amsulostat (SNT-5505)

P1/2, N=43, Completed, Syntara | Active, not recruiting --> Completed

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.

P1/2, N=43, Active, not recruiting, Syntara | Recruiting --> Active, not recruiting

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.

P1/2, N=39, Recruiting, Pharmaxis

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.

P1/2, N=39, Recruiting, Pharmaxis | N=24 --> 39

The lysyl oxidase family represents a promising target in stromal targeting of solid tumors due to the importance of this family in crosslinking and stabilizing fibrillar collagens and its known role in tumor desmoplasia. PXS-5505 is orally bioavailable, safe and effective at inhibiting lysyl oxidase activity in tissues. 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.

P1b/2, N=0, Withdrawn, University of Rochester | N=48 --> 0 | Recruiting --> Withdrawn

Mechanistically, P+A effects on the erythropoiesis required direct contact of HSPCs with BM stroma components including MSC and extracellular matrix and depended on integrin signaling. Conclusions These results lay out a strong pre-clinical rationale for treatment efficacy of PXS-5505 + 5-Azacytidine especially for anemic MN.

PXS5505-MF-101 is an ongoing, multi-center, open-label phase 1/2a study evaluating the safety and tolerability of PXS-5505 in patients with primary, post-polycythemia vera (PV) or post-essential thrombocythemia (ET) myelofibrosis (NCT04676529)...Eligible patients must have PMF or post-ET/PV MF of intermediate/high risk, relapsed/refractory, intolerant or not eligible to available JAK inhibitors (ruxolitinib, febratinib), including those with severe thrombocytopenia, and requiring therapy for symptomatic disease... These findings indicate that excellent targeted LOX and LOXL2 inhibition is being achieved at the 200mg BID level which has been selected as the recommended dose for the currently ongoing expansion phase with no dose limiting toxicity seen.