PNB-001 Cancer Program

Scientific Overview

Key Points

  • Core technology relies on bacteriophage and elements of AAV – Not associated with safety concerns/immune response neutralization of standard gene therapy vectors; straightforward regulatory process, precedent for favorable toxicity profile in the phage antibiotic space
  • Ligand-directed targeting feasible to any organ or tissue
  • Multiple ongoing applications of platform technology
  • COVID-19 program is leveraging novel approaches for vaccination
  • Manufacturing highlights – quantity (high yield, high purity), speed (time), efficient (COGS), flexible, aerosol formulation, no cold chain, long term stability

RGD4C

Lead tumor-targeting ligand, is well-characterized and ready for the clinic

Dosing Flexibility

Various dosing strategies have been successfully employed in pre-clinical models (mice, rats, dogs, rhesus), including single and repeat administrations and combinatorial approaches

Tumor Necrosis Factor (TNF⍺)

Transgene is well-characterized, and provides strong platform proof-of-concept

Specific Tumor Targeting

AAVP can be customized to target a variety of difficult to treat cancers. Ability to cross the blood brain barrier points to possible use in brain tumors

Safety & Efficacy

Successfully demonstrated at therapeutic doses in treating spontaneous tumors in prior dog study (Paoloni et al. PLoS One 2009)

AAVP Platform Applicable Beyond Cancer

Vaccine program starting with COVID-19 (PNB-V01)

Exploiting Targeted Ligands Drives Specificity to Tumor Tissues

  • Systemic accessibility via the circulation – does not depend on locoregional administration to deliver construct and achieve specificity and targeted gene expression
  • Proprietary ligand mapping and selection systems allows ligand-directed gene expression
  • Receptor-mediated internalization – upon delivery, immediate uptake
  • Environment-dependent receptor modifications increase specificity in vivo
  • PNB-001 relies on RGD4C ligand to selectively and specifically target tumor vasculature
  • The therapy is intended to be systematically administered, with no need for local delivery to achieve tumor localization
  • Able to package any gene payload into construct, and express specifically and exclusively at intended target – Multiple data has been generated evidencing that the effector transgene was expressed in tumor cells, but not in normal cells
  • Data confirms acceptable tolerability as well as selective trafficking of the vector (i.e. transport to and internalization by tumor associated vascular cells, but not to normal tissues) in tumor-bearing animals
  • Effector transgene expression (HSVtk followed by GCV treatment or TNFα) in rodent studies was associated with suppression of tumor growth, a key correlate with antitumor activity

PNB-V01 COVID-19 Vaccine Development Program

Ligand-Directed Phage Aerosol Delivery

  • Modified viral capsid to carry a ligand that promotes lung transcytosis, enhancing immune responses to the virus in a substantial way
  • Modified the phage genome & capsid by introducing genetic elements from adeno-associated virus – but not the genes that encode the AAV capsid – to deliver a viral protein transgene or protein fragments that induce a neutralizing immune response
  • Ease of manufacturing of bacteriophage under GMP conditions
  • Rapidly adaptable to account for variants that may evade existing vaccines
  • Aerosol formulation, no cold chain, rapid and wide distribution worldwide
  • Ability to rapidly “swap” targeting motifs and gene/epitope coding sequences providing flexibility to design a variety of vaccination strategies

New Ligand-directed Pulmonary Delivery System Initially Directed Towards Aerosol Vaccination

Identification of Safe and Effective Method of Delivering Medicines to the Lungs

  • First steps in leading to a safe and effective aerosol phage-based vaccines for human applications against multiple diseases
  • Proof-of-concept research and development focused on prevention of COVID-19 and other respiratory infections
  • Phage-based vaccines trigger a sustained and protective immune response, without any detectable toxic effects in the experimental
    models tested
  • Highly stable under harsh environmental conditions
  • Large-scale production is cost-effective compared with other vaccine strategies – does not need to be kept frozen in a strict cold-chain
  • Phage protein particles have already been safely used in clinics for almost a century to treat patients with bacterial infections – safe and approved for use in humans