at inhibiting lysyl oxidase activity in tissues, and has cleared Phase I safety trials thereby enabling Phase II trials. Our findings present the rationale for progression of a pan-lysyl oxidase inhibitor aimed at eliciting a reduction in stromal matrix to potentiate chemotherapy in pancreatic ductal adenocarcinoma (1)."

Stroma • Fibrosis • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

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=39 | Recruiting | Sponsor: Pharmaxis

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

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 • Hematological Disorders • Immunology • Infectious Disease • Myelofibrosis • Myeloproliferative Neoplasm • Myocardial Infarction • Neutropenia • Septic Shock • Thrombocytopenia • Thrombocytosis • Urticaria • LOX

PXS-5505: Safety and efficacy monotherapy data from part 2a of P1/2a trial (NCT04676529) for myelofibrosis at ASH (December 9-12, 2023) (Syntara) - Corporate Presentation: Completion of recruitment of part 2a of P1/2a trial for myelofibrosis in H1 2024; Initiation of P1c trial for MDS in H1 2024; Interim data from part 2a of P1/2a trial in combination with ruxolitinib for myelofibrosis in H2 2024; Safety and efficacy data from part 2a of P1/2a trial in combination with ruxolitinib for myelofibrosis at ASH (December 9-12, 2024)

Enrollment status • New P1 trial • P2a data • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

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=39 | Recruiting | Sponsor: Pharmaxis | N=24 ➔ 39

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