Video | September 9, 2020

What's Happening On The Front Lines of COVID-19: A CEO Roundtable On Technologies In Development For The Current Pandemic

Source: Life Science Leader

(recorded 9/9/2020)

Four biopharmaceutical industry CEOs and company cofounders converse with Rob Wright, chief editor of Life Science Leader, on what their organizations are doing to spur the development of diagnostic tests, therapeutics, and vaccines in order to turn the tide on the COVID-19 pandemic. Appearing in this video are:

  • Brian Culley, CEO, Lineage Cell Therapeutics
  • Peter Diamandis, M.D., founder and executive chairman, The XPRIZE Foundation; cofounder and vice chairman, COVAXX
  • Mei Mei Hu, J.D., cofounder and co-CEO, COVAXX
  • Jonathan Javitt, M.D., CEO, NeuroRx

Editor’s Note – The following is an edited transcript from a Zoom call virtual roundtable conducted on Wednesday, Sept. 9, 2020, with four biopharmaceutical industry CEOs and company founders.

Hello, I’m Rob Wright, chief editor of Life Science Leader. And as you can see, I’m still sporting my COVID-19 DIY [do it yourself] haircut. Speaking of COVID-19, we’ve seen a lot of media attention and hype around what is going on with regard to treatments, vaccines, and new diagnostic tests being developed. So, we thought it’d be really cool at Life Science Leader, to bring together some CEOs whose companies are working diligently on the front lines to develop everything from new tests, to vaccines, to therapeutics. So, let’s quickly meet our panel and then we will go into doing some direct questions. Starting with you, Brian, can you introduce yourself please?

Brian Culley, CEO, Lineage Cell Therapeutics: Hi Rob, I’m Brian Culley, and I’m the CEO of Lineage Cell Therapeutics.

Peter Diamandis, M.D., founder and executive chairman, XPRIZE Foundation; cofounder and vice chairman, COVAXX: Hi, Peter Diamandis. I wear a couple of different hats as executive founder of Singularity University and founder and executive chairman of XPRIZE. But here today, I’m serving as cofounder and vice chairman of COVAXX. And in that effect, I work for Mei Mei Hu, our CEO and cofounder.

Mei Mei Hu, J.D., cofounder and co-CEO, COVAXX: Hi, I’m Mei Mei Hu, and I’m the co-CEO and cofounder of COVAXX.

Jonathan Javitt, M.D., CEO, NeuroRx: I’m Jonathan Javitt, the CEO of NeuroRx.

Wright, Life Science Leader (LSL): Thanks everyone for being here today. I wanted to get started with some direct questions. Peter, you mentioned that you’re here today kind of representing COVAXX, but I think we’d be ignoring the pink elephant in the room, if we didn’t talk a little bit about a contest that you’re somewhat involved around COVID-19 diagnostic tests. Could you tell us a little bit about that?

Diamandis (XPRIZE Foundation, COVAXX): Sure. In response to the pandemic, hopefully anybody who has been able to try and bring to bear their resources to help address has. The XPRIZE Foundation, where I serve as executive chairman alongside CEO Anousheh Ansari, an amazing woman, we developed a number of areas. First off, we have a next generation mask XPRIZE that Marc Benioff, the chairman CEO of Salesforce, and Jim Kramer, host of Mad Money on CNBC, have co-funded an effort to reinvent the face mask. [The 8-month contest, launched in July 2020, invites young innovators ages 15-24 to rethink and redesign surgical-grade protective masks, to create an effective and accessible solution that overcomes common barriers for use. A grand prize winner, plus two additional teams, selected by a panel of judges and industry experts, will split a $1 million prize purse and be connected to rapid manufacturing opportunities in the U.S. to accelerate production.] With the help of some incredible individuals, including Jeff Huber, founding CEO and chairman of Grail, a cancer detection company, and Daniel Kraft, M.D., chair, XPRIZE Pandemic Alliance Task Force, we have developed an XPRIZE for rapid diagnostics. And this is really, what’s the next generation of PCR [polymerase chain reaction, a technique used in the lab to make millions of copies of a particular section of DNA first developed in the 1980s] that is super cheap, super fast, and super mobile, to help us identify super spreaders and identify people at places of work, school, worship, wherever it may be, to help us stem the COVID-19 pandemic from spreading further. So, that’s an ongoing competition. What’s amazing is we’ve had over 500 teams around the world register for this $5 million rapid diagnostic test competition in under 30 days.

Wright (LSL): You said it’s ongoing, but I thought there was a date of when the prize was going to be awarded.

Diamandis (XPRIZE Foundation, COVAXX): Yes, there is. I don’t have the final date right now, but registration is open, and then it’s going to go from a registration phase, to a competition phase, to a finals phase.

You can learn more about the XPRIZE Foundation via this short YouTube video.

Wright (LSL): Okay, great. You’ve got that going on that you’re involved with, so tell us a little bit about how COVAXX came about.

Diamandis (XPRIZE Foundation, COVAXX): I’ve had the pleasure of knowing two incredible CEOs, Mei Mei Hu, and Lou Reese, who are the co-CEOs [of COVAXX], and I’ve been on their board for a company called Vaxxinity [formerly United Neuroscience], and Mei Mei can go into the science there. But we’re talking about synthetic peptide multitope vaccines and diagnostics. About six months ago, it’s hard to remember the exact date, but it was early March, and Mei Mei calls me and says, “Listen. Our technology had looked at the original SARS-CoV virus that happened some 20 years ago, but never broke out [into a pandemic]. We think we could mount a vaccine and serology diagnostic rapidly.” And I said, “Great, let’s do it.” We ended up creating COVAXX. In the first 30 days we had 30 different vaccines that ultimately led to the lead vaccine for which we are selecting patients for entering a Phase 1 trial to launch within the next few weeks. We made a big announcement today in Brazil, but I’m going to leave that stuff for Mei Mei to talk about.

Wright (LSL): Okay. Well, I did have a question, because I know we are doing some things at unprecedented pace in regard to vaccine development. I’ve interviewed a lot of CEOs and executives, so this question is kind of to Peter and Mei Mei. To get a company up [and running] this quickly, and have a pipeline that rapidly, to put people in place, I would imagine you’re doing a variety of different things, probably outsourcing some things. Maybe you could tell us a little bit of how you do all of that so fast?

Diamandis (XPRIZE Foundation, COVAXX): Mei Mei [Hu], secret sauce? We talk about COVID speed, and I will say one thing and then hand it over to Mei Mei, which is, the entire leadership team has sort of been a capitalist commune. We’ve colocated and have been working together for the last six months. It’s been heads down from 6:00 AM to midnight. I’m sure, for many of the companies here, the level of intensity has been extraordinary.

Hu (COVAXX): It’s definitely on “COVID time,” which is essentially accelerating everything. We’re fortunate, because we have infrastructure from affiliate companies that we basically borrow from. So, we set up a new legal entity called COVAXX just to focus on COVID-19, put all IP [intellectual property] into that entity. But then, we basically borrowed from teams and said, “Who wants to work on COVID-19?” And I promise you, everyone was like, this [she raises her hand], I want to be part of it. So, we were fortunate that we have a platform, and that includes not just the technology, but also the infrastructure, the teams, and the manufacturing, to be lent and to be re-resourced to tackle this. We’ve been doing things at unprecedented speed, just like everyone else. But it’s been really remarkable and an honor to be working side by side with these folks. And as Peter [Diamandis] said, we had the pleasure of actually having most of the executive team living together, integrating together, and working nonstop on it. It has only been the last week or two since the whole pandemic started that we really haven’t been colocated. It’s about finding people who are willing to be impassioned by the mission, and basically dedicated to getting things done on an impossible timeline.

Wright (LSL): So, Mei Mei [Hu], I’m just curious, so you’re at your organization and you have this idea of where you can make a difference. A lot of us have ideas, and then we don’t do anything about ‘em. What made you decide to pick up the phone to call Peter, and tell me a little bit about your process of weighing this?

Hu (COVAXX): Everything just starts as an idea and you just got to kind of see what gets traction. To be honest, COVID is larger than anything we’ve ever seen before. So, if you have an opportunity to get involved and you really believe you can make a difference, why wouldn’t you make it happen right? Everything else is on hold anyway. We are all people who like to get things done that that help the world for a positive impact, so we couldn’t think of a better mission. Then the question is, “Are there other people who are like minded?” And so the first call we made was to Peter [Diamandis] because, you know, if you think of who in the world do you know that wants to make a positive impact, and can share the bright outlook of the future with others? You know, he’s at the top of the list, not to mention he’s a great friend, so that connection was easy. You know, pulling together the resources and finding other people who were aligned with that mission was also easy, because at the time everyone wanted to make a difference. Now, figuring out how to structure it was a little more difficult, along with getting everyone aligned. But once you’re aligned, then you just run.

Wright (LSL): One quick follow up question. So, I know Peter [Diamandis] had mentioned something about the science that was involved. And so the question is, what makes what COVAXX is doing a little bit different? Help us understand a little bit of the differentiation.

Hu (COVAXX): Well, I’m biased, because I love our platform. It’s a synthetic peptide vaccine platform that we’ve been developing and actually been repurposing into humans over the last six to eight years. We’ve run four clinical trials off of it. This is a proven vaccine platform. First, it’s completely synthetic, so there’s no biohazard risk, because we never touch the virus. We get the sequence, and like some of the newer technologies, we run off the sequence and mimic the biology through a chemical process. But you know, one of the differentiators and where we feel like we have a major advantage, is this isn’t theoretical. We’ve commercialized vaccines. Sure, they’re for animal health indications. But they’ve been against infectious diseases. Everyone’s going to face clinical risk, but where we can shine and move forward, is we know how to manufacture. We know how to scale up. We don’t require a special cold chain shipment at -80 degrees to deliver. So, there are other risks that we managed to mitigate off of our platform because we’ve done it before. Our parent company has done it before. And now Lou [Reese] and I have the great fortune and privilege of repurposing and redirecting it to COVID-19. What it allows us to do is actually attack COVID-19 in multiple ways, as we have a multitope approach. Everyone’s going after the spike protein, which is a very rational target, because that’s where the virus attaches, and we want to neutralize that. But also, there are other parts of the virus that the body responds to and elicits T-cell responses. So we’re not just relying on one part of the puzzle, we’re actually going multiple forms to make sure that we generate a broader immune response that activates both the B and the T-cell arms of the adaptive immune system, so that we can optimize our chances at getting something out there that is safe and efficacious. So, it’s all about mitigating risk that’s unnecessary, and increasing the probability of success when we do get out there.

Wright (LSL): Let me ask just one follow up question with regard to the trial status. We’ve seen a lot of attention being paid to, you know, Russia has something, and other people are saying we can have something sooner than we thought as so forth. There’s a lot of that, so I’m just wondering about an update as far as where COVAXX is as far as the clinical trials.

Hu (COVAXX): Yeah, there’s a lot of noise in the COVID space. We’re not worried about that, because it’s not a race to the clinic. It’s a race to the patient. Not only that, but t’s a race where many people can win. At the end of the day, we’re confident we’ll have a very good vaccine. We just filed and got approved for our IND in Taiwan. On the heels of that, we just announced a partnership for a Phase 2/3 efficacy trial in Brazil. We’re basically doing site prep and screening, and we’re about to dose that any day now. So, we’re well into our way on the clinical adventure, and it is not the traditional development path as probably everyone on this panel knows. We’re doing things on top of each other and in parallel, as opposed to serially. So, everything is happening alongside each other, just so we can put things and stagger them on the heels.

Wright (LSL): So, Peter [Diamandis] and Mei Mei [Hu], one of the questions that I want to ask, and I promise Jonathan [Javitt] and Brian [Culley] that I’m coming to you, but I was curious when you talk about the location of these trials, is there anything being done to help facilitate harmonization maybe between countries so they’re accepting data?

Hu (COVAXX): Traditional drug development is often on a global integrated basis as well. So, it’s very important to be communicating with the regulatory agencies so that different data is accepted by others. We’ve had history of doing trials in Taiwan and then moving into an FDA IND, so I see that as less of an issue. Really, it’s COVID chasing. There are logistics involved in running these trials. So, you want to go where the outbreaks are. You want to go where the patients are. You want to go where you can execute it. As a result, we’re not just betting on one location. We have an integrated global development plan and are running trials in multiple geographies. This is being done for two reasons. One is out of practicality, and two, because you are dealing with different regulatory agencies, you’re going to be essentially negotiating and communicating with each individually. While we want to be going after the big markets, and we may get approval in a different jurisdiction first, and that’s okay. The goal is to get this out there to people, once it’s shown to be safe and effective, as soon as possible.

Diamandis (XPRIZE Foundation, COVAXX): This is likely to be a long game, as COVID-19 is not miraculously going to go away. It’s going to enter our viral ecosystem and be something that we’re going to have to deal with for some time, just like a variety of flus are. My heart goes out to those who’ve been impacted economically and health wise, but I think of COVID-19 as a practice pandemic, and it could have been a lot worse, in terms of the mortality of this virus. We’re becoming aware about how we respond, because it’s not the first nor the last pandemic that we’re going to see. So, how do we respond faster, better, and more efficaciously in the future.

Wright (LSL): Thanks, Peter [Diamandis]. I wanted to transition real quick to Jonathan Javitt and NeuroRX. Cause I’m curious, and I bet other people on the call are probably curious as well Peter, about how a clinical-stage, small molecule company that’s developing CNS oriented therapeutics, gets involved in treating respiratory failure in COVID-19 patients. I just want to understand how that happens.

Javitt (NeuroRx): Well, you know, it’s one of those extraordinary accidents. Some people say that chance favors the prepared mind, and believe it or not, vasoactive intestinal peptide [VIP], which is the active ingredient we’re working with, is a neuroendocrine peptide. We were originally thinking about this in the CNS context, and one of our investors came along and said, well, we have this company, over in Switzerland, that’s been thinking about this from a COVID-19 perspective. And sure enough, it turns out that when, professor Sami Said [pronounced sigh-e-da], who spent his whole life developing this peptide, you know, really understood what it did, even though it was first identified in the intestine, which is why it has this funny name. Seventy percent of the VIP in the body is in the lung. And it seems to have one critical function in the lung, which is to protect the type II alveolar cell. Most people have never heard of the type II alveolar cell. In fact, when I was in medical school, I don’t even think we knew that there were type I and type II cells. But this rare cell that is only about 5 percent of all the cells that line the lung, is the cell that is critical for the flow of oxygen, from the air into the bloodstream. And it makes the surfactant that lines the lung. Without that surfactant, the lung can’t transmit oxygen. And this virus that humanity has never really encountered before SARS [severe acute respiratory syndrome] came along, attacks that one cell. It’s almost like hitting a needle in a haystack. And it attacks that one cell, because that cell happens to have ACE2 [angiotensin converting enzyme] receptors on its surface. So, those funny spikes that you see on the virus [images], they bind right to that receptor. It’s like a key fitting a lock, and the cell says, “Come on inside.” And as soon as the virus is inside the cell, it starts to make millions of copies of itself. It starts to let inflammatory cytokines loose all over the body. It ruptures the cell and it shuts down surfactant production. So, all of a sudden, people who don’t even look that sick have no oxygen in the blood. They can’t walk from their bed to the bathroom without falling down on the floor. And what we learned, what we expected is that this would be a potent anticytokine. We thought it would do a great job of blocking cytokines, and a great job of increasing surfactant production. And then, low and behold, a group of people we never heard of at the Oswaldo Cruz Institute in Rio de Janeiro, [Brazil], reached out to us and said, “You know, that molecule you’re working with, here’s the data that shows that it blocks the replication of the SARS virus in human lung cells. So, it was, it was a total “holy cow” moment for us. It was, “Now we see, why we’re seeing extraordinarily rapid recovery in the clinic.” When we went into the clinic with this drug, and we literally went from paper files, because nobody had used this drug in humans for 10 years, to freshly formulate a drug with a fresh FDA certificate of analysis in human beings in 10 weeks. When we went into the clinic, we expected to see an anti-inflammatory effect. We expected to see some of the same effects that Dr. Said saw in 2005, when he used this drug against acute respiratory distress syndrome caused by sepsis, where seven out of eight people walked out of the ICU alive, when you would expect at least five of them to have died. What we didn’t expect to see was chest X-rays clearing in three and four days. We didn’t expect to see that some of the early results we’ve reported, where out of the first 21 patients treated outside our clinical trial, as they were too sick to get into our clinical trial, and 11 of those people have done very well. And 19 out of those 21 people have survived to 28 days, which is the cutoff that NIH generally uses (i.e., 28-day survival is a critical endpoint). So, we’ve been very surprised by the magnitude of response we’ve seen in the open label studies. And now we’re about a month away from the first unblinded look at the Phase 3 randomized control data. So, you know, we’re wondering, are we seeing the world’s biggest placebo effect or we’re really onto something

Wright (LSL): I’ll be interested in hearing what you find out, but Jonathan [Javitt], I am curious about how it came about. I mean, I know I talk to a lot of executives in the business world, and when they’re talking about core competencies, you know, what is core to the company. And when I think about what was kind of core to your company, and then of course I could see you saying, well, patients are core, but was there some internal struggle just with thinking about, “Hey, we’re going to be pivoting here a little bit.”

Javitt (NeuroRx): I think the thing that is core to our company, is we’re just not afraid of anything. And we’re especially not afraid to go to FDA and say, “Please help us break the rules.” I mean, there was 10 weeks from paper files to drug in the clinic in patients. Well, that’s never gonna happen through traditional GMP manufacturing, or through standing up a fill and finish manufacturer. Those people take six months just to get their machines tuned up. So, we went to FDA and said, “You’ve got this list of 50 formulating pharmacies that you say, past your inspection. These are 50 tiny little pharmacies that you say are safe. You didn’t shut them down. You actually certified them as formulating pharmacies. How about we make this drug in one of those formulating pharmacies?” We’re literally making this drug by hand in order to be able to get it into a Phase 3 trial, you know, overnight and FDA was willing to help us break those rules, or at least willing to waive those rules and recognize that if we’re facing the worst public health crisis in the last hundred years, we’ve got to be willing to do things in new ways. Otherwise, we’re just dinosaurs, looking at that asteroid coming closer and closer.

Wright (LSL): I’m curious Jonathan [Javitt] about the formulating pharmacy’s idea. That’s kind of an interesting approach. I imagine you’re also trying to figure out how to do the scale up, as you’re doing it now and well in advance so things can continue to progress. Could you tell a little bit about where the idea came about?

Javitt (NeuroRx): Well, we’re not going to try that one twice. So, we’ve actually just signed a contract with one of those fill and finish manufacturers that we’re hoping to announce very shortly. They are actually the largest manufacturer of sterile inhaled drug in the world. Although our clinical trial is with intravenous drug, we’ve already announced a trial that we intend to start quite shortly with an inhaled version of this drug for people not with critical COVID-19 (i.e., not the people on ventilators we’re treating right now), but people with earlier stage disease, in the hopes of keeping them from going on to ventilators. We started out in a very nontraditional way, and we’re morphing as quickly as we possibly can to sort of rock-solid traditional scale up.

Wright (LSL): Want to get to Brian Culley with Lineage Cell Therapeutics. Brian, tell us what you’ve been doing at Lineage to tackle COVID-19.

Culley (Lineage Cell Therapeutics): Hey Rob. Well, you, whether intentional or not, you’ve got three groups that have non overlapping emphasis. And what I mean by that is that, Jonathan [Javitt], not to speak for him, but, I think he’s primarily concerned with the sickest of the sick patients. And I think Mei Mei [Hu] and Peter [Diamandis] are really concerned with things like, cost, scale, chain of custody, and friendly temperatures. We’re operating in a slightly different area. At Lineage, we are focused on trying to provide a real, what I’ll say, super vaccine. What do I mean by that? Well, all vaccines have something in common and that is that their job is to educate your immune system. So, the vaccines present foreign material to a person’s immune system, and a lot of vaccines rely on different kinds of boosters or adjuvants and carriers and so forth. What we do is, we rely on the body’s natural cell to perform that job. So, the body has a group of cells called dendritic cells, and they are nature’s most potent antigen presenting cells. They were designed to pick up foreign material and present it to your immune system and basically educate or teach your immune system, “Hey, this is what foreign material looks like, go eradicate it.” Whether that foreign material comes from a cell that’s lost its ability to control growth (i.e., a tumor), or whether that foreign material comes from a bacteria, or a virus, if it’s foreign and you want to get rid of it, you have to educate the immune system. So, we’re harnessing the power of the dendritic cell to educate a patient’s immune system. We could put, for example, a spike protein from a SARS-CoV-2, or other antigens or other foreign material, and load those messages into dendritic cells, and inject dendritic cells by the millions into patients. It’s almost like the post office. You’re carrying this most important information, but you’re not relying on the pony express or a carrier pigeon, but using the best system possible. And that’s really what our total technology is based on (i.e., the ability to manufacture a specific kind of cell and expand those cells into the many millions and then use those cells as treatment). And so, deploying one of our programs into COVID is simply choosing a viral antigen as the messenger, or the information which we’re carrying rather than a tumor antigen.

Wright (LSL): Got it. So, so where are you in the development process as far as clinical trials and so forth?

Culley (Lineage Cell Therapeutics): Yeah, it seems like it should be a straightforward question, but almost all of us in the space are doing some kind of repurposing. It’s almost impossible to come up with something completely from scratch. We’re all relying on some component of our business and repurposing or adapting. In our case, we have a clinical trial running right now. It’s actually the third in a series of clinical trials, though it is not a Phase 3, and it’s in a cancer setting. So, we have a cancer antigen, which is being delivered by these dendritic cells. What we can do, because that antigen is just a plug and play, is we can manufacture a different antigen “cassette” if you will, and drop that cassette into our dendritic cells, and then move forward into clinical trials. One of the convenient things is that we’ve been able to get into clinical trials without having to do any of the traditional animal studies. That has to do with the nature of dendritic cells, their safety profile, and what happens if you put them into a different species. So, we think that there’s an opportunity here to move very quickly. But our vision is really more about what Peter [Diamandis] referenced, which is we [as a society] got lucky. This one could have been a lot worse. And there’s no promise that the next pandemic that comes along is going to be any easier. It could be more deadly. It could be more infectious. It could mutate at a faster rate. So, our view is that there are patients out there for whom a really robust T-cell response [could be appropriate]. We’re not emphasizing the antibodies. That’s the job of some other companies (e.g., Pfizer and AstraZeneca). We’re really thinking about the T-cell response, because that’s where you’re going to get durable, multi-year protection. Nobody wants this pandemic, or a future pandemic, to be a seasonal problem. It starts to become incalculable, both on the economy and on the impact on human health. So, we are focused on using the power of dendritic cells to get these very strong T-cell responses, because that is where you get your multi-year protection.

Diamandis (XPRIZE Foundation, COVAXX): Brian, I like your notion of a platform and a cassette. I think a lot of where biology is going is platform plays. It’s the same and true for COVAXX, in terms of using this synthetic peptide platform that you then put in the appropriate elements that focus your immune system towards the COVID-19, which in this case is six different epitopes on the vaccine. But the thing that ultimate links all of the companies here [on the call] is agility (i.e., the ability to take what you have, and point it at a new enemy in a very agile fashion). And I think one of the key things is, how do we have the regulatory system allow for such agility, to maximize frankly, CEOs and entrepreneurs willingness to take the eye off this ball and focus it on that opportunity when it’s needed.

Wright (LSL): Which is a great question, because we’ve seen a lot of controversy. In fact, we saw an open letter, right from, nine executives saying, “Hey, we’re going to stand by the science, and we want the FDA making the approval based on science, not politics.” But then when you see the FDA kind of shifting and adjusting to be able to accelerate development, you get the concern about politics maybe helping to manipulate. So how do we do that?

Javitt (NeuroRx): I haven’t seen any evidence that FDA is being less stringent with people. They’re certainly not being less stringent with us. What they’re doing is being a lot quicker at being stringent. Meeting requests that used to take 60 and 90 days, all of a sudden take 60 and 90 hours to be answered. And when, when you send them a question, they’re turning around the answer in 48 hours. In 30 years of knowing the FDA, I’ve never seen anything like this. I’ve gotten emails from FDA scientists that they wrote and sent at 2 AM in the morning. It’s one thing to relax the standards, and it’s another to step up and apply those standards as quickly as you possibly can for the benefit of humanity.

Wright (LSL): When Mei Mei [Hu] talked about the [COVAXX] team being sequestered if you will, and working from like 6:00 AM till late at night, obviously the FDA has to be doing the same thing. Because I have been to at least three or four presentations, back when we went to in person meetings and presentations, and I remember seeing Janet Woodcock’s slide deck, and the number of vacancies at the FDA were consistent almost from year to year with regard to how many gaps they had, and wanting to fill those gaps. And yet, we’ve seen them be able to accelerate. So, I don’t know if we’re giving the FDA enough credit, as people are working pretty darn hard over there.

Javitt (NeuroRx): Well, part of what’s changed things, and we really have Scott Gottlieb to thank for this, is the 21st Century Cures Act that was passed some three and a half years ago. And then we had Scott [Gottlieb] come in as commissioner to really implement that act. And Congress finally gave the commissioner of the FDA, the tools that were needed to attract the best and the brightest, which included some real salaries. All of a sudden, FDA is able to pay salaries, that while certainly not at the top of industry scale (i.e., not paying anybody millions of dollars), but they’re able to pay somebody enough of a salary to leave a major pharmaceutical company and take a job as a regulatory scientist approving drugs. And without that the agency can’t work.

Hu (COVAXX): I think everyone’s doing their best, and like many things it’s, often a case by case basis. But, I think overall, I would not like to be in the FDA shoes right now. There’s a lot of, major decisions coming up and a lot of pressures, that take great strength to have high integrity. There’s a lot in the balance, right? Supreme court hearings usually say, you know, you’ll override a law in the interest of public health. I can’t imagine a time where we have more of that riding on these decisions, and you’re never going to please everyone. So, it’s not an enviable position. I think we have to give them credit, you know, they’re doing their best. Everyone is actually, I mean, we work with ANVISA [(Agência Nacional de Vigilância Sanitária), the Brazilian regulatory agency responsible for the approval and supervision of food, cosmetics, tobacco, pharmaceuticals, health services, and medical devices]. We work with the Taiwan FDA and CDE. They are all working overtime and overdrive and trying to get things back as fast as they can. Our frustrations are natural, and we just hope that people have the strength to do what’s right at the end of the day and let the data drive the decisions.

Wright (LSL): Mei Mei [Hu], I did want to come back to you and ask a question. Cause when you said there’s no cold chain, and you were talking about this synthetic vaccine that you’re working on, and you said no cold chain. I had to make a note of that, because that really, I’ve never heard a vaccine person really talk about that in human vaccines.

Hu (COVAXX): No special cold chain. We use a two to eight degrees cold chain, but it’s pretty standard for vaccines. There’s new technologies that require freezers, or even colder at -80 degrees. And so that’s talking about transporting things with liquid nitrogen, and that makes it a bit harder. Especially if you’re doing something to the masses. It’s one thing if you’re delivering packages or packets here and there. But when you’re talking about mass vaccination, this is a logistics challenge. And so now you’re not only building the car, you’re also building the road at the same time on which to drive it.

Javitt (NeuroRx): I’d love to go back to something Brian [Culley] said earlier. When he said we’re [NeuroRx] focusing on the patients with most severe disease. That’s certainly true that that’s where we started, because those are the patients who were dying by the hundreds and thousands. But, there really is a platform play that I think needs to be thought about by more people than just us. The whole story of this virus is its ability to enter very specific cells in the epithelium. It only enters those weird cells that have these two surface receptors, and that’s mostly a couple of cells in the nasal zone, cause that’s where the virus seems to get going. And then it goes down the lung and it enters these alveolar type II cells. If you can stop that process, then the SARS-CoV-2 virus is either asymptomatic or nothing, more than a mild cold. People are talking about grand platforms and systemic approaches and all of that. But in fact, this virus is doing us so much harm, because it’s figured out how to hit a needle in a haystack. And the more we can focus on that needle, the more we can focus on how does the virus get into that cell and how do we stop it in that cell? It may be that we’ll never have a vaccine. I hope we do. But so far as, as long as I’ve lived, we’ve never had a vaccine that’s able to stop an RNA virus. And yet, similarly with pneumonia, we invented penicillin in the 1920s, and it was 65 or 70 years before we had a vaccine against pneumococcus, but we did a great job of keeping people from dying of pneumonia over those 70 years, just because we were able to interdict the process. I truly hope we wind up with vaccines. I truly hope we wind up with global immunologic approaches to this virus. But in fact, there is some very focused things we could be doing that we’re not doing to deal with this particular family of viruses and their determination to eradicate the human race.

Wright (LSL): Peter [Diamandis], I wanted to come back to you with regard to, we talked about the testing, then we talked about vaccine development, and then we talked about some other means of delivery. And the question I had was, now we’re talking about the next phase. Let’s say we get an approved treatment and we’re looking at trying to deliver that treatment. How are we going to get it delivered?

Diamandis (XPRIZE Foundation, COVAXX): Yeah, I mean, that’s a great question. In fact, we had a conversation, at XPRIZE about a vaccine delivery competition, because once you have an effective treatment, how do you distribute it to seemingly 8 billion people? The current vaccine mechanisms are out there. There are mechanisms by which the majority of the world is vaccinated, and we can go through, say if it’s the United States, go through a Walgreens, go through a CVS and so forth. But what is the future once there is a “vaccination” or an alternate treatment found, is there a mechanism that makes it super easy? I’m looking around the room, and I think we’re all kind of all old enough to remember the early days of AOL, though maybe not Mei Mei [Hu]. But I remember AOL (i.e., America online) used to send out these CD ROMs and DVDs in the mail, and you get you’d get 20 of them. They were given out for free. You’d get one and you’d sign up. So, ultimately, is there a mechanism by which you literally get the vaccine or the therapeutic in the mail and you inject yourself? I mean, remember the day before something is truly a breakthrough it’s a crazy idea. The crazy ideas here are everything from little micro drones flying around to give you the therapeutic, to engineering mosquitoes to go around and distribute the therapeutic. But ultimately, it’s how do you do this? It’s fine in the first world, but how do you do this in the developing world where people don’t know they need it, or don’t have access to it? How do you make that happen cost effectively and efficiently? So yes, the distribution part of the equation once there is treatments. And again, it’s not just for this pandemic, it’s for all future ones. How do you make it easy and fast?

Wright (LSL): One of the things I’ve heard is that this vaccine, depending upon which one you’re getting given, can be pretty painful. And I was talking to a friend about that and he said, you know, I, my wife and I just got the shingles vaccine. And, and I was pointing out to him, like, if, if one requires a booster dose, which his shingles vaccine did, he said the first one was painful and, and he got pretty sick. And, you know, it really makes you think, do you want to go back for that booster shot? So, I think that’s another hurdle we’re looking at as well.

Diamandis (XPRIZE Foundation, COVAXX): I think Mei Mei [Hu] can speak to the platform that COVAXX is using, which has been used in parts of Asia and the most rural area for delivering five billion doses of vaccines to farmers where there’s zero infrastructure, so it can be done and done safely and done that scale. Mei Mei [Hu], do you want to address any of that?

Hu (COVAXX): To your question on the delivery standpoint, one of the benefits is we don’t require any new infrastructure, and 80 percent of the world today is vaccinated. So, there is some infrastructure, even in the developing world, that’s able to get vaccines there. That’s something that we can leverage on existing basis. But to your second question. You’re absolutely right that some of these [vaccines] can be painful, and that’s the reactogenicity of some of these vaccines, in particular, their adjuvants. You know, our immune system is a beautiful weapon against disease, but we have yet to conquer and fully figure it out. Some approaches are to stimulate. You got to stimulate it through adjuvants, and that’s sometimes painful. We just, on a company basis, use a very standard adjuvant called Adju-Phos [an aluminium phosphate wet gel suspension used in commercial human vaccine formulation], which is rather benign. We rely on our technology and of designing how the immunogenes are, but it’s always a cost benefit. Some of them may have to have this painful thing to work, and we’ll just see how many people opt for it. But, that’s something that it’s hard to predict, and you know if you do it’s going to be wrong. So, there are lots of considerations. That’s why it’s not a winner-take-all risk. There’s going to be different vaccines that work better in different populations that may work better for the elderly. Some may work better in pediatric situations, where you may want something to be milder, but those may just not be available in developing world because of the logistical challenges. So, I think, there’s going to be lots of niches and, lots of room for multiple players for different purposes and populations to serve.

Wright (LSL): Well, I for one am advocating for an XPRIZE for someone figuring out how to make temperature stable vaccines so you’d need zero cold chain. I think that would be a remarkable breakthrough. That’s probably just as crazy an idea as Peter [Diamandis] was throwing out there. But like you said, you got to nurture the idea along. So, one of the things we’re kind of getting towards the end of the call, and I often like to do on these virtual CEO round tables is offer the opportunity for each of the panelists to share a parting thought. So why don’t we start alphabetically with Brian [Culley], and give you the opportunity to offer a partying pearl.

Culley (Lineage Cell Therapeutics): One of the things that you heard today is, if there’s a will or an incentive, things can get done. We’ve done a wonderful job fighting malaria, because we figured out how to get a very powerful drug called artemisinin out into Southeast Asia and Africa. You have to have an incentive to get things done, and that’s what business is all about (i.e., identifying problems and trying to come up with solutions). Immunology speaking as a retired immunologist of sorts, immunology is one of the most complex areas. You also have to consider the social science that goes along. We sit here and we model the infectivity rate across the population, but how do you model people getting tired of being told to socially distance? There’s no predicate for that. The complexity just becomes absurd. So, what we really need are a lot of people working on many different approaches simultaneously. We as business managers, need to block out the noise from the critics, because no one has the predictive power to know exactly what’s going to work. Although many people claim to know [what will and won’t work], at the end of the day, we all have to try, and test. Ultimately, we are going to find the kinds of solutions that work in the right pockets, and we’re going to be okay against the next pandemic, and the one after that as well. But there’s going to be a lot of pain and a lot of effort that comes first. But that’s all right. That’s what a lot of us and our staff are really trying to push forward.

Wright (LSL): Thanks Brian. Peter [Diamandis], do you have a parting pearl for us today?

Diamandis (XPRIZE Foundation, COVAXX): I have two brief ones. First of all, I just hearken back to March/April at the beginning of when the pandemic was just beginning to build a momentum and so forth and all hope was lost. We forget that in the early days of response, the response seemed deceptively low. People are gathering, ideas are coming, capital’s beginning to flow. Teams are coming together. And then all of a sudden you start hearing about not one vaccine, but not two vaccines, but 100 and 200 vaccines, and 200 therapeutics. And so, there is a tsunami of solutions that end up coming to a problem this big, that you don’t see in the beginning, because the tide is going out? The second thing is, if you’re lucky enough, and I say this from the heart, if you’re lucky enough in your life to get involved in something as meaningful as going after a solution to COVID-19, cause this is a once in a lifetime [situation], make sure you partner with people you love, because you spend a lot of time with them. It’s serious, it’s like don’t hang out with assholes to be blunt. Hang out with people who you truly care for and love. It makes the journey a lot more enjoyable.

Wright (LSL): I appreciate the wisdom Peter. Mei Mei [Hu], how about your parting pearl?

Hu (COVAXX): You know, COVID-19 is probably one of the most devastating social events of my lifetime, of the decade, of the century. But, it’s also an unbelievable blessing and opportunity. I’ve seen more beautiful things come out of this time, from friendships, to opportunity, to opportunities for gratitude, and collaborations that we’ve never seen before, and levels of collaboration between competitors that were unimaginable previously. In other words, in every darkness there is beautiful light, and at the end of the day, light wins out. So, there’s so much to be optimistic for, and it’s an honor to be part of the journey to bring that out.

Wright (LSL): And finally, Jonathan [Javitt].

Javitt(NeuroRx): I think the most important thing is not to be afraid to break the rules. The pharmaceutical industry is a very tradition bound. People know that you’re supposed to do things a certain way. That’s good, because by and large, it’s kept the American pharmaceutical industry from having some of the crises that other pharmaceutical industries around the world have had. But this is a time where we have to break the rules. I once watched a major pharmaceutical company lose $2 billion of revenue that their shareholders would have enjoyed having because the person (and it was only one person) responsible for making clinical trial supplies, couldn’t figure out how to make clinical trial supplies for an existing drug, a 15-year old drug, within 24 months in order to satisfy the FDA’s request for a pediatric trial that would’ve given them a six month patent extension. Cause you know, making boxes of clinical trial supplies for 150 people was just too much work. If we don’t break the rules. And if we don’t break the rules consciously every day, we’re going to lose many more people to this pandemic than we need to.

Wright (LSL): Thanks Jonathan. And I want to thank everyone for making the time to participate in today’s call and providing their perspective during these unprecedented times. We hope everyone finds this information useful. We encourage you to become subscribers to life science leader, which you can do at Look for the subscribe button. I’m Rob Wright, thanks for watching reading and most importantly for contributing. Thanks everyone.