C-Suite Changes Help Biotech Narrow Focus But Maintain Drive To Treat Fatal Neonatal Brain Injury

A conversation among ReAlta Life Sciences’ Howard Berman, Ph.D., and Kia Motesharei, Ph.D., and Clinical Leader Executive Editor Abby Proch

When new leadership takes the helm, change is a given. To what extent things will change can be anyone’s guess.

When it happened for ReAlta Life Sciences — as both Howard Berman joined as CEO and Kia Motesharei joined as COO in March of this year — the two decided to go all-in on what the company is already doing well. At ReAlta, that means advancing a potential first-to-market therapy for hypoxic ischemic encephalopathy (HIE), a brain injury in newborns caused by a lack of oxygen and blood flow and the leading cause of neonatal mortality and long-term neurological disability. With their guidance, ReAlta has narrowed its pipeline (for now) to advance pegtarazimod, a novel peptide, into Phase 2 trials.

In this Q&A, Clinical Leader heard from both leaders about their skill sets, their goals for pegtarazimod, and how they keep momentum as they strive to help bring this potentially lifesaving therapy to market.

Clinical Leader: Dr. Berman, your background includes building and financing biopharma companies through critical development stages; ReAlta is in a Phase 2 trial right now. How does your experience shape the decisions you'll be making for this particular program?

Berman: Running a biotech company is not easy. It requires patience. It requires knowing that while the work that you have to do is laborious and expensive, you make decisions that are going to be very impactful for both the patient as well as for your employees.  The other thing is how you decide what programs you focus on.

Here at ReAlta, we're putting our time and our effort into very high unmet needs. And that's what's been very important for me in my career. I've always worked on the hardest problems; previously, that was ALS. This is HIE in neonates who otherwise would die or have a significant injury. And so, it comes with a huge responsibility.

And Dr. Motesharei, as COO, what are some of your biggest operational priorities?

Motesharei: One of the key areas beyond typical operational efficiencies and improvements is clinical operations. We’re recruiting babies right after birth, and we need to get them into our studies within 6 to 10 hours after birth. So, you can understand the amount of pressure to have the babies diagnosed, get consent from the parents, put the babies in the study, and administer the drug in a few hours. Having clinical operational efficiency is extremely important. And we've spent quite a bit of time making sure we have processes in place to do that under such intense time pressure.

How well, if at all, have you known each other prior to your appointment, and how closely do you work together now?

Berman: Kia and I have only known each other for a very short time. And what I found to be fascinating is that we're two very different personalities. It's a yin and a yang. I like to just get things done efficiently and go from A to Z very quickly. Kia is very methodical and thoughtful. When I want to move quickly, he is in the background saying, "Let's just slow down. Let's think about this carefully." That's a very powerful combination to have; his strengths are different than my strengths and vice versa.

Motesharei: We have had a great deal of respect for each other in the short amount of time that we've known each other. I actually joined the board of the company before taking on an operational role. And I did that because of the interactions I had with Howard while I was on the board and saw him operating as the executive chair. Seeing how he was moving the company, how he was making decisions — those were pretty important for me in making my determination. I come from a more structured pharma biotech background with some large companies. I spent a number of years at Merck, Madrigal, and Dyax. So, our skillsets and how we do things complement each other very well.

Dr. Motesharei, you mentioned the criticality of enrolling patients in a short window. Can you tell us about the strategy behind PI and site selection? And then also parent consent and education?

Motesharei: We have some of the biggest name KOLs as part of our PIs leading our studies. Currently, we have 18 centers, and we're looking to expand that. In the next couple of months, you're going to hear about additional sites to increase our recruitment rate.

One thing you mentioned that is very important is getting these babies enrolled in a short amount of time. As you know, babies come 24/7. They don't understand holidays or after hours. So being prepared to enroll and having the necessary staff at these trial sites has been challenging.

We've been working with the hospitals and their NICUs to ensure the drug’s availability and that the PI, study coordinator, and everybody is working in tune. The credit goes to our clinical operations team, the PIs, and the CROs that we're working with to make sure it works.

One thing we've been very diligent in doing is following the current standard of care, which is cooling within 6 or so hours after birth. We start the administration of the drug when the babies start the cooling. That's a very important step to ensure we're not reinventing the wheel. We follow the same process, which is what NICUs and neonatologists are accustomed to, and we're not changing the paradigm.

It must be somewhat comforting to parents to understand that their babies are getting treatment that's additive, not something entirely new and different.

Motesharei: It is, but parents are also overwhelmed. This is supposed to be the happiest day of their lives and all of a sudden, in a matter of minutes, they're told that their baby has had a lack of oxygen to their brain and they're developing a brain injury that can have lifelong neurodevelopmental consequences. Being able to process that is very difficult. So, we have educational material, and very soon we'll be launching an educational website with videos for parents. We're working very closely with the patient advocacy groups. We want to ensure awareness is there, but it’s not quite there yet.

I went through a similar exercise with my previous company, Madrigal, in NASH. This is a fatty liver disease, and we did the same type of market awareness and education, but that was a much larger marketplace. Here, we're talking about rare disease. Approximately 8,000 newborns are affected by HIE in the U.S. each year. We have a small group of NICUs to educate. Still, it’s one step at a time, and we're doing our best to both develop the drug and educate the market.

Once onboard, you both decided to pause some programs to focus on pegtarazimod in HIE. What else did you reassess as you came into your roles?

Motesharei: There are two upstream anti-inflammatory pathways that our platform or drugs hit: one is on the neutrophil side, and the other one is on the complement. Both block the inflammatory pathways upstream. Before we joined, the company was testing the same compound in other inflammatory diseases. From a commercial perspective, it's very difficult to develop the same compound for multiple indications, so we decided to pursue HIE. That's where the greatest unmet need is. However, the platform is extremely powerful. We have a number of other compounds that we're pursuing. They’re not shown in our pipeline, but they're in the preclinical stage.

When leadership changes, how do you ensure that the trial remains intact, that folks have the confidence in you?

Berman: We come in with urgency and look at things a little bit differently to get a better result and a faster result. That's called efficiency. And we want to make sure the company gets the job done quicker, but in a more homogenized way. We have years of experience making sure trials run on time and on track.

In fact, when we came in, we expanded the number of trial sites from 14 to nearly 20, and that's sped up enrollment. When you have confidence and it shows, it seems to harmonize across the spectrum with your partners and your vendors.

Motesharei: I echo what Howard mentioned, and I'll add the key to communication is transparency. There are many stakeholders — from our investors to our employee base, executive management, and our partners, all the way down to our patients — and transparency and communication with them is key. The best way to demonstrate what you say and what you plan to do is to deliver. And you have a very relatively short period of time to do that, whether it's two or three months, depending on what kind of promises you make.

And as Howard pointed out, we turbo-boosted our recruitment. That's something we communicated. Within the three months we've been here, we've delivered on that promise. So, with transparency, you gain confidence, you build on it, and that's how reputations are made. At the end of the day, it's our deliverables that are the best measure.

What do the next six to 12 months look like for this particular trial?

Berman: Number one is we want to get our trial completed. Top-line data should be released in the third quarter of this year. We're also working closely alongside the FDA to align our endpoints and surrogate markers. The next six months are going to be intensive in terms of data, and we're excited to unveil a new next generation of assets in our pipeline. These are third-generation peptide drugs that are new chemical entities.

Motesharei: Just continuing with the recruitment, finishing the study, the data readout. One thing to add is the interactions with the FDA. We're talking about a first-in-disease product, so we’re working with the FDA to develop a path to an approval that’s similar to other products that have also been first of their kind.

Speaking of the FDA, are you able to share any of the reassurances or recommendations they have given as you continue this trial?

Motesharei: I prefer not to get into those discussions because of confidentiality issues, but I can tell you the FDA has the objective and goal of making the right drugs available to patients. I don't see them as roadblocks. They're there to ensure the safety and the best efficacy of the products for the patients. Deep down, they're a partner.

Editor’s note: This transcript has been edited for clarity.

About The Experts:

Howard Berman, Ph.D., is chairman and CEO of ReAlta Life Sciences, where he leads the company’s overall strategy, clinical development and corporate execution. He has more than 20 years of biopharmaceutical leadership experience spanning company formation, drug development, strategic partnerships, financing and public market execution across neuroscience, immunology and other therapeutic areas. Before joining ReAlta, Dr. Berman founded and served as CEO of Coya Therapeutics, guiding the company through its Nasdaq initial public offering, multiple financings and strategic pharmaceutical partnerships. He continues to serve as Coya’s Executive Chairman and is a member of the board of directors of Atea Pharmaceuticals. Earlier in his career, Dr. Berman held senior leadership roles at AbbVie, Eli Lilly, and Novartis, where he contributed to the commercial launches of several major therapies. He earned a bachelor’s degree in biology from the University of Michigan and master’s and doctoral degrees in neuroscience and pharmacology from Weill Cornell Medical College.

Kia Motesharei, Ph.D., is president and COO of ReAlta Life Sciences, where he oversees operations, business development and strategic partnerships. He is an experienced biopharmaceutical executive who has completed more than 100 transactions involving licensing, mergers and acquisitions, financing and strategic collaborations. Before joining ReAlta, Dr. Motesharei held senior corporate development, licensing and investor relations roles at Madrigal Pharmaceuticals, Formation Bio, Akcea Therapeutics, Merck KGaA, Dyax, and GENFIT. At Madrigal, he played a key role in raising more than $1 billion in capital and supported the FDA approval of Rezdiffra, the first approved treatment for NASH/MASH. Earlier, he contributed to the strategic repositioning of GENFIT’s lead program and supported the development of Takhzyro at Dyax, which was later acquired by Shire. Dr. Motesharei earned a bachelor’s degree in chemistry from Colorado College and a Ph.D. in organic chemistry from UCLA. He also completed an NIH postdoctoral fellowship at The Scripps Research Institute.