Abstract

PheLiz™ represents a paradigm shift in antibiotic development – a novel combinatorial peptide mixture that defeats antimicrobial resistance through multiple mechanisms while maintaining broad-spectrum efficacy against critical priority pathogens.

Background

Antimicrobial resistance (AMR) poses one of the greatest threats to global health, causing million of deaths annually. The World Bank estimates AMR could result in $1-3.4 trillion GDP losses annually by 2030[1]. Current antibiotic development has stagnated, with no new drugs effective against carbapenem-resistant Acinetobacter baumannii (CRAB) or carbapenem-resistant Enterobacterales (CRE) – the WHO’s highest priority pathogens[2]. The global antibiotics market, valued at $23 billion in 2024 and projected to reach $30 billion by 2033[3], desperately needs innovative solutions that circumvent traditional resistance mechanisms.

Key Competitors:

  • Traditional antibiotics (carbapenems, β-lactams): Face increasing resistance, limited efficacy
  • Existing antimicrobial peptides: High production costs, single-target vulnerability
  • Novel antibiotic classes: Slow development, narrow spectrum, high failure rates

[1] https://www.genevaenvironmentnetwork.org/resources/updates/antimicrobial-resistance-and-the-environment/

[2] https://www.who.int/publications/i/item/9789240093461

[3] https://www.precedenceresearch.com/oral-antibiotics-market

Our Innovation

PheLiz is a breakthrough combinatorial peptide mixture consisting of short (5-amino acid) peptides composed of only lysine (cationic) and phenylalanine (hydrophobic), enhanced with N-terminal fatty acids. This elegant simplicity generates several sequences that creates an unprecedented multi-target antimicrobial arsenal.

Major Advantages over Existing Solutions:

  • Resistance-Proof Design: Targets bacterial membranes rather than specific proteins, making resistance development nearly impossible as membrane mutations would compromise bacterial viability
  • Rapid pathogen Killing Kinetics: Achieves bacterial membrane disruption within minutes versus hours for traditional antibiotics, reducing treatment duration
  • Broad-Spectrum Efficacy: Active against all WHO critical priority pathogens including CRAB and CRE with MIC values of 12-25 μg/mL and great safety and efficacy results in mouse model.
  • Manufacturing Efficiency: Simple two-amino acid synthesis reduces production costscompared to complex peptide therapeutics
  • Enhanced Stability: Fatty acid conjugation provides protease resistance and extended half-life, improving bioavailability

The global market for carbapenem-resistant bacterial infections represents a $5.7 billion opportunity⁹, with PheLiz positioned to capture significant market share through its unique resistance-resilient profile and cost-effective manufacturing.

Technology

PheLiz employs innovative solid-phase combinatorial synthesis using only two building blocks – lysine and phenylalanine – with palmitic acid N-terminal modification. The technology generates a controlled mixture of 5-mer peptides, each targeting bacterial membranes through electrostatic interaction (lysine) and membrane insertion (phenylalanine + fatty acid). This multi-modal mechanism prevents resistance development while maintaining potent antimicrobial activity.

Mechanism of Action:

  1. Cationic lysine residues bind to negatively charged bacterial membranes
  2. Hydrophobic phenylalanine and fatty acid components insert into membrane bilayers
  3. Membrane pore formation leads to rapid bacterial lysis
  4. Multiple peptide variants prevent adaptation and resistance evolution

Key Performance Metrics:

  • Effective against 15+ resistant bacterial strains
  • No resistance development observed after 30+ passages
  • Higher then 90% survival improvement in animal infection models
  • Acceptable safety profile with no cytotoxicity or hemolysis

Opportunity

Researchers seek an industry partner to sponsor additional R&D and advance toward clinical development. The partner will receive exclusive licensing options for the intellectual property upon successful completion of development milestones. This partnership offers entry into the high-growth antimicrobial market with a differentiated, resistance-proof technology addressing critical unmet medical needs.

Commercial Potential:

  • Market exclusivity through novel mechanism and IP protection
  • Applications across hospital-acquired infections, chronic wounds, and antibiotic-resistant sepsis
  • Regulatory pathway facilitated by FDA’s QIDP designation eligibility

Patents & Publications

PCT/IL2020/050681

Lau JZ, Kuo SH, Belo Y, Malach E, Maron B, Caraway HE, Oh MW, Zhang Y, Ismail N, Lau GW, Hayouka Z.2023.Antibacterial efficacy of an ultra-short palmitoylated random peptide mixture in mouse models of infection by carbapenem-resistant Klebsiella pneumoniae . Antimicrob Agents Chemother67:e00574-23. https://doi.org/10.1128/aac.00574-23