Single Peptides & Pig Testing: How Longhorn's Developing Its Universal Flu Shot
A conversation with Jeff Fischer, CEO, Longhorn Vaccines & Diagnostics
One of the perennial health decisions many of us make each fall is targeting the right time to get a flu shot. But what if we didn’t have to obsess over the best date, the one targeting maximum effectiveness through the winter holidays and into the new year? And what if we could get year-round, not just seasonal, coverage from the current strain as well as any others?
That’s the goal of Longhorn Vaccines & Diagnostics. And in this Q&A, its CEO Jeff Fischer walks us through the company’s decision to study LHNVD-110, its universal flu vaccine, in pigs, as well as its pursuit to overcome vaccine hesitancy and provide a flu shot with the potential to last one year, if not many more.
Clinical Leader: Longhorn is pursuing a Phase 1 trial for its single-peptide universal influenza vaccine candidate, LHNVD-110. You first conducted animal testing in pigs, which are vectors for viral reassortment. What are the benefits of testing this vaccine candidate in pigs?
Jeff Fischer: Pigs are a great model for influenza as they share many similarities in their immune system with humans, their size is comparable to humans, and they can be infected with human strains of influenza without modifying the virus. Specifically, when you're looking at safety profiles and immunogenicity, you're dealing with an animal that at different stages of its life represents different ages of people, from children and piglets to adult human beings and adult pigs. Working with pigs gives you a lot more information than you can get with rodents or even rabbits — you can give larger doses and you can put it in the muscle. The other thing is that we have used pig organs in transplants, and their organs act very similarly to human organs.
As they can be infected with both human and avian strains, pigs make the perfect reservoir for reassortment. A good universal vaccine should have markets in humans and pigs. We've been fortunate because through some of our work previously on the diagnostic side, we have an animal health team with experience in pigs.
What are the challenges of testing a drug in pigs?
One of the challenges is that they are constantly rubbing up against each other, fighting with each other, and can get infections. They also very naturally pick up influenza; it is hard to do a study where you don't get any potential exposure to the virus itself. Sometimes you can see rises in your placebo group that are unexplained but probably are just because of exposure. When you have an animal that is very good at getting the disease you're going after, it does have that downside.
The FDA recently introduced New Approach Methodologies (NAMs) that prioritize AI models, organoids, and organ-on-a-chip systems over animal data, beginning with monoclonal antibodies (mAbs). What do you make of this new requirement and its potential impact?
This new approach is very exciting. It takes into account decades of safety data around monoclonal antibodies and allows the focus to be on the target and mechanism of those antibodies and how they could affect safety. This is very beneficial to both of our antibody programs, as we are targeting conserved regions on bacteria and viruses and clearing the viruses, bacteria, and cell wall toxins that cause inflammation, both chronic and acute. Our antibodies will not turn off any components of the immune system but are targeted to clear the specific triggers to inflammation. This allows the immune system to remain intact to counter any other pathogens that need to be eliminated.
Longhorn has shifted from a dual peptide formulation to a single peptide formulation. Tell us about this decision and the benefits it might bring.
We took the dual peptide through GMP manufacturing. We were ready to go into the clinical trials. Then we took a step back because we found that we could do it in a single peptide. During the original process, we had to manufacture two peptides. We then had to transfer that to another facility where they would resuspend it, combine it, and then lyophilize it. It added another step to the manufacturing process that wasn't necessary with a single peptide.
The fact that you can do large-scale manufacturing of a single peptide, versus having to make similar amounts of two different peptides and then combine them, saves time, expense, and manufacturing capacity. Anything you can do to bring down the cost, increase the speed, and improve capacity makes it less expensive to put it into the market, especially in developing world markets.
Looking ahead to Phase 1 patient enrollment, what do you make of vaccine hesitancy, and how do you anticipate its impact on the LHNVD-110 trial?
Vaccine hesitancy does not seem to be a significant problem for early-stage trials. As the vaccine gets into Phase 2 studies and beyond, we believe we can overcome vaccine hesitancy in several ways. Some of the vaccine hesitancy is around different components or mechanisms of action and, certainly, this administration has focused on mRNA as one they are not necessarily supportive of.
However, our vaccine is a synthetic peptide. Synthetic peptides are the basis of GLP-1 medications and have seen no hesitancy. Our mechanism of action is consistent with how the body sees and reacts to the virus naturally.
Also, our expectation is a significantly higher efficacy compared to seasonal vaccines, and we have the potential to provide protection for multiple seasons, compared to seasonal vaccines that show efficacy for about two months.
If the efficacy is there and the timeframe of efficacy is there, we're not concerned about vaccine hesitancy. We've seen that with RSV vaccines, which have done quite well because they've been very effective. Same for the shingles vaccine. I've not heard anybody step back from the shingles vaccine. That's a great vaccine — 95% effective over 10-plus years. So that's what we're focusing on, and if we do that, hesitancy will not be a problem.
Finally, LHNVD-110 generates monoclonal antibodies modified for extended half-life to provide protection that lasts longer than currently approved seasonal flu vaccines. How does that affect the trial timeline, post-marketing studies, and commercialization?
We believe our monoclonal antibody cocktail for universal influenza is an ideal product to accelerate into the clinic. Unlike with the seasonal flu vaccines, the antibodies do not need to consider the host’s ability to mount a robust immune response. Once the proper dose is confirmed, the antibody trials can move rapidly. As mentioned earlier, IND-enabling studies have been streamlined. Phase 1 and Phase 1B challenge studies can confirm safety and efficacy, providing a fast track to approval for older patients and others at high risk. The most recent analysis of the seasonal vaccine showed that even the higher-dose vaccine did not provide adequate protection for these populations.
Given your goal to overtake seasonal vaccines, what are your expectations for the duration of efficacy with LHNVD-110?
Data from the 2023-24 flu vaccine showed it was only effective for two weeks to two months after you received it. However, the data we have from every animal model is that once we get those antibodies up, they stay up and, in many cases, for the life of the animal. At the very least, we want to cover a whole year, which allows you to get your shot whenever you go to the doctor. In fact, we should be able to get much more, like the Shingrix vaccine, where you're going out multiple years, maybe five to 10 years. There's no reason it shouldn't be that way.
About The Expert:
Jeff Fischer, MBA, president of Longhorn Vaccines and Diagnostics, is responsible for the oversight of all non-scientific aspects of the organization to include regulatory affairs. Mr. Fischer co-founded the company and has served as its chief financial officer from 2007-2017. From 1998-2005, Mr. Fischer served as an executive vice president and CFO in the biotechnology industry. He is a former infantry officer in the United States Marine Corps and holds an MBA from the University of Texas at Austin.