Photosoft shows activity against Dengue in Preliminary Assay
Released
Released
Announcement PDF
ASX ANNOUNCEMENT
PHOTOSOFTTM SHOWS ACTIVITY AGAINST DENGUE IN PRELIMINARY ASSAYS
Highlights:
Eight out of ten PhotosoftTM compounds showed antiviral activity against the Dengue
virus after exposure to light
The eight compounds have superior Therapeutic Index (TI) values to Monensin
The most effective compound had an EC50 (half maximal effective concentration)
value that is >90 times lower than Monensin (control drug)
No compound displayed antiviral activity when protected from light
The global Dengue treatment market is estimated to hit US$1.3bn by 2030 (11.2%
CAGR)1
MELBOURNE (AUSTRALIA) 24 October 2022: Invion Limited (ASX: IVX) (“Invion” or the
“Company”) is pleased to announce the positive screening results from in vitro studies of
PhotosoftTM on the inhibition of the Dengue virus.
The tests, which were done on ten PhotosoftTM photodynamic compounds at eight
concentrations, found that eight of the 10 compounds displayed antiviral activity against the
Dengue virus after exposure to a specific light wavelength (660nm).
The EC50 (half maximal effective concentration) values of the eight PhotosoftTM compounds
that showed antiviral activity ranged between 11.1nM and 539nM. These values were
significantly below that of Monensin (1031nM), an antibiotic with known activity against
Dengue virus was used as a control. None of the compounds were antiviral in the absence of
this light source.
Invion Limited ABN 76 094 730 417
100 Albert Road, South Melbourne, VIC 3205
P: +61 3 9692 7222 W: www.inviongroup.com
ASX ANNOUNCEMENT
Inhibition: Selected PhotosoftTM Compounds vs Dengue
100
% Inhibition
80
60
40
20
0
0
0.2
0.4
0.6
0.8
1
µM
Cytotoxicity: Selected PhotosoftTM Compounds vs Dengue
% Cytotoxicity
100
80
60
40
20
0
0
0.5
1
1.5
2
2.5
3
µM
Compound 5
Compound 7
Compound 8
Monensin
Figure 1. The percentage of inhibition of Dengue virus infection (y axis) as a function of the logarithm of
compound concentration in µM (x axis). (Right graph) The percentage of cytotoxicity of Vero E6 cells (y axis) as
a function of the logarithm of compound concentration in µM (x axis). Data are included for test compounds 5,
7, and 8, and the control drug Monensin, after LED exposure.
Further, test compound cytotoxicity against the assay cells was low, which together with lower
effective concentrations resulted in higher Therapeutic Indexes1 than Monensin, suggesting
higher safety potential for several of the PhotosoftTM compounds. In fact, the two most potent
anti-Dengue compounds demonstrated insufficient cytotoxicity to determine CC50 (the
concentration of the 50% cytotoxic effect) values.
Dengue is spread through the bite of an infected Aedes aegypti mosquito and causes intense
pain in joints and muscles, hence its nickname “breakbone fever”. The global Dengue
treatment market is forecast to hit US$1.3 billion by 2030, reflecting a compound annual growth
rate of 11.2%2.
Methods
Eight dilutions of each test compound were added with virus to the assay cells (Vero E6) and
subsequently exposed to a specific wavelength of LED light for 30 seconds or maintained
unexposed.
1
A Therapeutic Index (TI) is frequently determined in viral assays as the dose of a drug that kills 50% of the host cells (CC50) divided by the minimum effective dose to
cause 50% inhibition of the virus (EC50). It is generally considered that a drug has a good safety profile if its TI exceeds the value of 10.
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412688/#:~:text=It%20is%20generally%20considered%20that,exceeds%20the%20value%20of%2010)
2
https://www.biospace.com/article/-dengue-vaccines-market-size-to-reach-us-1-3-billion-by-2030/
Invion Limited ABN 76 094 730 417
100 Albert Road, South Melbourne, VIC 3205
P: +61 3 9692 7222 W: www.inviongroup.com
ASX ANNOUNCEMENT
Treated cells and virus were then incubated in the dark for 48 hours, and antiviral activity was
determined using an immunofluorescence-based assay.
Cytotoxicity was determined by MTT assay on uninfected cells treated with the same
concentrations of compounds, after exposure to LED light or maintained unexposed, for the
same incubation time.
Results Summary
Of the antiviral test articles, Compound 7 had the lowest EC50 at 11.1nM and Compound 8
had the highest at 539nM.
Compound 1 had the second lowest EC50 (13.5nM) and Compound 5 had the third lowest
(18.0nM). Compound 3 and Compound 10 did not display antiviral activity against Dengue
under the conditions tested.
Table 1: EC50, CC50, and Therapeutic Index (TI) values for test and control compounds against Dengue
virus after LED exposure or maintained unexposed ranked in order from lowest EC50 (top) to the highest.
TI = CC50/EC50.
Some cytotoxicity against the assay cells Vero E6, as measured by MTT assay, was observed
after light exposure for Compounds 2, 5, and 6, as well as for Compound 9 whether exposed
to light or not.
In each instance, greater than 50% cytotoxicity was detected at no more than the highest one
or two concentrations tested. The Therapeutic Indices (TI = CC50/EC50) for these compounds
after light exposure ranged from 7.85 (Compound 2) to 77.0 (Compound 5).
The two most potent anti-Dengue test articles, Compound 7 and Compound 1 did not
demonstrate sufficient cytotoxicity towards Vero E6 to determine CC50 values. Both
compounds displayed less than 48% cytotoxicity at the highest concentration tested and little
to no cytotoxicity at lower concentrations.
The control drug Monensin displayed antiviral activity against Dengue and demonstrated
notable cytotoxicity, both after light exposure and when left unexposed. After light exposure,
its EC50 was 1031nM and CC50 was 2670 (TI = 2.59).
Unexposed, its EC50 was 1066nM and CC50 was 2045nM (TI = 1.92). All EC50 determined for
the test compounds were lower than the Monensin values, including Compound 7 with an
EC50 against Dengue more than 90 times lower than control drug after light exposure.
Invion Limited ABN 76 094 730 417
100 Albert Road, South Melbourne, VIC 3205
P: +61 3 9692 7222 W: www.inviongroup.com
ASX ANNOUNCEMENT
Next Steps
The Dengue In Vitro studies are the third set of successful early-stage tests Invion has
undertaken on enveloped viruses, which are viruses with a lipid bilayer membrane on the outer
part of the virus.
The other two studies (previously released to the market) where PhotosoftTM displayed antiviral
activity were on the Zika virus and SARS-CoV-2 (Delta and Omicron variants) viruses.
These tests form part of the testing that Invion is conducting on infectious diseases using the
PhotosoftTM technology. The results from these and other studies will help the Company decide
which infectious disease target(s) have the most promise of advancing to human applications.
This announcement was approved for release by the Board of Directors.
____________________________________________
Investor and Media enquiries:
Thian Chew (Chairman & CEO)
T: +61 3 9692 7222
E: investor@inviongroup.com
Brendon Lau (Investor & Media Relations)
M: +61 409 341 613
E: brendon.lau@inviongroup.com
About Invion
Invion is a life-science company that is leading the global research and development of the
PhotosoftTM technology for the treatment of a range of cancers, atherosclerosis and infectious
diseases. Invion holds the exclusive Australia and New Zealand license rights and exclusive
distribution rights to Asia Pacific excluding China (other than Hong Kong, which is included in
the Territory), Macau, Taiwan, Japan and South Korea to the PhotosoftTM technology for all
cancer indications. It also holds the exclusive rights to the technology in Asia Pacific (excluding
Greater China) for atherosclerosis and infectious diseases. Research and clinical cancer trials
are funded by the technology licensor, RMW Cho Group Limited, via an R&D services
agreement with the Company. Invion is listed on the ASX (ASX: IVX). For more information, visit
www.inviongroup.com.
About Photodynamic Therapy (PDT)
Invion is developing PhotosoftTM technology as a novel next generation Photodynamic
Therapy (PDT). PDT uses non-toxic photosensitisers and light to selectively kill cancer cells and
promote an anti-cancer immune response. Less invasive than surgery and with minimal side
effects, PDT offers an alternative treatment option aimed at achieving complete tumour
regression and long-lasting remission.
Invion Limited ABN 76 094 730 417
100 Albert Road, South Melbourne, VIC 3205
P: +61 3 9692 7222 W: www.inviongroup.com
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