By Arthur Tzianabos, CEO of Lifordi Immunotherapeutics, as part of the From the Trenches feature of LifeSciVC
Well, this is a first…. while I have read and enjoyed the the LifeSci VC blog for years, being asked to contribute for the first time yielded a ‘holy crap’ moment in the ‘be careful what you wish for’ category. For those of you out there who know me, you know that I am not afraid to share my view and opinion. Now that there is a platform to do so…let us see how it goes. I was afforded this opportunity as a result of jumping in as CEO of a Series A newco that was formed by ARCH Venture Partners, Atlas Venture and 5AM Ventures that was funded last fall. But more on that later.
Having just returned from JP Morgan 2024, I can honestly say that I felt and experienced a definite sense of optimism after three brutal years in biotech. The downturn in the market combined with the pandemic has dropped our industry to its knees, leaving all of us to collectively ask ‘how much more can we take’?
This rough patch has been well documented in this space and particularly tough. It is the longest and deepest decline in biotech across most metrics that we have ever experienced. However, the good news is that after every downturn there has been a surge and renewal of confidence in the industry. But why is that?
Innovation and perseverance
Those of us in the biotech universe: scientists (in academia and industry), entrepreneurs and company builders, operational line function people working for small and large companies, venture capitalists, Wall Street and financial institutions, all have these two key traits in common: innovation and perseverance. These qualities unite us and keep us moving forward even in the toughest of times. I maintain that despite the disparate roles we have within the biotech industry we all ultimately believe that people need new meaningful medicines to help them lead better lives and, in some cases to actually stay alive.
Challenges in drug discovery and development
It is not easy moving new science and technology platforms forward. The discovery, validation, and publication of new biology and chemistry in academia is extraordinarily difficult. It takes a special mindset that can deal with failure after failure until one learns enough from those failures to ultimately succeed.
Translation of this novel science in the industry setting is just as daunting. Understanding how to drug a target, to elucidate mechanism of action, and to show that the drug is safe and effective requires people with special skill sets and experiences that share the same approach: no fear of failure. This mindset takes a while to accept and adopt. I have worked with and trained many scientists who struggle to come to terms with this concept given their competitive nature to succeed. But it is the only path to success in the long run.
Testing drugs that make it into clinical trials has its own specific challenges. Designing trials to show safety and efficacy in people and doing it in a way that complies with all the regulatory and ethical guidelines is where many drugs fail. I heard a great line from an analyst during this year’s JPM, “Don’t let the trial fail the drug”. One needs to pick the right therapeutic indication and patient population for initial clinical testing. Getting that early proof-of-concept data is so critical to demonstrating the benefit-risk profile of a drug. Many small companies only get one shot at this these days as positive data is crucial to potential fundraising for later stage trials.
The final stage of course is executing on a successful pivotal clinical trial that hopefully leads to regulatory approval. This process is an extremely difficult undertaking and requires the continued innovation and perseverance attributes across multiple functions within the company. The approval process does not necessarily equate to commercial success these days. And so the effort required to successfully commercialize a drug in the U.S. and globally is also a huge lift for a company.
I have had the good fortune to experience each stage of these discovery and drug development challenges in my career. First, as an academic scientist and Principal Investigator at Harvard Medical School where I operated two labs. One lab was focused on how bacterial surface carbohydrates activate T-regulatory cells and the other on the development of vaccines against bacterial pathogens. Getting funding and publishing papers in these two controversial fields was difficult, but the research teams I led there persevered for 15 years and succeeded in discovering new drugs that were licensed to pharma and biotech companies. Importantly, we were also able to publish the underlying work in high-quality journals.
When I felt the pull to be more directly involved in translating great science into drugs, I transitioned to a role as Head of Discovery at the newly established Shire Human Genetic Therapies business unit of Shire Pharmaceuticals following the acquisition of Transkaryotic Therapies (TKT) – shout out to Mike Heartlein for believing that I could make that move and hiring me. Over nearly a decade, I assumed different roles within the organization and learned first-hand how difficult it was to bring drugs from Research to Development and from Clinical to Commercial. Thank you to Sylvie Gregoire, Sue Bruhn, and Phil Vickers for giving me these opportunities and allowing me to help support the approval and commercialization of Elaprase for Hunter Syndrome, Vpriv for Gaucher disease, and Firazyr for Hereditary Angioedema. I am proud that these drugs are still helping patients today.
From there I went on to build and lead small, emerging biotech companies. Most recently, this included taking a small private company (Homology Medicines, founded by 5AM Ventures) to the public market in 2018. The importance of building a strong culture and working with people you can trust is an absolute requirement if a company is going to try and successfully navigate from early-stage research into the clinic and beyond. A strong culture of trust does not come easily or overnight for a young company. We all have our own way of building this and is a result of the lessons we learned along the way, many of which have been highlighted in LifeSciVC blogs by others.
In the fall of 2022, I moved on from my CEO role at Homology Medicines to Chairman of the company, and I joined 5AM Ventures as a Venture Partner. It is a great opportunity to work with Kush Parmar and Andy Schwab as Managing Directors and here, I have a front row seat to the amazing science that continues to be generated by academia, small and large biotech, and pharma. It is truly a pleasure to work with colleagues and advisors that have founded, funded, nurtured, and operated many successful companies.
In a way, I have come full circle 30+ years later and now have the opportunity to bring cutting-edge science forward by helping build and lead early-stage life science companies. Lifordi Immunotherapeutics is a product of this part of my journey, where I’ve taken on the CEO role, working closely with Arch’s Steve Gillis and Atlas’ Bruce Booth.
All I can say for now is that Lifordi is focused on applying new and proprietary ADC technology to the treatment of autoimmune and inflammatory diseases. I think the time is right to take this validated platform into new waters, and I am very excited about the opportunities we have to help patients with these diseases while leveraging my roots as an immunologist. Stay tuned for more on this later in the year.
2024 and beyond
This brings me back to my optimism as I return from JPM 2024. While the values of companies dropped to all time low levels over the past 3 years, we just kept plugging away like we always have because that is what we do. We are used to this work being tough and despite that, we keep moving the ball forward. That is how we were trained and that is how we know we can succeed. Clinical data wins were plentiful from 2020 to 2023. Drug approvals kept pace during this time. New science continued to emerge …did anything in the drug discovery and development process fundamentally change? I don’t think so.
Clearly, we have experienced a reset in biotech. Multiple companies have restructured, merged, or ceased operations altogether. We have never seen the number of layoffs in biotech that happened in 2022 and 2023… ever.
I believe we are in an equilibration phase for the industry and we will start to rebuild the value this year that has been lost. Innovation and perseverance have kept us going and the resilience we demonstrate every day in our respective roles in developing drugs for patients who need them has carried us through this into a more hopeful 2024. You see, we were down but never out. We are trained to survive the tough times and we will continue to deliver on our collective mission to bring new medicines to patients, their families, and caregivers.