Latest / CareTalk: Healthcare. Unfiltered. / Preparing for the Pandemic We Haven't Seen Yet w/ Dr. Dan Barouch & Kris Brown, Vector Sciences

Transcript

Preparing for the Pandemic We Haven't Seen Yet w/ Dr. Dan Barouch & Kris Brown, Vector Sciences · CareTalk: Healthcare. Unfiltered.

• 0:00
  David: The COVID-19 pandemic proved that vaccine platforms can move at unprecedented speed, but it also exposed how much of the world's response rested on a narrow set of technologies.
• 0:11
  David: mRNA dominated the headlines, but what happens next time when the threat is a hemorrhagic fever, a respiratory virus that spreads before symptoms appear, or a deliberate biological attack?
• 0:23
  David: Dr. Dan Barouch and Chris Brown have built Vector Sciences around a different concept that durable preparedness depends on optionality, multiple modalities, mucosal immunity that can block transmission, and a platform built for the threats we don't know yet.
• 0:46
  David: Welcome to CareTalk Executive Features, where we host leaders of innovative healthcare organizations.
• 0:51
  David: I'm David Williams, president of Health Business Group, and host of CareTalk.
• 0:55
  David: Today's guest, Dr. Dan Barouch, is a virologist and vaccine researcher whose work spans HIV, adenovirus- adenoviral vector platforms, and the COVID-19 vaccine effort, including the science underlying the single-dose Ad26 approach.
• 1:10
  David: He's co-founder of Vector Sciences and a developer of the Reovax platform, which is built on rhesus adenovirus vectors.
• 1:18
  David: Chris Brown, he's co-founder of Vector Sciences as well.
• 1:20
  David: He's an angel investor, senior law partner in the life sciences and technology practice group at Goodwin Procter LLP.
• 1:27
  David: He's advised on more than 250 life sciences transactions spanning M&A, public offerings, licensing, royalty monetizations, and strategic alliances, and he counsels investors, executives, and boards on governance and securities matters.
• 1:40
  David: Dan and Chris, welcome to CareTalk.
• 1:43
  Kristopher Brown: Thank you.
• 1:44
  Kristopher Brown: Thank you, David.
• 1:46
  David: So Dan, you spent your career in virology, and I wonder what did you see that convinced you the world still needs a new vaccine platform, and so what problem was Vector Sciences funded and founded to solve?
• 2:00
  Dr. Dan Barouch: The pandemic led to the emergence of novel vac- novel vaccine technologies, including mRNA vaccines, viral vector vaccines, and other vaccine platforms.
• 2:12
  Dr. Dan Barouch: These proved incredibly effective.
• 2:15
  Dr. Dan Barouch: However, no vaccine platform that we have today is perfect.
• 2:19
  Dr. Dan Barouch: They all have strengths and limitations.
• 2:21
  Dr. Dan Barouch: And so the rhesus Ad platform is intended to capitalize on a number of the positive features of prior adenovirus platforms, but with added efficacy and safety features
• 2:35
  David: So mRNA was certainly the story of the pandemic, and I think probably the, uh, recognition of that term went from 1% to 99% pretty quickly.
• 2:45
  David: Um, but you are both talking about its limitations as much as its strengths.
• 2:50
  David: So I'm wondering, what did COVID teach us about the strengths and the limits of mRNA, and why does relying on a single modality, no mat- no matter how good, concern you?
• 3:01
  Dr. Dan Barouch: mRNA vaccines have tremendous benefits.
• 3:05
  Dr. Dan Barouch: They're simple to make.
• 3:07
  Dr. Dan Barouch: They can be manufactured rapidly.
• 3:09
  Dr. Dan Barouch: They're flexible.
• 3:11
  Dr. Dan Barouch: They induce high titer antibody responses, at least in the short term.
• 3:16
  Dr. Dan Barouch: And they're easily deployable.
• 3:19
  Dr. Dan Barouch: However, they also have some limitations.
• 3:21
  Dr. Dan Barouch: Uh, they require a cold chain.
• 3:24
  Dr. Dan Barouch: Uh, in some cases, the durability has been limited, um, as well as, uh, the biophysical stability.
• 3:33
  Dr. Dan Barouch: And it's been known to be associated with certain, uh, cardiac toxicities in small numbers of cases as well.
• 3:40
  Dr. Dan Barouch: So while mRNA vaccines have tremendous benefits, then, uh, there is also a number of drawbacks.
• 3:45
  Dr. Dan Barouch: And so having a portfolio, having a variety of different vaccine platforms is beneficial, because ultimately, different vaccine platforms may be more useful in different settings.
• 3:59
  David: Okay, so you talk about optionality, and that's the idea of having, you know, multiple vaccine modalities in the toolkit, and I'm wondering, you know, why does that diversification matter, and what do we lose by consolidating around a single approach?
• 4:12
  David: You know, why not just consolidate around, like, the best approach?
• 4:15
  Kristopher Brown: I think what we saw with COVID is that there was a, a, a belief that vaccines were what we'd receive when we were kids.
• 4:26
  Kristopher Brown: You know, a single shot would protect us against mumps, rubella, you know, the other, the other childhood diseases that we were used to, um, getting vac- vaccinated against, and that that would have, uh, a lasting, almost lifetime, um, effect on our, on our ability to stave off those diseases.
• 4:43
  Kristopher Brown: When COVID came along, we used this term vaccine to describe what really were immune boosters, temporary reprieves or the ability to kind of increase antibody, uh, antibody levels in the body to stave off the disease for short periods of time.
• 5:01
  Kristopher Brown: We also found they were very, very expensive.
• 5:04
  Kristopher Brown: They had to be delivered via needle, and if you get jabbed, you know, f- three or four times a year, that's pretty tough.
• 5:11
  Kristopher Brown: So, um Coming up with a, a different modality that could give long-term effect, actually be a vaccine where you were protected for years, not months, and something that, in the case of Rheovax, the platform that we've developed, can be delivered mucosally, for example, through a, an inhalation to, you know, through the nose versus a jab to the arm, was, was something that we felt was needed to kind of bring trust back to the world of vaccines.
• 5:44
  Kristopher Brown: You know, people were being told they were getting a vaccine, and again, they were used to something that would last a long time.
• 5:50
  Kristopher Brown: That wasn't happening, and they were getting sick.
• 5:53
  Kristopher Brown: And, you know, what really should've been said, first by the, you know, first administration, then by the administration, in my opinion, was you're not really getting a vaccine so much as you're getting, um, a, a way of being protected against death from this virus.
• 6:09
  Kristopher Brown: Uh, you may get sick, but you won't die.
• 6:12
  Kristopher Brown: That would've been better messaging perhaps to a community of, of, of people who are already a little bit skeptical of vaccines.
• 6:19
  Kristopher Brown: And then you bring into the mix, um, the leadership in, in this HHS and FDA that are already somewhat skeptical of vaccines generally, and it was kind of adding fuel to the fire of that skepticism.
• 6:32
  Kristopher Brown: So we think that we need to bring kind of honesty about what's going on and an approach that's simple and understandable to people to treat infectious diseases which have been with mankind and plaguing mankind since the beginning of time.
• 6:47
  David: Okay, so adenoviral v- vaccines also have been around for a bit, and I think even for COVID, J&J's vaccine and then the Ebola vaccine are proof points that people may be, may be at least somewhat familiar with.
• 6:59
  David: But as I understand it, the Rheovax platform is using rhesus, uh, vectors specifically.
• 7:04
  David: So I'm wondering what makes those vectors different, and why does that difference matter?
• 7:09
  Dr. Dan Barouch: So the rhesus adenoviral platform is related to the human and the chimp adenoviral platforms that were used in the pandemic, uh, but has, uh, several advantages.
• 7:22
  Dr. Dan Barouch: One is, uh, likely efficacy advantage, uh, because there is no baseline immunity in the human population to the vectors themselves, whereas human adenoviruses are the common cold, and so everybody has had the common cold before.
• 7:39
  Dr. Dan Barouch: And perhaps more importantly, uh, there is a potential safety advantage as well.
• 7:45
  Dr. Dan Barouch: Uh, one of the limitations of the AstraZeneca and J&J vaccines, uh, despite their durable protective immunity, uh, is that in very, very rare cases, about three in a million, then they caused a thrombosis side effect, uh, which in some cases was very serious.
• 8:06
  Dr. Dan Barouch: Uh, and recently The molecular basis of this thrombosis effect has been reported, and is believed to be the, uh, cross-reactivity of an adenovirus protein called P7, uh, that led to antibodies that bound to a human coagulation protein called platelet factor 4, and is believed to, uh, trigger this cascade in very, very rare cases that lead- leads to thrombosis.
• 8:39
  Dr. Dan Barouch: So a key feature of the adenovirus platform is it does not have the key epitopes in the P7 protein that, uh, have been linked to this thrombosis effect.
• 8:53
  Dr. Dan Barouch: So, so our belief is that the rhesus Ad platform, uh, will likely have both efficacy advantages and safety advantages compared with the existing Ad platforms.
• 9:06
  David: So one of the interesting parts of the work is the focus on the mucosal intranasal immunity.
• 9:11
  David: And as I understand it, you know, respiratory viruses are typically entering through mucosal surfaces, but most of the vaccines are designed to generate systemic immunity.
• 9:20
  David: So can you help me understand the difference between systemic and mucosal immunity, and why that matters here?
• 9:28
  Dr. Dan Barouch: Sure, absolutely.
• 9:29
  Dr. Dan Barouch: So when we think of the immune system, we typically think of antibodies or T cells in the bloodstream that help fight off infections that are distributing throughout the body.
• 9:44
  Dr. Dan Barouch: And one of the best ways of inducing immune responses systemically in the bloodstream is through an intramuscular shot.
• 9:54
  Dr. Dan Barouch: However, there's another component of the immune system, which is the immune system on mucosal surfaces, such as antibodies in the, um, upper and lower respiratory tract.
• 10:07
  Dr. Dan Barouch: Turns out that antibodies in the bloodstream don't move very well to the mucosa and vice versa.
• 10:14
  Dr. Dan Barouch: So an intramuscular shot, even if it raises high antibody titers in the bloodstream, it really doesn't raise high antibody titers in the respiratory tract, particularly not the key antibodies known for mucosal immunity, which is called IgA.
• 10:34
  Dr. Dan Barouch: The way that we know can induce mucosal antibodies is by a viral infection, uh, delivered to the respiratory tract, for example, a native influenza or COVID-19 infection.
• 10:52
  Dr. Dan Barouch: So we had a hypothesis that The respiratory vaccines are often lower efficacy than other vaccines because the intramuscular shot does not optimally induce mucosal immunity.
• 11:10
  Dr. Dan Barouch: And an example is the influenza vaccine.
• 11:14
  Dr. Dan Barouch: It's known by the CDC to have about 19 to 60% effectiveness over the last 20 years.
• 11:20
  Dr. Dan Barouch: Uh, this year, uh, was one of the lower, on the lower end of that.
• 11:24
  Dr. Dan Barouch: The COVID-19 vaccines, although, uh, they do a very good job at preventing severe disease and hospitalization and death, which is incredibly important, they actually don't do a very good job at blocking acquisition of infection Um, so, so the, so the contrast is, uh, measles and polio and other classic vaccines that have 90, 99% efficacy.
• 11:50
  Dr. Dan Barouch: So we had a hypothesis that the difference between respiratory vaccine efficacy and other classic vaccines was because respiratory vaccines given by the intramuscular route failed to raise sufficient antibody and T-cell responses on mucosal surfaces.
• 12:08
  Dr. Dan Barouch: Essentially, that's the portal of entry of the virus, and then the virus can enter the respiratory tract, replicate unimpeded, causing, you know, mild but still troublesome, um, uh, upper and lower respiratory disease.
• 12:23
  Dr. Dan Barouch: And only once it distributes further out, uh, and goes systemically does the immune system really kick in.
• 12:29
  Dr. Dan Barouch: So we showed in a series of publications over this past year that the, uh, ResusAd platform can be delivered through, uh, the respiratory tract, intranasal, intratracheal, et cetera, and can raise robust responses on the mucosal surface, and that leads to, uh, in experimental models, leads to substantially improved protection against pathogens such as COVID-19 and influenza.
• 12:55
  David: Chris, before, um, you know, you had talked about some of the practical advantages.
• 13:00
  David: So Dan just explained some of the scientific advantages assuming a person gets the vaccine.
• 13:04
  David: But let's talk about some of the practical elements.
• 13:06
  David: So you mentioned, uh, you know, you don't need a needle.
• 13:10
  David: Uh, it's probably easier for someone to administer it as well, not just to, to receive it.
• 13:14
  David: The cold chain.
• 13:15
  David: You know, I remember when the, the Pfizer vaccine came out, and people needed these, you know, special freezers, and how are you gonna make sure it stays cold all the way through, and to be able to scale up, uh, quickly.
• 13:25
  David: So how much… If you look at this case for intranasal, how much is it about better immunity versus better deployment?
• 13:32
  David: And what are the, you know, what are the overall, uh, applications of it, if so?
• 13:36
  Kristopher Brown: Well, it's-- the good news is, is it's really both.
• 13:39
  Kristopher Brown: That's the beauty of this platform.
• 13:41
  Kristopher Brown: You do not need a cold chain.
• 13:42
  Kristopher Brown: In fact, you can p- lyophilize.
• 13:45
  Kristopher Brown: You can, you can put this in a powder form and, and re-administer it, um, so it's much easier to store at almost any temperature for much longer periods of time.
• 13:54
  Kristopher Brown: And of course, you don't need all the equipment associated with injections and new needles, et cetera, so you remove that element.
• 14:02
  Kristopher Brown: And again, um, as Dan mentioned, if you create a mucosal immunity, remember these, these- bugs are coming at us through the air, right?
• 14:13
  Kristopher Brown: So it kinda makes sense we would wanna stop them at the place where we first experience air in our lungs and in the mucosal system.
• 14:21
  Kristopher Brown: And if you do that, you actually wind up reducing what's called viral load in the body, which means that a person who has this mucosal immunity is not just not getting systemic, you know, um, uh, infections, but they're also not transmitting, uh, because they don't have a high viral load to third parties.
• 14:41
  Kristopher Brown: Remember, a big part of this was that you, you may have gotten your shot, your, your Pfizer, your Moderna, et cetera, but you still didn't want… couldn't be around people or had to wear a mask because despite the fact you might not be getting sick, you were still infecting other people.
• 14:58
  Kristopher Brown: We're able to eliminate that as well with this approach
• 15:03
  Dr. Dan Barouch: So I'll, I'll add one other, one other feature that, um, uh, many people are hesitant to get vaccines because they're needle phobic.
• 15:13
  Dr. Dan Barouch: They really just don't like needles.
• 15:15
  Dr. Dan Barouch: Uh, and so a vaccine that can be delivered as a spray in the nose or maybe a puff, um, uh, potentially could reach a group of people who otherwise, um, may be less enthusiastic to get vaccines if they don't like needles.
• 15:30
  Dr. Dan Barouch: So we think that's an additional practical deployment advantage.
• 15:34
  David: That makes sense.
• 15:34
  David: You know, I just tell people just, like, tough it out, but, uh, some- somehow that doesn't work as a public health message when you're trying to get someone to, to take your
• 15:40
  Kristopher Brown: friend's medicine.
• 15:40
  David: It's
• 15:40
  Kristopher Brown: not g- it's not good when you're telling kids to, to, to get a needle, does it?
• 15:45
  Kristopher Brown: I, uh, what about- Um, I also want to just echo, uh, the, the, the study that was done.
• 15:48
  Kristopher Brown: Actually, it was done with, uh, in collaboration with Pfizer, where they compared… Or one of the studies was done in collaboration with Pfizer, where they compared their, their phase three, uh, uh, stage, uh, mRNA platform for influenza against ours.
• 16:04
  Kristopher Brown: Um, we delivered ours both, uh, intramuscularly to compare it directly to how they do, and then also mucosally, and we compared that to the marketed, um, currently available, uh, flu vaccines, and ours was significantly superior both to what's marketed, but also to Pfizer's.
• 16:23
  Kristopher Brown: Um, again, Pfizer's is, is more advanced.
• 16:26
  Kristopher Brown: It's been through human clinical trials, and they have a lot invested in getting that out there.
• 16:30
  Kristopher Brown: But it was significant to, to, for us to show that ours was superior to even theirs.
• 16:34
  Kristopher Brown: We have a little more work to do, right, to get into humans, et cetera.
• 16:38
  Kristopher Brown: But, um, I think that's, that's quite exciting to think that, that we're outperforming even the, the, the, the latest versions of these mRNA drugs.
• 16:48
  Kristopher Brown: And, and one thing Dan alluded to, but just to be clear, the, the current-- with the current technologies, the lipid nanoparticles or the, the s- systems by which the, uh, mRNA medicines are delivered, the vaccines are delivered are, are… They, they can't get across the mucosal barrier.
• 17:03
  Kristopher Brown: The, it's just not possible.
• 17:05
  Kristopher Brown: So they can't be delivered, at least in current forms, mucosally.
• 17:08
  Kristopher Brown: So that's a limitation to mRNA vaccines full stop
• 17:13
  David: Got it.
• 17:14
  David: So I'm hearing about, you know, we've been talking about COVID, but also hearing recently about things like Ebola in particular, uh, Bundibugyo, if I'm saying that right, uh, hemorrhagic fever, and preparedness on the vaccine side, you know, is, is flagged as a gap.
• 17:29
  David: I think there's a, a lot of concerns about how we can actually handle such outbreaks, and especially, you know, with the US stepping back from its traditional role in global public health.
• 17:39
  David: So why is it so hard to establish a rapid re- a rapid response vaccine infrastructure for these viruses, and are you hoping to play in that area as well?
• 17:51
  Dr. Dan Barouch: So for Ebola, there are several licensed vaccines already.
• 17:57
  Dr. Dan Barouch: One is based on a VSV vector, the vesiculostomatitis virus vector, and a second one is based on an adenovirus vector, Ad26.
• 18:08
  Dr. Dan Barouch: Um, and there are funded efforts to bring, um- VSV-based vaccines, um, adenovirus vaccines, as well as mRNA vaccines forward for the Bundibugyo outbreak.
• 18:27
  Dr. Dan Barouch: Uh, the current vaccines against the traditional Ebola virus Zaire strain are believed to be less effective or maybe not effective against Bundibugyo because of strain differences.
• 18:41
  Dr. Dan Barouch: So the, the idea is that, that dedicated vaccines are likely gonna be needed.
• 18:47
  Dr. Dan Barouch: One of the problems with pandemic preparedness is that we don't know which is going to be the next outbreak.
• 18:53
  Dr. Dan Barouch: So the current, um, vaccines would've been immediately deployable if this were an Ebola virus Zaire strain outbreak.
• 19:03
  Dr. Dan Barouch: Uh, but it was a rare strain called Ebola virus Bundibugyo.
• 19:07
  Dr. Dan Barouch: So, so when a new vaccine needs to be made, we can do that now faster than ever before, as evidenced first by mRNA and second by adenoviral vaccines during the COVID-19 pandemic.
• 19:22
  Dr. Dan Barouch: But still, that still takes, um, uh, months, not days or weeks.
• 19:28
  Dr. Dan Barouch: And so that process is underway now to create new vaccines for the Bundibugyo outbreak.
• 19:36
  Dr. Dan Barouch: So I guess the answer to your question is really twofold.
• 19:39
  Dr. Dan Barouch: First, um, it still takes months to make a new vaccine and, uh, at least it's not years anymore, but it's, it is a number of months.
• 19:48
  Dr. Dan Barouch: And, and second, um, uh, the vaccines tend to be strain specific, so we need to invest in more, uh, vaccine platforms, and we also need to invest in vaccine antigens that are cross-reactive that could lead to reactivity against multiple strains of Ebola, not just one single, because the next Ebola outbreak might be even yet a new strain.
• 20:16
  David: So we've been talking about vaccines, and we've only kind of, uh, indirectly discussed, uh, the HHS, HHS Secretary Jr., who has notably strong views on this topic.
• 20:28
  David: I'm curious how you think that your platform will be viewed or has been viewed by him, uh, and his team.
• 20:36
  Kristopher Brown: Take a, take a stab at this.
• 20:37
  Kristopher Brown: I, I, I believe that, um, Junior is most concerned with safety.
• 20:47
  Kristopher Brown: Um, he is, uh, very concerned about often the adjuvants, the mercury and other additives that are put into the suspension to keep the vaccines stable.
• 21:01
  Kristopher Brown: Um, and I think frankly, he's concerned by the terminology again, that was used in describing these as vaccine to a popu- a population, which, which, you know, he's close with that are suspicious of, of the side effects and other things that come, that have come along with some of these medicines.
• 21:21
  Kristopher Brown: So I think what something like the Riovax platform will do and, and, and can do to, to someone like Junior, who's somewhat skeptical, is address each of those concerns in the sense it is a real vaccine creating durable long-term immunity.
• 21:41
  Kristopher Brown: It is safe, meaning it's addressed the known side effects.
• 21:47
  Kristopher Brown: Um, it is easy to manufacture and, uh, not expensive and so can be delivered quickly.
• 21:56
  Kristopher Brown: And it again, creates this, um, durable long-term, uh, uh, immunity that, you know, puts trust back into the, the word vaccine.
• 22:07
  Kristopher Brown: So I think someone like , um, is particularly interested in this.
• 22:13
  Kristopher Brown: We know this because a similar platform that's based upon a gorilla form of the adenovirus was approved this past August to treat a type of, um, it's called, uh, papillomavirus.
• 22:29
  Kristopher Brown: It's a, it's a treatment for a form of respiratory human papilloma, papillomavirus, which is HPV essentially, which you may know is quite a common, uh, type of, uh, infection that occurs in women and often leads to cancer, uh, cervical cancers in women and, and throat cancers in men.
• 22:49
  Kristopher Brown: And, uh, this was approved and, and under this administration.
• 22:53
  Kristopher Brown: So we feel that he would probably be quite keen to see this type of platform move forward
• 23:00
  David: Great.
• 23:00
  David: So if we look at, uh, biodefense in the US right now, you've got a lot of different alphabet soup agencies, BARDA, HHS, NIH, Department of Defense increasingly.
• 23:10
  David: So I'm thinking about when you're considering strategy and policy for a, a small company like yours, how do you build these relationships?
• 23:20
  David: How does that really work, and how can you kinda hit on the areas that government's gonna be interested in, uh, so that you actually are, are able to be a rising, you know, to rise with whatever tide may be, may be rising at the time?
• 23:35
  Kristopher Brown: Well, again, I'll just echo kind of what I said before.
• 23:37
  Kristopher Brown: I think it's r- super important to be honest about what we've had in the past and what has worked and what has not worked, to be critical of some of the approaches that were taken, frankly, by people on both side of the aisle, and to learn from those lessons and present options that address those limitations and that, that work, again, and that don't require, you know, every three to four months one having to get a, a jab again and again.
• 24:05
  Kristopher Brown: Um, I think that, that that is what this administration is looking for.
• 24:11
  Kristopher Brown: Uh, they put a lot of money into trying f- f- for example, focus on, uh, a, a universal flu influenza vaccine.
• 24:20
  Kristopher Brown: This is a major focus for this administration.
• 24:23
  Kristopher Brown: Dan, again, alluded to it somewhat in trying to deal with any infectious disease.
• 24:27
  Kristopher Brown: We deal with the various strains that come out.
• 24:29
  Kristopher Brown: Historically, every season, as you know, there's a different strain of flu.
• 24:34
  Kristopher Brown: But working to try to find those elements that are kind of conserved or exist year to year that can be presented in a vaccine such that even if the strain varies quite a bit, the, the fundamental or, or basic form of it is being addressed by the vaccine, is something that I think they are… will be very, very, um, likely to support.
• 24:56
  Kristopher Brown: Um, they wanna keep America healthy.
• 24:59
  Kristopher Brown: Um, it's not a situation where, um, they're looking to, you know, uh, not have people be vaccinated.
• 25:07
  Kristopher Brown: They just don't want people to get vaccinated and have side effects or discomfort associated.
• 25:13
  David: So you referred to the RioVax platform, but we're talking about also making individual vaccines.
• 25:20
  David: What's the relationship between the platform and a given product, and why is it important to describe yourself as a, you know, platform company as opposed to one that's making a vaccine for a given virus?
• 25:33
  Dr. Dan Barouch: So the, the, the rhesus ad vectors are a delivery tool in a similar way that the mRNA lipid nanoparticle is a delivery tool.
• 25:44
  Dr. Dan Barouch: It's a method of delivering any antigen of choice to the human immune system.
• 25:51
  Dr. Dan Barouch: So you can add to that any antigen you want, such as COVID spike to make a COVID vaccine, influenza hemagglutinin to make a flu vaccine, and you can go down the list of any pathogen you want.
• 26:04
  Dr. Dan Barouch: So the platform is really the delivery tool, and when that is coupled with, um, the key piece of a viral target or bacterial target, then that becomes the vaccine.
• 26:19
  Dr. Dan Barouch: So in a similar way that the mRNA platform is generalizable but can be deployed for COVID-19, for influenza, for RSV, then similarly, the rhesus ad platform is a general delivery platform and can be utilized for a target of choice.
• 26:39
  Kristopher Brown: And although we focused here in this conversation on infectious disease, what's really interesting about the rhesus adenovirus platform is that the, the body, we call it the capsid, is actually quite large and can hold quite a lot of genetic information.
• 26:55
  Kristopher Brown: So it could also be used for gene therapy, in theory, for cancer vaccine, for CRISPR delivery.
• 27:02
  Kristopher Brown: It has that potential.
• 27:04
  Kristopher Brown: Frankly, so does mRNA, in theory, but there's a lot more room and a lot more stability, as we just described to you, by using a, an a- an adenovirus.
• 27:13
  Kristopher Brown: So we're quite excited because it really is a platform upon which all sorts of infectious diseases could potentially be addressed.
• 27:21
  Kristopher Brown: And, um, we have focused for the, for the moment on, uh, on, on flu, um, because that's a, a major, major market.
• 27:29
  Kristopher Brown: There's a huge unmet need.
• 27:30
  Kristopher Brown: It's an area that, again, this, this administration is focused on.
• 27:34
  Kristopher Brown: But we would be able to very quickly, and have done preliminary work to show that it could work with this latest strain of Ebola, for example, if needed.
• 27:42
  Kristopher Brown: And others using those analogous platforms, albeit with some of the safety limitations, are also proceeding in that same way.
• 27:51
  Kristopher Brown: Um, so it-- there's just quite a lot of things one can do with this technology, and we'll see, we'll see what, what we wind up focusing on in the end.
• 28:01
  Dr. Dan Barouch: So if I, um, can add to that, then, you know, coming back to a theme at the earlier part of our conversation is one of diversity and options.
• 28:11
  Dr. Dan Barouch: That, uh, for, for the country or the world to have a, an arsenal of, of vaccine technologies is very important, and have diversity of platforms is very important because each one will have, uh, strengths and limitations.
• 28:28
  Dr. Dan Barouch: And there's some applications for which, uh, one will just be a better choice than another, and other, o- other targets in which there could be multiple adequate platforms, in which case patient choice is also very important
• 28:46
  David: So one technology that's certainly come to the fore since five years or six years ago with COVID is AI.
• 28:53
  David: And as I hear you, Chris, talking about, you know, a wide potential range of where this platform could be used, does AI and other technologies like computational biology, did those come into play as you consider how to leverage the platform?
• 29:07
  Kristopher Brown: They absolutely do.
• 29:09
  Kristopher Brown: AI is an incredibly useful tool, including, um, i- i- drug discovery, of course.
• 29:15
  Kristopher Brown: It's being used for understanding how proteins fold, et cetera.
• 29:19
  Kristopher Brown: That's made quite a lot of news, but also used in the, in the context of patient selection to see which drugs might work on certain subpopulations based upon the proteomic or multi-omic characteristics.
• 29:31
  Kristopher Brown: In, in, in our case, it c- it's a very, very useful tool for trying to best assess what are those antigens or epitopes that should be associated with the vector to induce the immune response.
• 29:45
  Kristopher Brown: I'm gonna make this really simple.
• 29:47
  Kristopher Brown: Dan sometimes makes fun of me when I use this example.
• 29:49
  Kristopher Brown: But think of this delivery system as a bit like a tank which has no ammo on board, no guns, but it looks pretty scary 'cause it's a tank.
• 29:59
  Kristopher Brown: And it shows up on the beach, and the Marines, you know, get crazy, and that's sort of your antibodies, and they get really excited.
• 30:07
  Kristopher Brown: But as we know, the Marines are sort of the, the expeditionary force there to stop things.
• 30:12
  Kristopher Brown: They can't really hold back the whole army, but they keep it at bay until the full army can arrive.
• 30:17
  Kristopher Brown: And, and so when you show up with an empty tank, they can't do much fighting, and the Marines keep it at bay.
• 30:22
  Kristopher Brown: That gives time for the army or this durable longer term immune system to get activated, so when the real tank with the real armor or the real virus with more than just the spike protein shows up, the body is ready to act and, and kill it, and fight, fight it.
• 30:39
  Kristopher Brown: And so, you know, AI is enabling us to have a better understanding of what are… what can, what can look like a really scary tank to the body and activate the immune system in the best way so that you create a very long-term durable response.
• 30:55
  David: Dan, I don't see how anybody could quibble with that characterization- and I could see it going right in, right into a GM, uh, abstract.
• 31:03
  Kristopher Brown: Now that I do, Dan.
• 31:04
  Kristopher Brown: You okay with it this time?
• 31:06
  Kristopher Brown: Dr. Dan Barouch: Now we'll
• 31:09
  David: Good.
• 31:09
  David: All right.
• 31:10
  David: So maybe a final question is, you know, we've been talking about, you know, how do you, how do you act within the current environment for public health, federal administration, and, and so on.
• 31:21
  David: But turn around a little bit and say if instead of trying to build the company and to fit into that, you're an advisor to policymakers, and you're trying to encourage innovation before the next crisis, which is, I think, something that, uh, generally speaking, uh, listeners would like to know about.
• 31:36
  David: You know, how would you advise on balancing speed, safety, public confidence so we get to a more optimal approach?
• 31:45
  Kristopher Brown: Well, I, I'll take a quick stab at this, but Dan, you should fully answer.
• 31:48
  Kristopher Brown: I would say, again, restoring trust, communicating to people about y- you know, really speaking the truth.
• 31:55
  Kristopher Brown: If, if you have to simplify it, that's fine, but, but don't tell people they're getting something that they're not getting.
• 32:01
  Kristopher Brown: Be very honest about it.
• 32:03
  Kristopher Brown: Don't underestimate the ability of people to understand, you know, what we're talking about here.
• 32:08
  Kristopher Brown: And if you have to use an a- analogy like the tank I did to convey that message, that's what we need to do.
• 32:13
  Kristopher Brown: We need politicians who are willing to do that.
• 32:16
  Kristopher Brown: Don't just tell people to take a shot, trust us, it's gonna work.
• 32:19
  Kristopher Brown: Explain the, the, the issues, ex- explain the advantages, some of the disadvantages.
• 32:24
  Kristopher Brown: And a- again, an educated population is going to, you know, make good decisions about protecting their health and the health of their families and communities.
• 32:36
  Dr. Dan Barouch: So, so I would, I would add that if I were an advisor to current policymakers, I would, I would suggest that, uh, there's investment in a variety of vaccine platforms, uh, each of which may have pros and cons.
• 32:53
  Dr. Dan Barouch: Um, I, I think that all the vaccine platforms we discussed today are… can be outstanding choices in certain situations, but may not be outstanding choices for all situations.
• 33:05
  Dr. Dan Barouch: And so having a diversity of selection is very important.
• 33:09
  Dr. Dan Barouch: Also, investing in the platforms so that they are ready to go when needed is very important.
• 33:15
  Dr. Dan Barouch: Um, uh, otherwise, we would only be going back to the same limited platforms.
• 33:22
  Dr. Dan Barouch: Um, uh, so, so, so I, I think, um, investing in a variety of platforms, a, a diversity of platforms, to the stage where they are all, uh, rapidly deployable is, uh, uh, would be very much in the public interest.
• 33:39
  David: Makes good sense.
• 33:40
  David: Well, thanks to Vector Sciences co-founders Dan Barouch and Chris Brown for a conversation that goes well beyond the last pandemic and how-- and gets into how we're gonna get ready for the next one.
• 33:51
  David: We've been talking about how preparedness means having a deep bench of technologies in place before we need them, rather than waiting and hoping that one breakthrough approach is going to save us.
• 34:01
  David: Well, that's it for this executive feature of Care Talk.
• 34:03
  David: I'm your host, David Williams.
• 34:05
  David: Thank you for listening, and thank you, Dan, and thank you, Chris.
• 34:10
  Dr. Dan Barouch: Thank you.
• 34:10
  Dr. Dan Barouch: Thank you very much.