James Kuo, MD, MBA | Director, Tryp Therapeutics

What is the genesis story of Tryp Therapeutics? When and Why did you get into the psychedelic drug discovery space?

The idea initially germinated last year during a regularly scheduled monthly industry update and brainstorming session with my business partner, Bill Garner. During this particular conversation, and based on our mutual personal experience, we discussed the unfortunate reality that too many rare or orphan neuropsychiatry diseases lack safe and effective standards of care.  Diseases such as Prader-Willi syndrome, which lacks effective treatments, not only affects the patients, but also meaningfully negatively impacts the lives of their families and caregivers.

We further developed a business strategy predicated on taking drugs with established safety profiles and evaluating them for the treatment of neuropsychiatry diseases.  During the course of our review of scientific literature and research, we learned that psilocybin met these criteria. As approximately 40% of drugs do not have successful outcomes from Phase 1 safety studies, we were enthusiastic about the approach of focusing on the development of de-risked product candidates as safety is one of the two major factors governing drug approval.

About that same time, the clinical results on ketamine and early clinical work on psychedelics by Johns Hopkins and Imperial College of London really attracted our attention because the drug effect in treatment resistant depression was so pronounced in patients who had failed all other therapies.  In addition, the effects were durable, meaning they lasted for months; something not often seen.  Psychedelic-based drugs also aligned well with our business strategy of targeting therapeutics with existing safety data given the years of human experience that exist with this class of therapeutics.  We then began evaluating neuropsychiatric diseases where psilocybin, our initial psychedelic drug candidate, may have a therapeutic signal. After researching multiple indications we concluded to pursue Prader-Willi syndrome, fibromyalgia, and a third yet undisclosed disease to commence drug development upon.

You’ve been involved in biotechnology for a long time. Can you walk us through the drug discovery process and what it takes to accomplish the mission Tryp has set out on?

Both Bill (Garner) and I have been involved with drug development for the past 20+ years.  During this time, we have both been intimately involved with the FDA approval of multiple drugs and the growth of life science businesses that achieved profitability.  

Generally speaking, firsthand drug development experience is essential due to the complex nature of drug development and navigating the US FDA regulatory process.  The process begins with selecting an appropriate drug candidate and then evaluating its safety and pharmacological effect.  Then the therapeutic profile of the drug candidate must be matched with a disease where it is hypothesized that the therapeutic effect would be beneficial.  There are a lot of nuances to this process. The clinical endpoints must be measurable, meaningful and inline with FDA guidance and standards.

Clinical trials can be protracted and expensive, so the clinical trial should be designed in manner such that they are conducted in a cost and time efficient manner.  The drug effect should be quantifiable and meaningful and in a trial population that is adequately powered to demonstrate the statistical significance of the therapy.  Bill and I have assembled a team of highly experienced drug developers who have worked at both major pharma and smaller biotech companies.

The cumulative experience of the team, including learning from drug development mistakes and best practices at predecessor companies, should enable us to efficiently and effectively advance our pipeline of product candidates.  Additionally, the team has an exceptional network of collaborators that we can leverage, as needed.  Drug development for the Tryp team is a scientific process.  We have been trained to systematically follow the data and science as apposed to where our individual biases might lead one of us.

Tell us a bit about the team at Tryp Therapeutics. What unique skill sets have you assembled together and how will those synergies be an advantage?

I really enjoy speaking about the talented team we have assembled as they are arguably the company’s strongest asset, particularly in the context of the drug development experience of some other companies developing psychedelic therapeutics. Our core management group has working relationships that go back as far 20 years.  Therefore, the team members know that they can rely on each other given the prior positive work experience and existing relationships.  There is good chemistry within the team, which is critical to the success of any company, and very important in managing workstreams and meeting important timelines and deadlines, such as filing an IND.  In addition to these strong working relationships, the team has complementary work experiences and skill sets.  I would like to highlight two of these exceptional individuals on the Tryp team.  The first is Larry Norder, our VP of Manufacturing.  He spent time at Syntex, a large pharma company, where he was involving in the processes related to the manufacturing of drug product. Given his vast manufacturing experience and understanding of the intricacies of theses processes, he is playing a key role in managing the development of novel intellectual property around the manufacturing processes we are developing for our pipeline.   Any findings that arise from the synthesis, formulation, and manufacturing of our drug candidates that is novel and has utility has the potential for patent filing, which we intend to aggressive pursue.  Tom D’Orazio, our VP of Operations, spent time at Pfizer and QLT and is our expert on the commercial side of the pharma business. Tom ensures that the product candidates we are developing are aligned with a sizeable pharmaceutical market that will attract the interest of a large pharma for partnering or licensing.  It is our stated strategy to transact our drug candidates based on Phase 2 clinical data.

Tryp has an advanced oncology asset. Could you tell us a bit about that and the path ahead?

Yes, Tryp has a cancer product candidate that we intend to initiate in Phase 2 clinical trials. The backstory here is that this sarcoma drug candidate has been the subject of multiple Phase 2 clinical trials already with remarkable results.  This work was done in Austria and largely forgotten about when the doctors who developed it and were most clinically active with it were forced into retirement.  Prior to that time, the drug had a de facto approval in Austria, meaning it was used to treat sarcoma patients despite not being formally approved.  Bill and I have been trained to search for pharmaceutical opportunities with this profile.  We have received estimates that to recapitulate this existing data for our sarcoma drug, would cost approximately between $50 to $100 million dollars and take several years to complete.  Tryp has an incredible opportunity to initiate clinical development with a Phase 2 study that addresses a cancer market that has not seen a first-line drug therapy approval in over 40 years.  We are currently in advanced discussions with possible manufacturing partners, dialoguing with regulatory consultants, and identifying and engaging with possible principal investigators for the clinical trial.

What have your experience within big Pharma and world class biotechs taught you about how to successful build a new biotechnology company from the ground up?

My experience with Pfizer taught me that to build a new successful biotech company, your timing has to be essentially perfect and you need to have an asset that is commercially attractive to Big Pharma.  That means being assiduously aware of the pharma business environment.  In particular, it is understanding which drugs insurance companies are paying a high margin or premium for since that is the basis of a drug franchise for a large pharma company.  I have also been taught that pharma is a winner-take-all business.  Either you are a huge winner or you are a loser.  There is really no middle ground.  To be the winner takes experience and the courage to say no to anything that is not on the critical path.  Otherwise, you become distracted and unfocused on what is truly important.

What obstacles does Tryp need to overcome to get novel therapeutics to the market and how do you plan on handling them?

Drug development is littered with obstacles, big and small.  There are a multitude of failed life science companies that shattered their hull on rocks they didn’t see.  

Our challenge, like that of many other life science companies, is to work well as a team.  While individuals may be blinded to a viable solution, rarely is the entire team.  The underlying psychology of a good team is that we are going to work hard and solve every problem that we face.  We expect that transforming the lives of desperately ill patients with a breakthrough new drug is hard.  The celebration only comes at the end and can take years.  So, there is lots of delayed gratification.  Each one of us has lived it and are not put off.  In fact, many of us continue to do this hard drug development work despite having achieved financial success because we are drawn to the challenge and making a difference.  We believe our drug development work has meaning so that draws upon a fifth gear of our humanity to get us the power to drive through any impediment.