CARB-X: Combating Antibiotic Resistance Globally

CARB-X: Combating Antibiotic Resistance Globally


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feature polling questions. When a poll is
displayed, simply check the box next to the
answer of your choice. And now it is my pleasure to
introduce today’s moderator, Maryn McKenna. Maryn McKenna is an
independent journalist who specializes in public
health, global health, and food policy. She is a columnist for
WIRED Ideas section, a Senior Fellow at the Schuster
Institute for Investigative Journalism at
Brandeis University, and the author of the 2017
bestseller Big Chicken, The Incredible Story of
How Antibiotics Created Modern Agriculture and Changed
the Way the World Eats, which received the 2018
Science in Society Award and was named a
Best Book of 2017 by Amazon, Smithsonian,
Science News, WIRED, Civil Eats, and other publications. She writes for the New York
Times Magazine, National Geographic, Mother Jones,
Newsweek, NPR, Smithsonian, Scientific American, Slate,
The Atlantic, Nature, and The Guardian, among
other publications. Welcome to the program, Maryn. Please begin. Thank you, Eric. And thanks, everyone,
for being here. And welcome to
today’s program, which is titled Combating
Antibiotic Resistance Globally, a Conversation
with Kevin Outterson, BU professor at
the School of Law and executive director of
CARB-X. Access to this event is being offered
exclusively to members of BU’s Giving Societies. And those of you on this call
represent loyal, generous donors to BU. And this event
has been organized to recognize your
donation’s impact and express gratitude
for your support. So professor Kevin Outterson
is a global thought leader on business models for
antibiotic development and use. He is Professor of Law and
the N. Neal Pike Scholar of Health and Disability
Law at Boston University School of Law, where he
leads multidisciplinary teams to solve global health issues. Professor Outterson is
also the executive director and principal
investigator of CARB-X and a partner in DRIVE-AB. Professor Outterson is also
the N. Neal Pike Scholar in Health and
Disability Law at BU and an expert on
pharmaceutical markets. So it’s now my distinct pleasure
to welcome Professor Outterson. Please begin. Hello, everybody. I’m here today to give you
an introduction to some of the issues that we
face around the planet with antibiotic
resistance and to tell you a little bit about what
we’re doing about that at Boston University. And as Maryn said,
I lead CARB-X, which the CARB is not a diet. CARB stands for Combating
Antibiotic Resistant Bacteria. It was a program that was
created under the Obama administration and
is carried forward into the current administration. And at Boston University, we
have the pleasure and the honor to lead a global
project that is directly addressing this problem. So if you had to pick where
at Boston University would you put this global partnership,
I know what you’re thinking. The first spot you’d put
such a global partnership would be at the law school. This is a picture of the
new law school building. If you’re an alum
from the school and remember the
old building, it’s been vastly improved as of late. But then, on the 12th
floor of the law school, it’s housed a small
team of people whose job it is to allocate,
to select and allocate funds to entrepreneurial developers
of innovative products, both new drugs, new
vaccines against bacteria, new diagnostics, as well as
some really amazing cutting edge products. The reason why this is
necessary is because we don’t have enough antibiotics. This slide, a lot of the data
is taken from both the WHO and from the Pew
Charitable Trust. And some people might look at
it and say, well, 42 antibiotics seems like a lot. There’s two problems with that. First is, if you compare
it to cancer drugs, there’s over 1,000
immuno-oncology drugs in clinical development today
and only 42 antibiotics. And secondly, most
of those antibiotics aren’t the type
that are targeting the most dangerous pathogens. They’re targeting
things that are easier to get a drug
approved, but not necessarily the things that keep the
people at the CDC up and awake at night. And even if we were able to
have perfect antibiotics, this is a problem that’s– it’s
more like painting the Golden Gate Bridge. As soon as you
started this project, as soon as you finished it,
you’d have to turn right around and go to the other
end of the bridge and start painting again,
because bacteria evolve. Whatever clever attack we have
on them, whatever clever drug, they will eventually
develop resistance to. It’s not true in the
same way for vaccines, which is an important reason
why bacterial vaccines are part of what we do at CARB-X. So here’s our first poll. And you heard the instructions. So I want you to click A through
F. There won’t be a grade. I’ll let you pick. But the question
is, how long has it been since we’ve had a new,
approved class of antibiotics that’s been approved by the FDA? So I’m not talking about a
discovery that’s just in a lab, but one that makes it all
the way through a pill that actually can help people. So we’ll pause. And click your answers. All right. I’m seeing C taking the
lead there, 20 or 30 years. One last chance before
I go into the next slide and show you the answer. There’s two main
types of bacteria– gram positives and
gram negatives. Gram negatives, all that
means is that the gram stain wouldn’t attach. They wouldn’t show up that
way under a microscope. They have two cell walls. They’re the more dangerous type. So for those of you who
picked 30 to 40 years, you’re correct for
gram positives. For those of you who
picked 50 or more, that’s the answer
per gram negatives. So to put this another way,
the most dangerous bacteria that the scientists
are worried about are those gram
negative bacteria. And how long has
it been since we’ve had a new class that made
it all the way to approval? It’s been my entire life. It’s been far too long. CARB-X is designed to try to
make these numbers go down. We want to see new approvals
of entirely novel classes. Now we can’t just pick
one or two companies and hope that they’re
the ones that work out. If we get nothing
from this slide, it’s the fact that
a lot of ideas start in the lab at
places like Boston University and many other
fine research universities around the world. And then they progress to
the small startup companies. And then, typically, they get
bought up by larger companies or licensed at some point. But most of the
projects don’t make it all the way to FDA approval. It’s not really a failure. It’s just normal science. When you try things with
science, most of the time it doesn’t work. You keep at it until
you get through it. But the import here is
that, if you want one drug, you might need to be investing
in 20 or 30 early topics, early projects, because
otherwise you’re not going to get what you really
want at the end of the day. So CARB-X, we’re not shooting
to pick one or two winners. We’re not that clever. Instead, we’re going to invest
in a portfolio of companies, as many as we can fund,
and that hopefully, at the end of the
day, we’ll have some exciting, powerful,
first in class products to help people. So this is a slide
about how we work. And I’d be a bad
principal investigator if I didn’t thank the people who
so generously provided funds. As of today, CARB-X has
up to $540 million US available over the first
five years of our project. That’s just north of a
half billion US dollars. And the largest funder is
the Assistant Secretary for Preparedness and Response
within the Department of Health and Human Services
through it’s group called BARDA, the
Biomedical Advanced Research and Development Authority. They initiated this accelerator,
CARB-X, with a $250 million request for proposals that
different groups applied for. And our group at
BU won that grant. The Wellcome Trust has committed
up to $155.5 million US. That’s 125 million pounds at
the time to CARB-X as well, the second largest funder. The NIAID, which is one
of the arms of the NIH, provides very
helpfully $50 million for the preclinical services
to products companies, which enables them to do
studies that they wouldn’t be able to do otherwise. We’re very proud to announce
and to have on our roster here two additional partners who were
not with us at the beginning. And that’s the government
of the United Kingdom, represented here by this
symbol, UK Aid, and the Bill and Melinda Gates Foundation. We’re in the late stages
of completing the agreement with the government of Germany,
who announced at the Grand Challenges Meeting in Berlin
some months ago that they were also joining CARB-X. So we take those funds. We take them through a rigorous
science review process. We use not lawyers,
thank goodness, but scientific experts
from our funders and a lot of experts that worked
commercially in antibiotic drug development over the past
decades, many of which no longer work at
large companies, because many of
the large companies have dropped out of this field. And they go through and
do a rigorous process by which more than 100
applications are sifted down to less than 10 for my
governance board, the funders, the joint oversight
committee, to select the ones that they want to fund. We administrate this
program in cooperation with Boston University,
like I said, the 12th floor the
law school, but also with many helpful partners. You see some of
them listed here. Wellcome Trust is
an accelerator. RTI, which is the original
tenant of the Research Triangle Park in North Carolina, is a
very important partner with us. California Life
Science is the group that represents and supports
small biotech companies of the West Coast and San
Francisco and San Diego and other parts of California. MassBio is a similar
organization here in Boston and then Broad
Institute and also DTRA, which is the US
government agency that tests pathogens that have
a bioterrorism potential. In other words, some drug
that CARB-X companies might be working on
might be intended to help against gram negative
infection in the hospital. It might also have
the additional benefit of being useful as a
defense in a bioterrorism sort of situation. So this is the basic
structure of CARB-X. There’s a lot going on. But our primary role is to
create a system by which we can select, with the
most integrity we can, the research projects
to go forward and then to support them with
as many resources as possible. If you thought back
a couple of decades, a lot of these companies or a
lot of these research projects would have been inside of a
large pharmaceutical company. Today, most of the large
companies are gone. And many, many of the
companies that we support are quite small. They might have a veteran from
a large company within it. But sometimes they’re 10 or 20
full-time equivalent employees. Some are even smaller than that. And we find that they need,
sometimes, conditional support. They may be very
strong in some areas, but not so strong in
some other things that are required to get the drug
all the way from the lab to the patient. And so we provide those
services, as well, to the companies. So we provide the money. We also provide
them with that sort of accelerator
business, scientific, and technical support. As of now, and you can see
this on our website, too, on carb-x.org. We’re funding projects today
in 32 different projects in six countries. This number will substantially
increase over this next year. We received over 400
applications last year. We’re in the process of
completing those now. And this number will
go up significantly over the next three months. The key point I
want to make here is that when we evaluate a
project, what we want to know is how powerful is the science? How impactful would the
program be to human health? And how good is
the team of people that are around this project? Can they really execute? Those are the things we ask. We don’t ask where they’re
from, which country or which part of the
country or what not. We’re agnostic in that
sense, to the geography. We’re looking for the
best science, wherever it’s found, which I think
is a tremendous advantage of the CARB-X system. You don’t have to be
from a given country in order to apply
for funding from us. We pick the science
where we see it. Now heretofore, a
lot of it has been in North America and Europe. But we are proud of one
company that successfully applied from India. And we try very hard to
encourage other applications from around the world. I talked about some
of this slide already. But just to emphasize,
we go after antibiotics and other therapeutics
including things like phage derived therapies, but
also rapid diagnostics, because a lot of
difficulties that we’re having is because we’re using
antibiotics inappropriately. We’re either giving
the wrong antibiotics or sometimes giving,
many times giving, antibiotics in situations
where we really don’t need to be giving an antibiotic. Better diagnostics would help
to reduce unnecessary use and help to target the use
of powerful antibiotics in the right setting. And then, as I said
at the beginning, it’s really important to think
about the long-term goal here. And prevention and
vaccines are tremendous. The best infection is the
one that never happened. And so we can
prevent them either through microbiome approaches
or monoclonal antibodies or through bacterial vaccines. All of that is good. When we need to know which
bacteria to be concerned about, we look to the list
generated for this purpose by the CDC and the World
Health Organization. There’s substantial
overlap between the two, as you would expect. Now when a company
is selected by us, they’re happy to receive money. CARB-X is non-profit. We don’t take a royalty. We don’t take ownership. It’s a grant. But we want to help
these companies succeed, because we want to see
impact, positive impact, on human health. So we also provide accelerators,
accelerator network. And we have the logo
here, at the bottom. And I think, before
the end of this month, we should be announcing six or
seven additional accelerators joining at CARB-X. I’m not in
a position to put the names out yet. But look for this. Look at the space. Check our website. By the end of the
month, it should be up. But what they’re providing
is all these other types of support, because we don’t
want a company or project to fail because they
the lack the money. We also don’t want it
to fail because they made a business, technical,
or a science mistake that could have been avoided. So we’re trying
to help them out. We’re looking for
the whole ecosystem. We’re trying to
invest in a portfolio and raise the tide
in a positive way for everybody, including
the companies we don’t fund. This is an important slide. Before I became
director of CARB-X, I ran a research program as
a law professor at BU Law. And this represents– it’s
kind of sad to think about it. This represents
many years of work between a whole host of
people that have been thinking about these sorts of issues. And it took a while for
this to come together. But it’s powerful. So let’s say that
all you cared about was access to antibiotics. You wanted them to be free
to everybody on the planet. That would ensure that
people got antibiotics. But it would also
destroy the ability of us to be careful with them. It would destroy
conservation or stewardship. It also would make it
hard for any company to make money on antibiotics,
if you’re giving them out for free. So it undermines innovation. If you just focus
on innovation, let’s create all sorts of
things like CARB-X to put new products
into the pipeline. But you didn’t care
at all about access, about how people both in the
United States and globally, whether the people who need
them the most whether they can afford them, whether
they can get them. If you don’t care about
that, then it’s unjust. And if you don’t do it without
thinking about conservation without stewardship,
without being careful not to waste them, then
you’re just running the same sort of mistake that
we made in past generations. We have to create new ones. We also have to be careful
with the ones we create. And finally, if all you do
is careful conservation, if you put every antibiotic
under lock and key, sure, they’ll last longer. But they’re not going to get
to the people that need them. And it’s also companies
can’t make money on something they’re not allowed to sell. So you have to do all three
of these things together. You have to focus on
all of them together. And at CARB-X, we’re
mainly about innovation. But we have significant
policies baked into our system which addresses
access and conservation or access to stewardship
simultaneously, because we know that do
one without the other two is ultimately a
waste of our time. So here comes our second poll. What do you think? Can we share
antibiotics [INAUDIBLE]?? Do save them in the
medicine cabinet or not? Please answer. I fear people have
listened too carefully to the rest of this message. I would encourage everyone to
listen carefully to your doctor when you’re in
prescription moment. There’s a lot of evidence that
patients push their doctors to prescribe an antibiotic
even when the doctor is reluctant to do so. It does you no good
to take an antibiotic if you have a viral infection. In fact, it does
you a lot of harm. It’s going to mess
up your microbiome. Similarly, if the
physician has told you to take that
course for five or 10 days, whatever the prescription
says, you should finish it. And the idea of taking an
antibiotic that was prescribed for you and offering to somebody
else for a couple of days if they get sick, these
are exactly the sort of things which are common. This happens all the time. But it’s clear that these types
of practices drive resistance. It might harm you. It might harm your family. And certainly it’s going
to harm the global effort to try to do
something significant about antimicrobial resistance. So this is a summation slide. I think I’ve talked about
most of the things on here. I could talk a little bit about
the access and stewardship provisions. In CARB-X, when the companies
receive funds from us, they make a promise. And the promise is
essentially that they’re going to work with
us and our partners to ensure that the
antibiotic, if it does make it all the way
to approval at the FDA or the European
equivalent or anywhere around the world
for that matter, that they’ll work with
us and our partners to try to get access and
stewardship as integral parts of that new drug
product that goes out. In the last couple
of minutes here I wanted to say something
about an ancillary program that, with the support
of President Brown, that we’ve been able to
start at Boston University really alongside of CARB-X.
This is a separate program. But it covers a similar topic. And this is called Social
Innovation on Drug Resistance, or SIDR for short. And this is what got
me thinking about SIDR. We have these amazing
innovations called antibiotics. And yet, when you
give them to people, to humans and the human
systems, they get misused. They get used in the wrong ways. They get overused and underused. And all sorts of negative
things happen as a result. When you take great vaccines and
you talk to people about them, sometimes people get
scared of vaccines and decide the
vaccines are dangerous. And that’s the reason
why we have outbreaks of things like measles
in the United States now and not sufficient uptake
on many other vaccines that were really
helpful to human health. And for diagnostics,
there is a number of companies with a
really clever technology that, if you understand what
they do, that you would think this is a great diagnostic. It’s a wonderful product. But when you try
to implement that in the human systems
of a hospital with all the complexities
of how hospitals are paid both for diagnostics
and paid for antibiotics and all the relationships
between the doctors who order tests and then how
those tests are interpreted and how long it
takes, it’s clear that what we lack right now
is not interesting technology, but a way to implement that
technology so that it actually changes clinical practice. Because, at the
end of the day, we don’t need a diagnostic that
does great things in the lab, we need a diagnostic that helps
people get better health care. And so SIDR is focused
on all of these issues of really the social
sciences of antibiotics. This is an area in which
we know that antibiotics or the whole problem
of resistance is a one that was
created by humans. We’ve made it worse through
the way that we treat and use antibiotics and whatnot. And so this effort
here is designed to begin research
programs in social science aspects of antibiotics. And like I said, the
initial seed funding was generously from
President Brown. We’re hiring postdocs. There’s I think, at
last count, 13 or 14 BU professors who are involved. And we’ll have five
or six postdocs eventually through the program. It’s housed not
at the law school but at the Institute for
Health System Innovation and Policy, which is another
part of Boston University. And they’ve provided
amazing support for getting this off the ground
in the past couple of months. And so with that, we
will have plenty of time, I think, for some questions. Thank you for your attention. And be careful with
antibiotics out there would be my closing word there. So Maryn, what
questions do we have? Thank you. We will now have our
question and answer segment of the webcast. As a reminder, if you would
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located next to the box. Your questions will
not be viewable by any other attendees. So Maryn, please go
ahead with their Q&A. So we have such
an active audience with so much response
to those polls that I’m sure people are going
to have a lot of questions. But while their questions are
amassing into the queue, Kevin, let me ask you a couple. My first thought is at
this point with the CARB-X having such a robust history
for the past couple of years, you have spoken to a lot
of antibiotic developers or potential developers. What’s the single
biggest deterrent to them actually
achieving the drugs that they envision creating? Without a doubt,
it’s not the science. It’s the money. I want to say that the NIH and
other funding organizations that fund basic science,
NIAID in the United States and the equivalents
in other countries, have done an amazing job funding
university-based projects. And we’ve seen
literally hundreds of interesting antibiotic small
companies that have spun out of universities,
and some of them homegrown research
within companies. But the science is really
an encouraging part. We will have, based
on our projections, by the end of this year,
by the end of calendar year 19, 20 projects within
CARB-X, that each of them would be a new class against
gram negative antibiotics. So if just one of
those succeeded, it’s the most innovative thing
in my lifetime for antibiotics. So the science is great. The problem has been the money. Antibiotics, the most
innovative antibiotic, we want to put behind glass
and not use it very much. And antibiotics have never
been high priced products. The most expensive antibiotic
in the world is about $10,000 for a course of treatment
which saves a life. Compare that to a lot of cancer
drugs and it’s really cheap. And so the problem
is that the companies don’t know how to make
money in this field anymore, which is why all the
big companies have left. They’re very
grateful for CARB-X. We’re a lifeline to these
companies in these late stages of translational research all
the way to the end of the phase one human trials. But there’s concern about
what happens afterwards, whether there’s any money
to be made when they finally reach the market. So that actually
dovetails beautifully with a question
that’s been asked by a member of the audience,
which is, if you, CARB-X, are taking care of that very
risky early stage funding, what happens after that? Let’s say that a
set of developers successfully leverage your
funds into a product that looks like it has potential
and can go into trials. Where do they find the
next tranche of money from? Well, there’s a
couple of sources. Traditionally, the big
companies would end license or would buy a product that
was ready for phase two trials. And so that would have
been the historic answer. But the company
are out there now, because they aren’t convinced
that there’s money to be made. In terms of charitable
money or government money, the US government, the agency
that leads our funding, BARDA, has been, for many
years now, the largest funder either in the US or
the world, depending how you count of
antibacterial phase two and phase three trials. And at counterpart
in Europe funded by the Innovative
Medicines Initiative, also part of the
European Commission, does have similar sort,
types of projects in Europe. But it’s not clear at all that
those funds are sufficient. In fact, I take
it more strongly. There’s not enough money to
advance all the way to approval the types of drugs that
we’re seeing coming through the CARB-X portfolio. We need more funds
for that purpose. And even upon approval,
for most companies, getting that stamp of
approval by the FDA is like you pop the champagne
cork and have a party. For antibiotics,
sometimes or even for most of the last companies
that have had an approval, it’s been quite a
disappointing event, because the sales after
approval are so thin. This is a great idea
for public health. We don’t want to abuse
these new antibiotics. We do want to save them. But we need to figure
out another way to reward these
companies, otherwise they’ll move on
to something else. So that’s depressing. So let’s dial back to a more
cheerful moment in the process, which is the moment
at which developers hear from you that
CARB-X is going to send them some funding. A member of the audience has a
multi-part question about this, which is, first, your
screening committee members who are helping you to
review applications, how do you choose them? How do you take into
account whatever biases are inherent in
their countries of origin or the work they’ve
otherwise done? And then, part two
of that question is, once you decide to make a
grant, what is the process, the milestones that the
person you’ve made the award to– or the company you’ve
made the award to or group– that they have to meet
in order to assure you that they were a good
selection and they’re doing what you funded them to do? Right. So I just want to have everyone
feel comfortable with the fact that lawyers are not
picking the companies. If lawyers are
good at something, it’s creating process
and following the rules. And so part of your question on
the scientific advisory board was how do we clear
them from conflicts. And we have just an
outstanding system of reviewing and adjudicating
any sort of conflicts of interest with our
advisors, with the companies that we’re dealing with. They have to disclose
all their financial ties, their consulting
ties, everything. And then we have an
external monitor, who’s not at Boston University,
who screens that and basically keeps us as unconflicted
as possible. But I’ll say it this other way. If you asked where
the people come from, a good number of them
are scientific experts from NIH and from some
of our other funders, from BARDA and other
technical academic experts. And then a number of them
are former antibiotic drug developers who used to
work at the large companies before the large companies
exited the field. And in the final
rounds of our process, we have generally 10 to 12
of these experts in a room. If the topic that
day is vaccines, then these are going
to be vaccines experts. If its microbiome,
we’ll focus on that. If it’s diagnostics,
we’ll set the room based on the topic that’s
coming in that day. But they come
physically to Boston. And the companies who are
finalists fly to Boston. They present live in
front of this group and have to stand
for what many of them say, what many of
the companies say, is the most scientifically
detailed, laser focused question and answer that
they ever have to stand for. And then they leave the room. And the group discusses
and argues for 30 minutes and then makes a recommendation
onto the funders. It’s an amazing process. I am really proud of
the robust discussion that happens and also
the fact that CARB-X is willing to take risk. We don’t want to just take
the things that are 12-0, everyone approves. We also want to
look at the things that a few people were
uncomfortable with. But we still think that the
risk and the reward, the reward is high enough that the
risk is worth taking. The second question– So let me prompt you to
the second part, yeah. Exactly. OK. The second question
is about milestones. And we don’t give them a
check for the whole $2 million or $3 million or
$5 million upfront. They send us
invoices every month. And we pay them
based on the budget that we’ve negotiated with them. And if it’s after a year
or a year and a half, we’ve built into
the budget, built into the system,
milestones that they’ll have to have met that
are generally scientific but occasionally
business and financial. So a scientific
milestone will say, you’re going to run a
series of animal tests. We want to see a
certain type of result before we’ll pay
for the next round to take the project
up to the next level. For a project that comes to
us in a very early stage, there might be two milestones,
two different milestone moments in which a significant
number of technical things have to be met. That’s reviewed again by members
of our science advisory board. It’s a formal process. And if the decision
is yes to go forward, that again goes back to my
board for approval to fund. So we’re serious in the same
way that venture capital or private investors
would be by milestones. We make both positive
and negative decisions at that milestone review. We’ve got a number of projects
that didn’t get the numbers. And we said thank
you, but we’re not choosing to exercise the option
to fund you going forward. And that’s not failure. That’s just science. And we want to encourage
those companies. And maybe they’ll come back
with something better later. But we’re going to
focus our funding on things that continue
to meet those milestones and move forward. So a couple of the
audience members have asked questions that I’m
going to knit together here that have to do
with what happens after the potential
products that you’re funding the early
research for leave from under the CARB-X roof. One audience member
would like to know, if a product is
successfully achieved, gets all the way
through development, how can adoption of that
product be guaranteed? And a second
related question is, if new products are
successful, whether it’s an antibiotic or
a diagnostic, how can they be put into the
market in a way that maintains the integrity of all
the sides of that triad that you discussed? Well, currently, there’s
no one who does that. Some companies will try
to do their very best. But they’re just a single
company involved in a market. We’re going to have a
portfolio of companies. By the end of this
year, we’ll have 50. Today we have 32. And by the time CARB-X
is done, whether it’s at the end of the first
five years or, more likely, this five year should be
renewed for another five, there’s literally going
to be dozens upon dozens of an unknown
number of companies that have come through the
CARB-X system and graduate. So we’re trying to change
how every company thinks about this. Every company is
introduced to thinking about access and stewardship. You work with them. When they graduate,
their obligations don’t cease to us on
access to stewardship that the proposal is successful. If the drug keeps
going forward, they’ll continue to work with us
and with our partners, like the Wellcome Trust, who
is the world’s second largest funder of biomedical research,
second only to the Bill and Melinda Gates
Foundation in terms of private funders of
biomedical research. And they’re very
interested in helping this process go forward,
as are the governments that support CARB-X. So I don’t have an answer. You can evaluate how
we’re doing in a decade, because that’s how long it will
take for one of our projects to actually get approved. But we have in place really
good global health leadership at institutional levels that
care deeply about this problem and will have a central role
in helping to move it forward. So because we’re talking
about stewardship, I have to ask the
following question because several audience
members have sent it in. I think it may, again, not
be under CARB-X’s roof. But I’m sure they’re interested
in your opinion, which is, how can you influence
the triad, I guess, of antibiotic development
and antibiotic use outside of medicine,
particularly in agriculture and agriculture in
the environment? Is there any– do you
have an opinion on that? Do you have any
thoughts to offer about controlling those uses? I think the chances
are low that anybody with the intellectual property
with the patent to a new class against the new class of
antibiotics useful in humans would license those
anymore into animal uses. That was a traditional
strategy many years ago. And some of the
other antibiotics used in animal agriculture and
non-animal agriculture today were antibiotics that
didn’t work out for humans. It fell out of the human
development program and it went over to the
animal side instead. So I think the key
will be finding ways to adequately reward the
companies for what they’ve done in terms of bringing
an amazing product to market without leaving them with
the terrible temptation of over utilizing it
in unnecessary ways. So the animals need
antibiotics, too. There should be more
research development for classes that work in the
species that need the most. But we shouldn’t be put in the
situation in which things that are important to
global human health are wasted in other capacities. A subject close to my heart. So we’ve talked a number of
times in this conversation about the role of
the government, ways in which the government is
assisting with this process and not. What’s going on right now, given
that a good portion of the US government is shut down? Is that affecting CARB-X’s
process or the things that developers need to
be doing at this point? We are not at every agency. We’re trustees of
Boston University. So CARB-X is 100% functioning. A lot of our funding comes
from Health and Human Services, which, just due to the
way things happened, had appropriations before this
shutdown for the most part. There’s a couple of parts
within HHS that lack funding, but none that
directly touch CARB-X. But more broadly, there’s some
elements of CDC that, I think, don’t have money. I think [INAUDIBLE]
health service is one. And in the FDA, the
commissioner has been tweeting about how many
things are not functional right now at FDA. He’s restarted the high risk
food safety surveillance program and inspections using
unpaid volunteers and people who– just like when
I got on the plane yesterday at Boston
Logan, I asked the person checking my passport after
she was done whether she was on furlough and not being paid. She said, yes, none
of us are being paid. So it’s astonishing
what people, the service that they’re rendering right now
and without having a paycheck now for almost a month. But there are parts
within the FDA that will increasingly
have strain. And our strain today will
be strained even more over the coming weeks. But they don’t
directly affect us yet. Long-term though,
there’s a lot of things that CDC and HHS and
other parts of HHS do that are just
behind the scenes. They collect data. They do surveillance. They sponsor scientific work on
trying to track new outbreaks. None of that is front page news. But it’s exactly the
sort of hardcore science that we need to have continue
to go forward in order to know who the enemy is. It’s like, you wouldn’t
go into battle with all of your soldiers blindfolded. The agencies that are on the
front line of this battle need to have their tools. So let’s all hope that the
government comes back soon, that Congress and the White
House reach an agreement and we have full functioning
at all federal health agencies again. Is there anything,
looking forward, that you would like to see
the federal health agencies– particularly, I
suppose, the FDA– be doing differently around
antibiotic development and approval and associate
approval of, like, diagnostics? Or are there things about speed
of approvals or trial structure or anything that
you’re picking up that is dissatisfying
to drug developers? So I think this is the one area
in which if you asked 50 drug developers how the FDA is doing,
I think almost all of them would say the FDA is
really doing a great job. I know the drug developers
love to complain about the FDA in some other categories. But in this area and the folks
that lead this at US FDA, I think the industry understands
they’re doing a wonderful job. Do you remember, earlier,
that I said something about how hard the market was? And you said, that’s
really depressing. That’s the thing I
would go and fix. If I was able to wave a
wand and get governments to do something, I
would design a way to pay antibiotic
developers’ companies for the wonderful,
powerful social value of these antibiotics in a way
that was completely not linked to how many pills they sell. This is one product that
we want to pay people today really for generations
of value, but not what it’s going to
be used for tomorrow. That’s called, in the
policy lingo, delinkage or a pull incentive or
a market entry reward. But these are ideas of ways to
pay for antibiotic innovation based on how valuable
it is for society, not based on the volume of pills
that are put into patients. So I just forced
you to talk about what, possibly, the government
could do differently. But most of the
people on this call probably are not members
of the government. So is there anything you can
say to the audience about– is there any role in this
complicated conversation about getting more and
better antibiotics where individual action
makes a difference? Is there anything that people
on this call can do to help? The CDC puts out a
scary chart every year of how many antibiotics
people are taking by state. And if you looked at the
states in Appalachia, like West Virginia, and
compared them to some places like California, you’d find
twice as many antibiotics being taken in certain
parts of the country than they are in California. And so it raises the
question, are people dying of antibiotic
bacteria, resistant bacteria in California? Or are they pretty healthy? It’s probably true that
the difference represents not a mistake, you know,
too little antibiotics in California. It might be people taking
too many antibiotics in other parts of the country. And it’s really not
just one region. If you looked on the map. It’s a lot of states
that fall onto that. The CDC estimates
that more than half of the antibiotics that are
taken by people probably are inappropriate in the United
States, that they’re being taken for a condition that
would resolve on its own if you waited another day or
two or that were never bacterial to begin with, were viral. And so if we wanted to
eliminate half of the problem with generating resistance,
it would be just everybody not pushing their doctor
to get an antibiotic when the physician really
thinks they can wait. So thinking a bit more
about who’s on this call, we’ve actually gotten a question
from the audience about what is the submission process
to CARB-X. I think we’re going to have to assume
that some developers dialed in at the last minute. So I assume that
in your audience is someone who
actually is a developer and wants to approach
CARB-X for a grant. What should they do next? And where do they
find that information? So it’s on our
website, carb-x.org. And it shouldn’t
be hard to find. We’ll open rounds. We don’t have any
open rounds today, because we’re digestion
those 400 applications we received last year. But in short order, we’ll
be announcing the rounds that we’ll have open for 2019. And there will be
multiple rounds that will be open in 2019. And on the website, we’ll
put the dates that they open and what the topics are. So if I’d say diagnostics,
the application date is this week in
the certain month. And for vaccines,
here’s the dates. And that will all be
available on the website when we’ve made a final
decision on the 2019 rounds. You apply during that
week that it’s open. And our initial
application is called an expression of interest. We designed it to
be non-confidential. We don’t want to know
anything that’s business confidential at that point. And it’s designed to be
the sort of thing that could be filled out by the
scientific lead of a company in about an hour. We didn’t want hundreds of
companies spending weeks on creating this thing. We wanted the first application
to be relatively simple. The next middle round
of applications, it’s about a 10
page application. The final application
is quite serious. It’s 50 pages. Plus you come and stand up
live in front of our ad board and answer questions. So we wait most of the work
towards the latter stages of the program when your chances
of success as a developer are higher. So we’re coming up on
the top of the hour. And I’m going to close the
call in a moment or two. But before we do,
I wonder, Kevin, if there’s any kind
of final statement you’d like to make about
CARB-X, about the urgency of the project
you’ve undertaken, about what you’d most
like people to take away from this encounter today. The history of the
antibiotic era, since we’ve had
antibiotics and medicine, it’s a tremendous thing. It’s probably the most
important, most impactful class of drugs in human history. It would be hard pressed to
point to another one right now in terms of the total
number of lives saved. And unlike most of these other
drugs, you have to maintain it. You have to take care of it. It goes away if you
ignore it because of the way the bacteria
evolve and respond and mutate over time. And so we’d love what the
antibiotic era has given us, the ability to do
things like hip implants or cancer treatment, which
depresses your immune system and would make you
susceptible to infections but for antibiotics. Cesarean sections
and common things that are done in the
hospital, all of them would be much more dangerous
without antibiotics. So I think it’s something
most of us take for granted. And we think of them as
inexpensive and always available and easy to get. And the goal of CARB-X is
so that the world does not change radically. We don’t want our
kids or grandchildren to be living in a
post-antibiotic era. So we’re trying to get
new classes, new vaccines, new devices teed up and ready
to go so that things don’t have to change dramatically. It’s kind of an
anti-revolution [INAUDIBLE].. The idea of a post-antibiotic
era and all the ways that society would change
if we lost antibiotics is profoundly terrifying to me. As you say, everything
from the loss of major surgery to the
losses of minor things we take for granted, to me,
more than anything, it’s the loss of just a casual
comfort with which we live our lives now, a comfort
that our grandparents and great-grandparents didn’t
have because they didn’t have the protection of antibiotics,
that we would go back to the terror they
felt at any infection, at any scratch at the
advance of any dirt is a profoundly
disturbing thing. And we’ll hope that
the work that CARB-X is doing in identifying
worthy developers is going to hold that era
off as long as possible. So thank you so
much for sharing. Go ahead. I was going to say, when
you read Jane Austen, people are always writing
letters to each other. And the first thing
they ask is how everyone’s doing, if anyone’s
sick or about to die. And everyone’s eager to
get on a horse or carriage and ride off if
somebody is sick, because they know that
if they wait a day, mom or their sister or
their spouse could be dead. We don’t even,
when we read books like that from prior centuries,
we can miss just how prevalent and how quick death
came by infection. We have mostly forgotten that
the most, the very first human to receive penicillin
experimentally, police constable Albert
Alexander, in the UK, was so desperately sick that he
needed this experimental drug because what he had done
was walked into his garden and scratched his
face on a rosebush. And that rosebush infection
eventually killed him. We will hope we will
never be back there again. So now I really must
end the program. Thank you for sharing
your insight with us, to this complex world of
antibiotic development, the pharmaceutical industry,
and this profound need to develop new antibiotics for
these superbugs that menace us. And we’ll trust that
the research that CARB-X is supporting is going
to bring us further along the path of always
having new antibiotics. And audience, thank you so
much for being here today. We’re about to
conclude the webcast. But first, it’s my
job and my honor to thank you for your
participation and for all that you do to support
Boston University. The university is
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