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Having spent the first half of her career as an academic physician at Massachusetts General Hospital focusing on the care of patients with malignant brain tumors and other nervous system cancer-associated issues, Dr. Alison O’Neill’s entry into industry was “serendipitous.”

During a visit with an old colleague, O’Neill realized that the meeting was not just a casual conversation but a job interview within a small start-up biotech focused on malignant gliomas.

“They were looking to bring a physician in house who understood their science and the early phase drug development paradigm,” she said. “It ended up being a very good decision with a thoughtful CEO. There was a lot about the industry that was going to be new to me, but it was a small company where we could work as a very cohesive team and I could have the experience of seeing a lot of different areas of drug development from the other side of the table.”

The timing was perfect, as O’Neill was looking to have a greater impact on oncology drug development.

“I would be lying to say that there aren’t times that I miss direct patient care. There is an immediacy there that is so rewarding,” she said. “But ultimately, I feel as though my ability to have an impact, my ability to really make some forward progress in terms of bringing new drugs forward has been very rewarding on the industry side.”

In her current role as chief medical officer of Surface Oncology, a clinical-stage biotech taking an immune-enhancing approach to immuno-oncology, she and her team are focused on understanding the science behind the tumor microenvironment. Beyond checkpoint inhibitors, which have become the standard of care in immuno-oncology, O’Neill believes “there are a lot of other targets within the tumor microenvironment that could be impactful in terms of revving up an immune response or taking the breaks off on immune response to be more effective in terms of tumor treatment.”

The most advanced candidate in Surface’s current pipeline is SRF388, an antibody that targets against IL-27. According to O’Neill, this “very novel target” has had some early positive results as a monotherapy to shrink tumors.

Beyond the science, O’Neill revels in a role she describes as ever-changing.

“There are always new challenges, always new opportunities, new problems to solve and one day is never liked the next in terms of what might come down the pike. For me, it’s certainly one of the things that I appreciate about the role, but, more importantly, appreciate about biotech. I think that working in a smaller company and having that ability to wear different hats on different days and respond to challenges as they come up is one of the more exciting things about it.”

In this episode of the Woman of the Week podcast, O’Neill talked about the advances being made in immune-oncology therapeutics, the team aspect of drug development and what it means to be a role model. 

Welcome to WoW, the Woman of the Week Podcast by PharmaVoice, powered by Industry Dive.

In this episode, Taren Grom, editor-in-chief emeritus at PharmaVoice, meets with Dr. Alison O’Neill, chief medical officer, Surface Oncology.

Taren: Welcome to the WoW podcast program.

Alison: Hi Taren. Thanks so much for having me.

Taren: Dr. O’Neill, it’s our pleasure. And I would love if you could share a bit of your backstory and what led you to a career in medicine and then into industry?

Alison: That’s a long question that could have a long answer, but I’ll try to be brief. I mean, certainly, my interest in science began very early in my school career and really, from a young age, the idea of going either into basic science or into medicine was foremost. And it was probably really around the time that I was in college, having serious thoughts about do I want to go into a PhD program or become a physician that I was really drawn ultimately, I think to the immediacy of the connection with patients. And that way of sort of employing, understanding of what’s going on in science, what’s changing really having a direct impact on patient care. And that really propelled me much more into medicine as a way to, I guess, follow my love of science.

In terms of the question about changing course from patient care and academia into an industry-focused career, I think that’s where it’s a little bit more about serendipity. I probably spent the first half of my career as an academic physician. Specifically, a neuro-oncologist, focusing on the care of patients with malignant brain tumors and other cancer associated issues with the nervous system. Working in a way where I was doing early phase studies looking at new compounds that we could hopefully, improve the care of those patients with. But also doing teaching, guiding medical students, residents, fellows — all of those things that are sort of part and parcel of an academic practice and was finding more and more that, the ability to make an impact in terms of really bringing new drugs forward and neuro-oncology is one of those areas where there has really been a paucity of new drugs and new breakthroughs.

And doing that, as an individual investigator was getting to be a bit more frustrating and rather out of the blue, I had a visitor to my office who introduce himself as the new CEO of a biotech that I had worked with early in my career when they were doing some first gene human studies, using a technology that had been licensed out of the university I was working at. And I thought he was just wanting me to take a look at the next study. See if I’d be interested in opening it at the institution I was working at. And it really took me quite some time to realize I was on a job interview. They were looking to bring a physician in-house who understood their science, who understood the early phase drug development paradigm and specifically in malignant glioma.

So it was, as I say, a good part of it was serendipity, but it ended up being a very good decision with a thoughtful CEO who realized that I was going to need a lot of support. There was a lot about the industry that was going to be new to me, but it was a small company where we could work as a very cohesive team and I could have the experience of seeing a lot of different areas of drug development from the other side of the table, if you will.

So, that’s that story but I would be lying to say that there aren’t times that I miss, direct patient care, I think as I say there is an immediacy there that is so rewarding. But ultimately, I feel as though my ability to have an impact, my ability to really make some forward progress in terms of bringing new drugs forward has really been very rewarding on the industry side.

Taren: That’s excellent. Awesome. Thank you so much. And who was this very smart CEO who got you this job interview?

Alison: His name is Michael Legan, and sadly, Michael died. He actually ended up succumbing to malignant melanoma several years after I started working with him. But yeah, he was a great guy and very patient.

Taren: That’s so tragic, but kudos to him for recognizing talent when he saw it and to bringing you into the industry to move forward science that is so desperately needed, obviously from this man’s passing. And all of those cancers that really are still have so many unmet needs. You talked about the immediacy of serving patients but yet, you have 20 years of clinical research experience in oncology drug development, in clinical neuro-oncology. I’d love to know from you, what are some of those breakthroughs that you’ve seen over this time?

Alison: Well, it’s obviously been a fascinating time in oncology. Our understanding of cancer biology has grown so much in the last 20 years. Everything from moving forward from more conventional cytotoxic chemotherapeutics into targeted drugs. But to me, I think one of the most exciting changes has really been the emergence of immuno-oncology, as yet another really critical pillar in the treatment of patients with cancer. And the promise there, which has been a long time coming of unleashing the body’s immune system to really help fight cancer in a way that potentially can really eradicate the disease. To me, that has been probably the most exciting change that I’ve been able to experience. And it’s a story that we’re just at the beginning of.

Taren: I was going to say, you talked about it as a promise. And are we really truly on the precipice of a breakthrough here where it’s going to become almost standard of care? How far away are we?

Alison: I think we clearly have drugs that now are fully approved and having an enormous impact on patients. Thinking of PD-1s and CTLA-4 molecules that really are becoming the standard of care for many patients with many different types of solid tumors. The reason I say we’re really at the beginning of this though, is that those drugs are really impactful, still for a minority of patients. And we don’t fully understand, for example, in the patients who don’t respond to them, what else should we be doing to try to promote an immune response in those patients that don’t seem to respond initially to those drugs? So there’s much more I think to be unpacked in terms of fully realizing the potential there. But make no mistake, we are already seeing an enormous impact of those drugs.

Taren: Fantastic. Thank you so much for that. In your current role as the chief medical officer, talked to me about how you’re shaping the strategy around the company’s pipeline.

Alison: Yeah. Well, Surface is a very interesting company. We were really founded around the idea that there was indeed much to be unlocked in terms of understanding the science of the tumor microenvironment and looking at different ways of modulating the immune response by impacting that tumor microenvironment. So I think from the outset, we’ve relied very much on a very strong scientific advisory board to really help us and partner with us in thinking through what are novel targets that we should pursue. In terms of developing drugs, how can we develop drugs that might be differentiated in a very positive way, again, some of these targets? And that has really remained Surface’s core strength and our core ability in terms of identifying those targets, prosecuting against them, and bringing those drugs into the clinic.

So it’s not a role that I take on alone by any means, this is very much a team sport and being able to be part of those discussions, about why do we think this is differentiated? Do we have enough scientific understanding of what’s going on here to move this forward? Are we ready to move into the clinic is definitely one of the more exciting parts of my job. But certainly, not something I do alone.

Taren: I appreciate that this is a team sport for sure. Can you share a little bit more about the science behind the company’s approach to creating these new kinds of differentiated drugs?

Alison: Certainly. I mean, I’ve referenced obviously, checkpoint inhibitors, which have now really become the standard of care in immuno-oncology. Drugs against targets like PD-1, but there are a lot of other targets within the tumor microenvironment that we think could really be impactful in terms of revving up an immune response or taking the breaks off on immune response to really be more effective in terms of tumor treatment.

So Surface’s current pipeline, we have a number of targets that we’re actively moving forward. Probably one of the more interesting and certainly from our recent clinical data very exciting is our SRF388 molecule which is targeted against IL-27. And again, this is a target that is very novel. Not a lot of other competing drugs out there. No other competing drugs that we know of going after this target. And it’s a different way of really trying to unleash that immune response by removing what is an immunosuppressive cytokine and in certain tumor context, certain solid tumors like hepatocellular carcinoma, non-small cell lung carcinoma. We believe that IL-27 has a very important role to play in the tumor microenvironment. And we’ve actually seen now in a number of patients that we have treated with just SRF388 that we’re able to see monotherapy responses with tumor shrinkage.

And again, in the immuno-oncology space seeing that kind of monotherapy activity early in development is really interesting and really encouraging. We’re also moving forward now with another target, our SRF114 molecule which targets CCR8. And this is a very specific molecule that shows up on a certain class of immune cells in the tumor microenvironment. And that actually, can depress the body’s ability to respond to cancer cells in that microenvironment. SRF114 is a very specific molecule that targets CCR8 and removes these suppressive cells and really has the ability then to unleash a more normal immune response against the tumor. So these are the kinds of molecules which as I say, certainly are distinct from the checkpoint inhibitors that are currently out there and being used so effectively. But the promise is that we can really see more patients who respond to these types of immune therapies or deepen responses when combined with other immune agents.

Taren: That’s exciting stuff. So go back again to tell me about your most advanced product and how close are you to getting it into the clinic?

Alison: Well, actually our most advanced program, the SRF388 program is already in the clinic and we’re currently in phase 2 trials. So we’ve established the safety of the molecule in our phase 1 dose escalation, feel comfortable that we have the right dose to move forward with and are now looking at the activity of the molecule in more specific patient populations. And then 114, which I mentioned second is actually a drug that we are just in the process of moving into the clinic. We’ve filed the IND and are moving forward to treat patients in the very near future.

Taren: Well, that’s exciting.

Alison: Yeah. It’s an exciting time.

Taren: I was going to say, what is the general feel around the company? I would think you’re all very excited and R&D, this is really tough stuff, because sometimes it works and sometimes it doesn’t, right? So how do you keep the teams like all energized?

Alison: That’s a great question. And I wish I knew how to break down Surface’s secret sauce easily. I don’t think it’s an easy thing, but it is one of the things we’re very proud of in terms of maintaining the sense of community, the sense of excitement around what we do, and really keeping people engaged in that mission. And I think part of it is as simple as the ability to work in very close knit cross-functional teams where the excitement of the science, the excitement of seeing changes in the clinic, seeing changes in translational data that’s coming out. All of these things help us, I think all remain focused on the mission at hand and feel very connected to it, whether you’re a scientist in the lab, whether you’re on the clinical side or whether you’re on the finance team. Making sure that we’ve got our contracts in place and we’re paying our bills on time. They’re all part of the mission.

Taren: Absolutely. Somebody’s got to keep the lights on, right?

Alison: Absolutely.

Taren: So, tell me, as the chief medical officer, what’s the most interesting part of your job?

Alison: Well, I actually think that the most interesting part of my job is the fact that it is so variable, that it’s ever-changing. There are always new challenges, always new opportunities, new problems to solve and one day is never liked the next in terms of what might come down the pike. So for me, personally, it’s certainly one of the things that I appreciate about the role, but, more importantly, appreciate about biotech. I think that working in a smaller company and having that ability to wear different hats on different days and respond to challenges as they come up is one of the more exciting things about it.

Taren: I think it’s interesting to notice that in the biotech arena certainly, that C-suite experience is different than if you’re in a big pharma company.

Alison: Absolutely, yeah.

Taren: Yeah. So tell me about your C-suite experience. How have you found it? And obviously, you are enjoying it, I can hear it in your voice and you’re obviously very good at it. So, how have you found that personally, though?

Alison: Well, I think I feel very fortunate that I had the advantage of having worked with many members of this executive team prior to joining the C-suite. So I think one of the things that drew me to Surface was feeling that the executive team was very much aligned with the mission of the company. I felt that they placed a high value on maintaining a culture that kept their employees engaged and that this was not a top down management team, but a management team that very much appreciated getting the input from all parts of the company to move things forward. And as I’ve been able to join the executive team now in the last, I guess, about a year and a half that is very much held true. There’s a lot of time and attention that we spend really making sure that we’re able to maintain the company’s culture that keeping science first and foremost, and the mission to serve the patients at the center of what we do has really remained true.

So I feel very fortunate that I had a chance to sort of experience the company before moving up into the C-suite. But also, seeing that those values were really validated.

Taren: Wonderful. We talked a second ago about the variability of the biotech experience and drug development being a risky proposition. What are the things that keep you up at night, if there is anything at all?

Alison: Well, I’d be lying to say that I never lose sleep over work-related concerns, whether it’s about a big presentation or a naughty operational problem. But quite honestly, I do make it a priority to try to get good rest and maintain a sense of perspective, simply because I think, the world of biotech is a challenging one. And we don’t give our best if we’re sort of lost in the worry or in the anxiety and lose focus on that sense of perspective and what the broader mission is.

Taren: Absolutely. And so, how do you keep yourself energized during the day, as you say, you need the rest? But what do you do particularly for yourself? Is there some self-care that you do during the day to keep your energy up?

Alison: I mean, for me, getting outside regularly making sure that I’m making time to spend time with family and friends are probably the most critical things and trying very much to unplug a little bit on weekends. And at least have some downtime to go and pursue something that has nothing to do with work.

Taren: What are those favorite pursuits for you? What is it that draws your attention?

Alison: Well for me, kayaking is a great release. It’s obviously something not available to me in the winter around here, but most of the year that provides a nice way to get out and be truly away from phones and everything.

Taren: I was going to say, it’s hard to multitask and to be on your phone answering an email if you’re kayaking. 

Alison: Exactly. Scuba diving would be another one. Really difficult to get emails out when you’re scuba diving.

Taren: Again, we talked about you being in the C-suite and you are absolutely a role model to other women coming up through the bench, et cetera. How does this mental responsibility feel to you? Do you feel like you’re a role model?

Alison: I mean, no. That is something that is a difficult thing for me as sort of an introvert and private person to really embrace. But I would say, certainly in the course of my career, I have often been in situations where I was one of a small number of women with a voice and so, it’s not alien to me. But I think the interesting thing is that at Surface, actually, the majority of our executive team at this point is women. So, I don’t feel like I’m a trailblazer there, let me put it that way.

Taren: Okay, I’m not going to push you to where you don’t want to go, but you are sitting in a seat of influence, let’s put it that way. You noted that you were an introvert, but you also had to find your voice at the table. How did you do that?

Alison: It’s not an easy thing. I think some very good advice that I have received along the way is the importance of making sure that you can be authentic, that you can actually speak up in a way that might not feel comfortable, but that it’s important to do. That if you believe in what you’re doing and have sort of the strength of your convictions that it is important to make that effort even if it doesn’t feel particularly comfortable to do so. And in smaller groups, that’s usually not a problem for me. But I will say, that some of the external facing parts of the role in the C-suite, I definitely still work on every day.

Taren: I understand. And it’s purposeful work, right? And it’s good work that you have to put into yourself to continue on that self-discovery, I would think.

Alison: No, absolutely. And it’s part of continuing to grow and stretch which I think is one of the things that drives happiness in your career, no matter what you’re doing.

Taren: Absolutely. So let me ask you. Sitting in that leadership position, what are some of the best leadership you provide to others? And then I’d like to hear, what are some of the best leadership advice you’ve been given?

Alison: I’ll take the first part first or I should say, the second part first. As I said, some of the best leadership advice, I don’t know that you’d call it leadership advice exactly, but that sense of bring your true self, find a way to be authentic even in doing things that may not feel particularly comfortable, I found has been very helpful to me as leadership advice. And it’s funny because, as you said, how do you feel as a role model and I think for me, it’s less about trying to provide advice and counsel to more junior colleagues, but more to try to lead by example and be encouraging in terms of people finding what it is that they enjoy and sort of how to move forward in the role that makes sense. It’s less a single piece of advice, I guess.

Taren: Understood. You noted the gentlemen, the CEO who put you on your fast track into the industry earlier. Who else has had a big influence on you in your career?

Alison: There have been so many, mentors and then colleagues even over the years that I would have a hard time pointing to just one. I mean, everyone from obviously, professors, clinicians that were such role models for me as I was moving through my training. And I think maybe one of the things that is underappreciated is how much it may not be the people who are your bosses or who are senior people in the organization that impact you. It can also really be the colleagues that you’re working with day-to-day or the people who are from a completely different function, who provide a different perspective and help you grow and learn. And that’s something that I’ve felt throughout my career, whether I was working as a clinician or in industry, I’ve always found those colleagues that are working right next to you are often the people you’re learning the most from.

Taren: I agree with you there as well. You noted that the majority of Surface’s management team is women. Was that purposeful or was that just a happy coincidence?

Alison: I believe it was a happy coincidence and it is a management team that has evolved over time, but interestingly, we have managed to kind of keep picking up women along the way.

Taren: That’s great. And you talk too about mentors, are you a mentor yourself?

Alison: Formally, I am not in a mentorship program, but I certainly feel like everybody who is on my team is somebody who I care very much about their development and their growth. So hopefully, I’m actually helping them grow in their careers. But I am not in a formal mentorship program, no.

Taren: Very good. And I like the fact that I wouldn’t call that almost like quiet mentorship. It’s not formal, but you’re certainly providing those tools and role modeling the behaviors that are so necessary for others to understand and appreciate as they look to progress their careers. So wonderful. As we do with all of our podcasts, I’m going to ask you or challenge you rather to identify that wow-moment that either change the trajectory of your career or has left a lasting impression on you, what would that be?

Alison: It’s a fascinating question because you can think of lots of, “yeah, that was a really important insight.” But interestingly, the one moment that kind of comes to me repeatedly as I have moved through my life is actually something that happened quite early on. I was actually still in college and meeting with an advisor and I was spinning through all sorts of grand long-term goal, thoughts and this woman, very calmly just stop me and said, “you know, it’s great, you want to have goals. You want to have those sorts of objectives, but don’t forget, you know, life is what’s going on, while you’re getting there and it’s important to pay attention to that too.” I found that to be something I’ve come back to again and again, as sort of grounding as we start sort of spinning and focusing on long-term objectives to say, “okay, but my life is actually happening right here and right now and I need to pay attention to what’s in front of me.”

Taren: It’s such an important insight that to be present in the moment is so important, because as you said, the future is there, but right now is now. So I love that. It’s been so nice to speak with you and I loved you’re telling me about Surface’s pipeline and thank you so much for sharing that technology in a way that I can understand it, in a way that gets me excited about the future of oncology, and so for our listeners as well who may not be proficient in oncology or scientist. So thank you for that. I want to wish you great success as you move forward. Thank you so much for being part of our WoW podcast program.

Alison: It’s been a delight. Thank you so much, Taren.

Thanks for listening to this episode of WoW, the Woman of the Week podcast. For more WoW episodes visit pharmavoice.com.