PTX_V1

PTX_V1: MUSOCAL HPV VACCINE

Infection with the human papilloma virus (HPV) is the most common sexually transmitted disease and leads to genital warts, pre-cancerous lesions and cancer. Current treatment is defined by prophylactic vaccines that have absolutely no impact for the 200 million already infected with the HPV globally. There is an unmet need to create a therapeutic that can clear the HPV infection for these patients and the development of a therapeutic vaccine is the focus of this project.

pHion Therapeutics has developed a RALA/E6-E7 mRNA vaccine (PHN_V1) that can deliver to antigen producing cells and induce a potent therapeutic CD8+ and CD4+ vaccine response. The vision for PTX_V1 is to take this therapeutic vaccination through pre-clinical studies using RALA to deliver mRNA encoding HPV antigens. Outputs are designed to provide definitive evidence of viral clearance in multiple in vivo models. Specifically, the validation of a stable RALA/E6-E7 vaccine, with evidence of HPV clearance in in vivo models for MUCOSAL HPV followed by scale-up and functionality/toxicology studies in a larger animal model. End points include robust data pack that will be used to move this technology into toxicology studies and onward to Phase-I/II clinical trials. 

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Our technology is synonymous with innovation, including the design of the RALA peptide, the first of its kind therapeutic mRNA CD8+ vaccine and the potential application of this technology beyond HPV to clear other viral infections such as HSV and SARS/MERS. We believe that the RALA/mRNA technology marks the advent of a new generation of therapeutic vaccines that could clear viral infections on a global scale. 
 

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PTX_V2

PTX_V2: CUTANEOUS HPV VACCINE

Active HPV infections exist in 42.5% of adults, aged 16-69, with 22.8% of all adults currently with a high risk genital strains associated with cervical and vaginal cancers.  For, cutaneous HPV, the prevalence is estimated to be ~50% of healthy individuals. These epidemiological numbers equate to an incidence of over 80 million individuals in the EU and US for which a prophylactic, mucosal HPV vaccine is ineffective.  Further market demand exists with ~ 200 million individuals possessing cutaneous HPV infections that would benefit from a therapeutic vaccination.

pHion Therapeutics has developed a RALA/E6-E7 mRNA vaccine (PHN_V2) that targets non-basal cell carcinoma for the therapeutic treatment of  CUTANEOUS HPV. 

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Our technology is synonymous with innovation, including the design of the RALA peptide, and the potential application of this technology beyond HPV to clear other viral infections such as HSV and SARS/MERS. We believe that the RALA/mRNA technology marks the advent of a new generation of therapeutic vaccines that could clear viral infections on a global scale. 
 

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PTX_V3

PTX_V3: PROSTATE CANCER VACCINE

pHion Therapeutics are currently engaged in pre-clinical development of a therapeutic vaccine for PROSTATE CANCER (supported by Prostate Cancer UK) using a unique triple mRNA system (PTX_V3).

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PTX_G1

PTX_G1: RNAi Therapy for COVID-19

pHion Therapeutics are fast tracking a pre-clinical program to optimise an RNAi therapeutic for the treatment of COVID-19 using the RALA nanoparticle system (PTX_G1) targeting transient knockdown of the ACE2 receptor.  pHion have developed a solution to RNAi delivery that when formulated preferentially goes to the lung, does not cause any immunogenicity which is critical for patients who are already immune-compromised and is cost-effective thereby enabling widespread adoption of this technology.

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Transient knockdown is critical to ultimately help patients get over the acute phase but not permanent knockdown of the receptor as this is required for many biological functions. Key objectives of this project include i) production and evaluation of RALA/RNAi nanoparticles, ii) determining appropriate dose for the knockdown of ACE2 receptors in human lung cells, iii) In vivo evaluation of transient ACE2 knockdown. The outputs of this project will provide the evidence that this therapy should be further developed with toxicology and clinical trials for short-term and long-term coronavirus outbreaks.

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PTX_C1

PTX_C1: ADVANCED CHEMOTHERAPY FOR PANCREATIC CANCER

Gemcitabine is the most widely indicated of the nucleoside chemotherapies, prescribed as a first line of therapy for pancreatic cancer and when patients have failed other treatment options in lung and ovarian cancer.  However, gemcitabine rapidly develops drug resistance that yields a clinical response rate as low as 6%. Notably, drug resistance mechanisms are related to: (1) mutation of the active transporters needed for cellular uptake, (2) upregulation of metabolic enzymes that inactivate gemcitabine, and (3) downregulation of cellular enzymes that convert gemcitabine to the active triphosphate metabolite that have proven impossible to overcome.

This leads to a healthcare need for targeted drug delivery systems that will increase tumour accumulation, improve cell entry, half-life, and drug stability. In the case of gemcitabine (and other nucleosides), if a drug delivery system could deliver the active, triphosphate form into the cell, mechanisms that lead to drug resistance could also be bypassed.

pHion are validating and developing our tumour specific small molecule therapeutic RALA nanoparticle (PTX_C1) delivering gemcitabine triphosphate (dFdCTP) for the treatment of PANCREATIC CANCER.

The innovation is found in the use of the RALA delivery system to small molecule chemotherapeutics given RALA’s ability to accumulate compounds at 25-fold higher concentrations in solid tumours over any other site in vivo. This has the potential to greatly increase the therapeutic index of what is already the main option for treating pancreatic cancer.

pHion is capable of delivering the normally undeliverable and active triphosphate metabolite which ensures an absolute dose, whilst the RALA++ also protects other organs from off-target effects and bypasses typical intracellular resistance mechanisms.

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RALA-V

RALA-V: A New Benchmark in AAV Manufacture

Gene therapy through recombinant adeno-associated viruses (AAV) has the potential to truly transform healthcare interventions, from the delivery of therapeutic genes to the correction of genetic errors of inherited disorders. Global viral vector and plasmid DNA manufacturing is a large and growing market estimated at USD $368.3 million in 2019 and projected to expand at a CAGR of 14.52% to USD $1.1bn 2027 [Grand View Research 2020]. AAVs are widely recognised as a leading gene delivery vector with 27% of 290 ongoing clinical trials utilising gene delivery vectors (viral and non-viral) as of H1 2019, utilising AAV vectors.

Despite the potential, the costs of this therapy are extremely prohibitive and do not enable widespread adoption. The majority of focus has centred around the downstream processing of AAV particles, yet nearly 60% of costs lie with the amount of DNA required to make the AAV particles and the highly inefficient production of ‘empty viruses’. It is pHion’s vision to apply the RALA nanoparticle technology (RALA-V) for the improved upstream PRODUCTION OF AAV PARTICLES, thus providing a streamlined cost-effective solution to the UK viral gene therapy market.

With the potential to be applied to the global gene therapy market, pHion have developed a solution to AAV production that is both safer and more efficient than the current industry standard (Polyethyleneimine, PEI), and also costs significantly less thereby enabling widespread adoption of this technology by the industry. pHion have already exhibited a 67% increase in the number of viral particles that can be produced with like-for-like conditions using PEI with a decrease in associated toxicity (20x less)

The AAV-producing nanoparticles formed with RALA do not require cold chain storage, do not impact the cells in terms of receptor status or viability and can be stored for many months without losing functionality. Therefore, this innovation is ideally positioned to become the ‘gold standard’ for the production of AAV particles.

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RALA

RALA :RALA for ex vivo applications

pHion Therapeutics are engaged with Cell and Gene Therapy Catapult and a number of industrial Pharma partners to develop RALA   for use in EX-VIVO APPLICATIONS.

RALA has already proven successful in the treatment of induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) without any associated toxicity or phenotypical alterations.

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