What happens when a newborn does not receive enough oxygen and blood flow around birth, putting the brain at risk of serious injury? Cooling can help slow the damage, but it does not directly treat the underlying causes. Dr. Howard Berman, CEO of ReAlta Life Sciences, joins Solomon Wilcots to discuss hypoxic ischemic encephalopathy, or HIE, a severe neonatal condition that can lead to brain injury, disability, cerebral palsy, and death. While therapeutic hypothermia can help slow inflammation, there are currently no approved drug therapies that directly address the biological drivers of HIE.
Howard explains how ReAlta’s investigational therapy, pegtarazimod, is designed to target multiple components of the inflammatory response. He also discusses the company’s Phase 2 STAR trial, which is evaluating pegtarazimod in combination with therapeutic hypothermia and using MRI to measure changes in brain injury.
Solomon Wilcots: Today we’re joined by Dr. Howard Berman of ReAlta Life Sciences. Now, Howard is a scientist, entrepreneur, and company builder. He earned his Ph.D. at Cornell University Medical School, worked across major biopharma companies including Novartis, Lilly, and AbbVie, and then moved into building companies of his own. He founded companies, raised capital, and completed an IPO. He’s even led a public biotech company and now he has taken on new challenges at ReAlta Life Sciences. ReAlta is developing pegtarazimod for Hypoxic Ischemic Encephalopathy or HIE, a severe neonatal condition caused by a lack of oxygen and blood flow to the brain around birth. It is a medical emergency and today, there is no approved pharmacological therapy for HIE. Howard, welcome to the Russo Edge. Great to have you with us. How are you doing today?
Dr. Howard Berman: Thank you for having me, Solomon.
From Scientist to Biotech Entrepreneur
Solomon Wilcots: Well, that was a long introduction, and well-deserved because you’ve done a lot of work.
Let’s get started by talking about your path. You are trained as a scientist, and you worked inside major biopharma companies. When did you realize you were an entrepreneur at heart?
Dr. Howard Berman: I think you’re born with it. I believe it’s innate to you and it’s something that doesn’t really develop. It’s in your DNA. You’re genetically predisposed. I knew it all along and everyone who’s an entrepreneur knows in their heart of hearts what they are all about. I like to build, I like to create, I like to innovate and I like to solve problems that there are no solutions for.
Solomon Wilcots: I know you said that Coya Therapeutics had a very personal origin because of your father’s experience with dementia. How did that moment help to shape the way that you think about patients, disease and urgency?
Dr. Howard Berman: Well, my father was a triple board-certified physician. One of the smartest people that I’ve known—an incredible person. I thought, and I believe that anyone who would not be affected by a mind-robbing disease like dementia would be him because of his cognitive reserve, because of all of the brain synapses that have formed over the years, but dementia and the underlying processes are so pernicious and so terrible that it can actually just demolish even the smartest and the most intellectual people. When I saw my father going through it, and when you have a front-row seat, it is a devastating thing to see how it affects not just him, but also the family and everyone around him.
We are all unfortunately getting older, each of us, so we all have a risk as we get older to suffer the same fate. It’s a major issue that we need to address. I just realized that that was a stimulating and motivating factor for me to really try and solve that problem. I just had the benefit of working with an incredible physician and scientist at Houston Methodist, Dr. Stanley Appel.
ReAlta’s Mission to Solve an Unmet Need in HIE
Solomon Wilcots: Let’s turn to ReAlta. You came into a company that already had science, clinical work underway, and investors behind it. What made this opportunity stand out?
Dr. Howard Berman: Well, this also solves a problem that has no solutions. This is a terrible disease that babies face at the beginning of their lives, and the only treatment that they have is cooling—to put on a cooling cap and essentially put the baby on ice to slow the metabolic rate. There is no drug approved. I was called about this opportunity and found the mission to be so important, similar to ALS because of the unmet need that I just jumped right into the deep end of this.
I’m very pleased to say that a lot of good things have happened since I joined. Enrollment has increased, the number of sites has increased, the investors have put in more capital, and everyone’s extremely excited about our upcoming clinical data readout.
Solomon Wilcots: Dr. Berman, for people who may not know the term, what is Hypoxic Ischemic Encephalopathy or HIE?
Dr. Howard Berman: HIE is initially an acute condition in which, for numerous reasons, the baby is born with little or no oxygen. The placenta may be dysfunctional in the mother’s womb; it may not be delivering enough oxygen to the baby’s brain. It could be over time. It could be an emergency. The cord may be wrapped around the baby’s neck. The mom could be in a motor vehicle accident. Because of that, the baby is born, unfortunately, with no or a limited amount of oxygen. That causes terrible damage to the brain. It causes a reperfusion injury where the oxygen in the blood rushes back and it results in a tremendous amount of inflammation that causes more damage. Ultimately, babies with HIE can have a 40% mortality rate. And in many instances, the babies that survive have a higher rate of cerebral palsy and other developmental issues down the line. It is a serious matter that needs urgent care.
Solomon Wilcots: Dr. Berman, today therapeutic hypothermia or cooling is the standard intervention for moderate to severe HIE. What does cooling really do and why does it fall short?
Dr. Howard Berman: Yes. Cooling is analogous to treating a sports injury. Let’s say you sprain your ankle. It is essentially reducing the amount of inflammation at that site. That’s all that cooling is doing. It’s not healing your injury per se, but it is just lowering the amount, tempering the inflammation. That is what hypothermia does to the brain. It lowers the metabolic rate, slows the inflammation, but it doesn’t really ameliorate or relieve the neuronal injury and the underlying pathology of the disease.
Targeting Brain Inflammation: Pegtarazimod and the STAR Trial
Solomon Wilcots: So let’s talk about ReAlta’s lead program. What is pegtarazimod and what is it designed to do and why does its ability to reach the brain really matter in HIE?
Dr. Howard Berman: Pegtarazimod is one of the most interesting compounds I’ve ever seen. It’s derived from a virus. This virus is called the astrovirus and the astrovirus has a unique feature that it doesn’t cause inflammation. The drug essentially isolates the best components of the virus, the outside part of the protein, the capsid protein of the virus, that makes it unique as an anti-inflammatory drug. So that’s what the drug is all about. It’s a compound synthetically derived from a virus, and it acts to block many components of inflammation. These include the complement pathway, activated neutrophils, neutrophil traps, and myeloperoxidase. These are all complicated terms, but what it essentially means is that this is a unique compound that addresses many aspects of the immune system that are unfortunately at the root of the problem for HIE.
Solomon Wilcots: So ReAlta is advancing pegtarazimod through the Phase 2 STAR trial in newborns with moderate to severe HIE undergoing therapeutic hypothermia. What is the core question this study is trying to answer?
Dr. Howard Berman: We are running a trial that compares our drug in combination with hypothermia with a placebo in combination with hypothermia. It’s a drug versus placebo effect. We’re looking at the amount of reduction in brain injury as measured by MRI. MRIs are then taken of these babies on days 4 and 12. We are aiming to show in the brain that this drug works to mitigate or reduce the quantifiable brain injury, which is a very objective way of assessing if the drug is having an effect.
Funding ReAlta’s Path Through Clinical Readout
Solomon Wilcots: So Dr. Berman, ReAlta has raised more than $150 million to date. What do you think about where the company is today, where it is now from a capital and strategy standpoint?
Dr. Howard Berman: We are in a very unique spot, in that we’ve raised enough money to get us through the important catalysts. That’s what any biotech company wants to do. We have sufficient capital to get us through this clinical trial, a pivotal trial readout, and Phase 2 trial. We’re also closely collaborating with the FDA and the agency on a number of things, including surrogate endpoints and the regulatory pathway to accelerated approval, hopefully. So that gives us enough leverage with respect to our runway so that we can see the results and we can hopefully see how well the drug is working and then we have the optionality to then move to the next steps.
Solomon Wilcots: I want to come back to biotech leadership. You said one of the biggest lessons for CEOs is to focus and concentrate on your main assets and avoid distractions. Why is that so hard in biotech? Why is that a difficult thing to achieve?
Dr. Howard Berman: Because CEOs or leaders see bright shiny objects and they want to put their efforts toward anything that may be efficacious. The problem is that when you do so, you burn capital and in small companies, you don’t put your dollars where it counts the most. It’s like playing football. Do you want to spread your dollars among quarterbacks or do you want to put most of your dollars on the top quarterback, the backup quarterback, and the head quarterback?
Well, it’s not very dissimilar to a biotech. Here we’re putting our dollars on our Tom Brady or our Patrick Mahomes. That’s what this program is—I think if more biotech CEOs understood that then their runways would be expanded and they would be in better positions.
Solomon Wilcots: Well Howard, I can see you know your football. I love the analogy there. When you look at ReAlta today, what does success look like over the next phase of the company?
Dr. Howard Berman: We are going to read out our clinical data very soon. We’ll discuss with the FDA about our path forward. We are the company furthest along in HIE, and I don’t know of many companies that are even close to where we are. We’re even creating the plane—building the plane as we fly it because this is new uncharted territory in terms of MRI as a surrogate endpoint. It’s exciting to be sort of at the cutting edge of regulatory development.
I think the data from this clinical trial will be pivotal in terms of what we decide to do as a next step. Do we take this and commercialize it ourselves, which we can certainly do? There is a very concentrated number of sites to commercialize to, so we can do it ourselves. Those discussions will happen very soon. And this could be a very meaningful mission that we’re making, not just for ourselves, but for our investors.
Solomon Wilcots: Well, we want to thank you. That was very informative. Dr. Howard Berman reminds us that some of the hardest problems in medicine demand both scientific ambition and disciplined leadership. For ReAlta, that means focusing on HIE, a severe neonatal condition, for which families and clinicians still have limited options. It also reminds us that in biotech, the work is never just about the asset. It is about focus, judgment, and building around the needs of patients. I’m Solomon Wilcots, thank you for listening.
The Russo Edge Podcast is hosted by Solomon Wilcots and features candid conversations at the intersection of biotech, healthcare, and innovation, spotlighting leaders, scientists, and investors moving medicine forward. The following transcript has been edited for clarity.
