Ann: Quarterly Activities Report, page-5

Hi all and thanks for the commentary.

I have looked at this announcement in detail and only going to comment on the science. The rest I leave it fellow Hot Copperites to explain.

First the laypersons version. Some ASX announcement are intense. Including this one.
Then the advanced version .

1 .Myelofibrosis Treatment (SNT-5505)

This experimental drug aims to treat a bone marrow cancer that causes scarring (fibrosis) and blood problems. The latest trial results (showing good safety and early signs it works) will be presented at a major European blood cancer conference in June 2025. Previous tests showed it could reduce harmful scar tissue in bone marrow.

2. New Scar Treatment (SNT-9465)

A next-gen anti-scar gel being developed for raised, thick scars (hypertrophic/keloid types). Unlike current painful treatments like steroid injections, this daily-use cream aims to remodel scars to look/feel more like normal skin. Human safety tests start mid-2025.

3. Scar Science Breakthrough

Advanced imaging showed their first scar cream (SNT-6302) actually helps old scars:

Blood flow improves to match normal skin

Scar structure becomes less rigid (like healthy skin)

Collagen levels drop (excess collagen causes thick scars)

4. Sleep Disorder Study (SNT-4728)

Testing a drug for people with violent dream behaviors (iRBD), which often leads to Parkinson's disease. This UK trial will check if treatment improves sleep quality and reduces brain inflammation (a Parkinson's trigger).


The advanced version


Results expected SNT-5505 in Myelofibrosis (MF)

Mechanism of Action: Pan-lysyl oxidase (LOX) inhibitor targeting LOX, LOXL1, LOXL2, LOXL3, and LOXL4 enzymes. LOX enzymes catalyze collagen/elastin cross-linking, driving fibrotic extracellular matrix (ECM) deposition in bone marrow. By inhibiting LOX, SNT-5505 reduces ECM stiffness, improving hematopoietic niche function and alleviating cytopenias.

Phase 2a Trial Design:

Population: Intermediate-2/high-risk MF patients (n=16) with suboptimal response to ruxolitinib (JAK inhibitor), median symptom score 23 (MF-SAF TSS).

Regimen: SNT-5505 (200 mg BID) + stable ruxolitinib dose for 52 weeks.early 2026.

Endpoints:

Primary: Safety/tolerability.

Secondary:

≥50% reduction in Total Symptom Score (TSS50)

Spleen Volume Reduction (SVR35/SVR25) via MRI/CT

Biomarker correlations (e.g., LOX activity, collagen turnover).



Interim Data (ASH 2024):

TSS50: 46% (6/13) at Week 12 → 80% (4/5) at Week 38.

SVR:

30% achieved SVR25 (≥25% reduction)

20% achieved SVR35 (≥35% reduction) by Week 38.

Safety: No treatment-related SAEs; stable hematologic parameters (hemoglobin, platelets).

Differentiation: Symptom/spleen improvements continued beyond 9 months, unlike other LOX/JAK inhibitors.


Scientific Significance:

Bone Marrow Remodeling: Reduced collagen cross-linking may reverse fibrosis, enabling hematopoiesis.

Synergy with Ruxolitinib: LOX inhibition complements JAK-STAT pathway blockade, addressing both inflammation and fibrosis.

2. SNT-9465 in Hypertrophic/Keloid Scars

Mechanism: Next-generation topical pan-LOX inhibitor (improved formulation vs. SNT-6302) targeting dermal fibrosis.

Phase 1a/b Trial Design:

Phase 1a: Dose-escalation in healthy volunteers (Q2 2025) to assess safety/pharmacokinetics.

Phase 1b: Open-label in hypertrophic scars (<2 years old) to evaluate cosmetic/physical improvements (H1 2026)

Preclinical Rationale:

LOX Inhibition: Reduces collagen density, normalizes ECM architecture.

Tolerability: Daily dosing feasible vs. thrice-weekly SNT-63021.



3. SNT-6302 in Established Scars

SOLARIA2 Phase 1c Data:

Imaging: Optical Coherence Tomography (OCT) showed vascular/structural normalization in treated scars vs. placebo (p=0.03)

Biochemistry: Collagen content ↓ (p<0.01) after 3 months.

Implication: Pan-LOX inhibition reverses mature scar pathology, a first-in-class achievement.


4. SNT-4728 in iRBD (Prodromal Parkinson’s)

Phase 2a Trial:

Population: 40 iRBD patients (high α-synucleinopathy risk)

Endpoints: Sleep quality (polysomnography), motor function (MDS-UPDRS), neuroinflammation (PET imaging)1.

Timeline: Recruitment completion by late 2025; data H1 20261.

4. Biomarker and Imaging Correlates.

MF: LOX enzyme activity, collagen degradation markers (e.g., PRO-C3), and JAK2 V617F burden.

Scars: OCT-based vascular density, collagen fibril organization.

Regulatory Pathways

SNT-5505: Potential Breakthrough Therapy Designation (FDA) if SVR35/TSS50 improvements persist.

SNT-9465: Phase 1b data to support IND filing for global Phase 2


Competitive Landscape

MF: Competitors include momelotinib (JAK1/2/ACVR1 inhibitor) and navitoclax (BCL-2 inhibitor), but none target LOX-driven fibrosis.

Scars: No approved anti-fibrotic topicals; SNT-6302/9465 address unmet need for non-invasive remodeling1.

Risks

MF: Small cohort size (n=16) limits statistical power; final data (H2 2025) needed for validation.

Scars: Phase 1b efficacy signals required to de-risk Phase 2.


Key Catalysts:

SNT-5505: Updated interim data (H1 2025); EHA 2025 presentation (June 14–15)1.

SNT-9465: Phase 1a safety readout (H2 2025)


What can I say ? First in class drug, better than the rest.

Don't sell unless you have a genuine reason.


Kpax