The main components of the SnPPIX thermoresponsive injectable formulation (SnPPIX-TIF) include: 1) Tin Protoporphyrin IX (SnPPIX): The active therapeutic agent that functions as an immunomodulatory, host-directed therapy. 2) Poloxamer: A temperature-sensitive polymer that enables the formulation to remain liquid at room temperature and transition into a gel at body temperature. 3) Poly(acrylic acid): A polymer integrated with the poloxamer to form the structural microparticulate carrier matrix that encapsulates the drug and controls its release.

Not provided

Histopathological evaluation revealed no TEAE safety concerns in preclinical animal studies.

1) Mean bacterial colony-forming unit (CFU) loads in the IM SnPPIX-TIF-treated cohort were 5.8 logs. This was significantly lower (p< 0.0001) than the average values recorded for untreated infected animals (7.2 logs) and placebo-TIF treated animals (7.4 logs).

Preclinical histopathological evaluations identified no treatment-related safety concerns. Furthermore, once-weekly intramuscular administration of the SnPPIX-TIF formulation demonstrated antimicrobial efficacy comparable to that of daily intramuscular injections of the aqueous SnPPIX formulation (SnPPIX-WBS), achieving a 6.0-log reduction in bacterial burden. Overall, treatment with SnPPIX-TIF reduced pulmonary bacterial loads by more than 1 log, supporting its potential as a less frequent dosing strategy without compromising therapeutic efficacy.

Not provided

Not provided

1) ULTRA-TURRAX Tube Drive Control Disperser (IKA Works, Inc., Wilmington, NC, USA) 2) 0.22 µm Whatman cellulose acetate membrane syringe filter (Cytiva, MA, USA) 3) Biosafety Cabinet 4) Refrigerator

The thermoresponsive injectable formulation can be manufactured using a scalable cold-process method, whereby poloxamer 407 and sodium polyacrylate are dissolved under controlled low-temperature conditions prior to direct incorporation of the active pharmaceutical ingredient. Critical quality attributes include polymer concentration, gelation temperature, viscosity, syringeability, injectability, particle size distribution, and drug content uniformity. Sterile manufacturing and aseptic filtration are essential for parenteral administration. Process controls should ensure batch-to-batch consist

1) Differential Scanning Calorimetry (DSC) 2) Rotational rheometers 3) High-Performance Liquid Chromatography (HPLC) or UPLC 4) Dynamic Light Scattering (DLS) 5) UV-Vis spectrophotometry

No proprietary excipient used

1) Poloxamer 2) Poly(acrylic acid)

Not provided

Not provided

• Biodegradable

The encapsulation of the drug within the thermoresponsive polymeric carrier notably delays and improves in vivo drug release and absorption. The prolonged release profile significantly enhances overall bioavailability over 24 hours compared to conventional water-based solutions, demonstrating a higher AUC0-24 (575.10 - 38.51 mcg h/mL), maximum plasma concentration (Cmax=46.50-11.80 mcg/mL), time to peak concentration (tmax=1 h), and an extended half-life (t1/2=2.77 h).

This technology is intended to be adminstered by intramuscular route (IM) through 25G hypodermic needle equipped with a 1 mL syringe.

Not provided

Not provided