- Product development activities for SPL7013, repurposed as an
antiviral nasal spray, are now well advanced with formulations
developed, a manufacturer selected and pilot manufacture
undertaken
- Additional antiviral testing of SPL7013 has been completed,
confirming potent antiviral activity against SARS-CoV-2 and
providing supporting data on mechanism of action indicating that
SPL7013 acts early in the viral replication cycle
- Potent activity of SPL7013 against SARS-CoV-2 was evident
when used either before or after exposure to the virus
- Compiled regulatory documentation in preparation for
submission; an expedited regulatory pathway has been confirmed for
a number of important markets including Europe
- A publication of the antiviral data has been submitted to
peer reviewed scientific journal and is now available on
bioRχiv1
Starpharma (ASX: SPL, OTCQX: SPHRY) today announced progress
with development, regulatory and manufacturing activities
associated with a nasal spray for protection against COVID-19 based
on the company’s proprietary antiviral dendrimer, SPL7013.
Starpharma has undertaken extensive development activities for
the SPL7013 nasal spray. To date, SPL7013 has been reformulated
into several nasal spray formulations, the company has identified a
manufacturer and device components, undertaken pilot manufacture,
and compiled regulatory documentation in preparation for
submission. Based on discussions with regulators, the company
expects to be able to expedite approval of a SPL7013 nasal spray by
leveraging existing nonclinical and clinical data of Starpharma’s
currently approved and marketed products.
As first announced in April, data has shown the potent antiviral
activity of SPL7013 against SARS-CoV-2 (the virus that causes
COVID-19). Extensive antiviral data has been generated and
submitted to a peer reviewed scientific journal and is now
available on the preprint server, bioRχiv.2
The data confirms that SPL7013 inhibits infection of host cells
by SARS‑CoV-2 when it is applied to the cells either before or
after exposure to the virus. The selectivity of SPL7013 for
SARS-CoV-2 in these assays was very high (selectivity index3 up to
~2200), indicating potent antiviral efficacy compared with minimal
cellular toxicity. The selectivity index is a measure of
therapeutic window. The high selectivity index of SPL7013 compares
very favourably with the selectivity index against SARS-CoV-2
reported in the literature of 279 for remdesivir and 172 for
chloroquine.4
In an assay to detect virucidal activity, SPL7013 also rendered
SARS-CoV-2 inactive and prevented infection when it was mixed with
the virus prior to adding to cells.
The high potency and high selectivity index of SPL7013 indicate
that a final formulated product can and will have a concentration
of SPL7013 that is several thousand-fold higher than the
concentration shown to exert an antiviral effect on SARS-CoV-2.
SPL7013 has broad spectrum antiviral and virucidal effects, with
activity demonstrated against a range of viruses, including HIV,
herpes simplex virus (HSV), human papillomavirus (HPV), adenovirus,
H1N1 influenza virus, hepatitis B virus (HBV) and Zika virus. Given
the broad antiviral activity, a SPL7013 nasal spray also has
potential for application beyond SARS-CoV-2 for other common
respiratory viruses, and could be useful in pandemic preparedness
in the future.
Mechanism of action
SPL7013 inactivates viruses by blocking the interaction between
viral surface proteins and the human cell receptor proteins. As for
other viruses inhibited by SPL7013, SARS-CoV-2 infects human cells
by using the characteristic viral surface proteins, or “spikes”, to
attach to receptor proteins on the surface of human cells.
The data generated indicate that SPL7013 acts early in the
SARS-CoV-2 replication cycle. When SPL7013 was added to cells
before or at various stages of the virus replication lifecycle
after infection with SARS-CoV-2, no infectious virus was detected,
regardless of the initial time of addition of SPL7013. This finding
was in contrast to other antivirals, remdesivir and
hydroxychloroquine, for which infectious virus was detectable at
all times of addition, when tested in the same assay. Remdesivir
only partly reduced infectious virus when it was added at early
stages of the virus replication lifecycle, while hydroxychloroquine
did not reduce infectious virus at any time of addition.
These data are consistent with SPL7013 inhibiting the initial
stages of SARS-CoV-2 attachment and entry into cells, and
inactivating the virus, as has been demonstrated for other viruses
such as HIV. This mechanism of action, the high selectivity
described above, and the fact that it is a large dendrimer molecule
that is not systemically absorbed, make SPL7013 well-suited to
being applied topically as a nasal spray to help prevent SARS-CoV-2
infection.
SPL7013 is the active ingredient in marketed VivaGel® products
and has been shown to be safe and well tolerated in multiple large
international clinical trials. VivaGel® products are approved and
marketed in the UK, Europe, Asia, Canada, Australia, and New
Zealand, and are already manufactured at industrial scale.
SPL7013 active is already scaled up for commercial supply, and
the availability of existing stocks of SPL7013 will further
expedite development and commercialisation of the nasal spray
product.
Dr Jackie Fairley, Starpharma CEO, commented: “We are pleased to
provide an update on the progress with development of the SPL7013
nasal spray. The potent activity of SPL7013 in SARS-CoV-2, its
action early in the replication cycle and its selectivity are all
positive product features. Whilst effective vaccines will be
central to the fight against COVID-19, other preventative measures
will continue to be important to reduce the risk of transmission
and exposure to SARS-CoV-2. Our strategy for the product includes
leveraging Starpharma’s vast body of existing technical data and
existing regulatory approvals for SPL7013, to fast-track the
regulatory and commercialisation pathways to have the product ready
for market as soon as possible.”
The SPL7013 nasal spray has the potential to complement vaccine
strategies to further reduce risk by preventing acquisition and
transmission of SARS-CoV-2, and reducing disease progression due to
ongoing viral replication in mild forms of COVID-19. Feedback from
infectious disease specialists and other healthcare agencies has
confirmed that a cost-effective and readily available product to
help prevent SARS-CoV-2 infection would be highly valued and play
an important role in reducing transmission for the broader
population and especially for frontline workers in the health, aged
care and travel industries.
Whilst the initial focus is on a nasal spray as the most rapid
path to market, the company also notes that SPL7013 could be
applied via other routes of administration, such as ocular,
nebulised or injection.
The SPL7013 active is patented by Starpharma in major markets,
and a specific patent application has been filed for the COVID-19
nasal spray. Starpharma has also commenced confidential
commercialisation discussions, having shared product details and
supporting technical data with a number of interested
pharmaceutical companies, covering a range of geographic
markets.
For the full announcement and appendices click this link:
https://starpharma.com/news/508
About Starpharma
Starpharma Holdings Limited (ASX: SPL, OTCQX:SPHRY), located in
Melbourne Australia, is an ASX 300 company and is a world leader in
the development of dendrimer products for pharmaceutical, life
science and other applications.
Starpharma’s underlying technology is built around dendrimers –
a type of synthetic nanoscale polymer that is highly regular in
size and structure and well suited to pharmaceutical and medical
uses. Starpharma has two core development programs: VivaGel®
portfolio and DEP® drug delivery with the Company developing
several products internally and others via commercial
partnerships.
1 bioRχiv (pronounced “bio-archive”) is a preprint website for
biology to allow early access to scientific manuscripts operated by
Cold Spring Harbor Laboratory in the US.
https://doi.org/10.1101/2020.08.20.260190
2 Paull, J.R.A. et al., 2020. Astodrimer sodium, dendrimer
antiviral, inhibits replication of SARS-CoV-2 in vitro. bioRχiv
2020.08.20.260190. https://doi.org/10.1101/2020.08.20.260190
3 Selectivity index is a ratio of antiviral activity to cellular
toxicity. The higher the selectivity index, the theoretically safer
and more effective a compound would be in humans.
4 Pizzorno, A., et al., 2020. In vitro evaluation of antiviral
activity of single and combined repurposable drugs against
SARS‑CoV-2. Antiviral Res. 104878. Advance online publication.
https://doi.org/10.1016/j.antiviral.2020.104878
Disclosure This ASX Announcement was authorised for
release by the Chairman, Mr Rob Thomas.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20200825005403/en/
Media: WE Communications Rebecca Wilson Mob: +61
417 382 391 rwilson@we-worldwide.com Arthur Chan +61 2 9237 2805
arthurc@we-worldwide.com
Starpharma Holdings Limited Dr Jackie Fairley, Chief
Executive Officer Nigel Baade, CFO and Company Secretary +61 3 8532
2704 investor.relations@starpharma.com
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