Our fourth webinar in the MDC Connects Series 2021 | A Guide to Complex Medicines. This slide deck takes a closer look at alternative delivery for mRNA vaccines. Helen McCarthy, pHion Therapeutics

1. Under the Radar: Alternative Delivery of mRNA Vaccines

2. BACKGROUND TO TECHNOLOGY
pHion have developed RALA, a patented, peptide based Drug Delivery System [DDS] with
full and tunable bio-distribution for anionic cargo (negatively charged DNA, RNA, and small
molecules)
RALA : WEARLARALARALARHLARALARALRACEA
Based on research of Professor Helen McCarthy, Chair of Nanomedicine at the School
of Pharmacy, Queen’s University Belfast.
15 years of research
>130 Original Research Articles
3 Patents
Over £5M in Grants from MRC, BBSRC, EPSRC,CRUK, PCUK, Royal Society, NSF

3. EXECUTIVE SUMMARY
Pre-clinical Stage Therapeutic Vaccine Development
Developing promising preclinical assets pipeline:
PTX_V1 Therapeutic Vaccine for Mucosal HPV
PTX_V4 Therapeutic Vaccine for COVID-19
PTX_G1 RNAi Therapy for COVID-19
£2m Innovate UK, non-dilutive funding secured to support pre-clinical development
and formulation scale up.
Pharma Partnering Traction

4. TECHNOLOGY ENTERS CELL WITHOUT TOXICITY

5. DEVELOPMENT PIPELINE

6. RALA for mRNA VACCINES
Therapeutic Vaccines
CD8+ Therapeutic vaccines remain elusive
RALA delivered mRNA produces Th1 / CD8+ cytolytic response
Result is achieved by:
delivery to antigen presenting cells
delivery in a manner that does not provoke cellular, innate immune response
RALA Oligonucleotide vaccines do not require cold chain storage

7. RALA/mRNA VACCINES
RALA bypasses innate immunity for optimal adaptive immune response.
7-12 week old luciferase reporter mice (IFN-β+/Δβ-Luc)
2 week Prime Boost vaccination: 7 μg OVA mRNA in 20 μL
2 days post CFSE-labelled cells in eitherWT orType-I Interferon knock out mice
Udhayakumar, Vimal K., et al. "Arginine‐Rich Peptide‐Based mRNA Nanocomplexes Efficiently Instigate Cytotoxic
T-Cell Immunity Dependent on the Amphipathic Organization of the Peptide." Advanced Healthcare Materials (2017).
Uncomplexed
mRNA
DOTAP/mRNA
RALA/mRNA

8. RALA/mRNA THERAPEUTIC VACCINES
Naked Cy5
mRNA only
RALA/Cy5 mRNA
Nanoparticle
RALA/Cy5-mRNA nanoparticles migrate from
the site of administration to draining lymph
nodes in the neck (imaged at 2 h post-
administration)
0
h
24
h
48
h
96
h
24
h
48
h
96
h
0
5
10
15
20
25
%
CD11c
+
cells
Cy5 mRNA only RALA/Cy5 mRNA
0
h
24
h
48
h
0
5
10
15
20
25
%
F4/80
+
cells
Cy5 mRNA
RALA/Cy5-mRNA enter CD11c+ Antigen
Presenting Cells

9. BACKGROUND : PTX_V1
pHion are validating and developing a therapeutic vaccine (PTX_V1) that comprises RALA complexed
with E7 mRNA for therapeutic vaccination against HPV-ASSOCIATED CANCER.
THE FACTS ( CANCER RESEARCH UK )
E6 & E7
HPV antigens E6
and E7 well
characterized, and
common targets for
vaccine
development
3,200
New cervical
cancer cases in
the UK every
year, making it
the 14th most
common cancer
in women.
90%
Human Papilloma Virus (HPV) is
responsible for around 90% of
cervical cancers.

10. PHASE I/IIa STUDY DESIGN – PTX_V1
Phase I/IIa open-label, multicentre, modular study of PTX_V1 administered by intradermal injection
to assess the safety and tolerability in patients with Human PapillomaVirus (HPV) - driven solid
malignancies
Dosing Phase
Expansion
Phase
Pre-Treatment Window Study
Invasive HPV+ Cervical Carcinoma
Pre-Treatment Window Study
HPV+ SCC HN
Module 2
Module 3
Module 1,
Part A
Module 1,
Part B
Women with HPV+ CIN 2/3

11. RALA/mRNA ARE STABLE AT ROOM TEMPERATURE
400 μM
400 μM
T0 80%
T6 75%
RALA/mRNA nanoparticles retain functionality 6 months post lyophilization, stored at room temperature

12. Scale Up/ CPI Tech Transfer

13. Scale Up/ CPI Tech Transfer

14. Nanoparticle scale up to clinical doses ongoing using Precision NanoSystems Microfluidics
NanoAssemblr Platform – IUK supported, in collaboration with CPI
Scale Up/ CPI Tech Transfer

15. Scale Up/ CPI Tech Transfer

16. RALA TECHNOLOGY: BENEFITS
STABLE
Highly stable formulations
(>6 months) that are resistant
to extremes of time and
temperature with no
reduction in functionality
following lyophilisation
VERSATILE
High efficiency condensing
of any size of nucleic acid or
small molecule into
nanoparticles with industry
acceptable characteristics
EFFICIENT
Cellular delivery of any size of
nucleic acid that outperforms
current delivery platforms
RESISTANT
Physiologically stable
nanoparticles with no protein
binding, nanoparticle
disassembly or aggregation
SAFE
Natural amino acid
composition ensures no
toxicity even after multiple
transfections or injections
THERAPEUTIC
RALA nanoparticles exhibit
low immunogenicity. No
vector neutralisation or anti-
RALA antibodies detected
following repeat exposure

17. PHION MANAGEMENT TEAM
Experienced Pharma
Executive, former CEO
Merrion Pharmaceuticals
PLC
Director at Shire and Hunter
Fleming
Inventor of RALA drug
delivery system
Chair of Nanomedicine,
Queen’s University Belfast
PROF. HELEN McCARTHY DARACH NEESON DR. JOHN FOX
C.E.O. & FOUNDER C.O.O. CHAIRPERSON & NON-EXEC DIRECTOR
IP Lawyer at A&LGoodbody
and Spinout Manager at
QUBIS
Over 10 years experience
with startups, scale ups and
IP licensing
WIDER TEAM
NED: David Moore, Head of Spinouts,
QUBIS
Consultant: Dr Lyn Rosenbrier, Dr
Sarah Brockbank, ex-AstraZeneca
6 R&D Scientists
Regulatory Consultant: Dr Stephen
Liggett
Clinical Development: Aptus Clinical
Safety and Toxicology: ApconiX
CMC Oversight: SEDA Pharmaceutical
Development Services
IP: Alembia IP

18. CONTACT
@phiontx