Neuron23: Nancy Stagliano, CEO

“This is a watershed moment for neuroscience—so let’s get going and change how drug discovery is done.”

Neuron23 is taking a precision approach to treating genetically defined neurodegenerative and systemic inflammatory disorders. The company uses machine learning models to identify pathways dysregulated in disease, and then it develops selective small molecule drugs to treat both central nervous system and peripheral disorders. Finally, Neuron23 leverages cutting-edge AI/ML algorithms to stratify patients into potential responder and non-responder groups. Its lead program targets the LRRK2 protein to treat subsets of Parkinson’s patients, as well as those with Crohn’s disease and ulcerative colitis. The company has a second program centered on inhibiting TYK2—an intracellular kinase that when genetically mutated in patients protects against development multiple sclerosis and other autoimmune conditions. Both programs are currently in preclinical development, and Neuron23 is gearing up for Ph1 trials for its centrally acting LRRK2 therapeutic in Q4 ’22 and early 2023. Neuron 23 was founded in 2018; most recently they raised a 100M series C in December ’21 led by SoftBank Vision Fund 2, bringing the company’s total financing raised to date to $213.5 million.

Dr. Nancy Stagliano (CEO) is an engineer-by training with a PhD in neuroscience (U Miami) and a post-doctoral fellowship from Harvard Medical School. Throughout her career in pharma, she has prided herself on adopting an engineering mindset, letting “first principles” help guide the organizations she leads. Dr. Stagliano has been CEO of three companies—True North Therapeutics, iPierian, and CytomX Therapeutics. She considers her crowning achievement to be the work she did with True North in developing sutimilimab (now sold by Sanofi), for the treatment of cold agglutinin disease. In addition to her role at Neuron23, Dr. Stagliano serves as chair of the board of Star Therapeutics, Electra Therapeutics, and Latigo Biosciences. She is active in philanthropy and is a board member of the not-for-profit organization PanCAN.

Below is an interview with Dr. Nancy Stagliano from July 2022:

1.     Tell us a bit about your academic career as a grad student and then postdoc. What drew you to science initially, and what led you to make the jump to industry? What was this initial transition like? 

I’ll back up to my undergraduate degree at Drexel in electrical engineering, which was where the understanding of my options started. As part of a co-op program, I had the ability to work in different environments, with different people. This made a huge difference. Although I landed a number of interesting jobs—at IBM and in hardcore engineering—my favorite was therapeutics. I worked on an assembly line and did really applied, hardcore mechanical engineering work. But I got to see the questions that pharmaceutical companies were asking. I also got to see the types of people that were in the biotech work environment. This really stuck in my brain as I considered my path.  

When I moved from engineering to neuroscience at the University of Miami, I applied my systems learning approaches that come from engineering. As I kept thinking about my options—I was working always in translation research, never in reductionist biology—I realized that I was probably better suited to a bigger environment, to an industry setting where applied questions were going to be asked. I made the leap to MGH and Harvard Medical School for my fellowship with the understanding that this would be applied, translational research. What this [postdoc] really taught me was about the interaction between scientists and clinicians, and the special partnership that could be formed to shape the way medicine was done.

Also, from these experiences [at UM and HMS] I knew that I eventually wanted to work in a bigger collaborative space, and not just write grants and pursue academia. So, I took my first job at Millennium Pharmaceuticals after my post-doc.

[On the topic of her background as an engineer]:

I say ‘first principles’ to my team every week. There is pattern recognition once you do this job for a bit, and there is no reason not to take advantage of that.

[On the topic of transitioning from postdoc at HMS to industry at Millennium]:

I didn’t feel equipped, I didn’t know that world. Millennium had a completely different approach to anything I had worked on—it was a genomics company, and I was far away from genes and DNA in my postdoctoral work. It was a fast-paced, high-powered organization, which was growing really quickly…and they gave me a lot of responsibility. I had never managed someone, been responsible for reporting on a weekly basis, or planned projects for a group of people. The science was new and exciting, but the management role I was not prepared for. You learn new biology, new science, new heuristics. It [Millennium] was a welcoming environment and extremely entrepreneurial—everyone was running hard toward the same goal, but no one got left behind.

2.     What is one book that has influenced the way you think, which you would recommend to fellow scientists or entrepreneurs? 

Think Again by Adam Grant. He [Grant] specializes in team psychology and business thinking. It is so timely for people to read. It is about rethinking your position on various things—now more than ever in the world, whether it is in your family, your company or society, we are forced to rethink. This is a good thing. I believe in instinct, but once in a while you have to take a step back and evaluate. He [Grant] gives terrific examples in this book about how various people, whether they are entrepreneurs or first responders, succeed or fail based on whether they rethink a situation. The book gives you permission to not have to get it right the first time in your brain, and to give yourself the time to rethink.

3.     At your current role at Neuron23 excites you most about the job? On a day-to-day basis what makes you feel most fulfilled? What is special about Neuron23?

I get excited everyday about the people at Neuron23. The team is outstanding, we are 39 people now and growing, which is not something a lot of companies can say in this environment. We have an interesting blend of chemists, biologists, data scientists, clinicians, entrepreneurs—everyone has a spirit and energy that is palpable. It is the reason I do what I do—I love to mentor, and I love to build teams. At the end of the day, the team gets me up in the morning, and makes me smile many times during the day. Also, working with younger people [motivates me] – the latest generation out of college with new ideas to contribute to what culture looks like and how science is done. It is a lot of fun.

What is our magic or special sauce? Well, Neuron23 is bringing data science and computational biology directly to neuroscience. Lots of people use the buzzword “AI” in medicine today, but we are actually doing it. We are doing it with our first program, LRRK2 in Parkinson’s and have a companion diagnostic composed of a SNP chip that will help us pick who will be responders. It has been so interesting to think about how our oncology colleagues have done really well with precision medicine, and we in neurology have not. At Neuron23 we intend to change this.

4.     What is the company’s origin story? 

Neuron23 was founded by Beth Seidenberg and Adam Knight at Kleiner Perkins. Beth is a seasoned investor in our industry and a leader in the space, and in building companies – she thought it was the time, and was clearly right, for neuroscience companies to be focused differently. We knew each other from working together at iPierian and True North. She asked me to get involved at its [N23] inception as executive chair in October 2018. The interesting part of Neuron23’s story is that we had partnered with a chemistry company and started in-licensing some early chemistry, which was based on an AI-driven discovery effort.  We thought we were going to keep a very lean team and not build out. However, we ended up turning this model on its head. We soon realized we needed to bring expertise in-house. If you are going to be a therapeutics company with this special focus and emphasis, you need to contain all functions. So, we ended up changing the initial shape, but not the mission of the company. The origin was really in thinking that this is a watershed moment for neuroscience—so let’s get going and change how drug discovery is done.

5.     What are you currently working hardest on at Neuron23? What are the upcoming milestones you are using to keep your team motivated? 

Drug discovery for LRRK2 has been a challenge for the whole industry. Many pharma companies got in and then out, and many are still trying to find inhibitors. Kinases are hard to drug, and they have been more widely used and accepted in oncology. But the selectivity for a LRRK2 inhibitor, and the therapeutic window you are trying to hit, has been challenging. So right now, we are focused on choosing between two lead molecules [LRRK2 inhibitors] and determining if we are going to take one or both into the clinic later this year. Each drug has slightly different properties, and each is currently in animal studies. What we are doing on a day-to-day basis is trying to manage all aspects of this work and get to the best decision—for the company and for patients. Doing animal and toxicology studies are challenging, and the field is overburdened with demand. Right now, it is an all-hands-on deck focus on looking at the new data and seeing how it tips the balance between these two molecules. Where is the risk benefit calculus? At all levels, the team is sitting together to figure out: what is the right next step?

We are funded well enough to take both molecules into the clinic. But in this marketplace, you don’t want to do that unless it is really the right thing. In parallel, we will be developing a companion diagnostic to help us select sporadic PD patients most likely to respond to the therapy. In the next few weeks, we will announce more about this effort.

6. What is another biotech (public or private) that you think serves as a paragon of an impactful company? What are the key learnings from this case study? 

It is hard when you think about impact to not acknowledge Moderna. Maybe it’s an answer that to most people will seem obvious, but really think about what they did as a solo company working for 10 years on a platform. There are huge lessons to be learned from that company: success didn’t happen overnight. They started as an infectious disease and an mRNA platform company, but at a time when it wasn’t clear if platform was ‘En Vogue’. But they persevered and were committed to their mission. [Before success] they had a lot of challenges that they overcame. Now you look at their vaccine and the areas they are approaching—everything from influenza to Ebola—I think they have a world-changing platform. But it didn’t happen without perseverance. Now the company itself is impressive—the shape and form, what they focus on, what they message around their values. They have a foundation that supports grants, charities and diversity and inclusivity. I like what I see at Moderna and think they have done a masterful job of getting to this point. I am also grateful for what they did for the world. 

7. Today’s climate may be intimidating for first time biotech entrepreneurs. What is one short piece of advice you would give to prospective and first-time entrepreneurs?

Be flexible and listen. It gets back to Adam Grant’s book Think Again. If you are an entrepreneur with a vision for a company, therapeutic, platform or technology, it may not be the easiest thing right now to get funded or move at the pace you’d like. However, make sure that you are flexible in your thinking. If you do receive input from investors and peers, listen to it and think about it. Then adapt. You may have had this perfect plan in your mind, but across the industry we have had to be flexible. We are doing it [being flexible] at Neuron23 even with more than $200M raised. You have to be flexible about your business model, and how you do what you do. It may not all get done today, but that is the reality. Listen to the world around you. But I don’t think anyone should let go or give up on their passion. This [current climate] too will pass, and good science, novel science, will be funded. Adjust if you need to and keep going.

8. What has most impressed you the most about any experienced or thoughtful investors with which you have interacted? What is one piece of advice you would give to new biotech investors? 

The best investors have enough experience and pattern recognition in our industry to clearly understanding the challenges we face as entrepreneurs and as small companies. Some of the best funds I have seen have a clear understanding of what we do every day, as entrepreneurs. The best investors really get to know the leadership team, the people doing the work and the players at the company—and understand what all of their jobs are. I have a great dialog with our investors, and we talk regularly so that they know what is going on. Transparency is paramount on both ends.

I always say to investors, ‘We both have jobs to do here. How do we partner to get these done?’ Where investors and board members contribute most to the company, is in their ability to push when you need a push, or sometimes just allow you the space to breathe. It is hard. It’s sometimes an investor’s job to say: ‘I have seen it done this way, because I have been on a number of boards of companies who have faced similar challenges.’ If investors can bring this pattern recognition to a company, it is incredibly valuable.

9. Any recent announcements (hires, abstracts/publications, funding, awards, job openings) or key milestones regarding Neuron23 that you want the public to be aware of?

I think people should look at Neuron23! We are hiring and building out our data science group and other functional areas. We have this commitment to do drug discovery in neurodegenerative disease differently. If you want to join a team that will make a difference, check out Neuron23.