Syntara Limited (ASX:SNT), a clinical-stage drug development company, 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). The interim results suggest that SNT-5505 has potential as a breakthrough therapy for MF and are being presented today at the 66th American Society of Hematology annual meeting (ASH). Further interim data will be released in 1H 2025 and final data in 2H 2025.
The interim data suggests that SNT-5505 compares favourably thus far to other drugs being trialled for MF demonstrating excellent tolerability and improvements in symptoms and spleen volume that increase over time.
This is in line with the anticipated disease modifying effects of a pan-LOX inhibitor that works to improve the bone marrow microenvironment and inhibits a growth factor receptor (PDGFR-) that regulates cell expansion and division. This is encouraging, particularly given the trial patient population with a suboptimal response to existing standard of care and a high disease burden. Despite long prior RUX usage, most patients had high symptom scores and enlarged spleens at their entry into the trial.
Highlights:
- At 12 weeks of treatment, 46% of evaluable patients achieved a 50% improvement in Total Symptom Score (TSS50) which improved to 80% at 38 weeks of treatment. TSS50 is a standard efficacy endpoint used as the primary endpoint in MF clinical trials.
- 30% of evaluable patients achieved a spleen volume reduction (SVR) of 25% and 20% achieved an SVR of 35%. Both levels are considered clinically meaningful, with SVR35 a typical endpoint used in MF clinical trials.
- Patient symptoms and spleen volume continued to improve over the duration of the interim data which 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 is safe & well tolerated with no treatment related serious adverse events noted at this interim stage – viewed together with the excellent safety profile seen in the earlier monotherapy study this is emerging as another key differentiator to MF drugs on the market and in development.
- 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. Concurrently, the company will also engage with potential global and regional partners.
The open-label study, which aims to assess the safety and efficacy of SNT-5505 over 52 weeks, has enrolled 16 patients with intermediate-2 or high-risk MF to date, with data extracted for use at ASH on 14 November 2024:
- 13 patients had reached 12-week visit
- 8 patients had reached 24-week visit
- 5 patients had reached 38-week visit
Patients enrolled had a median RUX exposure of 3.2 years and a median baseline symptom score of 23, indicative of a high disease burden.
Professor Claire Harrison, Professor of myeloproliferative neoplasms at Guy’s and St Thomas’ NHS Foundation Trust, commented:
“This interim data confirms the excellent safety profile of SNT-5505 and also suggests that the mechanism of SNT-5505 may exert a long-term effect on the disease, with both symptoms and spleen volume continuing to improve as we now see patients on drug for 9 months. This hasn’t been seen before with this class of drug and holds potential for real long-term benefits for MF patients. I look forward to seeing the data mature in the coming months to confirm these important Syntara announces positive interim data in Phase 2 study of SNT-5505 in myelofibrosisearly findings.”
