A-Alpha Bio CEO and AlphaSeq platform co-inventor David Younger found himself frustrated by academic science’s seeming tendency to “do science for the sake of science,” which he acknowledges is critically important for the innovative therapies of tomorrow. When one of Younger’s own co-inventions started to point toward applications that could have a serious medical impact, he decided academia was no longer the best place to move the technology forward. In 2017, Younger and cofounder Randolph Lopez (currently chief technology officer) spun A-Alpha Bio out of the University of Washington. The company is developing immunocytokine therapies in oncology and autoimmunity, as well as “glueable” protein pairs intended to degrade cancer targets. Life Science Leader spoke with Younger about the challenges of launching a new company, tips for partnering with Big Pharma, and strategies for progressing preclinical assets during a downturn in public market investment and biotech IPOs. This interview has been edited and condensed for clarity.
CAN YOU DESCRIBE THE PROCESS OF SPINNING OUT A-ALPHA BIO FROM THE UNIVERSITY OF WASHINGTON? WHAT OBSTACLES DID YOU ENCOUNTER?
David Younger: Starting a company is hard. I think that’s one of the things that drew my cofounder Randolph Lopez and I to it; it’s not an easy thing to do, but there’s the potential to have so much impact. One of my frustrations with academic science is that it sometimes feels like doing science for the sake of science. That work is really important. But when you've hit on a technology that seems to clearly have broader applicability, keeping it in an academic system is not usually the place to really maximize its impact. That was ultimately why we decided to spin out a company. Randolph and I both come from an academic background, and we got to know each other as graduate students in the bioengineering department at the University of Washington. After a short stint as a as a postdoc – getting our ducks in a row to spin out – we moved straight into starting the company. I think there are advantages and disadvantages to moving straight into being company founders from an academic environment. One of the obstacles we had to overcome is bringing in experience, because we have not walked down all of those well-trodden paths, and we have not encountered all of the pitfalls that someone who has spent years as an entrepreneur, or years in Big Pharma or biotech, inevitably would have experienced. The onus has really been on us to put together a very strong board, a strong group of investors, and a strong management and advisory team. We have learned a lot as a result, although it’s definitely drinking through a firehose. However, I think it’s an advantage that we aren't necessarily tied into some of the existing preconceptions about the industry. In the life sciences generally, we're very much at a transition point where the need to integrate computation and dry lab tools is so important. And there are many kinds of new business models, new ways of partnering, and new ways to think about building a pharmaceutical pipeline.
YOU ARE AN INVENTOR OF A-ALPHA BIO’S ALPHASEQ PLATFORM. WAS THERE A SPECIFIC EVENT OR TRIGGER THAT TOLD YOU IT WAS TIME TO BUILD A COMPANY AROUND IT?
DY: The decision was more informed by experimental inputs than by business. Once we realized the platform worked – and exceeded our expectations – we knew that we had to do something with it. At that point we thought, do we try to out-license this to an existing biotech? Do we open source it and hope that someone builds on it and gets it to a point where it can have an impact? Or do we drive this technology forward ourselves? We were in an exciting space, an academic environment where the technology was essentially invented between two University of Washington (UW) labs: one at UW’s Center for Synthetic Biology, and David Baker's lab at UW’s Institute for Protein Design. The technology is rooted in synthetic biology, but essentially the customers, or users, are protein engineers; we are generating very large datasets that can inform new sequences of proteins that will have enhanced binding properties. Because we were building in a highly translatable platform, with our customers essentially right in the same lab as us, it became very clear once the technology worked. Protein engineers in David Baker's lab were getting excited about what they could do with this platform, indicating a potential broad utility. Then the question became, how do we capture that value and maximize the impact?
WHAT RESOURCES WERE AVAILABLE THROUGH THE UNIVERSITY OF WASHINGTON TO HELP YOU LAUNCH THE COMPANY? HOW DID YOU SECURE THE FOUNDATIONAL IP?
DY: Right away, we started having conversations with UW’s commercialization center, called CoMotion. We started to get organized with provisional patent filings before going out and speaking at conferences, or presenting posters, or anything like that. CoMotion was incredibly supportive of that work. Part of that has to do with the track record that the Institute for Protein Design (IPD) had already started to establish: Cyrus Biotechnology had already spun out of IPD, our data had already spun out of IPD, and PvP Biologics had also started to spin out of IPD. There was already a budding entrepreneurial ecosystem for us to follow, which was hugely important and influential. And that pathway has only grown; we were among the first companies to spin out of IPD, but now there are maybe up to 15 or so companies that have been spun out of the IPD, which is exciting to see. From early on, UW was supportive with IP, and supportive in helping us lay the foundations for what the company would become. They also paid for my year of post-doc work after I completed a Ph.D.. During that time, Randolph, and I were able to apply for grants and enter into some business plan competitions, and move our company plans forward. Once we did spin out, we exclusively licensed the UW-owned IP; we were the inventors, but we had to license that IP from the university.
A-ALPHA BIO HAS ACTIVE PARTNERSHIPS WITH AMGEN, BMS, AND GILEAD. WHAT TIPS WOULD YOU OFFER TO EARLY-STAGE BIOTECH EXECS HOPING TO PARTNER WITH BIG PHARMA?
DY: Obviously, the science is paramount. Deals are done in this space based on the quality of science and preliminary data. But I think the relationship aspect also cannot be understated. Randolph and I made a very significant push from the beginning on customer discovery. We learned from programs at UW, and through initiatives at the National Science Foundation such as the I-CORP program, just how important it is to get outside of the walls of the company or the academic institution, and to start learning from industry experts. We started building those connections, learning about what the needs are, and learning about how we fit into that ecosystem. Back in 2017, when we were kind of just getting off the ground and well before we were ready to partner, we were going to partnering conferences, like BIO, JPM, and others. We were talking to people, asking for their advice and sharing the progress that we'd made, and building those connections. Thinking about our partnerships with Amgen, BMS, and Gilead, some of it is the result of not a single meeting, but years of meetings, and having these consistent touch points to share what we are working on, and to get feedback. By having those multiple touch points, it gives a partner not only the confidence that the science is good, but it is also a chance to share progress. Partners are not only interested in what you’re bringing to the table on day one, because partnerships can last for months or years; they want to know that we’re going to continue making strong scientific progress during that time.
BEYOND PARTNERSHIPS, WHAT OTHER STRATEGIES ARE YOU USING AS CEO TO MAKE SURE A-ALPHA HAS THE CASH TO MOVE FROM PRECLINICAL RESEARCH TO HUMAN TRIALS AND REGULATORY SUBMISSION?
DY: Partnerships are great because they allow us to bring in non-dilutive revenue while capital is super expensive. It allows us to take additional shots on goal; we don’t have to put as much capital into the programs our partners continue to support. But for us to continue building value as a company over the long term, we also want to invest heavily in our internal pipeline, and be really strategic about where we invest. And you need the right investors. About eight months ago, when we wanted to go out and extend our Series A, we had such an outpouring of support from our existing investors that the funding was insider led, even as an up round. And we brought one new investor – Breakout Ventures – into the fold as well. But the fact that we were able to get that done as a [$22.4 million] up round with insider support, during a tough financial time, is really a testament to both the progress that we've made as a company, and the fantastic community and support that we've cultivated through our investors.