[Music]
hey folks um I'm s sankran I'm the
founder of a company called Popa which
works on uh verifiable open source
vaccines intended to save millions of
lives from the developing World up and
I'll explain what all of that
means first let me say something that I
think has unfortunately become
controversial of recent times vaccines
are one of the most effective Public
Health interventions known to man
over the last 50 years they are
estimated and this is just childhood
vaccines are estimated to have saved
over 150 million lives across key
pathogens that uh that attack uh younger
Children and adolescents and when you
add adult vaccinations they're uh likely
tens of millions
more but there are pathogens uh
important pathogens that are quite
prevalent for which there are no
existing vaccines um these include uh
tuberculosis uh Strep a and hcv in
particular so just these three pathogens
and here I'm talking about tuberculosis
in adults not tuberculosis in children
uh kill uh over 1.8 million people per
year across the world and there are no
effective vaccines for them
today unfortunately instead of speeding
up vaccine development is slowing down
uh it it took uh the malaria vaccine
which is one of the more recent
infectious disease vaccines to be
licensed 35 years to go from concept to
lure um and uh these programs now
routinely cost 1 billion plus dollars
which is a a very large amount of money
to invest in a in a single drug um and
then because they're only dos let's say
between one and three times usually
unlike say gp1 Agonist like a zic which
are which are dosed considerably more
frequently uh farma companies do not see
them as a particularly High return on
investment and so they have pulled back
especially in the postco era from
investing in new infectious dis vaccine
programs in particular for pathogens
like TB which they see as being only
relevant in developing countries which
are
poorer uh but there's a potential
solution here so this is a a sort of
graphic of the top 10 vaccine
manufacturers in the world by volume in
2021 uh during covid but excluding the
covid-19 vaccines and what you can see
here is that Indian vaccine
manufacturers including the serum
Institute of India are very substantial
in their presence they account for
almost % of the volume of vaccine doses
shipped
globally um and so why don't we vac so
to speak why don't we uh accelerate
vaccine development by relying on uh
this capacity that we have in India and
other developing countries um and also
the fact that you know you can do things
cheaper in countries like India right we
can do this we think 10x faster and 10x
cheaper and you might ask why aren't
people doing this already there are
already these big vaccine companies in
India surely they must be thinking on
these uh lines um unfortunately India as
a country spends almost nothing on
research and development um it is a joke
how little we spend on R&D across
government uh and across Private
Industry and Indian companies including
vaccine companies are not particularly
interested in taking technical risks uh
such as developing new vaccines for
pathogens where vaccines have been hard
to develop um and so Popa is trying to
solve this problem we are trying to
solve long-standing problems in vaccine
design including the three pathogens
that I mentioned where people have made
attempts but no success um using mRNA
and computational protein design tools
that have just reached the point where
we can actually use them to make novel
vaccines that couldn't have been made
before as I'm sure many of you are aware
uh Demis sabis John jumper um and David
Baker just won the Nobel Prize in
chemistry recently for their work in
protein structure prediction and uh and
protein design and so these tools are
just now reaching the maturity where we
can actually use them productively um
and we want to leverage as I said the
talent cost and speed advantages of
operating in India which is to say uh
you know we are the only company or one
of the only companies doing this kind of
Novel vaccine development in India and
so the best talent in the country folks
who want to work on these world uh
changing problems but you know don't
have the opportunity uh essentially come
to
us unfortunately no one wanted to fund
Popa when I started this three years ago
um VCS and nonprofits essentially didn't
believe that the talent pool existed in
India to do this um The Gates Foundation
gave us an early 100K check um but that
was not enough to build a vaccine
platform or take anything to Clinic as I
said these vaccine programs they
routinely cost a billion dollars even if
you can do it for 10x cheaper that's
still hundreds of millions of dollars
right um and uh we had some good early
data about you know two and a half years
ago uh but it had rendered both me and
the company bankrupt uh then there was a
massive pump in Shiba Inu coin which I'm
given to understand is a mem coin of a
mem coin um and vitalic founded the bio
security and Public Health Organization
baly uh and one of their Investments was
us um and so they've now us accumulative
15 plus million dollar and I think it's
it's interesting that it took uh vitalic
somebody who is outside of the sort of
General hierarchy of of you know Public
Health funding to see what I think is
obvious which is that the talent is
there it was really a resource
constraint that meant that folks in
India had not had the opportunity to go
after these
problems so let me talk a bit about what
we've actually done with that money and
and what that means for the future so
this is extremely dense and I apologize
in advance but I'll explain what's going
on here uh that green thing that you see
there is the receptor binding domain or
RBD of the SARS CO2 virus it is the
immunodominant antigen of SARS CO2
antibodies against that particular
protein are the key drivers of
neutralization and protection in the
covid vaccines so it's a subset of the
spike protein that I'm sure all of you
have heard of it's not the entire Spike
it's just a part of it right what we've
done is we've pioneered an approach
where within mRNA we can encode uh a
self assembling virus-like particle
which is what is in the blue um that
basically displays a whole bunch of
copies of this RBD protein and in doing
so we've achieved two things one is uh
We've achieved considerably more potency
so what that if you look at at our sort
of uh highlighted you know bolded bar
here two micrograms of our RBD vlp
display mRNA which uses this approach
provides 22x greater neutralizing
antibody response which correlates quite
highly with protection uh compared with
two micrograms of the full Spike mRNA
sequence from one of the US approved
covid vaccines and this is all in mice
uh and what's particularly interesting
about this is you know we can use it to
make a vaccine that's more potent we can
also use it to make a vaccine that's
potentially safer uh because we can
achieve with 95% less dose as you can
see at the top with just 0.1 micrograms
we can achieve the same result as you
would without using our strategy with 2
micrograms and so I can inject much less
mRNA much less lipid nanoparticle and
have potentially a much safer product
overall and the kinds of things that
Philip was talking about uh you know all
get worse as you increase the dose of
whatever your vaccine product or drug
product is the other interesting thing
that we got here is breath so uh if you
think about covid-19 and why the
vaccines were less effective as we got
later into the pandemic the reason isn't
that they they didn't have a durable
response the reason is that the pathogen
evolved uh variants of the path pen that
were no longer susceptible to the
antibodies El listed by the original
vaccines became prevalent um and as a
result of that we ended up with a
situation where uh what were very
effective vaccines at even preventing
transmission became relatively
ineffective as new variants evolved
however using this mRNA encoded VP
strategy what we've been able to do
actually is elicit antibodies that
neutralize a whole breadth of of
variance so our uh construct is the red
line which is able to potently
neutralize you know even as it's diluted
a whole bunch of these other V variants
wild type gamma Lambda Omicron ba1 um
whereas the the US approved CID vaccines
the original ones in blue are not able
to to neutralize those other variants so
this approach which we are uh you know
among the first to to Pioneer in uh in
MRN protein design uh has potential
substantial gains for covid and and for
other pathogens like
influenza now let me talk a little bit
more broadly about what strategies like
this are actually trying to do right if
you think about any pathogen uh you know
it has a whole bunch of antigens which
are in the case of a virus those are
going to be proteins um that elicit
certain kinds of immune responses
certain types of antibodies right uh and
then some of those antibodies are going
to be uh functional you know they they
they they might sort of uh neutralize
the pathogen right some of those
antibodies are going to be
non-functional they might bind but not
neutralize or or not bind at all right
and then within the context of of these
functional uh antibodies there's some
subset set of antibodies that you might
consider broadly functional and what
that means is even as the pathogen
evolves even as there are additional
variants that come up those antibodies
which are some subset of the original
antibodies remain effective so the
intention of our vaccine design approach
is basically to move the distribution of
antibodies listed whether it's in an
animal or a human towards these broadly
functional antibodies which have a
chance of providing durable protection
against even new variants that might
emerge um and this is relevant in the
context of of Co for uh this variant
evolution story uh in the case of some
of the other pathogens that I mentioned
for example hcv it is absolutely
essential because hcv as a pathogen like
HIV evolves within its own host and so
you know if you were to be infected with
hcv you might have thousands of
different variants of the hcv pathogen
within your own body and so uh an
antibody response that is effective
against just one of them is not going to
be effective at clearing the pathogen uh
so we've used this uh you know we've
used a variant of of what's called an
epitope scaffolding approach uh to
basically attempt to elicit specific
types of antibodies that provide this
kind of broad functionality and Broad
protection um and what we've been able
to do in just three years uh is to run
these processes of Designing and testing
in animals uh these these novel
immunogens which can elicit these
antibodies uh much faster than anybody
typically does in in vaccine R&D
programs again as I said leveraging the
fact that we can do this research much
more cheaply and much more quickly in
India uh and what we found is mRNA in
particular gives us an advantage here uh
mRNA is of course not the actual
immunogen what you're injecting in mRNA
is almost code that encodes a a specific
design of immunogen that's intended to
elicit some antibody response um and so
because we're using mRNA which is a
standardized process we can test
thousands of different immunogens um and
then when we allight upon one that that
actually gives us the response we want
we can translate it not just into a sort
of lab environment but into an actual
GMP manufacturing environment apologies
uh we can translate not just into a lab
environment but into an actual clinical
environment into a into a clinical study
very quickly which is not something that
you can do with conventional vaccines as
easily which is why you get these
extremely long timelines
right um and so what what we know so far
is basically this vac approach in India
it works right uh we've been able to do
this uh at 20x cheaper than you would
usually spend on a pre-clinical vaccine
program to build a new platform and get
to phase one uh We've 10x the testing
througho of a normal vaccine program uh
We've tested you know thousands and
thousands of of novel l&p formulations
of Novel designed immunogens which are
basically vaccine designs we've tested
them in vitro but we've also tested them
in Vivo 500 plus and we've been able to
achieve the results you saw in the
beginning which is that our vaccine
appears to be much much better than the
existing covid-19 vaccines so what that
means is I can take 10x the number of
shots on goal for the same amount of
funding as a company in Boston or San
Francisco and potentially save 10x the
number of lives in the long run right if
somebody gives me $300 million a company
in Boston and this is all based on a
real comparison with a uh you know with
a a biotech company that's developing
vaccines and doing quite well doing so
uh you know they might take uh one
candidate to a through a phase one
clinical trial and be getting ready for
a phase two clinical trial with a new
platform for us we've been able to build
a new platform and with that amount of
money with $300 million we would be able
to take 10 new candidates to phase 1 and
two and potentially bring multiple
products to lure and again you know in
the long run that saves a lot of lives
right because every year we wait to
develop these vaccines millions of
people are
dying um another key piece of this is
that we've built our own GMP
manufacturing facility so what that
means is uh we have the ability within
our own facility to make clinical doses
uh in a way that's safe to inject in
humans uh such that we can very quickly
take these new candidates and Advance
them to clinical studies and here I'll
reference what Philip was talking about
a little bit right I think it's critical
to ensure
uh that we build a process that is not
only uh you know safe by the standards
of existing regulatory Norms but is
legible enough and is understandable by
the general public that they trust what
comes out of our work right
um and so the good news here is and in
fact I'll be I'm announcing this today
we just announced it via press release
this morning is that NAD which is part
of the US National Institutes of Health
has selected our next Generation
covid-19 vaccine as part of the US
government governs project NextGen for a
phase one trial which will happen in the
US early next year which to my knowledge
is one of the first clinical trials of
an Indian design vaccine in the US in
fact no Indian vaccine or Indian design
vaccine uh has ever been approved in the
US no Indian company's vaccine has ever
been approved in the US and Our
intention is to to have our vaccines
available all over the world right not
just in rich countries not just in poor
countries but but to everybody um and so
this is very exciting news because I
think what this means is our approach uh
which as I said up top is an approach
that at the beginning nobody supported
right nobody believed that we had the
talent India to do this nobody was
certain you know or people in fact were
quite certain that we wouldn't be able
to do this right and it took an early
bet from Gates and a substantial bet
from vitalik and his team to support
this has now been essentially co-signed
by one of the most credible
organizations in public has right so NAD
thinks that this vaccine works very well
um at least pre-clinically and they
think it's worth evaluating in in
humans uh the covid vaccines have you
know have been somewhat maligned but
best estimates suggest they saved tens
of millions of lives we can quibble
about specific numbers but it's it's
likely a very large number right but
again as Philip was talking about
there's been there been a lot of
questions about whether the process
followed and approving these vaccines um
you know were processes that are
appropriate for human health um and at
the same time you know on the other side
of the coin the reality is that a lot of
people who wanted these vaccines in
developing countries didn't get them uh
because fizer and Mna were not that
interested in selling their vaccines at
knockdown prices in poor countries right
um and so what what we've done is we've
worked with Bal to come up with a model
um where we will be open sourcing our
covid-19 vaccine we will not be
enforcing our intellectual property on
that vaccine uh for a number of years
and what we'll be allowing people to do
is to verify not just the R&D processes
that led to That vaccine but also the
manufacturing processes so that
manufacturers across the rest of the
world uh can not only make copies of
this vaccine themselves they can
distribute at low cost um but also that
people can understand whether the
processes that we've used in developing
and Manufacturing this vaccine are
compatible with what we say out in
public um and are safe for them right
they can have independent scientists
evaluate these processes in a way that
existing vaccine companies don't make
enough information available to do um
and that's something that we can do
because we are comfortable releasing far
more information than anybody has ever
done um for a vaccine development or
manufacturing program before let me just
briefly talk about what we call the
popac Million Lives Mission uh as I said
there are these three pathogens that
collectively kill 1.8 million plus
people per year um we want to develop
effective vaccines against all three of
them that we think can save over a
million lives per year um we want to do
this using a new sustainable model for
funding for public health vaccines
similar to what we've done with vitalik
and his team um where you know we will
provide full details needed for vaccine
verification R&D Improvement and
Manufacturing openly we'll cap profits
in developing countries and allow for
open licensing on transparent terms of
of this intellectual property um and we
will have uncapped profits in rich
countries right and this is a model that
you know that we want to advance uh that
we think could be the future of of
sustainable vaccine
development uh yeah I'm I'm happy to
take your questions outside and please
feel free to email me if you're
interested in working with us funding us
or collaborating with us thank you so
much thank you so much that was