In our long and laborious research pursuits, we often ask ourselves “Can my research be translated into a product that is of benefit to the society?”. There are times when we do stumble upon a great candidate for translation into a useful product, but we may lack the entrepreneurial skills necessary to take it forward. In this article, we talk to Scott Shandler who combined his business acumen and his scientific expertise to bridge the gap between academic innovation and industrial translation. He co-founded Longevity Biotech, along with Prof. Samuel Gellman, University of Wisconsin-Madison, a platform therapeutics company that is developing a novel class of stable peptides addressing a variety of disorders ranging from Diabetes to Parkinson’s disease. The traditional outlook that the pace of innovation is too gradual for a profitable business is changing steadily as more and more people like Scott are finding effective strategies to work with at the interface.
In conversation with Scott Shandler, Founder and CEO Longevity Biotech
Hi Scott, you have a striking educational profile, having started off with a bachelor’s degree in computer science and traversing into the realm of Biology with an MBA in Healthcare, followed by a doctorate in Biophysics. What factors influenced your career trajectory?
Prior to my graduate studies, I had worked for a leading global consulting firm assisting various top 10 pharmaceutical companies across a range of projects. Unfortunately, these projects often were designed to validate the stakeholders initial objectives or were ancillary to core business objectives rather than create real and meaningful change. So at this point in my career I felt the need to decide whether I was going to be another businessperson working in the life science industry or someone with credential scientific training that also was capable of running a business. These are essentially two sides of the same coin, however I figured if I am going to be in the business of science then I should really know the science! So, I applied for a PhD program, left my consulting career and landed in a PhD program at the University of Pennsylvania School of Medicine.
I figured if I am going to be in the business of science then I should really know the science!
Can you tell us a bit about the journey from being a fresh PhD graduate to the founder of Longevity Biotech?
I always knew that I was going to be the field of entrepreneurship and healthcare, the question was exactly how was I going to get there. My thesis was focused on the denovo computational design of peptides with specific properties, a growing field at the time that has seen many interesting successes lately. However as I was finishing my research and looking for my next move, there was some new, yet related, research coming out of Prof. Sam Gellman’s lab at the University of Wisconsin. Essentially, at that time, other emerging peptide companies were changing the surface of protein molecules (e.g. lactam bridge or a disulfide), my co-founder Sam Gellman had developed a new strategy for changing the molecular interior. This fundamental and important difference shielded the stabilizing changes made by Gellman et. al. from the desired biological interactions, which provides a more ‘natural like’ surface of the peptide and thus less chance for undesirable / off-target interactions. This unique approach allows the pursuit of larger, more complex targets without having to significantly change the surface.
So recognizing the uniqueness of this this approach, my professional background really helped in knowing what was going on in the commercial landscape of different peptide platform companies at that time such as Aileron and PeptiDream. The difference between this technology and everybody else’s was that Sam’s peptides, what we eventually dubbed ‘Hybridtides’, were much more stable and resistant to digestion in the gastrointestinal tract. We used the Hybridtide approach to establish a technology platform to generate metabolically stable therapeutic peptides that can be used in oral formulations, which is essentially what we do at Longevity Biotech.
Could you give us some background on how the Hybridtide technology works?
Hybridtides are synthetic peptides built using a unique combination of alpha and beta amino acids. They can be used to target specific receptors to activate specific biological pathways. The interaction between the peptide and the target can be explained with two analogies, either like a key into a lock or like turning a switch on. The peptides are the keys that are specific to particular receptors, the locks. Currently we are using Hybriditides to target a specific family of receptors, class B GPCRs, which are good drug targets and have seen great success in various clinical applications to date.
Could you expand a little on this using LBT-6030, the drug you have developed against type 2 diabetes as an example?
The predominant product for type 2 diabetes in the market at the time we started was metformin. Another class of molecules used for treatment were peptides targeting the Glucagon-like peptide (GLP)-1 receptor. GLP1 peptides, such as Exenatide and Liraglutide marketed by Amylin and Novo Nordisk were generating billions of dollars in revenue at the time, however we started to develop our own GLP1 peptide a little differently. We developed a dual agonist Hybridtide, LBT-6030, something that could activate both GLP1 and another interesting receptor GIP (Gastric inhibitory peptide receptor) at the same time, almost like a chimera. Having one molecule that can interact with both these receptors at the same time is desirable because biologically it gives you control over both glucose production as well as weight loss. Having the science to do this gave us the opportunity to make a product unique from other ones in the market at that time.
You also have Hybridtides for neurodegeneration which is a growing problem in today’s world. What is the strategy you have adopted here?
That’s a really exciting program. Unfortunately, there are not enough products in the market that can treat neurodegeneration. There’s a tremendous need for disease modifying therapeutics. The growing belief in this field is that the immune system is playing a critical role in neurodegeneration. LBT-3627 addresses the inflammation and immunological imbalances observed in patients with neurodegenerative diseases. Biologically, what we are aiming to do with our peptide LBT-3627 is to turn down pro-inflammatory pathways while simultaneously turning up the anti-inflammatory pathways. The analogy that we like to use is “rebalance”. We are trying to rebalance the immune system because we believe that in degenerative states, there is background neuroinflammation that is at least a major contributor, if not the direct cause, of the degenerative aspects of Parkinson’s and other neurological disorders such as MS and Alzheimer’s. Other similar biological strategies like anti-TNF-alpha antibodies are multibillion-dollar drugs already, however these approaches focus on turning off one inflammatory marker while we target a control pathway that is upstream of many key inflammatory targets.
You have developed Hybridtides to treat disorders ranging from diabetes and neuroinflammation to asthma and multiple sclerosis. What criteria do you use to select specific projects?
It’s a combination of knowing what markets need better products or solutions, and understanding what the Hybridtide technology can deliver. For example, when I first met Sam, he was working on a project using Hybridtides as a potential HIV therapy. Commercially though, this was a challenging market, since there already were effective small molecule products on the market. Further, when I was at Merck prior to Longevity, they were literally giving away their HIV drugs for free. It made it really challenging to develop a competitive standalone product. Commercially, it didn’t make a whole lot of sense to start a new company around that single asset. Even though it is still an important and valuable approach, it was hard to raise capital for a standalone HIV product at that time.
Diseases like cancer, neurodegeneration and diabetes are a little different however. Most of them have a few standalone therapeutic products that can be improved upon (e.g. poor side effect profiles, or poor efficacy) or worse – no products at all, which gives us an opportunity to raise capital and develop new assets to fill these gaps. That is the kind of business and scientific analysis that goes into choosing which markets we want to head towards and which to avoid. Generally, we try to avoid incremental improvements and are working towards larger impact programs.
How did you attract investors for this start up in the very beginning?
We started with a friends-and-family round, that was the first money into the company which really helped get us started. It was followed by federal funding for our cancer program, which was essentially the springboard to other subsequent funding opportunities. It is also important to highlight that Breakout Labs was one of our early investors and supporters of big-picture, science driven companies.
How have you kept the funding going over the years?
It is a full time job to attract capital. It requires an understanding of who the different players are in the world of finance. It could be a large private equity fund, a financially motivated venture capital fund, a strategically aligned venture fund within the pharmaceutical industry, a foundation that has a disease centric focus or a government agency. We have established relationships across the industry in the corporate world, the venture capital landscape, and foundations. As always, results matter and you have to keep developing your programs.
You need to really understand which of those groups have a similar objective as your corporate strategy and explain why your technology has the ability to change the market. Most meetings that we have with big pharmaceuticals or venture capitalists include both a team of scientists and a team of business analysts. You need to be adept to answer questions from both teams. We have done okay in terms of attracting capital, however we have to always be working hard to keep the assets moving forward. We are comfortable but never satisfied.
We are comfortable but never satisfied.
How are these agencies fundamentally different from each other in their motivations and expectations from the projects they fund?
It is a data-driven environment, especially with the folks at pharma industry. They will often pay after something works in a pivotal clinical trial, rather than pay less for a project that might fail. There is risk, so they would rather wait for you to demonstrate signs of clinical success and then either fund or acquire you rather than fund you to get to a certain point before they see more data. However, there is price different in terms of valuation. The venture capital community is more generally focused on “when can I get to the exit” and “what’s the risk profile associated with getting to that exit”. So there are different driving forces. Pharma is driven by pipeline issues, and whether they can fill the pipeline with great assets, whereas the venture capital community is primarily looking for financial returns.
What has been the biggest challenge so far in setting up the Longevity Biotech platform?
Funding is always a big challenge. It’s a very competitive world and making sure that there is sufficient funding to support the progress and development is challenging, there are always setbacks! Sometimes in experiments you get results that you did not expect, or maybe in business your partner or investor has a change of leadership. Being comfortable with change is essential. Being comfortable in a dynamic environment, with personal relationships, with science and finance are important because things can and do change fairly quickly.
What is your vision for the company in the future?
We want to deliver clinical impact, that’s the objective. The board and everyone here really believe in the therapeutics we are currently developing, the science and the opportunity. We recently launched our initial subclinical work using patient samples and treating them with our drugs rather than using outdated animal models. Especially in neuroscience, where animal models are frankly not correlated with any sort of clinical success, we are moving away from animal models and more towards clinical interactions. We are excited about that types of datasets. It may provide transformative insights as to what is going on with these diseases and how our therapeutic strategy can make a big difference.
Do you have any hobbies to take your mind off work?
I like sports especially basketball and softball, to just run around and get my mind free and clear of science, business and finance. Going on bike rides and camping with my kids are always fun things to do when I’m away from the office.
Do you have a role model?
I have a lot of them! I am still in touch with friends I’ve made along various stops in my career – at Merck, BioAdvance or other places. When I have a question that I don’t have a perfect answer to, I reach out to them. The people I worked with in the past are a great resource for where we are going in the future.
What are the qualities you seek while selecting new members for your team?
We just finished hiring for an open position and there are a lot of things that go into the evaluation. Obviously, the ability to communicate is important; having the technical skills and background are things that we initially screen for. But then it is also about the fit, the insights and the passion that the person has for working on the subject. It’s always better to have somebody who is highly motivated, excited and passionate rather than somebody who is just looking for a paycheck. We try to screen the best we can also knowing that we have to find the best fit for the company.
Get comfortable being uncomfortable… do the most challenging and risky experiment first!
What is your advice for researchers who are looking to be entrepreneurs?
Get comfortable being uncomfortable, that’s what it comes down to. Potentially it’s really hard to take that first jump and even once you have taken it, it’s hard to stay with it. You have the whole company riding on a single experiment sometimes, that’s an uncomfortable position. But by design, as a scientist, if the experiment works you learn something interesting and even if it doesn’t work you learn something important.
Some of the early advice I received during my PhD was to do the most challenging and risky experiment first rather than the safe experiment first because the safe experiment might not teach you much whereas the risky experiment that may or may not work is going to be the one which gives you the most insights. Do your best to try and mitigate the risks (technical, financial or experimental) as soon as possible. The sooner you can address them, the sooner you get to moving forward. Even if it doesn’t work, you learn something that will set you up for the next experiment and help you move forward. Do the hard part first!
Author
Shwetha Shivaprasad is a postdoctoral fellow in the Department of Microbiology and Immunology at Stanford University. She is a virologist by training and loves to learn something new every day, expanding her knowledge base and skill set. She is currently in a phase of career exploration and trying her hand at science writing and reviewing.
Editor
Arunima Singh obtained her PhD from the University of Georgia, and is currently a postdoctoral researcher at the New York University. A computational structural biologist by training, she enjoys traveling, reading, and the process of mastering new cuisines in her spare time. Her motivation to move to New York was to be a part of this rich scientific, cultural, and social hub.
Artist
The cover image was designed by Vinita Bharat, Ph.D. Follow her work as Fuzzy Synapse at Instagram, Facebook, and Twitter.
Blog design: Arunima Singh
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