Andrea Miyahira: Hi, everyone. I'm Andrea Miyahira at the Prostate Cancer Foundation. I'm very excited for this women in science special to feature Dr. Margaret Yu, the chief medical officer of ARTBIO, a company that is developing alpha radioligand therapy for cancer. She previously worked at Johnson where she played many roles in advancing the prostate cancer pipeline, but has a long career that I'm very excited to talk to her about today. Thanks for joining us.

Margaret Yu: Thank you, Andrea, for having me.

Andrea Miyahira: So Dr. Yu, tell us about your career path and how you got to where you are today?

Margaret Yu: My focus in academia in the clinic and in the lab was actually chronic lymphocytic leukemia and AML. And I had joined a lab during my heme-onc fellowship where the lab focused on inflammation and colon cancer. My mentor, Frank Fitzpatrick, was a medicinal chemist who previously had worked at Upjohn before he became faculty I think. That's when I-- working with his grad students and postdocs, when I realized how important it was to have clinicians involved in drug discovery and therapeutic development.

I loved my academic job.

I was also very fortunate because the university protected my time when I was a young investigator. And then it was incredibly validating and a confidence booster when ASCO also recognized it and gave me a career development award. So it was just a very, very great, I would say beginning of my time. But when I was transitioning from being a fellow to a faculty member, it became very clear I was about two or three years away from independent funding. My mentor was retiring and I was becoming a full-time clinician.

So the fact that I didn't have a backing of a well-funded lab, I was a young investigator was really intimidating to get research funding. At that time, the NIH funding line was about 6%. And so that's when it was incredibly intimidating, and I started looking for a job elsewhere, how I ended up in industry.

So that's why I ended up initially actually joining a mid-size company that had a diagnostic business. It also had a biotech in developing drugs for different therapeutic areas including oncology. I actually loved it as a first job. I got to wear lots of different hats, had a lot of fun. But then I think I really learned how to do drug development when I went into big pharma with Johnson &Johnson and did over a decade of that where I worked on some really amazing drugs, had a great experience, and ultimately ended at ARTBIO because I wanted to do something that I think will make a difference in the future.

Andrea Miyahira: OK, thank you. And so you did work at Johnson for many years. And what led you to make the decision to make this most recent move to ARTBIO?

Margaret Yu: I was I think hired in the oncology R&D group when Janssen was in a growth phase for the prostate cancer disease area business and the franchise, the portfolio was expanding. And I had a lot of opportunities.

And then when ARTBIO presented with this opportunity, it was actually at a good time when a couple of the things I had worked on in preclinical went into phase 1, they were transitioning into late development, and we had just forged some new collaborations and discovery. And the opportunity at ARTBIO really excited me. So the timing was really good.

I think one of the things I worked on when I was at J&J was the actinium HK2 antibody for prostate cancer. I think that really convinced me that alpha emitters can be a little better than betas with the double-strand DNA breaks.

It was really gratifying to see some of the early data where some patients really had a benefit and the responders really had durability. And so I think it helped me understand that even in a patient with maybe tumors that have this hypoxic environment or even like an immunosuppressive tumor microenvironment, radiation can really help. So when the opportunity presented itself with ARTBIO, I was excited to join.

Andrea Miyahira: OK, thank you. And were there any barriers or issues that you faced that you want to discuss, or what qualities do you think helped you to get where you are today?

Margaret Yu: Success means different things to different people. I define success as when an experiment that was designed asked a question that you were able to answer. And sometimes I don't think we always like the answer we get to that question, but you still learn from the results. And so that's how I've looked at it in my career.

I've had a lot of male role models I would say in my professional career. All of my mentors and bosses, coaches were male role models. And I owe a lot to them because many of them gave me opportunities where I got to grow and learn a lot of new things that I don't think I knew why I could be part of when I was a clinician.

And when I think about all of these different roles-- I've never had a female manager or a boss. And when I was a young physician scientist, I did see that as a gap. And so with the help of my male bosses I was able to connect up with some clinical leaders outside of pharma who were executive level women role models. I think that was really helpful to have female role models who were able to get to positions that I aspired to that inspired me to become something greater. And I think it was really helpful for my mental health.

I think the most important quality in success is resilience. Very few molecules make it into the clinic, and fewer than 10% make it past phase I. So when you look at those types of numbers and statistics, it can seem kind of depressing.

But even in my fellowship days, I remember designing experiments that just continued not to work out, progress was very slow. I was a little frustrated. And my lab mentor Frank at the time said, it's not how many times you get knocked down, it's how many times you get up. And we've all heard that. I think it was attributed to Vince Lombardi in the early days.

And I still think back to those days, when I have a lot of challenges today, is I reflect on why I went into medicine and how when things work out, it's so incredibly gratifying and humbling to know that you were part of that coming up with a new therapeutic option for patients. It makes it really rewarding. And I think until we truly can talk about cures in cancer, we all have a lot of work to do.

Andrea Miyahira: Thank you. And so for others who are interested in following in your footsteps and making the jump from medical oncology and academics to industry, what advice would you have for them and what factors should they consider?

Margaret Yu: The recent cuts in funding, changes in policies, all of this volatility in the marketplace, I think really have thrown additional challenges for anyone thinking about pursuing a career mostly in research. And I think it's true whether or not you are an academician or you're part of a private or a public company. I actually find it a little worse when you're an academician, a young investigator who doesn't have the backing of a well-funded lab. It's hard to even think about where your salary is going to be coming from.

We've heard a lot about the great advances in Artificial intelligence, machine learning. But at the end of the day, I don't think tumor biology is something you can do very well with Artificial intelligence. We really do need a well-trained workforce who know how to think about innovation. And so I do worry about what happens to us 10 years from now. What does it look like?

And for a woman in oncology who wants to pursue and make that transition into industry, I would want to that this person really wants to go into it for the right reasons, because the work is not easy. So a good reason, for example, would be you're really excited about doing clinical research to get some therapeutic, a diagnostic, a device for patients.

And you understand that really a lot that's worked on in the lab. And even when it goes in the clinic, they don't make it. And that you have to be OK with being uncomfortably comfortable with uncertainty and risks. And making decisions with very little information, you find that exciting rather than difficult or challenging, and you love to problem solve.

And going into industry because this is what you love. But don't go into the industry because you're burnt out in the patient care, and you're not getting the right support at work, because this kind of job may not be right for you. And you won't necessarily be happier. The other thing I think to consider is an industry job requires travel oftentimes. And do you have the right support system at home?

Andrea Miyahira: That is all great advice. So you've held several very impressive leadership positions. So what do you think makes a good leader and what advice would you have for the younger generation, especially women who are interested in positioning themselves to become leaders in these fields?

Margaret Yu: So a good leader is someone others want to follow. And I think about great leaders, they really have a vision that others also can believe in. They really understand the importance of building a team and unifying that team. And in the words of Felix Feng, you have fun doing team science. And I think that's when everyone on the team wanted just take that extra time and go that extra mile to do what's needed for patients. I think that's the characteristic of a great leader.

"My advice for women who are interested in that next job, your dream job, really never refuse an opportunity even if it sounds like something that you might not have thought of for yourself. Because you may not how to do it today, and it might seem difficult or it's not part of your job, but you always learn something. And that skill, good or bad, in terms of the experience you've had, that will position you for maybe the next role."

Andrea Miyahira: OK, thanks. And so tell us more about what you're doing now at ARTBIO and some of the things that you're most excited about?

Margaret Yu: We're about to start a phase 1 company-sponsored study this summer. It's a lead-212 PSMA radioligand, that I'm really excited about, because lead-212 is a short-acting alpha emitter like actinium, but it only decays into one daughter. So you really can control it a lot better. You can really for the first time in radioligand therapy, explore what it means to push that dose rate, which is a well-known principle in radiation biology. But we've never had the opportunity to do that, dosing patients every 6 to 8 weeks, patients progress during that time.

And so having something that you can really try to push the boundary and maximize the efficacy is something that's exciting not only for prostate cancer but for other radiosensitive tumors. So I'm very excited about that.

This molecule also has an interesting profile. Has good tumor retention and it doesn't have salivary gland uptake, because of its molecular profile. It's a little more hydrophobic. And because you need active uptake through a transport system in salivary glands. By the time the drug gets there, it's cold. And so that's something else that's exciting to me. Developing a drug that not only is efficacious, but helps patients live longer and maintain that quality of life. I really can see how that can help.

Actinium, look, we've been developing radioligands with actinium for over 10 years. It's hard. Xofigo today is still the only alpha emitter that's approved for treatment of prostate cancer. And so when you think about radioligands, it's not easy because it requires you to have scaling up, manufacturing, global supply chain, a lot of investment not only in the development of the molecule, but also in supply chain in parallel.

And it takes just as many years sometimes to have a robust supply chain, I mean, that played out in terms of even the PLUVICTO launch, we saw that as an example. And so what I really liked about ARTBIO was that the company was really intentional in building that in parallel with the pipeline. And so even for a startup, it had done tremendous amount in a very short period of time. It also was started the founding person was it is Roy Larson who also founded the only alpha that's approved.

And so all of those things are exciting to me because I do think, much like a lot of what we've heard in heme malignancies with CAR-Ts and bispecific T-cell engagers. And now even in different solid tumors, you've heard about some good responses with T-cell engagers. I really think we can make radioligands more available to not just prostate cancer, make it more efficacious, but also for other radiosensitive tumors. And I think when we get there, then all of this will be worthwhile.

Andrea Miyahira: OK, thank you so much for sharing with us today. I'm looking forward to the results from this trial. And thank you again for your leadership in this field for so many years.

Margaret Yu: Thank you for having me, Andrea.