Written for and originally published on BioSpace
BioSpace recently spoke with James Oliviero, CEO and president at Checkpoint Therapeutics, an immuno-oncology, late-stage development company. The company’s goal is to bring novel cancer drugs to market to be commercialized at a lower price point than its big pharmaceutical company competition.
Q: What are your daily activities as CEO and president?
A: We’re a small company so my role is very much hands-on. That’s part of my personality as well. I like to have my finger on the pulse of the different aspects of the company. I would say half the job of a CEO in a publicly traded biotechnology company is on the investor outreach and relations front, presenting the company to the investment community. And then the other half of the time is managing your development programs and overseeing the company. I am heavily involved in working with my team to design our clinical trials and manage the clinical research organizations that we outsource to.
Q: What background do you have in biotech?
A: My love is clinical development; bringing new, potentially life-saving therapies to the patients who need them. I joined Checkpoint in 2015 after successfully developing and launching a new drug at my former company. I was attracted to Checkpoint for its interesting and cutting-edge pipeline of immunotherapy products. Cancer affects too many of us in so many ways, and so I’m driven to bring our oncology drugs to market and have a positive impact on our world.
Q: What is Checkpoint’s business model?
A: Checkpoint does not discover or invent its products. We license or acquire the rights to novel therapeutics at an early stage of development from academic institutions or other small biotechnology companies. Our most advanced immunotherapy product, cosibelimab, was licensed from the Dana-Farber Cancer Institute in 2015. Dana-Farber employs the scientists that discovered our novel antibody. After obtaining rights to our product candidates, we then conduct the necessary pre-clinical studies, including pharmacology and animal toxicity studies, and manufacturing development, to enable a clinical development program in humans. We use and manage contract clinical research organizations and contract manufacturers to conduct our pre-clinical and clinical development programs.
Q: What is your pricing strategy?
A: Maybe 10 years ago, large pharmaceutical companies would charge $50,000 per patient, per year for a novel oncology drug. So why are they charging $165,000 annually now? It’s not because it’s so much more expensive to manufacture and develop these drugs. It’s because big pharmaceutical companies need to charge such inflated prices in order to support and continue to grow their large market values. If they lowered their prices, you would see their market capitalizations quickly reflect it in a negative way.
As a small company, we can price substantially lower and our profit margins will be plenty sufficient for us to continue to grow substantially. Our strategy is good for Checkpoint and for the entire health care system, from the insurance companies to patients who can pay up to 20% of the price of a drug as a co-insurance payment. It’s a very novel commercialization strategy in oncology. We’ve already conducted surveys with insurance companies regarding our planned pricing strategy, asking how will you, the insurance company, position our product to help us help you?
We know insurance companies want lower-priced drugs that are comparable in safety and efficacy to established products. And they responded that they would provide our lower-priced products with preferred reimbursement coverage or removal of restrictions on use, effectively positioning our product as first-choice therapy on their formularies, which can influence and increase patient access without the need for a large salesforce on our part. Again, it’s truly a unique strategy that hasn’t been done before in oncology.
Q: You mentioned that Checkpoint is a fast follower. What does that mean?
A: Part of our strategy in our clinical development is that we’re utilizing a fast-follower approach. What that means is when we license our lead immunotherapy product from Dana-Farber, other drugs in the same class are ahead of us or approved. We can use this to our advantage and compare the drugs that we license against them to ensure that we have a drug that is comparable or better than the ones that are out there already. We’re just following the path through clinical trials that they’ve already established. That’s what’s called a fast-follower approach.
This approach enables us to move very quickly through clinical development as compared to other products. Meanwhile, the FDA has been vocal about bringing competition into the market to lower prices, and we believe the FDA will appreciate our lower price point strategy.
Q: Anything I haven’t asked?
A: We’ve quickly transitioned into a late clinical-stage oncology company and anticipate 2021 to be a transformational year for us. We’re expecting to report pivotal data on cosibelimab by year-end. With a successful study result, we intend to file an application for marketing approval with the FDA early next year.
Upon successfully obtaining marketing approval, our plan is to commercialize our approved products ourselves, at least in the United States. We’ll likely evaluate potential commercialization partners for Europe and Asia for our programs. We’re looking to change the world, coming out with novel drugs to help patients in need, but also doing so at a fair price point that allows our company and the healthcare community to benefit.
Written for and originally published on BioSpace
BioSpace recently spoke with Mir Imran, CEO and Chief Innovator at Rani Therapeutics, a company developing and testing a “robotic” pill that delivers biologics orally.
Q: What is your role at Rani?
A: In the early days, as an entrepreneur building a company from scratch, I did everything, including cleaning the conference room table after a meeting. Today, as the company grows, I am working to develop and build a team. As we grow, I spend a lot of time with the scientists and engineers, mentoring them and helping them understand the problem we are solving. I really enjoy that part, working with brilliant scientists and engineers. We have an amazing team. Ultimately, I’m deeply involved with all aspects of our business from engineering and manufacturing to business development, finance and clinical and regulatory matters. It’s a dynamic environment.
Q: What is your background and why Rani?
A: My training is in engineering – electrical and mechanical engineering and materials science. I went to medical school but never practiced; skipped all the residency and all the difficult parts, and decided to start up a company. And this was ’79, I think. We developed the first implantable defibrillator using my engineering background and medical knowledge. INTEC SYSTEMS was the first medical company I did. That company was acquired by Eli Lilly five years later. They came in as an investor in 1985. And several years later, they spun out a company called Guidant, which was acquired by Boston Scientific in 2006 for $27.5 billion. So the implantable cardioverter defibrillator came out of my work, and it has been implanted in millions of patients, saving millions of lives.
What I learned from that is that what shapes you is really the kind of things you do in life, the kinds of problems you work on. If you work on big and difficult problems, it helps you grow. And even if you fail at those, it really shapes you and deepens your understanding of the problem. In 1995, I set up an applied research lab called InCube Labs. It is in this laboratory that we identified big problems, unmet needs and tried to figure the problem out and see if we can create a solution. And some of those things become companies. So periodically, a company comes out of this research lab, and Rani was one of those companies.
Q: What is the RaniPill™ capsule?
A The oral delivery of biologics is considered the holy grail of drug delivery. I was in a meeting where I heard of a small company that was trying to convert a peptide into an oral formulation. They just couldn’t get the bioavailability that was needed. So, I left the meeting thinking about that, and why not create a capsule that the patient takes and which passes through the stomach into the intestine? The intestines don’t have pain receptors like your skin does. You can poke needles all day long, and you won’t feel a thing. So, we could actually create a capsule that would transform itself once it’s in the intestine and deliver a pain-free injection of the drug that’s contained in it.
Q: How big is this pill?
A: You are familiar with fish oil capsules? And calcium pills or Centrum? So, it’s closer to the size of the fish oil pill. And it has a lubricious coating, very slick. As soon as it comes in contact with fluid in your mouth, it becomes slippery and just goes down; it’s very easy to swallow.
Q: And there is powdered medication in there with a dissolvable needle?
A: Yes. When I was examining the problem of delivering biologics into the gut, I asked myself, why can’t we use a dissolvable needle? The minute you talk about a dissolvable needle, you really cannot push a liquid drug through it because as it’s going through, it’s dissolving the needle. So I said, okay, the drug can’t be liquid, so it has to be solid. That sort of converged to a solution, where we have a dissolvable needle made out of injectable-grade materials. And it’s hollow, and inside that hollow lumen, we stuff it with the drug that we want to deliver. The intestinal wall is a muscle, and it’s highly vascularized because the intestines are designed to absorb the nutrients. The blood supply is incredible, the microvascular supply. Much better than a subcutaneous injection. We get a much faster uptake because of the rich blood supply.
Q: Do you think this will work?
A: It does. We have done hundreds of preclinical studies. We have conducted two human studies. A phase one study – one of those was a phase one study with a biologic. And we’ve talked to the FDA several times. They’ve given us a pathway going forward. We have a pipeline of drugs that we plan to develop. And in order to support that, we have invested heavily in manufacturing automation. So we’re scaling up sufficiently to support the clinical trials that are going to happen this year and next year.
Q: Why did you tackle this?
A: My passion is going after unsolved problems, unsolved mysteries and leveraging my engineering skills and other skills to create solutions. To, first of all, understand the problem, and then create solutions. We did a survey of hundreds of patients and hundreds of physicians, and 85 to 90 percent said, “we’ll switch to oral.” We decided to have Frost and Sullivan survey patients who are currently taking insulin, for instance, or Humira and talk to physicians who prescribe these drugs. They both said 85 to 90 percent will switch. For the patient, it’s a huge improvement in quality of life; you don’t have to poke yourself periodically.
Q: That’s amazing. You are the Chief Innovator at Rani. What does that mean for you?
BioSpace recently spoke with Mir Imran, CEO and Chief Innovator at Rani Therapeutics, a company developing and testing a “robotic” pill that delivers biologics orally.
Q: What is your role at Rani?
A: In the early days, as an entrepreneur building a company from scratch, I did everything, including cleaning the conference room table after a meeting. Today, as the company grows, I am working to develop and build a team. As we grow, I spend a lot of time with the scientists and engineers, mentoring them and helping them understand the problem we are solving. I really enjoy that part, working with brilliant scientists and engineers. We have an amazing team. Ultimately, I’m deeply involved with all aspects of our business from engineering and manufacturing to business development, finance and clinical and regulatory matters. It’s a dynamic environment.
Q: What is your background and why Rani?
A: My training is in engineering – electrical and mechanical engineering and materials science. I went to medical school but never practiced; skipped all the residency and all the difficult parts, and decided to start up a company. And this was ’79, I think. We developed the first implantable defibrillator using my engineering background and medical knowledge. INTEC SYSTEMS was the first medical company I did. That company was acquired by Eli Lilly five years later. They came in as an investor in 1985. And several years later, they spun out a company called Guidant, which was acquired by Boston Scientific in 2006 for $27.5 billion. So the implantable cardioverter defibrillator came out of my work, and it has been implanted in millions of patients, saving millions of lives.
What I learned from that is that what shapes you is really the kind of things you do in life, the kinds of problems you work on. If you work on big and difficult problems, it helps you grow. And even if you fail at those, it really shapes you and deepens your understanding of the problem. In 1995, I set up an applied research lab called InCube Labs. It is in this laboratory that we identified big problems, unmet needs and tried to figure the problem out and see if we can create a solution. And some of those things become companies. So periodically, a company comes out of this research lab, and Rani was one of those companies.
Q: What is the RaniPill™ capsule?
A The oral delivery of biologics is considered the holy grail of drug delivery. I was in a meeting where I heard of a small company that was trying to convert a peptide into an oral formulation. They just couldn’t get the bioavailability that was needed. So, I left the meeting thinking about that, and why not create a capsule that the patient takes and which passes through the stomach into the intestine? The intestines don’t have pain receptors like your skin does. You can poke needles all day long, and you won’t feel a thing. So, we could actually create a capsule that would transform itself once it’s in the intestine and deliver a pain-free injection of the drug that’s contained in it.
Q: How big is this pill?
A: You are familiar with fish oil capsules? And calcium pills or Centrum? So, it’s closer to the size of the fish oil pill. And it has a lubricious coating, very slick. As soon as it comes in contact with fluid in your mouth, it becomes slippery and just goes down; it’s very easy to swallow.
Q: And there is powdered medication in there with a dissolvable needle?
A: Yes. When I was examining the problem of delivering biologics into the gut, I asked myself, why can’t we use a dissolvable needle? The minute you talk about a dissolvable needle, you really cannot push a liquid drug through it because as it’s going through, it’s dissolving the needle. So I said, okay, the drug can’t be liquid, so it has to be solid. That sort of converged to a solution, where we have a dissolvable needle made out of injectable-grade materials. And it’s hollow, and inside that hollow lumen, we stuff it with the drug that we want to deliver. The intestinal wall is a muscle, and it’s highly vascularized because the intestines are designed to absorb the nutrients. The blood supply is incredible, the microvascular supply. Much better than a subcutaneous injection. We get a much faster uptake because of the rich blood supply.
Q: Do you think this will work?
A: It does. We have done hundreds of preclinical studies. We have conducted two human studies. A phase one study – one of those was a phase one study with a biologic. And we’ve talked to the FDA several times. They’ve given us a pathway going forward. We have a pipeline of drugs that we plan to develop. And in order to support that, we have invested heavily in manufacturing automation. So we’re scaling up sufficiently to support the clinical trials that are going to happen this year and next year.
Q: Why did you tackle this?
A: My passion is going after unsolved problems, unsolved mysteries and leveraging my engineering skills and other skills to create solutions. To, first of all, understand the problem, and then create solutions. We did a survey of hundreds of patients and hundreds of physicians, and 85 to 90 percent said, “we’ll switch to oral.” We decided to have Frost and Sullivan survey patients who are currently taking insulin, for instance, or Humira and talk to physicians who prescribe these drugs. They both said 85 to 90 percent will switch. For the patient, it’s a huge improvement in quality of life; you don’t have to poke yourself periodically.
Q: That’s amazing. You are the Chief Innovator at Rani. What does that mean for you?
A: I was fascinated by the innovation process at a very young age. I was intrigued by why I innovate. Why am I able to do it? Why can I do it well? And why are some people better and others are not at innovation or invention? And I couldn’t find any explanation. I read a number of books. This was in my early 20s. So I decided to become a conscious observer of my work, the thought process that was going on as I was inventing things or solving problems. And so observing that for about 10, 15 years, over a dozen companies I had started. It really came together with the clarity on how to innovate – how to innovate, not what to innovate. And then I asked the question, can I make it teachable? We all have the capacity to be inventors and innovators, and I happened to stumble on it early in life. But I’ve turned it into a teachable subject. So I think that, to me, the second– the parallel journey that I have is the journey to figure out innovation and figure out a way to teach innovation. As a result, I’ve gone around the country to a number of universities giving talks and lectures on innovation.
Written for and originally published on BioSpace
BioSpace recently spoke with Yoav Kimchy, founder and chief technology officer of Check-Cap, a company developing the C-Scan® system to detect precancerous polyps.
Q: What is your role at Check-Cap?
A: I founded the company in 2005. My background in high-energy physics was significant in finding a solution to the problem of people’s resistance to the colonoscopy. I am and have been involved in each step – from conceptualization to miniaturization to manufacture and trials.
Q: How did you get into colon screening?
A: I got to know the colonoscopy– the colon cancer space, when I was trying to persuade my father to do a colonoscopy. His mother died of colon cancer and he’s not a shy guy. Yet, it was difficult to persuade him, and I understood that there’s a problem. People don’t like this procedure. It’s invasive and it’s really not something that people are happy to do.
But, unlike other cancers, this cancer gives you a warning sign: something like 5 to 10 years before the cancer develops, you have polyps. If you find the polyps, you can prevent the cancer. It’s something very rare in cancer. And this is a really big opportunity if you can avert this devastating disease. I understood that the idea should be to try to find polyps, not to find cancer. To find it before it becomes cancer, and to find it in a way that is patient-friendly, so people don’t shy away from this procedure.
Q: Was it difficult to get backing for the concept of a capsule with these capabilities?
A: I started looking for investors in 2004. As it turns out, my real anchor was Dr. Walter Robb. He took GE Healthcare from a small company and developed the CT there, and the MRI. He headed GE Healthcare and the GE research center. In March 2020, he died of COVID. He was a very, very clever guy. It took him about 10 minutes in a café in New York to understand the concept. He jumped on it. He was excited. We had a lot of talks about the technology and how it works. He was a friend and mentor, and he was on our board for many years. His death was heartbreaking. We decided to name our conference room the Walter Robb conference room, in memory of this great man.
Q: Does the capsule you developed contain the equipment required to screen for polyps?
A: Yes, I have a background in high-energy physics and scattering and, naturally, I looked in that direction and came to realize that it’s possible to use x-rays to see into the colon contents, so you don’t need to clean it up. And this is the big hurdle for people who do colonoscopies.
So, you can think of the capsule as a submarine that goes inside a very dark place, and it uses sonar to understand what’s around it. Not visually because it’s a dark or murky water, but you can use sonar. In our application, it’s x-rays that help look through the murky water and find what the colon walls look like. And if you find something that looks like a polyp or is suspicious, then it gives an alert so the physician can know where it is.
Q: You swallow this capsule and then what happens? And, how big is it?
A: The capsule is somewhat larger than the size of an omega-3 capsule. Inside, there’s a whole lot of technology. There is an x-ray source, motor, scanner, detectors, electronics, processor, communication and positioning system like a GPS that connects with an external positioning and recording system. There is also a battery, of course, to power it. The trick was to make it so that you can swallow it, but we have worked to make it small and safe for human use. The capsule can detect when it is in the colon and it only scans while there. It requires no preparation or sedation, allowing patients to continue their daily routine with no interruption as the capsule is propelled through the gastrointestinal tract by natural motility.
Q: How do you retrieve the data? How do you know where the images were captured?
A: We have developed a GPS system that is a device that the patients put on their back. This GPS system has two functions. One is to locate the capsule within a centimeter of where it is. It’s very accurate. You can walk with it, shower and sleep with it. It also has a two-way communication with the capsule so it knows where it is, if it’s moving, it tells the capsule to scan, and then it collects all of the data from the capsule so you don’t need to retrieve the capsule once excreted.
Q: What currently stands between you and being on the market in the U.S.?
A: We recently received IDE approval from the FDA to initiate a pivotal study for C-Scan® in the U.S., which we plan to initiate in late 2021 and should be the last step before commercialization, if approved.
We believe C-Scan® has the potential to significantly contribute to improving the current colorectal cancer screening landscape worldwide by offering a patient-friendly option that can detect precancerous polyps and enable early intervention and cancer prevention. The goal is to enable millions of people to avoid the disruption and morbidity associated with cancer treatment and its progression.
Most patient-friendly CRC screening tests currently available or poised to enter the market, such as fecal or liquid biopsy tests, are primarily designed to detect cancer and demonstrate low sensitivity in detecting precancerous polyps. They don’t necessarily provide patients with the time window to pre-empt the disease.
We believe there is a genuine unmet need for a patient-friendly screening option, such as C-Scan®, that can overcome barriers to colonoscopy screening while also enabling precancerous polyp detection. Recently, the American College of Gastroenterology (ACG) also updated its recommended CRC screening guidelines and recommended colon capsules as an option for CRC screening in people who are either unwilling or unable to undergo a colonoscopy or Fecal Immunochemical Test (FIT). As screening for precancerous polyps provides an opportunity for early intervention and cancer prevention, I believe C-Scan® could be considered as a relevant option for those individuals.
Written for and originally published on BioSpace
BioSpace recently spoke with Jonathan Rigby, Group CEO of Revolo Biotherapeutics, a biotherapeutic company working to revolutionize the treatment of autoimmune and allergic diseases by achieving superior long-term disease remission through resetting the immune system.
Q: What is your role at Revolo?
A: I’m Group CEO of our revolutionary company Revolo Biotherapeutics, which includes Revolo Biotherapeutics Inc. in the U.S. and Revolo Biotherapeutics Limited in the U.K. It’s my job to look after both and I love it.
Q: What are you working on at Revolo?
A: We are working on two therapies that reset the immune system with the goal of superior long-term remission of autoimmune and allergic disease with less frequent dosing and without chronic suppression of the immune system. We have two drugs in development, ‘1104 and ‘1805. ‘1104 is a peptide and ‘1805 is a protein, both with immune resetting properties.
We’ve demonstrated that these drugs have a short pharmacokinetic life, but have pharmacodynamic effects that last weeks to months. Within a few hours of being given an injection, the drug is gone. During that time, we reset the immune system from a pro-inflammatory state to a regulated homeostatic state. We’ve fundamentally reset it.
Drugs like biologics work after the inflammation has happened, and there is an inflammatory cascade, often referred to as the cytokine storm, that’s when your immune system goes haywire and can cause damage. Current drugs are trying to tackle the inflammation downstream of this cytokine release, whereas we are targeting the process right at the beginning and resetting the immune system. In a Phase II trial of ‘1805 in rheumatoid arthritis some patients went into remission of disease, from a single dose, that was observed for the 3-month duration of the study. In addition, these were rheumatoid arthritis patients that had failed on other biologics and other therapeutics. We gave them one injection and we had patients in remission.
Q: What is the mechanism for this effect?
A: Right at the beginning of an inflammatory cascade, you have dendritic cells, and they communicate with T-cells. If there’s an allergen, in the case of allergic disease, or an autoantigen, in the case of autoimmune disease, the dendritic cell instructs these T-cells to change into certain types of T-cells, e.g., T effector cells. And these T effector cells cause this inflammatory cascade to happen. What both ‘1104 and ‘1805 do is interfere with the communication between the dendritic cell and the T-cell, so that the T-cells become T helper cells instead, which don’t cause this inflammatory cascade and reset the immune system.
Q: How did you come to be at Revolo?
A: I’ve been in this industry for 30+ years. Over this timeframe I’ve told my colleagues, let’s not forget about the patients and their suffering and let’s do something about it. I saw that Revolo could do this and that’s why I’m here.
A lot of people’s primary focus is other than patients, but the core of a good company is trying to help them. I started my career working for big pharma companies and, over time, I’ve gone to smaller ones and those with a focus on rare diseases, where there are fewer treatments available.
I co-founded a company in 2006 called Zogenix, which is now a rare disease company, and another one in 2012, SteadyMed, which worked on a rare disease called pulmonary arterial hypertension, another life-threatening disease. SteadyMed was acquired in 2018. And then just over a year ago, I was looking for something new to do and I’d found out that Revolo Biotherapeutics, formerly called Immune Regulation, was looking for a CEO. I looked at the data and it got me really excited. I became the first employee in the U.S., R&D remains in the U.K., and since then I led the closing of a $53.4 million Series B financing and grew our U.S. presence with the hiring of expert executives that are passionate about and driven by our mission.
We are planning the initiation of four Phase II clinical trials in the U.S. and Europe in 2021 for rheumatoid arthritis, non-infectious uveitis, eosinophilic esophagitis (EoE) and allergic disease. Despite challenges from the COVID-19 pandemic, it has been a very successful year for Revolo and we are excited for new successes ahead with our revolutionary drugs.
Q: What’s the best part of your job?
A: I love it. People say, “You need to think outside of the box.” I say, “No, no, no. You have to get outside of the box and make things happen.” I love working with a team that works with passion. If you’re not passionate about what you’re doing, then you should probably go and work somewhere else. You’re passionate about the disease. You’re passionate about making it better. You enjoy working with the people that you work with. And the Zoom boom last year, it’s fascinating, I’ve managed to build a team, and all of us either know each other or somebody knows somebody. That’s how we’ve organically grown the team. We all get along great. We’re all singularly focused on the same mission. We’re all in the same boat, rowing in the same direction, at the same rate. I really enjoy it. I get a great deal of satisfaction.
I love talking about it to new people, new investors. We’re just starting a new investor outreach imminently, looking at additional sources of capital to help us continue to move forward to advance our revolutionary therapies that have the potential to fundamentally reshape the treatment landscape for autoimmune and allergic diseases and make patients better.
Written for and originally published on AGT
Big Picture
Genomic medicine is bringing hope where none previously existed. This approach to cure and treat human diseases uses human biology rather than chemical compounds made in the lab to unlock techniques and therapies with the power to cure formerly incurable diseases. The use of gene therapy, CAR T cell therapy, stem cell, and other therapies is revolutionizing medicine.
What Are Stem Cells?
Stem cells are the cells the human body uses to create differentiated cells with special functions. Some stem cells become kidney tissue. Some become lung tissue. Every cell begins as a stem cell, then goes on to specialize. Because stem cells are flexible, the body also uses them to repair systems in the body. When a fetus is forming, the stem cells are called embryonic stem cells. Adult stem cells are more commonly used in therapeutics, and in the U.S., the use of human stem cells is subject to regulation.
How Are Stem Cells Used?
The National Institutes of Health (NIH) maintains a registry of human stem cell lines that can be used legally for research. On an individual level, stem cell (also known as bone marrow) transplants are a treatment for diseases such as leukemia. Healthy stem cells are harvested from a living donor (allogeneic cells) who is considered a match and introduced into the patient’s body during stem cell transplantation through a transfusion that is much like a blood transfusion. This is a risky procedure because the patient’s immune system must first be destroyed so that it will accept the donor stem cells. Figure 1 illustrates the stem cell transplant process.
Outcome
Even when all precautions are taken, the patient’s body may reject the new stem cells, which may cause death. Patients must take an immunosuppressant for the rest of their lives to mitigate side effects and keep their bodies from rejecting these cells.1 In many stem cell therapies, the stem cells are not treated or amended in any way before they are introduced by transfusion into the patient’s body. One important note is that it is possible to save and freeze stem cells from the umbilical cord blood of newborn infants. Parents can elect to do this and may choose to do so because if those stem cells are needed in the future, they are an exact match to their child.
Written for and originally published on BioSpace
BioSpace recently spoke with Norman Sussman, chief medical officer at DURECT, a company committed to transforming the treatment of acute organ injury and chronic liver diseases by advancing novel and lifesaving therapies based on its endogenous epigenetic regulator program.
Q: What are your daily activities as Chief Medical Officer at DURECT?
A: I have several jobs. Number one is to establish the centers for our trials, make sure that we have good-quality investigators, keep an eye on the data and review any safety issues that arise. Our leading trial is a Phase IIb trial evaluating our lead epigenetic regulator drug (DUR-928) in alcohol-associated hepatitis (AH), previously called alcoholic hepatitis. AH is a life-threatening acute alcoholic liver disease caused by chronic heavy alcohol use and a recent increase in alcohol consumption, and has no approved treatments. These patients can be very ill, so they may have complications related to or unrelated to a medication they’re getting. It’s very helpful for the company to have a liver doctor, especially at this stage of development.
Q: What drew you to DURECT?
A: I was just about ready to retire as a hepatologist, and at my last planned liver meeting in November 2019 I saw the Phase IIa data of DUR-928 in AH patients. I’m not joking when I tell you that I just could not believe that after 50 years, something could be this good. AH has been a frustrating disease for all the time I’ve practiced, and I just couldn’t believe I was seeing those results, and I thought, “That’s fascinating. I have to know more about it.” Results from the trial showed that 100% of the treated patients survived the 28-day follow-up period, compared to a 26% historical 28-day mortality rate, which is higher than some cancers. Then when Jim and WeiQi called me and said “Hey, would you like to join the company?”, I thought I was dreaming because I didn’t think I would have had the chance to help in this way. DURECT’s drug is the kind of approach that we need to solve this immense problem. AH affects both old and young people, people with young families. It’s a terrible disease and if we can come up with a cure, this will be a huge contribution. That’s why I’m here.
Q: What is it about liver disease that intrigues you?
A: I trained in South Africa, and the requirement then was to do a medical and surgical specialty, six months of each, before you could get licensed. I was licensed in South Africa and I really wanted to expand what I was doing. I had the choice of going to London or the United States. The US offered such a wide range of opportunities. I actually worked for a while in London. Then, I ended up at Saint Louis University where I was a resident and then chief resident. One of my jobs as the chief resident was to do a weekly conference called an M&M—morbidity and mortality, conference. It was my job to find someone to discuss a difficult case. For the last one of the year, my mentor said, “This is going to be your case to present.” He gave me a case of acute liver failure. I found it so fascinating that I’ve had an interest in it since then. I participated in the acute liver failure study group. I published on it. We developed the artificial liver to specifically treat that condition. It’s really been a lifelong interest. Also, it’s important to have the opportunity to help patients, especially as younger and younger people are being affected by alcohol-associated hepatitis.
Q: Anything I haven’t asked?
The frequency of drinking and amount of alcohol consumed has increased during the course of the COVID pandemic. However, even before the pandemic, we were seeing an increasing number of people coming into the hospital with AH. With the current standard of care, approximately one-third of those patients could die of liver failure within the first three months. New treatments are needed to address acute liver diseases such as AH. Acute liver failure occurs when your liver loses function or shuts down suddenly and, once it reaches a certain level of damage, can no longer recover. If the liver starts to regenerate before you hit that point, however, the health of the liver and the patient can improve. Achieving this has been an interest of mine for nearly all of my professional life, and DUR-928 has the potential to help with it, considering its mechanism of action as an epigenetic regulator, which we published recently. Our ongoing Phase IIb trial is evaluating DUR-928 on a severe form of AH which will involve 300 patients with two different doses of DUR-928 and a control, and it will be tested at multiple sites in the United States.