Moderate to Severe Hidradenitis Suppurativa (HS)

There is a huge need for oral targeted therapies and Phoenicis is addressing this need. Recent data highlights the role of P2X7, IL-1β, other cytokines in HS

Oral P2X7 antagonist prevents activation of IL-1β, other cytokines in HS. Phase 2 clinical PoC started in 2021, top line results will be available in 2022.

Hidradenitis suppurativa is a large orphan indication with substantial unmet need

~250k patients across the US and EU with front-line biologic failure(1)

U.S. prevalence

~200K patients with moderate-to-severe HS
~100k patients with front-line biologic failure

EU prevalence

~280K patients with moderate-to-severe HS
~140k patients with front-line biologic failure

Phase 1-2 Clinical Trial for PTM-001 Oral P2X7 Antagonist is Open and Enrolling Patients

Drug candidate and target are substantially de-risked (licensed from AstraZeneca).

Comprehensive and complete non-clinical safety assessment package and clinical safety data in >600 patients and healthy volunteers

Chronic GLP toxicology complete: 6-month rat, 6-month dog, 12-month non-human primate and reproductive toxicity studies.

• AEs were mostly GI and transient in nature
• 12-Month cynomolgus monkey NOEL was 25 mg/kg/ day.
• PTM-001 is moderate inhibitor of CYP3A4: drug-drug interaction study planned

Excellent drug-like characteristics – potent, selective, established safety profile

• Small molecule drug with once daily oral dosing
• Human P2X7 IC50 = 1-13nM with 1000x fold selectivity versus P2X family members and >100x fold selective for other targets

Initial GMP campaign complete

• 30 Kg drug substance requalified and released with additional 50 Kg API available
• Drug product (tablet) manufactured and released for Hidradenitis suppurativa

Study description: 12-week Double-blind, Placebo- controlled, randomized trial with q4 monthly assessments

Patient population: 50 patients with moderate to severe HS

Dosing and administration: PTM-001 400 mg or placebo once daily

Primary outcome: 50% reduction in IL-1β levels in peri- lesional skin biopsies

Secondary objectives:

Reduction in other pro-inflammatory tissue cytokines and serum amyloid A

Reduction in pain on 10-point visual analog scale

Change from Baseline in disease severity scales

Quality of life (DLQI)

AN count of 2 or less at each visit (total count of abscesses and inflammatory nodules)

PTM-001 Target Product Profile

Product Description
P2X7 antagonist

Age
Adolescence through adulthood

Route of administration
Oral

Dose
Chronic administration of 400 mg once daily

Co-medication
N/A

Mechanism of action
Pleiotropic inhibition of relevant cytokine pathways including expression of IL-1β and other relevant cytokines related to HS

Mechanistic endpoints

• 50% reduction in IL-1β levels in peri-lesional skin biopsies
• AN count of 2 or less at each visit (total count of abscesses and inflammatory nodules)

Registration endpoints and claims

• Reduction from baseline in 10-point visual pain score
• Assessment of HS Quality of Life using DLQI
• Change from baseline in the HiSCR, International Hidradenitis Suppurativa Severity Score System (IHS4) or Sartorius Scale
• Achieve an AN count of 2 or less at each visit

Safety endpoints
Safe and well tolerated (local and systemic)

Product characteristics
100 mg Tablets