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Ep. 1 COVID CHAOS

Navigating NAFLD/NASH clinical trials through the pandemic
Stephen Harrison, MD, Hepatology Researcher and KOL

Dr. Stephen Harrison discusses several ways the pandemic is affecting the planning and execution of clinical trials and our panelists discuss implications for investors, C-suite executives and forecasters in our first episode, COVID CHAOS: Navigating NAFLD/NASH clinical trials through the pandemic.



 
Browse Our NASH and COVID-19 Coverage
 
Dr. Stephen Harrison says, “We are excited about this podcast series and the impact it will make in advancing innovation in NASH drug and diagnostic development.”


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, Stephen 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 (00:31): Hi. This is Roger Green, and welcome to the initial podcast of Surfing the NASH Tsunami, a podcast for people who are involved with drug development and commercialization in the liver disease space. We’ve developed this podcast because over the last month we’ve heard tons of questions from virtually everybody involved in this community about the impact of COVID, first, and then how that’s going to affect the entire domino chain of upcoming market events, product readouts, clinical trials, launches, all that going forward.

Roger Green (01:01): We have assembled a panel of four people, each of whom is probably the defined expert or one of the top two or three in one of the areas that is critical to this market, and the way this is going to work is that each week we will have a topic. One of the presenters will start by kicking the topic around, and then folks will react, and then we’ll have discussion.

Roger Green (01:19): After the podcast, you will have the opportunity to ask questions and send them in to us… not this time because you didn’t have a chance to ask questions, but on all subsequent podcasts we will start by answering the questions that you send us. Those are the rules. We’re having fun. Enjoy listening, and here we go.

Roger Green (01:33): We’re going to start with a round of introductions of the panelists. State your name, tell us a little bit about your background, and then one positive thing that’s happened in your personal life in the last week and one positive thing that you’ve observed in the professional environment you live in for the past week. Peter, kick us off.

Peter Traber (01:49): Thank you very much, Roger. My name is Peter Traber. I’m trained as a gastroenterologist, hepatologist. Over my 35-year-plus career, I have spent about half my time in academia in leadership positions and half my time in industry in both large pharma and biotech, also in leadership positions, often in the C-suite. I’m very happy to join this illustrious group to try to help think through how we navigate major change in our world and industry.

Peter Traber (02:24): Within the last week, in terms of professional life, I’ve taken on the role of acting chief medical officer at a company called Selecta Biosciences in Boston. It’s very exciting because they have a phase two program that is finishing up, and on the cusp of a phase three program, so, thinking through these issues from a C-suite as the chief medical officer of this company is a very gratifying thing and very challenging to do.

Peter Traber (02:56): From a personal standpoint, on April 6, I had a birthday, and my teenage daughters made multiple baked goods, and one of the most beautiful cakes I’ve ever seen, and surprised me by inviting over some dear cousins of mine, where we practiced social distancing, but I was at least able to talk to them from across the room, whom I hadn’t seen for a long time. That was an exciting personal vignette.

Roger Green (03:22): Peter, that’s a great start. Stephen, why don’t you go next?

Stephen Harrison (03:24): Stephen Harrison. I am a gastroenterologist and hepatologist in San Antonio, Texas, and I focus my energies these days on nonalcoholic fatty liver disease in three main areas.

Stephen Harrison (03:36): One, epidemiology, helping to define the prevalence of this disease and the severity of the disease here in Texas predominantly, and then also noninvasive testing. I work with the LITMUS consortium and run the work package five, which is focused on imaging, noninvasive testing for NASH.

Stephen Harrison (03:53): Then, finally, I work at Pinnacle Clinical Research where I have a site focused on NASH clinical trial enrollment, and then I run a site network called Summit Clinical Research as well. Happy to be a part of this terrific group of people to debate and talk about the current issues in NASH, particularly as it relates to the virus at present.

Stephen Harrison (04:15): In the field of NASH, the past year has been kind of a daunting year to say the least. I’ve been on the front end of some negative clinical data relative to NASH. It’s refreshing to finally get some positive news, actually, several bits of positive news, recently with several different companies pressing positive results, most recently, with Akero showing positive data, and being the PI on that study is an honor for sure.

Stephen Harrison (04:41): Personally, I didn’t have a birthday, thank goodness. At age 51, birthdays are not something I look forward to except to say that the alternative isn’t very good either, but I would say that a good thing that’s happened to me is being able to spend time with the family a little bit more and realizing the importance of that, and being able to see what my kids do on a daily basis when they’re not in school and what’s going on around the house, and just being more of a husband and a father. That’s been a good thing to be a part of.

Roger Green (05:11): That’s great, Stephen. Thank you. Yas?

Yasmeen Rahimi (05:16): I’m Yasmeen Rahimi, a senior research analyst and co-head of Biotech Research team at ROTH Capital Partners. As a [inaudible 00:05:22] analyst, I’m sort of the liaison between the investors, as well as publicly traded companies. A large percentage of my companies that I currently cover are in the liver and NASH space. It came naturally. I’ve gravitated towards liver and NASH, given my background and PhD in liver metabolism.

Yasmeen Rahimi (05:40): I had the privilege to study with Gerry Shulman during my postdoc working on lipid-induced insulin resistance and understanding the pathways, and sort of continued to stay up to speed on it. I’ve had the pleasure of working with numerous drug developers who are in this space and had the honor of working with Peter and Stephen and Roger on many different other projects.

Yasmeen Rahimi (06:01): In regard to two developments, I think, let me start on the professional update. As of about… It’s been now a month, we actually launched a daily COVID-19 Note as part of our series, and every day we track the numbers. We track key publications and what is happening.

Yasmeen Rahimi (06:19): I think the perspective of this is just to kind of help investors, as well as many of our companies that we work with, to make a decision on when are we going to return back to normal? Do we have a good handle on the virus? I think it was really rewarding to hear from a number of my companies who are utilizing these notes internally, sharing them, and trying to make key decisions.

Yasmeen Rahimi (06:39): I even heard from one company whose son is actually head [inaudible 00:06:43] Pennsylvania, and he utilized a couple of the works that we have done to really predict sort of hospitalization rates. We were really excited to know that the work we’re doing, even though it seems really small at that point, that’s our way to contributing to bring informative information to investors and companies and everyone that’s affected by it.

Yasmeen Rahimi (07:04): Then, on a personal level, my aunt actually was hospitalized in LA for coronavirus. She had the symptoms. She was in the hospital. Thank God she wasn’t on a ventilator or anything like that, but she was monitored because she has dyslipidemia.

Yasmeen Rahimi (07:19): I heard yesterday that she was let go from the hospital, and she’s feeling much better. It was something that was really kind of scary, and I think many families have been going through it. It’s kind of really exciting, and my mom’s a nervous Nelly in my family, so it was really a big burden off our shoulders to know that she’s out of the hospital, and she’s doing better.

Roger Green (07:41): Thanks Yas, and I’m Roger Green. I have a marketing research firm called RG&A, Inc., and a consulting firm called HEP Dynamics, and I’m partner with Stephen in an asset development firm called Go To Market Advisors, LLC, and do a couple of other things in my spare time.

Roger Green (07:56): Mostly, the things I’m involved with have to do with marketing and marketing strategy, and trying to help people find different and interesting ways to look at commercialization. We do that through a lens of forecasting and pricing, figuring out what products are worth and what markets are likely to pay for them, and then forecasting what uptake might look like and what peak sales might look like, the theory being that the best way to figure out what people value is to figure out what they’re willing to spend money on, whether those people are insurers or payers writing prescription or patients filling parts of prescriptions on their own.

Roger Green (08:26): It’s interesting work, and extremely rewarding, particularly when you get to work with people on diseases and in situations where there has not been treatment, and there is about to be, NASH, I think, being one of those.

Roger Green (08:38): My personal events over the last week is not so different than Yas’s. My brother was one of the earlier cases found in Westchester County, New York, and in the past week he actually tested negative for the first time since he was tested positive. That’s a really exciting thing because he’s a guy in his 60s who smoked two packs a day for 25 years, so you worry about that kind of thing.

Roger Green (08:59): Personally, I think my personal thing is doing this. I have gone through life picking up new titles and things I’ve never done before, but executive producer is a new one for me, so I’ve had a lot of fun working with you guys and with our studio at New Pod City and putting this together, and I’m excited to get started and see where it goes.

Roger Green (09:15): Moving on, the topic for today’s discussion is COVID Chaos: Navigating NAFLD and NASH Clinical Trials Through the Pandemic. Obviously, the biggest question that any of us are hearing right now is about what kind of havoc is all this putting on clinical trials, and what is the downstream on that going to look like? We’re all making decisions and recommendations based on the answers.

Roger Green (09:36): Given how involved Stephen is with so many trials, I thought a great way to start the first podcast would be for Stephen to take several minutes to discuss what he’s seeing.

Roger Green (09:46): Before he does that, I want to note, starting next week, this session, the first several minutes after the introductions, will be dedicated to questions that you, the listener, send in through our website, and we’ll provide more information on that later. We will make the first five to seven minutes of every session about answering those questions. That’s next time. This time, we start with Stephen.

Stephen Harrison (10:05): Hey, thanks Roger. So, this is a hot topic for sure. It’s April 14th, 2020, as we tape this, and I guess we’ve been impacted significantly I would say the past three to four weeks, really kind of finding out about the virus impacting the U.S. maybe early as end of January or first of February, but it really didn’t take ahold in our world, the clinical trial arena, until towards the end of March.

Stephen Harrison (10:33): We don’t have a playbook. There’s no textbook. I can’t call up my mentors and ask them how they handled the situation in the past. There’s no experience to draw on in managing what’s going on right now. We’re making this up as we go along. We’re creating our own playbook.

Stephen Harrison (10:49): It’s all surrounding this notion of social distancing, constant media attention, fear of the unknown… the asymptomatic patient that’s spreading disease potentially, the quarantines, the travel limitations, the lockdowns, the shelter in place, all this leads to worry on the patient’s part, worry on the investigation staff’s part, and worry on the PI and sub-I’s part, and, ultimately, this has led to interruptions in clinical trial enrollment.

Stephen Harrison (11:19): There’s been a recent bit of knowledge put out by the WCG Knowledge Base, and they highlight a couple important facts. They track more than a thousand sites in 29 countries. Only 14% of those sites are currently enrolling. That’s down 8% in just the past week. If you look at 100-plus non-COVID-19 trials, over 100-plus non-COVID-19 trials have been placed on official hold within the past month.

Stephen Harrison (11:46): For context, prior to the pandemic, in the preceding months, only 12 trials were put on hold, and I’ll just go on to say that in the field of NASH, I’m aware of at least three trials that have been put on hold, so how do we get through this? How do we minimize patient risk, staff risk, and risk to trial integrity while keeping data solid, data sound, particularly for some of our larger trials or late-stage phase two B and phase three trials?

Stephen Harrison (12:15): I think I can break it down into a couple different groups that have been affected and then focus on how we’re managing those sorts of things. The first group would be patients. Patients are often restricted in their ability to move around. I know here in Texas, we’re under a shelter in place order, and only essential businesses are open. Fortunately, that would include ours, but patients are often unwilling or scared to travel.

Stephen Harrison (12:43): Some are quarantined, and almost all of them are practicing socially distancing practices, and they’re fearful. They’re fearful of, sometimes, not themselves being infected, but who they’re caring for at home. This could be maybe a parent or an immunocompromised spouse or sibling or child that lives in the home, and they’re fearful of coming in to be evaluated.

Stephen Harrison (13:08): Looking at that a little bit closer, how do we keep these people in the study if they’re already enrolled, and for that I think we can talk about a couple different things. For people that are already in a study receiving investigational product, that’s a special situation. How do we keep drug being delivered to the patient? How do we draw the safety labs? How do we communicate with those patients?

Stephen Harrison (13:34): There’s been a ton of work done by our group and by many others to try to make that happen, thinking outside the box, getting creative to keep people on study drug during this time. I think the FDA recognizes that there may be unavoidable protocol deviations and violations because people are out of window or because they’re unable to get a certain lab, and they’re working very diligently with sponsors and with the clinical research organizations and sites to make that happen.

Stephen Harrison (14:06): The other thing is what happens with people that are currently in screening? Some studies have ongoing screening operations, and people may have screened four, five, six weeks ago, and there are several different gates they typically have to go through.

Stephen Harrison (14:21): First, they have to pass labs, then they usually have to pass an imaging study, such as an MRI, and then, often, they have to pass a liver biopsy. What we’ve been able to do in many situations is extend the screening windows so that they can get the necessary tests that they need.

Stephen Harrison (14:36): We’ve also had an unforeseen issue arise where some of our imaging centers are unable to open to perform MRIs or some of our interventional radiology groups that do liver biopsies cannot do them because the PPE that’s required to do those procedures are moved to the front lines. In those situations, we’re in a pause or a wait and hold situation.

Stephen Harrison (15:01): Then, finally, for studies that… many studies are still recruiting, what we found is that most of our sites, although this isn’t the case for all of them, but many of them have decided to halt screening of new patients until such time that they’re able to lift the restrictions and open back up.

Stephen Harrison (15:19): Ultimately, what we’re trying to do at the site level is produce safe care to our patients that continue to get investigational product and obtain the safety labs that are necessary to do that. I’ll say this as I wrap this up, for the sponsors, this has been an issue. It’s been a challenge to try to work through, “What’s the right thing to do in this situation?”

Stephen Harrison (15:41): It isn’t just an issue for the sponsors. I’d back up and say it’s an issue for everybody, for the patients, for the investigator, for the staff, for the sponsors, the CROs, everybody. I think, at the end of the day, I look to the CDC website, and I see that patients that are morbidly obese with BMIs over 40, those that have diabetes, and those that have underlying liver disease are at increased risk for having a poor outcome if they’re infected with COVID-19.

Stephen Harrison (16:06): So, for me, that gives me hope that we’re doing the right thing. We’re keeping people on investigational product that potentially could have major positive implications on their liver disease in such a time where COVID-19 is rampant. It’s a pandemic. We’re not out of the woods yet. Our patients potentially are at risk of getting infected, and if we can manage their liver disease, we give them a better chance of doing well if they do get infected. For that reason, within our Summit network, we’ve worked hard to try to keep sites open and running and moving, but I think, at the end of the day, what we’ve learned is a couple things.

Stephen Harrison (16:42): That clinical trial enrollment is likely to be pushed out by about one quarter. That’s just my estimation that studies that were set to end probably won’t end for… We’ll add another two to three months onto the recruiting time frame. For studies that are wrapping up, there are several that are kind of in just the final data collection phase. We’re working hard to make sure those data points get collected so that we have a robust data set from which to analyze.

Stephen Harrison (17:10): I think, for sponsors that were thinking about starting trials during this time, the better part of valor is to hold those trials until we are through with the major impact of COVID-19, and I think that’s going to roughly be a quarter or so that those trials are delayed. Having said that, I’ll stop there, and maybe we can turn it back over to you, Roger.

Roger Green (17:32): Thanks Stephen. That was fantastic. On the program, the next thing is for each of the three of us to comment on how what you said affects the way that we look at markets, and, Yas, I think since everybody is most interested in investors, I’m going to ask you to go first.

Yasmeen Rahimi (17:47): Thanks Roger, and thank you, Stephen, for sharing this perspective. I think that this view is critically important for many investors who are obviously trying to figure out, like everyone else, when do we have a good handle on the virus, and it appears that when we have faith and a good handle on the virus, the market conditions are improving.

Yasmeen Rahimi (18:08): Many investors at this point who are investing in companies who are focused NASH therapeutics, are wondering around the same things. What are their timelines in regards to finishing enrollment, starting enrollment? Are they delayed by a quarter? Will they be delayed by three quarters?

Yasmeen Rahimi (18:26): What is the current cash of the company? If the company’s well financed, that allows them to stretch and have that delay built in. Then, ultimately, we have investors who are wondering around what about timelines that are coinciding during COVID-19?

Yasmeen Rahimi (18:46): I think a lot of them wonder, even though there are companies who may have key milestones upcoming in the third quarter, but they’re challenged that maybe market conditions are dominating and preventing the stock to react to the positive news.

Yasmeen Rahimi (19:02): I think, from the investor perspective, they are very, very engaged and monitoring the progress on COVID and really having a good understanding when to buy back into the market and what investments they should make. However, they are still looking at great investment opportunities, and I get the question, well, what are NASH companies, who, recently, its valuations significantly came down due to COVID and, therefore, they feel like if I missed a buying opportunity a few months ago, I need to get back into the stock.

Yasmeen Rahimi (19:35): We definitely have still investors engaged, wanting to do work on [inaudible 00:19:40], but, again, all that is dictated by having a clear understanding how these companies are going to meet their timeline.

Yasmeen Rahimi (19:48): I think Steve’s perspective on the fact that you’re continuing to push patients through screening, they’re already in the trials, continuing to monitor them, finding creative ways, and I think investors are really interested. What we need to get at is, on a granular level, how this patient processing is performed. That is something that is really critical for investors to figure out.

Yasmeen Rahimi (20:13): Then, the question that we get is… Given that NASH patients have comorbidities like cardiovascular disease, obesity, type-two diabetes, or at highest risk, the biggest fear that we get from investors is, even if we resume semi-normal life, would the trials be impacted in that patients would be hesitant to be part of a trial because they’re the high at-risk population, especially if we don’t have a vaccine available for them?

Yasmeen Rahimi (20:41): That would be my thoughts for you, Stephen, is that there is a significant fear that we’re hearing from investors. How would patients be still incentivized to be part of a trial, especially if they’re very worried for their lives, given their comorbidities that puts them at the high-risk patient population?

Peter Traber (21:01): All right. I appreciate both what Stephen and Yasmeen have mentioned. I think, from the perspective of leadership and the C-suite of the development companies that may be developing NASH agents or others, the pause in the global economy and activities does not mean that your company pauses. In fact, it means you have to work harder, smarter, and more creatively during this period of time, and you need to have a strategy about how to proceed forward, but just as Stephen talked about strategy for continuing to enroll patients, keeping patients on their study drug, you have to have a strategy as a company.

Peter Traber (21:47): As it’s been said many times, hope is not a strategy, so you can’t sit and hope that COVID-19 is going to fade away. Actually, the repercussions of COVID-19 are going to be here for a long time, and we are going to end up with a new normal. The company leadership that thinks through things strategically and creatively are going to be in better shape.

Peter Traber (22:12): I would just comment on a couple of things that leadership groups should be involved with. Number one is communication, and communication I think is critical to keep the awareness of your company up and to address the various stakeholders effectively during this time. You need to communicate effectively with agencies such as the FDA and the EMA, market and investors, PIs in your sites because you want to maintain those relationships so that they’re still there once things have gotten back to normal, and, above all, patients. I think that communication is critical.

Peter Traber (22:55): The next thing to think about in terms of studies is, yes, there are timelines and how is your financing going to affect the timelines? Do you have enough financing to get through, but the other key point is quality of data. Once you do get data from your clinical trials, you want to make sure that you can minimize the impact on the quality of the data.

Peter Traber (23:19): One thing that I’ve been stressing with companies is as you assess what’s going on in your clinical trials, communicate with the FDA, update your SAPs, look at how mitigation strategies for the COVID-19 virus is going to affect both end points, but also study groups such as protocol groups and so forth. Communicating with the FDA and updating SAPs are I think very, very important.

Peter Traber (23:51): The keys from a leadership standpoint are to think about this crisis as evolving into a new normal for your company, and to increase your efforts around creative communications. As Yas said, there are investors that are interested in deploying money. Be the creative companies that they see as strong to invest in even during this time of crisis.

Peter Traber (24:21): I want to just give you a short vignette to tell you how you have to continually rethink your strategy. There was a patient in a clinical trial that needed a blood draw. We talked to the site. The site said they’re willing to send out one of their staff to draw the blood. The patient said, “No. I don’t want the staff coming to my house.” The staff said, “I don’t want to go to their house.”

Peter Traber (24:46): Then we hired a group of phlebotomists that would go out to draw her blood. The patient said, “I don’t want anybody coming to my house.” I’m not going to give a solution to this conundrum, but each step of the way, you make decisions, and then patient preferences, the situation in the particular region changes your ability to do what you thought was a good idea.

Peter Traber (25:10): There has to be a continual process of evaluating that, and that’s something that leadership teams under the CMO and the CEO and others in the C-suite need to really be focused on in a continual fashion during this crisis.

Roger Green (25:26): Peter, thanks for that, and thanks to all of you for some really interesting and informative responses. I’m going to try to boil mine down to three important questions for forecasters and for people trying to analyze how this markets going to develop, one around adoption curves, one around market access, and one around enthusiasm.

Roger Green (25:45): The adoption curve issue goes like this. If you are coming to market, and you have a competitor who is behind you in the clinical development cascade in such a way that what you used to think was a, say, one-year difference between you, might now be an 18 to 21-month difference between you, that means you’re going to have a lot more time to develop market and build share before you see competition. That’s the good news side of the coin.

Roger Green (26:08): If you’re the company coming not a year later, but 18-21 months later, you have to take a very realistic view at whether your product is going to be different enough to continue to stand up successfully in comparison to somebody who now has much more lead time against you. I think that’s a huge forecasting question. This might be exacerbated by a market access issue, which is that healthcare insurers are about to get pounded with a range of costs, extensive costs related to COVID that were not in anybody’s budgets.

Roger Green (26:38): If they are not adequately benefited by the myriad bail-out programs that we’re seeing right now, they’re going to be stuck in a position where they can’t spend as much money as they would want to on other things, and new products would be one of those. My guess is that might be a two to three-year roll through the system before it’s all straightened out.

Roger Green (26:55): Last issue is enthusiasm. I think, in general, everybody is less enthusiastic about everything than they probably were a month or month and a half ago. I hear that talking to my kids. I hear that talking to my grandkids. I hear that talking to my friends. What it will do is it will take the next couple of major identifiable events that get public legs and make them more important.

Roger Green (27:14): Yas mentioned the Intercept AdCom meeting for CA. Elafibranor phase three data will come out, and those are two things that’ll happen within the next couple few months that, as important as they used to look, may look more important now because you’re in a less enthusiastic audience. Just a couple of thoughts. With that, I’d like to move to some time for question and answer, and, Yas, I want you to go back to the question that you were asking Stephen, that you were hoping he’d respond to.

Yasmeen Rahimi (27:38): Yes. Stephen, just out of curiosity then, investors are really wondering if… How do you ensure that patients continue to be incentivized to being part of a study, especially if they might fear, given that they are at the at-risk population due to their comorbidities?

Stephen Harrison (27:55): I think that’s a question that’s going through not just investors’ minds, but investigators’ minds, and even the patients’ minds. Look, hope is not a strategy. We know that, and, oftentimes, our patients sit and listen to the news, and they listen to the media, and they listen to their friends, and they have real concerns. These concerns are about the virus, and they tend to forget that they have real comorbidities, that they have liver disease that in some cases is relatively advanced, and I’m referring to stage two and stage three and stage four fibrosis.

Stephen Harrison (28:32): Yes, the virus fears are real. It’s a concern, but the paradox with all this is that we now have incredibly impactful drugs for this disease. We’ve learned about aldafermin and the FGF19 drug. We’ve learned about thyroid hormone receptor beta drugs. You have Madrigal and Viking and many others are developing those as well. We have the FGF21’s and you saw the preliminary data out with Akero. These drugs are moving the needle. They’re not just moving the needle in fact. They’re moving the needle impactfully on noninvasive tests that reflect improvement in histology, or they’re quite frankly just moving histology in a positive direction.

Stephen Harrison (29:13): The paradox… We have a fear of a virus that may or may not impact a patient’s life, but we have a real liver disease that for sure is impacting their life, but we have drugs that can move that needle. I think, if you look at it from my perspective, there’s a meaningful benefit to a patient that outweighs a theoretical risk in many situations.

Stephen Harrison (29:41): I think our studies can have a positive impact on these patients’ outcomes, and so I’m thinking that that’s what we need to be doing. We need to encourage our patients to continue to seek treatment of their underlying liver disease. Right now, that’s in the setting of a clinical trial.

Stephen Harrison (29:59): There is a positive impact of this that I forgot to mention, and that is these patients that do come forward. They are all in. I often talk about the difference between the chicken and the pig at breakfast. The chicken just contributes an egg every morning. The pig is totally committed, all in, and these patients are all in.

Stephen Harrison (30:17): Where that’s going to be impactful is the point that Peter made, and that is retention and gathering the important data that comes from these trials, and these people that are all in are likely to be the ones that retain in the study and allow us to get those end points 24 or 52 weeks down the road..

Roger Green (30:36): Thanks Stephen. One of the questions that leads me to wonder about is whether it makes sense for manufacturers or maybe for pharma or whoever to be running campaigns emphasizing for patients the relative risk of a virus they’re afraid of, but might never affect them, versus these kinds of products. I think your statement was tremendously compelling. I wonder on how broad of scale we can get it to patients and what we do to do that. Peter, do you have any thoughts on that?

Peter Traber (31:05): I think that what Stephen has said is very important from the standpoint that we have shifted over the last year from a number of disappointing situations in NASH drug development and disappointing outcomes to a series now with FGF19, FGF21, and resmetrion that are very, very encouraging. I think that a lot of the market is still in the doldrums of some of the large negative trials, but what we’re seeing I think is turning the corner on doing some real benefit.

Peter Traber (31:43): This has an implication I think for industry as it looks at NASH as a whole, but it also has an impact on companies that have a variety of other agents that are in development because it gives a relatively high bar for having to hit results. The overall picture is getting more positive from that standpoint. I don’t know, Roger, if that hit at what you were asking.

Roger Green (32:08): I think reasonably well. I want to do this right now because Yas has to step off in a minute. Yas, final question for you, and then the rest of us can go a couple more minutes… What’s one thing you heard today that you weren’t aware of before you got on the call, and what impact is it having on how you look at things?

Yasmeen Rahimi (32:23): I think the [inaudible 00:32:24] that Peter’s emphasis on creativity, as well as the comments that Stephen made in regards to the ways that they’re thinking and really using creative ways to continue these trials, I think are really ignored by the community and especially also among the analysts.

Yasmeen Rahimi (32:40): I think it’s really clear that the cohesiveness of the sponsor, as well as the execution when it comes to Pinnacle and key investigators like Stephen, really are working and learning week by week, and adapting and making these changes. I think that’s very encouraging to hear, and I think we really need to communicate that even more clear as we go into these weeks and realize that there’s going to be a new normal. Both of those comments were very helpful to learn.

Roger Green (33:13): Thanks Yas. We’ll see you next week. Peter, do you have a question?

Peter Traber (33:16): I do have a question for you, Roger. You mentioned this tangentially, that this is also a time for companies to think about how their drug may fit into the overall armamentarium in the future and how you might take that into account in terms of valuation and market evaluation. Can you expand on that a little bit?

Roger Green (33:37): Sure. Visualize every product that comes to market as having a peak market potential and a time to get there, which is a curve, and that curve can be anywhere from 15 to 18 months to five to seven years, depending upon how novel the therapy is, how much is known about the disease, and how much noise there is from other places.

Roger Green (33:58): One of the things that may come out of COVID is everything may be noisier, but forget about that for a minute. At the point in time where another product comes into the market that competes directly with me, that alters my curve.

Roger Green (34:10): If, for example, I am first of any of these modes of action to market, and a second product that is roughly comparable looks like it’s a year behind me, then I know I have a year lead time, which means a heavy up-front investment, and probably not as close to my sales peak as I would like to be, but if I know, because of where the hurdles are going to be in clinical trials, that that product is, say, six to nine months more behind me than they were, that adjusts my curve.

Roger Green (34:37): It means I’ve got more time alone. It makes up-front investment more attractive. The tougher question is if you’re on the other side of the line, because not only is hope not a strategy, but loving your baby is not a way to make money, and everybody loves their children a little too much if their children is the drugs they’re developing.

Roger Green (34:54): In fact, a friend of mine says strategy starts when you say no. Figuring out whether you still have enough running room as time changes is going to be, I think, a pivotal consideration for people. Does that help?

Peter Traber (35:05): It helps a lot, and another thing that I always think about when looking at longer term strategy is start by being brutally honest. That is very challenging with one’s own child. As you’ve just said, all babies are wonderful, but they’re not all equal, and you have to make choices.

Peter Traber (35:23): I think that’s where we’re starting to get in the NASH field. Not all 300 assets can go through phase two. There’s going to have to be some choices made, and they’re going to be challenging choices up front. You would ordinarily think that the market would be able to make those choices, but we may be in a bit of a different time that companies and investors need to start thinking in that way a little bit earlier.

Roger Green (35:47): Thank you. Stephen, do you have a question because, if not, I’ve got one for you.

Stephen Harrison (35:51): No. I’m anxious to hear yours though.

Roger Green (35:53): Keeping in mind the trial enrollments will be delayed a quarter and that it may be more difficult to pull patients through, how much time do you think somebody who’s in enrollment right now is likely actually to lose over the course of, say, a one or two-year trial?

Stephen Harrison (36:09): That’s a little bit like looking at the crystal ball. What I would say is that the way that we approach clinical trials moving forward, it’s unlikely it’ll go back to the way it was before. At least, until we have a vaccine, there’s going to be concern. Not everybody’s going to get tested for antibodies. Not everybody’s going to walk around with an immunity card. I doubt we’re going to be wearing masks forever.

Stephen Harrison (36:33): Having said that, there will be people that are fearful of being around other people for a long time. There will be social distancing that goes on even when governments say that there’s no reason for that. Until there’s a vaccine, until people can feel safe, it’s going to be a challenge.

Stephen Harrison (36:54): I would say about a third of our patients right now don’t want to come in. Just to Peter’s point earlier, they don’t want anybody coming in their home to draw blood and being so close they’re sticking a needle in their arm. It doesn’t matter how protected they are. They’re wearing a mask. They’re wearing gloves.

Stephen Harrison (37:10): I would say there will be a delay. Right now, it appears to be about a quarter if you’re currently enrolling a trial. That’s a big trial, a big study. I think what is going to happen is the PIs are going to have to get more involved. What we’ve seen locally, what we’ve seen throughout the Summit network, is when the PIs actually get involved with talking to the patients, explaining their liver disease, explaining their risk factors, explaining the study, explaining the data that we have relative to the drug that’s being studied, then, patients are much more willing to get involved.

Stephen Harrison (37:49): So, I think, where we’re able to do that, we’ll be able to make up some ground in the future, but, for now, I would say, ultimately, the damage that’s been done is a significant, but not insurmountable delay. Maybe this is more important for the sponsors that haven’t started yet because they’re now going to be competing with trials that should have resolved, and they’re still going to be enrolling, so the competitive pool of patients is likely to diminish slightly, but the competitive pool of sponsors throwing their study into the ring will increase. Ultimately, we will have that new calculus to consider.

Roger Green (38:31): If I’m planning a trial, will this change at all what makes a trial site attractive to me?

Stephen Harrison (38:37): I think it will. What makes trial sites attractive are, number one, a passionate PI because we know that studies enroll when there’s a passionate investigator that really has a focus in nonalcoholic steatohepatitis. We also need a site that has access to patients that have the disease, and we need sites that can get up and running quickly that can do budgets and contracting concurrently and that are nimble enough to pivot quickly when new opportunities or new challenges arise.

Stephen Harrison (39:12): I think we’ve seen a pivot from purely academic sites enrolling clinical trials… This was the FLINT trial, for instance, and some of the early trials were mainly driven through academia, and then there’s been this slower trend towards more personalized or private sites such as Pinnacle Research here in San Antonio. They exist to enroll liver disease studies, NASH currently, and I think we’ll see more of that paradigm shift as the competition increases and as disease state awareness begins to increase, not just in our country, but around the world.

Roger Green (39:51): Stephen, thanks. Before you sign off, one thing you heard in the last hour that you weren’t aware of or that you’re thinking differently about because of the discussion?

Stephen Harrison (40:00): I’ll just have to hit on what I heard Peter saying, and I’ll hit it again. Hope is not a strategy, and for these sponsors, they really can’t fall back on what they were taught or what they gathered from their prior experience in industry. They have to really break new barriers and realize that these are unprecedented times, that there’s no playbook, and that they have to be willing to bend and look at things differently moving forward.

Stephen Harrison (40:30): Now’s the time to bend your ear, to work harder, to get in there and actually get involved rather than take a step back and wait for things to kind of settle out. I think that’s critical for the industry as a whole. If we want to move forward, we have to lean into this together. We have to find mitigating strategies, and we have to lock arms to tackle the situation together.

Roger Green (40:54): Thank you, Stephen. That’s great. Peter, one thing you heard in the last hour that is either new or is leading you to think differently?

Peter Traber (41:02): Yeah. One thing that Stephen said really resonates with me, and that is that the COVID crisis is going to accelerate some of the changes that we already saw happening slowly.

Peter Traber (41:15): Clinical trial sites that aren’t attached to large medical facilities, whether they be academic or otherwise, are going to be more attractive because they’re going to have more control over the facilities, more control over the mitigation processes for viral control, more focused patients, and the clinical groups that focus on places like that or the CROs that accumulate wholly owned, operated clinical trial sites, I think, are going to be more successful than the traditional sites that are attached to large health systems or hospitals. That really resonated with me from what Stephen said.

Roger Green (41:58): Thank you, Peter. Several things resonated with me, but the one that we’ve not touched on is something Yasmeen mentioned, which is the idea that there are investors looking for value in this space right now. Most of what I think we’ve all heard in the last year was that the space just got beaten up, bad trial results, and general market issues, so the idea that this is a place where somebody with intelligent strategy and a decent trial can produce investors, maybe not premiums… The Akero stock didn’t get the bump it might have gotten two years ago out of the results they published recently, but can interest investors and get people to stay in and stay focused on NASH is, I think, really important because without investment, obviously, all this become infinitely harder to do.

Roger Green (42:38): I want to thank Yasmeen, and I want to thank Peter, I want to thank Stephen for being along with us today, and Frank Sasso from New Pod City for putting this together. We look forward to seeing you next week when our focus will be in more detail on investors. Please remember, send your questions at Surfing NASH, S-U-R-F-I-N-G-N-A-S-H.com, to get them included in next week’s conversation. Everybody have a good week. Stay safe. Stay healthy. Do interesting work and [inaudible 00:43:07] forward. Thanks. Bye-bye now.

Speaker 1 (43:08): You’ve been listening to Surfing the NASH Tsunami. Send in your questions to Surfing NASH.com, and our panelists will spend the first five minutes of next week’s episode answering your questions. Visit us online today, Surfing NASH.com.

 

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