Critical considerations for companies developing NASH drugs

Peter Traber focuses on ways COVID-19 can affect drug development and broader corporate strategies while our panelists weigh in on implications for clinical researchers, investors and forecasters in our third episode: C-SUITE COVID-19 CHALLENGES.


Browse Our NASH and COVID-19 Coverage

Drug developers, investors, researchers, and corporate executives wrestle weekly to understand what is happening in commercial development of Nash medications, join hepatology researcher and key opinion leader Steven Harrison, star equity analyst, Yasmeen Rahimi, C-suite veteran, Peter Traber and forecasting and pricing guru, Roger Green, as they discuss the issues affecting the evolving Nash market from their own unique perspectives on this week’s edition of Surfing the NASH Tsunami.

Roger Green (00:30): Hello, fellow NASH interested parties. This is Roger Green and welcome to the third episode of Surfing the NASH Tsunami. On behalf of all of us, we want to thank you. We’ve gotten letters, we’ve gotten messages. We’ve gotten listeners. We’ve gotten our podcast shared in places that we didn’t know it was going to and all that’s been fantastic. I’d like to encourage each of you to remember to tell five more friends this week, what a spectacular podcast this is because we are shameless and encouraging as much participation as possible. That’s number one.

Roger Green (01:03): Now I would like to ask my fellow surfers to say hi and answer this week’s question, which is what’s the most encouraging thing you’ve seen in your personal life in the last week. We’ll go alphabetically forward this week on first names. Peter, why don’t you kick us off?

Peter Traber (01:16): Most encouraging thing in my personal life has got to be within the lines of my property, right? So and my home, because that’s where my personal life is lived right now and they’re really two things. One, I’m seeing my children get the hang of the new experience of online learning, which is quite interesting to see evolve. I’m not sure they’re going to want to go back to the classrooms they’re enjoying that and the other important issue for me is that our relatively new dog is getting the hang of where it is appropriate to relieve herself. That is a very important development.

Roger Green (01:50): Peter, congratulations. We are all thrilled for you. Okay, Steven, you’re up next.

Stephen Harrison (01:58): Hey everybody. Thanks for joining us again. Great to have you. Personal life, two things. Number one, we’re getting an eight week old puppy tomorrow. So Peter, we’re picking up where you left off and beginning that whole saga potty training and everything else. It’ll be fun and challenging at the same time. Number two, like Peter, I’ve had to deal with children doing distance learning or online learning. For my 17-year-old 11th grader, it hasn’t been a challenge. For my freshmen, Texas A&M son who had to move out of his dorm back into home, leaving the freedom that he has cherished for the past eight months.

Stephen Harrison (02:39): It’s been a bit of an eye opener for us having him back and trying to find a new order of life, still giving him freedom, but understanding he’s living with us and it’s been an eye opener to see him study. He’s an engineering student. He has pretty tough classes in physics and calculus and that sort of thing. I was a little nervous going into the physics final. He got his grade back this afternoon and he did amazing. We’re all relieved that he is going to be able to continue his training in engineering. That’s my two for this week.

Roger Green (03:14): Okay. Yasmeen, both of these gentlemen took this conversation straight to the dogs, where are you going to start?

Yasmeen Rahimi (03:20): Yeah. Mine are actually two different things, completely unrelated, but one is, I love bread and I always wanted to make bread and so I over the last two weekends in a row attempted to make homemade wheat bread. The first batch was disastrous because the entire matrix was in grams and I didn’t have a scale to really measure it out properly. Then batch two that I attempted past week and actually ended up being really good. That’s a mini tramp, so I’m still perfecting my bread and if I succeed, I will be sending you bread in the mail.

Yasmeen Rahimi (03:55): The second one is seeing my in-laws this week and my father-in-law birthday was last Thursday. We got together on Saturday. I live in Connecticut, the weather was actually, we had finally a decent day, it was 55 degrees. We went over to their yard and it was remarkable to see how my in-laws, how they have really adopted their lives for COVID and just stayed away from everything and really, I mean, drastically changed their behavior. Even as we were sitting, everybody brought their own coolers, their own drinks.

Yasmeen Rahimi (04:27): My mother-in-law ordered for everyone at something else so that nobody would be touching someone else’s pizza. So she was as thoughtful and careful in the way she was passing, even passing a chip or anything, she threw the disinfect in your way, so it was pretty remarkable to see how thoughtful and careful she was. You know, there are social butterflies normally, and I was actually really proud of them that they did a really great job. It was definitely, and it felt like a normal weekend after many, many weeks of being really isolated as we were six feet away from each other and just being able to see one another and spend some time.

Roger Green (05:03): That’s great. So I’m going to digress for a minute. Here’s a shock. When you asked me and talked about sending bread in the mail, my senior year in high school, which was longer ago than I care to admit, the college I really wanted to get into, I wound up talking about my first job in my on campus interview. That job was baking bagels. The interviewer was fascinated. What I did was I went back to my work and I crafted a bagel about three foot by two foot in the shape and look of the college mascot, baked it, put it in a very large packing shelf and sent it to her.

Roger Green (05:37): Unfortunately, it didn’t arrive as soon as I would have liked and it arrived two days after they shut down for a four week winter break. When she came back, her office was uninhabitable for a day, needless to say, I did not get into that university. So if you’re going to bake bread, make sure we know it’s coming, because it can be really ugly if we don’t.

Yasmeen Rahimi (05:59): Don’t you worry, I will send you the overnighted and the tracking numbers. So you don’t miss out.

Roger Green (06:04): Excellent, excellent. I don’t have dogs and I live in a condo, but my animal story of the weekend was that this was the weekend on the canal where we live, that the geese had their babies out for the first time. It’s a fantastic thing every year to watch the baby geese turn into little swimmers in formation to turn into awkward teenagers, to kind of fly away. We see this rhythm every year about this time and it’s one of the most reassuring annual rituals in my life. This was that weekend, so it was fantastic.

Roger Green (06:34): Another fantastic thing is we got some wonderful queries this week. four that I want to comment on. In one case, we’re going to actually ask a question and then the other three cases, we’re going to be doing something different. First of all, to the woman who wrote about a sibling and issues that sibling was having, I want to make this clear. We cannot dispense medical advice on the show, despite the fact that we have two MDs, we concur with you that your sibling needs to see hepatologist for evaluation. A couple of the facts that you provided suggested potential for liver disease, but short of saying, you need to go see a doctor. We really can’t cover that any further.

Roger Green (07:10): Also just a note to everybody who writes to us, please make sure to leave your email address because I would not have made this an on air comment. I would have written back a note, except that I did not have an email address or a Twitter to send something back to in private. Number two, Nile asked a question apropos of Stephen’s comment early on last week about NASH and NAFLD and as if we would make that the focus of a future episode, we are currently planning to do that not next week, but maybe the week after that or two weeks and we will give everybody a heads up notice and yes, we will try to get somebody who was on the consensus paper to take that side of the argument when we bring the conversation onto the podcast.

Roger Green (07:49): Number three, we had planned to have a special segment right now, which I think Yasmeen even mentioned at her weekly note for Roth about a journal of hepatology pre press article about the relationship between COVID-19 and NAFLD, but I’ve decided that next week, which is my forecasting session, I really would like to make that article, the focus of my part of the conversation. I believe I will also have a guest with me, which will be the first time we bring a guest on to this podcast and this will be cool. I’m very, very excited about it.

Roger Green (08:22): Finally, Kyle, a biotech researcher from a global CRO asked the question that we’re going to attempt to answer. The question was, do you know of a particular process to tell the difference or distinguished between NASH and NAFLD? Okay. Which one of the MDs wants to take this one?

Stephen Harrison (08:36): Hey, Roger, I’ll take it. So this is Steven. That’s a great question. It’s when people often get confused about if they’re reading papers and they’re trying to sort out is nonalcoholic fatty liver disease different from NASH, what’s Nash. Here’s the easy spelled out in crayon way to analyze this. NAFLD is an umbrella term, all encompassing. Nonalcoholic fatty liver disease includes everything from isolated steatosis. That means all you’ve got on that liver biopsy is fatty, [inaudible 00:09:07]. It’s just fat. All the way through adding inflammation, dying cells and patio cellular injury, scar tissue, that down you have NASH, NASH progresses through stage one, stage two, stage three and all the way to stage four and that we call cirrhosis decompensating liver disease and liver cancer. So NAFLD is this umbrella term that really includes all those things. Now I’m going to digress a moment on NASH.

Stephen Harrison (09:36): NASH stands for nonalcoholic steatohepatitis, and that is believed to be the injury pattern that can progress to cirrhosis and decompensation and so that’s been the target of a lot of work to try to develop a target drug or a therapeutic that can reverse halt or eliminate that disease. So let me tell you why we’re doing that. There’s about a 100 million Americans with fatty liver, about 25 million of those have NASH. And so we’re really focused on what we can do to minimize the progression of liver disease in those 25 million Americans. Those are rough estimates, but it’s pretty close.

Stephen Harrison (10:20): It doesn’t mean we ignore the 75 other million with fatty liver because they’re still at risk of developing diabetes and other comorbidities that are linked to fatty liver. I want to take it one step further. Patients always ask me, how does NASH lead to scarring? Well, that’s pretty simple too, if you think of it like the skin, remember the liver regenerates. It’s one of the only organs that can heal itself. The skin is another good example of that. Let’s use the skin as this analogy. When you cut the skin, you form a scab, that scab allows skin cells to grow across the wound and heal.

Stephen Harrison (11:01): Once the skin is healed, the scab falls off or you pick it off because it begins to itch. But let’s suppose that you cut yourself in the same spot every day for 20 years, the scab gets bigger and bigger and bigger and never goes away. Well, that’s exactly what happens to people with NASH, the injury of fat coming into the liver, leads to inflammation. This inflammation drives the development of cells that normally are very quiet. They don’t do anything. They’re called stellate cells. Basically they come alive, they wake up and they begin to lay down the scab. That scab allows new hepatocytes or liver cells to grow. Once they’re grown, the liver reabsorbs the scab. It can’t fall off like the skin can, it has to be reabsorbed.

Stephen Harrison (11:50): If you don’t get the fat out of the liver and it continues to irritate the liver, then you’re going to continue to lay down the scab and so it starts with minimal scab. We call that stage one disease or stage one fibrosis or scar tissue. Then it progresses to stage two, which is a little bit more, stage three, which is more and stage four. So if your doctor tells you, you have stage two NASH, that means you’re halfway to cirrhosis and halfway to no fibrosis. And so that’s fatty liver, that’s NAFLD and NASH and everything in between.

Roger Green (12:27): Thanks Stephen. That’s great. This week, Peter is the lead presenter. The question really is what are the issues C-suite should be thinking about today in the context of the pandemic and COVID-19 and what it means to the liver disease. Peter, floor is yours.

Peter Traber (12:43): Thanks, Roger and that was a brilliant answer from Steven on NASH and NAFLD. I have been privileged to be in the C-suite, both as a CEO and a CMO for both large and small public and private academic institutions. I’ve seen what CEOs and CMOs have to consider from multiple angles during a time of relative calm and times of crises. I’ve reflected a little bit on my experiences and also my current experiences with companies thinking about COVID-19 to come up with three issues, not an exhaustive discussion of issues that are on the minds of leadership, but three issues that might add value to a particular company during this time of pandemic.

Peter Traber (13:38): Now I’m going to briefly discuss these three issues, and then I’m going to have a question for each of our panelists, and I’m going to have a little fun with this. I’m going to mix it up. I’m going to ask a question interspersed between the three issues. So people don’t get bored with my monologue. The first thing I want to talk about is the involvement of the company in the COVID pandemic response. What is the company doing to help the global or local or regional response to this pandemic? The way a company approaches. This can be very important to elevate the visibility of the company to make the company part of the community and some of the ideas that I’ve heard, discussed and seen implemented are first of all, involving executives and scientists in their local, regional national and international groups or discussions on mitigation strategies, get your experts into the mix to help the community think through what’s going to be the best response and mitigation strategies, the best ways to communicate.

Peter Traber (14:51): Another way to do this is to find ways to serve the local community. I’ve been the acting CFO for a company in Boston, Morphic Therapeutic, which has actually found ways to both manufacturer find and distribute personal protective equipment to hospitals and clinics in the Boston area. That’s a real direct way of figuring out how to serve the local community. These things can be very important to become visible in your regions as an important company and player in the market.

Peter Traber (15:27): Another area that I think is very important is figuring out ways to collaborate with CROs, with clinical sites when with your KOLs, in finding solutions to conducting trials during and following the pandemic. And this is where I want to ask a question. I’m going to ask Stephen, Stephen companies may be currently recruiting or considering starting a trial in NASH. What type of involvement would clinical sites like you have a major area in where KOLs like yourself value from companies in this process of the company, working with the community?

Stephen Harrison (16:11): Well, I can tell you directly one area that we’ve seen a significant amount of interest, not only from my local site, but from sites throughout our network has been this notion we’re coming together on Zoom webinars and that sort of thing to talk about the challenges of maintaining patient safety, data integrity, continuing to drive enrollment, where it is important to do so. I know we’ll, we’ll talk about NASH in the era of COVID and why we think that’s important to treat NASH. We’ve talked about it a little bit already, and I think there’s more to come and I’m a big advocate for that.

Stephen Harrison (16:50): But one of the areas where we’ve really noticed, I guess we hadn’t thought about it, but it became apparent when it happened. We actually had a sponsor that wanted to join us on the call. We said, we were having these calls just to kind of brainstorm back and forth, and they actually got on the call and it was amazing to see the C-suite level team members, not just the CMO, but the CSO, the CEO, the CFO, all of them on the phone, working through situations that each of our sites had, but more than anything else, showing that they were fully involved, they were all in. That they wanted to do whatever they could to help our patients and to help our sites through this challenging time.

Stephen Harrison (17:40): I would say where that can be replicated, that’s only going to have a positive impact on the company and the sponsor. So that would be my reply to that question.

Peter Traber (17:51): Stephen, that’s a great message for C-suite people and managers of all levels and companies to hear and to think about how to emulate. I’m having a recent experience right now with a company that I’m advising. They happened to be transitioning from a phase two to a phase three program. One of the challenges they have is how to keep their sites that they want to be involved in the phase three program involved in the program, and also how to keep them viable.

Peter Traber (18:24): One of the things that companies have to recognize is that a clinical trial sites build up infrastructure. They have personnel and so forth and with industry stopping trials or not starting them on time, they’re stressed in terms of their economic viability. And I think where companies can, if they can focus on those sites and help support them through this challenging time, that’s going to pay off big dividends in loyalty and your ability to recruit your trials once it starts. That’s something I would encourage leadership to think about. Yasmeen or Roger, do you have anything to add to this first discussion point before I move onto the next one?

Yasmeen Rahimi (19:10): The only comment that I like to make is thank you, Peter and thank you Stephen for the insight you provided. I think from an investor perspective, when companies continue to support the local communities and work together in being able to convey this message to their shareholders could be quite impactful. So not only I think it’s what they’re doing behind the scenes, but putting that in the press release and making the investor community aware of all the work that they’re doing behind the scenes to really fight against COVID could be extremely well received.

Yasmeen Rahimi (19:49): Of course, it’s very challenging to think that if you press release that the stock would move a substantial amount, but it definitely builds credibility and it just signals to the market that you are doing everything in your power to be creative and continue making progress. I think overall that’s been really well received and not waiting for the earnings update to just unveil whether there’s the delay or progress has been made. I think unexpectedly sharing that with the investor world is incredibly impactful.

Roger Green (20:23): These are all fantastic answers. I don’t know that I have anything to say that’s equally helpful. We do advise clients, have advised clients for years in different kinds of crisis situations and on one level, what COVID is, is the all time crisis situation. What we like to remind clients in those moments is that crisis management is all about relationship. You never know if you have a relationship, you need one, but the things that you can do in those moments to ensure that you have relationship are question, honestly, listen openly, don’t over represent what you can achieve. Then the classic, right, which is under promise and over deliver.

Roger Green (21:00): If everybody brings that perspective that we’re here to listen, we’re here to learn. We’re here to help, and we’re going to do whatever they set out to do I think it works out a lot better and everything that you guys have talked about would fall into that category.

Peter Traber (21:12): Now, thank you, Roger and Yasmeen. In fact, the points that all three of you have made related to how you serve the community, but also how you allow your good acts to rise to the surface without thinking about the press release, I think is very important and it dovetails with this next topic that I’m going to discuss. This may seem a little bit odd to you initially, but bear with me for a moment. I think that all companies should either long or for just a short period of time consider how their company’s products or their development assets may be involved in the prevention or treatment of COVID-19.

Peter Traber (21:54): I think all companies should at least give a short bit of thought to that. For some companies, that’s going to be a very short thinking process, but for others, it might take more insightful discussion and believe me, when I tell you that this is a question that shareholders and other stakeholders will likely ask because the whole world is focused on COVID-19, because the pathophysiology and the complications of COVID touch many areas, and there will be many hypotheses about how drugs might be important in the overall process.

Peter Traber (22:28): Now, while some of the notions that you’ll hear from stakeholders or stockholders and things that people might put forward will be ill conceived. I guarantee you that, but I feel that management should have considered the questions before they get the question and have a position. I think you want to maintain that level of responsibility globally. If you have a drug that could potentially be involved in some way, you should think about it and have answers when stockholders or shareholders ask you.

Peter Traber (23:02): Now, let me just give you the next step. If you think about that, and there is a potential role, I think the company should evaluate how development might proceed. Now, of course, this is going on with all kinds of vaccine and diagnostic companies and so forth. But let me give you an example of a company that I’m on the board of Caladrius Biosciences. One of their assets are autologous CD34 cells, and they have a potential in mitigating COVID-19 lung damage.

Peter Traber (23:34): The company recently announced, and this is why I can tell you this public information that the FDA authorized it’s IND application for this study of a CD34 cell therapy for repair of COVID-19 induced lung damage. This is a trial that obviously has not started yet, but the trial has been approved. Now, in my mind, this company Caladrius Biosciences did this in the right way. They analyzed their agent, they did their research, they designed a clinical trial.

Peter Traber (24:03): They submitted to the FDA and the FDA approved it, and then they announced it. So they went the extra mile to make sure that what they were announcing was credible, was approved by the FDA. One more point to make here and that is while there may be NASH assets that affect inflammation and fibrosis and could be useful. It’s critical that companies only put forward scientifically credible options. I can’t emphasize this enough. For the credibility of your company avoid at all costs of looking like you’re trying to cash in on the COVID-19 crisis by making overly promotional statements based on suppositions, or if there’s no hope of clinical results in a reasonable timeframe.

Peter Traber (24:55): That’s why I say in my view, Caladrius did it the right way. There were already existing I&Ds for this CD34 cell therapy. There was a path forward to investigate patients with COVID-19 lung damage and they submitted an I&D and they announced it when it was accepted, but companies should consider this, but they shouldn’t put out any information based on wild supposition or hypotheses, because that’s only going to hurt your credibility in my view.

Peter Traber (25:31): This, I think is something that C-suites should talk about and be prepared to discuss when ultimately they will be asked. Let me ask Yasmeen, how do you think investors Yasmeen would view a thoughtful analysis of a company’s assets for the treatment of COVID-19 if it seemed reasonable?

Yasmeen Rahimi (25:53): Thanks Peter for the insight. I think it’s an important question that you asked, and I think it would be very meaningful when that information is shared with the public. When it presents the data presents the timeline, it has gotten clearance from the FDA, or if the path is forward. I agree with you that press releasing sort of the process that has been already in play, and especially when they are comfortable to share the preclinical data that they may have generated the scientific rationale, why it could potentially work is a treatment for COVID-19 and then followed by a timeline and a clinical trial design.

Yasmeen Rahimi (26:35): Having these three pieces in alignment and in a clear fashion, and not only press release, but also hosting a call to really being able to spend some time on a phone so that shareholders, as well as other parties that are interested could be listening rather than simplistic press release could be very important. So individuals also have the chance to ask questions. I agree with you, I think press releasing just content that says we’re evaluating early assets without a timeline, without the biology rationale, and potentially also without clinical data can make it very challenging from being positively received.

Yasmeen Rahimi (27:18): Especially as we see almost every day, more than 20 to 30 press releases come out, establishing that an agent has entered clinical testing for COVID-19, that’s become extremely challenging for investors to really pay attention to the different mechanisms of action. With that, I think it’s better that if you are a company working on it diligently to wait till you have all of the three pieces, the mechanistic rationale, that preclinical data that you could share the path forward, and potentially also the green light from the FDA to go into the clinic on the clinical design, to being able to unveil all that in one setting, then it puts a lot far more confidence in the investors and thoughtfulness of the execution.

Yasmeen Rahimi (28:07): That would be my thought. One of the questions that we really fundamentally get is, and this is something in relation is how much is the liver community hepatologists, ASLD every stakeholder involved in liver therapies, working on having a deep understanding why patients with NASH are most effected. That’s a question that comes up frequently. A question going back to you guys is and we can talk about that in a later time point, is, are we generating data sets where we show, why NASH patients are at higher risk and how much work is being done, collecting that data?

Peter Traber (28:48): Yeah. Yasmeen I think they’re brilliant answers and really underscore what I was getting at. Your view from the investor side, I think is very important and you bring up another issue and that is what studies can the liver community do to help our understanding of the disease in liver patients, regardless of whether the company’s assets have importance or potential importance in the disease, it would be important to learn more about NASH in the era of COVID-19 Steven or Roger. Do you have other thoughts on this?

Roger Green (29:25): Yeah, I do. And I’ll let Stephen go last because he’s generally the most eloquent except for you Peter. Anyway, so I’m a big fan of something called catastrophe theory and the way catastrophe theory works is that everything goes along the same way until it doesn’t. Think of getting to the edge of the waterfall, except either you go over or you don’t, and that would be catastrophe theory. The question is what happens at that moment that makes you go over or not? I think one of the fantastic things about Yas’s extremely eloquent answer is that it tied together a lot of threads of this.

Roger Green (30:00): We know that there are issues around fatty liver and why patients with fatty liver are more susceptible to COVID. We don’t know what that means for the fatty liver drugs or really from… we have no answers yet, but we have this compelling question. If the liver disease community and the companies developing product medications in that space, treat this responsibly and thoughtfully in a manner that the two of you were talking about. We run very little risk of looking overly opportunistic, and as it turns out that there are products that have opportunity related to COVID, those products will benefit from the good work that everybody has done to learn and to be transparent and to be open.

Roger Green (30:44): Going back to Peter’s original point, the real downside of what happens if we appear too opportunistic is that good data will be looked at skeptically and since liver doesn’t start in a particularly powerful place within the galaxy of therapies right now, we would like to look as good as possible, as scientific as possible and be as appropriate as possible. It’s in our hands. We have this fantastic opportunity and I think the two of you [inaudible 00:31:11] you did a great job of elucidating how to take full advantage of it.

Peter Traber (31:14): Stephen, would you like to comment on this topic?

Stephen Harrison (31:17): Well, I’ll just speak to what Yas mentioned from a clinical perspective, as a hepatologist. We know patients with fatty liver disease don’t do as well if infected with COVID-19. There’s been now more than one publication that has alluded to that, and we know that the virus can attach to both liver cells and biliary epithelial cells, ACE receptors, but really what we don’t understand fully is the liver injury because of a direct result of infected liver cells, or is it injured because it’s an innocent bystander in the cytokine storm and the systemic [inaudible 00:32:08] you, that this virus has caused in the body.

Stephen Harrison (32:14): I think to that end, we do need more studies. The studies that have come out have been prolific, but they really kind of been focused on epidemiologic type data rather than mechanistic type data. And so, as we transition to the next phase of attacking this virus, then I think it becomes critical for us to understand pathophysiologically how this virus is interacting inside the liver and is there something we can do to mitigate that? So to that end, I think lots of people are beginning to look at this, but from a liver company perspective where we have bench scientists that are well versed at handling viral infections within hepatocytes, this becomes a prime opportunity to take that to the cellular level and then into the animal model and then onward from there. So lots more to do, but I think there’s a great opportunity.

Peter Traber (33:13): That’s an outstanding answer and I think that it really says that in the face of this pandemic, we really need all brains on deck and those people thinking about liver can have just as big an impact. I want to end this segment just going back to the cautionary note that you have to take in talking about how you might be able to… how your company might be involved in this pandemic. There already have been companies whose hands have been slapped by the SEC for over promoting potential therapies in COVID-19 and that will continue. You want to avoid like the plague, so to speak being one of those companies that gets their hand slapped by the SEC.

Peter Traber (33:59): So you must be thoughtful and conservative. The last issue I’m going to bring up is something we’ve touched on last couple of weeks, and even in the last couple of questions, and that is evaluating your assets, considering a COVID-19 world. Now, I’m one of those people who thinks that this pandemic could be a watershed moment in history. I think that behaviors and markets may have longterm shifts, which ultimately have a change in direction for different industries.

Peter Traber (34:32): Now, I know this is going to be a very broad question, but you guys are smart people. So I’m going to ask you to kind of play a futurist and I’m going to start with the smartest one of us. Roger, I’m going to ask you to think about the future here and how might the drug consumer market for NASH shift and how might companies consider positioning their assets going forward. Thinking about that future world where the risk of COVID-19 and pandemic or potential increase in pandemic is a possibility. Roger, you want to take that on?

Roger Green (35:15): It’s a fantastic question. Thank you, Peter, and thanks for just a great presentation of all three of these issues. I think what makes this issue so complicated is going back to what Stephen just pointed out. We don’t know enough about the pathophysiology of the disease or diseases yet to understand exactly the role that different kinds of liver targeted therapies can play in the pandemic. The answer could be anywhere from the liver is heavily implicated and a more robust liver will lead to way better outcomes for people far better outcomes for people, to the liver as an innocent bystander and will not have that significant role.

Roger Green (35:55): I both are possible and if this sounds like I’m ducking your question, please forgive, but I think about what I would do if I had to make that decision from a managerial perspective, and this is why people get heavily engaged in the concept of scenario planning that you could have four, five, six radically different outcomes. Peter, I’m not smart enough to tell you which one you’re going to get yet, but what I do know is that when you look managerially at the critical success factors for outcomes ranging from livers, right at the heart of it delivers way at the periphery. You’re going to identify four, five, six critical success factors, and some will be common and some will not.

Roger Green (36:33): This is a pivotal moment to understand the cognitive factors, because those are the things that your company has to get, right? And they’ll vary from company to company and in the rest of the cases, it’s being extremely aggressive and extremely agnostic and scanning the environment to figure out what direction things are going at, and then being nimble enough to respond appropriately. If I had to guess, I would guess that what we’re going to learn is that liver is meaningfully implicated and that if the companies behave responsibly and do good research and discuss these issues intelligently, that this will be a moment at which over the next couple of few years, liver medications and liver therapy plays a much more prominent role in terms of how we think about overall treatment.

Roger Green (37:15): That’s just my speculation, the other scenarios, careful planning, identifying commonalities that I know everybody has to do, because if they don’t, they’re going to lose either money or opportunities or both.

Peter Traber (37:25): Well, that’s very good. Roger. I can tell as a future is your glass half full type of person. I think that’s a potential vision of scenario planning for the future that can be practical for people. I want to ask Yasmeen, are investors open to thinking about how COVID-19 will affect the potential NASH market? I’m sure that investors always plan for the worst and hope for the best, in some ways, but what are some of their concerns and vision for how COVID-19 might affect potential NASH markets? If you can put on your futurist hat a bit?

Yasmeen Rahimi (38:01): I think for right now, I think investors are sort of concerned about companies that are in the developing therapies in NASH given that they fear that patients might be worried to be part of a clinical study because they would be at high risk of leaving their house, visiting a clinical site and that could introduce a delay in enrollment and timelines, especially given that phase two trials are large studies of 1,000 to 2,000 patients and lengthy. So every patient that gets enrolled, it’s really incredibly meaningful, important to be part in the analysis.

Yasmeen Rahimi (38:38): Right now I think they’re more concerned and trying to understand how each drug developer is coming with creative solutions to maintain their timelines and maintain the integrity of their trucks. That’s one, however, I think fast forward six months from now, what I suspect could be happening is that as we’re continuing to collect data from patients who are affected and we start characterizing the cormobidities that are present, I think we will have a better understanding that these patients have elevated liver enzymes, have fatty liver disease, and we will discuss it in our next episode, but ultimately we will learn or have an answer what percentage of the COVID patients are NASH patients.

Yasmeen Rahimi (39:26): I think that to me is going to be meaningful and one that could spark is that patients and the public will become aware of NASH as a risk factor for COVID. And the biggest criticism that exists in the NASH landscape has been the lack of M&A activity. I think that when public awareness is shifted towards NASH, especially if we identified as one of the strongest core morbidities and putting patients at risk and given that large pharma commitment in developing therapies and vaccines is going to even further spark their interest to wanting to move forward therapies.

Yasmeen Rahimi (40:05): Not only for the sake of reducing liver related events, but truly COVID related mortalities that is present. I do think that we don’t have that data yet, and we will be collecting that and I think that mentality will change. I’m actually very optimistic that the excitement for NASH will be rejuvenated as we are headed over the next six months and a lot of answers we will get also of course, over the next second half of this year, in regards to the first ad com, the approval reimbursement and many other answers that will be addressed. I think COVID-19 could help the NASH market to bring awareness from the public and awareness to a asymptomatic disease and get everyone on the same page to work against not only COVID, but also against NASH.

Peter Traber (40:58): That’s a very insightful answer Yasmeen, thank you. I think that Yasmeen gentlemen has mentioned a phrase that might be part of a future podcast when she said M&A activity and what’s going on there and what’s keeping things moving or not moving. I want to end this section just by asking Stephen to comment on something. So Stephen, you and I have been clinicians and scientists for many years, some, a few more than the other, but really have seen practice and of medicine and development progressed dramatically in liver. Also, you’re a positive guy with a military foundation who looks at the future and sees positivity. What would be your message to our colleagues out there who are on the front lines and thinking about this disease and how to approach it? Do you have some words for them?

Stephen Harrison (41:58): Well, sure. I thank you for that opportunity. First of all, I’d say my hat goes off to you. Having served in Iraq in 2009 and to crit, and then blessed by taking care of America’s finest, that you’re in the same battle. It’s just in the US and you’re on the front lines. Whether you’re in New York city, Detroit, small town USA my little brother is an ER doc in Jackson, Mississippi, and fights the battle every day. He goes to work. So I’d say thank you very much for that. My hat goes off to you, a standing ovation, and please stay safe, beyond the front lines, become the next battlefront. That battlefront is vaccines. It’s antibody testing. It’s really what we talked about before. Understanding the interplay of viral connection with the patio sites if you’re a liver doctor or lung cells or infectious disease or whatever you happen to be an expert in all hands on deck, all brains on deck, as you alluded to in trying to get at not only putting this thing to bed, but preventing it from coming back.

Stephen Harrison (43:12): I mean, there’s speculation that this may be seasonal and so there’s a lot more to this story than just developing a vaccine, wiping our hands off and moving on to the next thing. I would say, stay attentive, stay in tune with what’s happening and where you can help deliver some sort of answer to this virus please, please do.

Peter Traber (43:37): Thanks, Stephen. I’ll turn it back to you, Roger.

Roger Green (43:41): We’ve got about eight or nine minutes left. Peter, I had one question for you, and then I think we’ll wrap up unless someone else, and it’s not just for Peter. You get to see how corporate execs in your clients and the other people you talk with are handling these issues in the industry trenches on a day to day basis right now. I’m wondering what the balance is, A, between realistic optimism and crazy optimism and B, between practical focus and aspirational focus in what you’re seeing in the environment right now, how real are people keeping it and how aggressively positive are they being? However, real they’re keeping it.

Stephen Harrison (44:22): A good question, Roger. And I think the responsibility of a CEO or a CFO or a CSO, CFO, all those people that are leading a company, particularly when it’s a public company, their responsibility is to the owners of that company and the shareholders. They need to keep that in mind at all times, they need to be focusing on delivering the programs, impressing the street, serving their patients and their other constituencies and doing what the mission of their organization is.

Stephen Harrison (44:59): At the same time, on the flip side, they can’t turn their entire company over to a cause that is going to greatly diminish that effort. However, you can make the pandemic an integral part of your activities and your business, because it is so important to all those other things. It’s easy to take disparate kind of approaches in a company. One is the let’s stick our head in the ground where we understand this science and development and just work in that area.

Stephen Harrison (45:38): The other is to lift your head to the heavens and forget all about the day-to-day activities and you have to find that happy medium. It’s very clear to me that that’s a leadership issue. That approach is driven from the top down into the company. There are plenty of people in the company that can add to that and be critically important, but the leadership has to think about that balance and do some scenario testing internally, as you mentioned, Roger, think about the different scenarios of effort and so forth and constantly shift to find the right balance of serving the company’s mission and the shareholders along with serving the global community as we approach this pandemic.

Stephen Harrison (46:29): It’s those leadership teams that find that balance that I think are going to be most successful and I have seen companies struggle with that balance, but as long as you continue to struggle and scenario plan, you’re going to end up finding the right approach.

Roger Green (46:47): Peter, just a personal comment at the end of the first one first episode, I said, “Boy, this might be pretty good.” The end of the second episode, I said, “Boy, that was better. How do we top that.” Peter, that was fantastic and Yasmeen and then Stephen, thank you for some wonderful answers. I actually think we’ve taught that, which scares the Dickens out of me when I have to take the lead next week. But you know, a healthy fear is a great motivator. So there we go.

Roger Green (47:09): Last round of questions for everybody. Okay. What’s the one thing that you heard from one of your colleagues or even coming out of your own mouth during the last hour that surprised you, that you wouldn’t have expected to learn or hear tonight. Peter, since this was your session, I’m going to let you go first.

Peter Traber (47:27): I think that this has been an outstanding discussion and I’ve learned a lot from all three of you. I appreciated your very insightful and thoughtful answers. The one surprising thing I learned a bit is Yasmeen’s comment where, she’s been involved with investors a lot and she thought that there be a positive view of companies trying to do the right thing in their communities related to this pandemic. I think that’s a very positive message that everything you do does not have to accrue to the bottom line with investors, particularly if you’re doing good for your community in the world related to this pandemic and hearing Yasmeen say that was I think, encouraging and a bit surprising.

Roger Green (48:17): Okay. Yasmeen, Peter pointed the finger at you. You get to go next.

Yasmeen Rahimi (48:21): Thank you, Peter, and things, Stephen and Roger for all your comments. I have to say what really stood out. I think Peter’s point of view as he worked closely with many of the management teams and provides great advice is the fact that companies really need to be thoughtful as they’re thinking to position their assets in NASH. I think it becomes really critical that for drug developers who are listening to this really take that to heart and what was Peter your phrase knock the [inaudible 00:48:59] into for COVID, just for the sake of publicity, but rather have strong data.

Yasmeen Rahimi (49:06): I think having individuals like Peter to really urge companies to be thoughtful in their R&D plan, especially if they think that their assets has a potential for a treatment for COVID-19. That to me was really thoughtful that to educate them. So that was very valuable in my view.

Roger Green (49:27): Thank you Yasmeem. Stephen

Stephen Harrison (49:28): I think there was so many awesome comments made. It’s hard to find the one that sticks out the most, but again, this has been Peter’s show. I think there were many things he said that are foot stomp worthy, if you will and that need to be reverberated and I think mentioned a second time and maybe the biggest one for me is folks that are studying therapeutics for NASH that have taken a pause for maybe multiple legitimate reasons that instead of sitting back and waiting for somebody to say that it’s okay to start back up. I would use this time to double down on your engagement with the sites to help them.

Stephen Harrison (50:21): I can just speak from my own site at Pinnacle, reflecting on what Peter said. It would be great if these sponsors that have put their studies on hold would reach out to me and my fellow principal investigators to really let us know what they’re feeling, let us dialogue with them about what we’re seeing boots on ground, what our concerns are, what the patient’s concerns are, what they relate to us so that we can pass that information through.

Stephen Harrison (50:54): At this point, I like to think of it. As Peter said, I’m an optimistic guy. I mean, for me, the glass is always three quarters full, not half full. What can we do at this time to really laser focus our efforts on fatty liver, such that when we’re through this epidemic, that we will come out of this better for our patients, we’ll have disease awareness and as Yas mentioned, disease awareness may become first and foremost, moved to the forefront because of COVID.

Stephen Harrison (51:30): Again, that may be another positive that sponsors can hang their hat on and use that as a leverage point to reach out and build capital on disease awareness. You also Yas mentioned about the [peduphadate 00:51:45] and maybe our first drug coming. That’s great news for patients with NASH, but it’s also great news for disease awareness. So I think there’s lots of things we can learn from this. And I’ve learned a lot from this podcast relative to those comments.

Roger Green (51:58): So thank you, Stephen. Thank you all. As I said, I think this has been fantastic. What I find myself thinking about as I’ve been listening and I tend to think of myself as being three quarters full and Stephen being about a sip and a half from the top. There’s an optimism. Is that a lot of the papers that are being published now about the coveted relationship aren’t Nash, they’re fatty liver, they’re NAFLD in part because of my clients, aren’t imperfect as how these drugs are developed and one of the questions I’ve kept asking myself since I’ve gotten involved with liver disease is what happens to drugs that are better for F1 and F2 than they are for F3, because the economics of early stage fibrosis have not yet been clear, but if it turns out that fatty liver in and of itself, therefore early stage NASH even worse, will have an impact on susceptibility to pandemic.

Roger Green (52:42): Then all those products, those medications have a stronger rationale. Now they’re going to have to rethink how they do some of the things they do. And it may take them a few years to get there. The ones that are earlier to market, but it really opens up far more broadly. The opportunity for the Nash category for lots of medications serve lots of different purposes. I think that’s fantastically exciting part because it just hit me in the last 15 minutes.

Roger Green (53:06): I want to thank everybody for a fantastic session, Peter, for some excellent preparation upfront and giving us questions that we all had time to think through and a standard that the four of us now to live up to. I want to thank Frank for being fantastic as always on the board. I want to thank Eric Rams, our social media guru, who never makes it to these things, but has been exceptional in getting us awareness out in the world. I want to thank everybody who’s been listening. Tell your friends we’re having fun. You should have fun listening. We look forward to seeing you next week. Bye-bye now.

Speaker 1 (53:37): You’ve been listening to Surfing the NASH Tsunami, send in your questions to surfingnash.com and our panelists will spend the first five minutes of next week’s episode, answering your questions. Visit us online today. Surfingnash.com.