First in Human Episode #27 featuring Sean P. Bohen

For episode 27, we sit down with Sean Bohen,  CEO of Olema Oncology. Stay tuned to learn what the future of personalized cancer treatment holds, and learn how Olema is helping to address the disparity in available care for women. First In Human is a biotech-focused podcast that interviews industry leaders and investors to learn about their journey to in-human clinical trials. Presented by Vial, a tech-enabled CRO, hosted by Simon Burns, CEO & Co-Founder & guest host Co-Founder, Andrew Brackin. Episodes launch weekly on Tuesdays. 

Andrew Brackin: [00:00:00] This is First In Human. I’m Andrew Brackin, the cofounder of Vial. Vial is a tech-enabled CRO that offers faster and more efficient trials for biotech companies. Today, we’re here with Sean Bohen, the CEO of Olema Oncology, which is a biotech company in oncology. Sean, great to meet you. Tell us a little bit about Olema.

Sean Bohen: Thank you, Andrew. It’s a pleasure to be here. Olema is a biotech company that is focused on the treatment of cancers occurring primarily in women. Our lead clinical candidate, OP-1250, is a complete estrogen receptor antagonist focusing on estrogen receptor positive breast cancer, which is by far, the most common subset of breast cancer, with breast cancer being the second most common cancer diagnosis in the world.

Andrew Brackin: Tell us more about OP-1250 and how it differs from other therapies that are available today for ER positive breast cancer.

Sean Bohen: Its primary differentiation it is, as I said, a complete estrogen receptor antagonist. In that respect, when it binds the estrogen receptor, whether it is the wild-type receptor or, has been evolving as a more common resistance mutation, the activating mutant receptor. It locks that receptor in a completely inactive confirmation.

And by doing so, it stops the receptor from its cell growth and proliferation signal that is used by the cancer cells to grow inappropriately. It also has very favorable pharmacokinetics, once daily oral dosing with a quite extended half life, eight days, and as well, a very favorable tolerability and combinability profile.

Finally, it is also a selective estrogen receptor degrader. However, we don’t believe degradation is the primary mechanism. We think it’s antagonism, because all of the degraders leave a significant amount of intact estrogen receptors.

Andrew Brackin: And OP-1250 has been granted fast track designation by FDA. Can you explain to us, what is fast track designation and why is it a game changer for the availability of this drug and your ability to run trials?

Sean Bohen: The biggest advantage of fast track designation, obviously, one is that it’s an acknowledgement by the FDA that, the indication you are seeking, in this case, the fast track designation, is in the second third line setting, which would be after a CDK4/6 inhibitor plus an AI or [inaudible 00:03:02] that you had progressed on that. That indication is an unmet need.

In order to help make new and better drugs available in that indication what the FDA does is they give you an opportunity to make the filing process, which is quite arduous, a bit easier, in part by being able to file different sections in a rolling fashion. Also, they make it easier for you to get interaction with the FDA, which is obviously vitally important when, if you are, as we are right now, planning a phase three . Trial.

Andrew Brackin: Tell us more about the company. How did you get involved? Where is the company at in terms of the team and scale?

Sean Bohen: So, as a company, we’re located in San Francisco and Cambridge, Massachusetts. Our primary clinical asset is OP-1250 in ER positive, HER2 negative breast cancer. We also do have a research program also focused on women’s cancers.

The company has been in existence for quite some time. But really, it was in 2020 when we saw a real uptick in the ability to raise money. That was because of OP-1250’s progress toward the clinic. In November of 2020, we took the company public. I joined in September of 2020.

Obviously, for all biotech companies, that has been a blessing and a curse, a bit, in this period of time. We were able to raise a significant amount of capital, which has us in a great position now with a good runway and the ability to execute a phase three trial. And, also to study combinations with CDK4/6 inhibitors. We are hoping that the generation of that data will not only create a new medicine for patients, but generate great shareholder value over the coming couple of years.

Andrew Brackin: I’d love to know more about your thoughts on how the biotech industry can work toward reducing disparities in cancer care and treatment for women. I know that’s core to your mission and would love to hear your thoughts.

Sean Bohen: It’s been challenging, not just for biotech, but for pharma in general, as well for clinical investigation that actually doesn’t involve the development of new drugs. There are a number of things we can do. One is definitely awareness. By awareness, I mean awareness of clinical trials as an option for treatment, of the disparities that do occur in treatment based on a number of factors, be they, race, socioeconomic, or geographic.

One thing that fundamentally is really challenging to address and that we need to find a more effective way to address it, is trust. Clinical investigation history, in the United States, and really other places throughout the world, does not engender [00:05:00] trust.

There needs to be some very directed effort. This is across patient advocacy groups, pharma partners, biotechs, public health agencies, to educate and engender trust on why it’s a good thing and why it is a safe thing to participate in clinical research.

A few years ago, there was analysis done on participants in clinical trials. The analysis showed that the outcome of patients participating in clinical trials was superior to the general population. That was true also in the control arm.

 If you were receiving what was then the standard of care, not the investigational agent, you were having a better outcome. It probably has to do with the level of rigor with which clinical trials are being conducted.

We need to use things like that to try to help people understand that there are advantages to participating in clinical trials, even beyond the ability to access a potentially more effective new agent.

Andrew Brackin: One challenge that we see, and I’d love your thoughts on, is that the investigators behind these trials are also not very representative of the real physicians who are going to be prescribing these medications and helping patients. We’ve seen that when we’re running a trial. All of the biggest sites generally skew toward men and more caucasian investigators. How do you think we change that? Why do you think that’s important to making clinical trials more accessible and representative?

Sean Bohen: It has to do with availability of the clinical investigation, to a large extent. That’s a very complex one, because it has problems in it that definitely go to your question about disparity. But, it has a broader concern in it as well, which is that the participation in clinical trials for adults in the United States, adults with cancer, I’m speaking specifically about now, is really quite low. Most of the treatment occurs in a community oncology setting, where you have two things going on. One, not a high motivation to participate in clinical trials, because it’s a lot of work. It takes some infrastructure. 

I would say beyond that, also the pressures of clinical practice are so complicated to start with, when you go back in a community setting and say, “Hey, let’s add some more stuff that you have to worry about by managing a clinical trial and a protocol, et cetera,” that really becomes a bit of a disincentive. So, I think, simplifying the clinical trials, increasing the awareness, in terms of the diversity, is absolutely true. It is a longer term problem. I will say that we have a great representation of extraordinary women oncologists and clinical investigators in our trials. Progress there is quite recognizable.

Some of the other aspects of diversity of geographical location community versus academic setting, racial diversity, those things are much slower to change. 

Andrew Brackin: There’s been great consolidation in the world of oncology. Thinking about how we can tap into these community settings is going to be important. But it’s obviously the chicken and the egg, right? You made a great point about the sites needing infrastructure, and these community sites likely lack the infrastructure that, large academic setting has. An interesting challenge, one we think about a lot at Vial. I’m not quite sure I have this solved today, but the idea that more patients in the community setting should be seen is really important.

Sean Bohen: You would think technology would help here. My observation through years in big pharma and now in biotech is what we’ve done with technology is we’ve just used it largely to make trials more complicated.

While it is true that technology can make things more efficient, when you, instead, say, “Hey, we can add this in, and that in, and all these different aspects of trial conduct”, you have a paradoxical effect, which is technology doesn’t make things simple. It just means that more things are collected. It can be more arduous for the patient and the investigator 

Andrew Brackin: Our business is all about building technology for sponsors and making trials more efficient. We have a vision for the way that trials should work. Today, it feels like there’s a huge disconnect from that vision. The way we’re thinking about it is building technology that makes the life of a CRC, a CRE on the sponsor side of the sponsor easier, and giving them superpowers. 

Much of their time today, as we know, there’s a huge shortage of talent in this field. It’s an incredible challenge. So, the more you can give them their time back, the better. One of the challenges with CROs today, and I can say this because, I work for a CRO, and other CROs are our competition. There’s a disconnect where they’re not really incentivized to be more efficient. Our business model encourages us to use technology to be more efficient. Going back to Olema, how are you thinking about engaging patients and patient advocacy groups? You’re obviously in a very specific area of oncology, and I’m sure you’ve spent a lot of time thinking about this problem. 

Sean Bohen: It is specific, but it’s big. [laughs] That’s the interesting aspect of it. ER positive breast cancer is 75% of breast cancer in the US alone. Over 300 breast cancer diagnoses in the United States. You can just amplify that throughout the world.

Patient advocacy [00:10:00] groups are a very useful mechanism to communicate the potential of a new therapy like OP-1250, but also very importantly, to gain the perspective of breast cancer patients who, in one case, obviously are clinical trial subjects, but in another case, obviously are the people who we hope to benefit from this and who will be taking this new therapy, provided we are successful.

Their perspective is extremely valuable in terms of what they are thinking about? What are they looking for? What are barriers to them? We’re using that interaction in two ways. One is to educate about what we’re trying to do and why we think it provides a meaningful new therapeutic option, and how we will prove that. Also, to understand what kinds of data might we generate? What endpoints might we incorporate that actually are meaningful to patients whose lives are affected by this?

 Obviously with such a common indication, almost everyone’s life in some way or another is touched by this disease. If it’s not the individual themselves, then we all have mothers and aunts and possibly sisters who may have been affected by this. 1% of cases are men. That occasionally happens as well. There’s a wealth of information. There’s a wealth of perspectives. It is a challenge organizing it in a way that’s usable.

Andrew Brackin: What do you think the future of cancer treatments look like? We’ve made a ton of progress in the last 10 years. It’s incredibly exciting, some of the new developments we’ve seen in the field. There’s an advent of precision medicine and personalized therapies. How do you think those will play into this market? 

Sean Bohen: We’re already seeing the precision medicine play into the market. We have it a little bit, where we are. Arguably, the estrogen receptor is the oldest identified validated molecular target. Tamoxifen was proved in 1977.

Obviously, characterizing breast cancer by hormone receptor expression status, HER2 expression status, has been going on for decades now. What we’ve seen is throughout therapies, evolution into even more subsets. These are specific molecular markers, oftentimes, specific gene mutations, as we have with the ESR1 activating mutations.

We’ll continue to see identification of those things, and then also, where the science makes plausible attempts to target them, for therapeutic benefit. That will just continue to go. Obviously, that is a very complicated thing. It has diagnostic modalities. Ours is DNA sequencing. It’s probably the simpler end. But, there are much more complex ones that are being used.

Certainly regulatory interactions and what do those mean? Practice patterns, how do they change? Reimbursement patterns, how do they change? Underneath that, what you’ll see is the war on cancer declared in the 1970s, has actually played out, not as quickly [laughs] as the people who started it wanted it to.

Taking apart what might have been a bit of irrational optimism, now what we’re seeing in terms of the evolution of cancer care, both in terms of efficacy and increased tolerability of therapies, is truly remarkable. Even in my career as an oncologist, it is amazing to look at how treatments across many areas have evolved.

The fact remains, though, there are some diseases that just remain truly terrible where we still need to be able to find a foothold and make progress.

Andrew Brackin: We spoke earlier about raising money at a great time. Timing is everything. What advice do you have to biotech CEOs that are building today and dealing with this challenging market, hopefully, with exciting companies and a lot of great science to be commercialized? How would you advise them in this challenging time? 

Sean Bohen: First of all, I would say, “good luck.” It is a very difficult market right now. It is reasonable to say there was an irrational exuberance in biotech markets in possibly 2020 going into 2021. That has vastly overcorrected in the irrational pessimism direction. It’s pretty broadly applied, unfortunately. 

Make sure you can really tell your story. What we do is extremely complicated. If you want to go out and say why this is some simple technology and it’s going to change your life, when you download the app, we can’t do that. We have a lot of very complicated ideas that we have to convey. So, refining that message so you can get it across to a broad audience is vitally important.

The other thing is be very realistic about your goals versus your resources. If you get overextended, you may run into a situation where you just don’t find a reasonable alternative to access more capital. That puts companies in the position, and we see this every day as we read the press, relevant to our industry, having to shut down, having to stop.

Some of that’s okay. This is a risky business. It’s a normal process where people find out and say, “Hey, [00:15:00] we thought the science was going to lead us in this direction, and it just hasn’t played out.”

 We’re seeing evidence that we’re losing really meaningful potential advancements, by virtue of this capital crunch. I would say be very careful about how you manage your capital.

Andrew Brackin: That’s great advice. Sean, thanks so much for the time today. This was an enlightening conversation. I appreciate it, and wish you the best of luck with Olema. It sounds like an incredibly exciting company with an exciting phase three trial ahead of it.

Sean Bohen: Thank you, Andrew. I really appreciate it. Good luck with Vial as well.

Andrew Brackin: Thank you. 

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