Interview with Scott Applebaum, President of Context Therapeutics


Acquiring and developing medicines that transform the lives of cancer patients and reduce the fear that follows a cancer diagnosis

Scott Applebaum is the president of Context Therapeutics, a biopharmaceutical company based in Philadelphia, PA. Founded in 215, Context is dedicated to discovering, acquiring, and developing medicines for patients with breast, prostate, ovarian, and other hormone-driven cancers. The company is currently focused on development of Apristor (Onapristone XR), an investigational Phase 2 drug that targets progesterone receptor positive (PR+) metastatic breast cancer.


EDWIN WARFIELD: You’re originally a lawyer. How did you transition into the pharma industry?

SCOTT APPLEBAUM: When I went to Stanford Law School, I really didn’t have a great idea of exactly what I wanted to do after law school. I wasn’t even sure where I wanted to end up, but I decided to come back to Philadelphia. My wife and I are both from Philadelphia and lifelong Philadelphians. We enjoyed it here, wanted to come back and start a family here, so I started to look for opportunities in Philadelphia. At the time, I started with Dechert, Price & Rhoads. Dechert is one of the largest firms in the world now; at the time, it was the largest firm in Philadelphia. I started as a tax associate, working in the area of tax, corporate tax, individual tax, employee benefits. I worked on a number of corporate transactions—M&A-type transactions—and did a variety of counseling. It was a great environment in which to learn. I worked with some great people there, some great mentors. But I also decided that I did not want to spend the rest of my life in a law firm. As much as I enjoyed it, I felt that there were probably more opportunities that would be a better fit for me in the corporate world, so I started to listen to and pursue opportunities outside of the law firm.

When I had the opportunity to join Bristol-Myers Squibb, that was something that really excited me, because I was able to use my expertise as a lawyer in part of an organization that I felt was really a dynamic industry and a great industry—one ultimately that’s focused on helping patients. When I started at Bristol-Myers Squibb, it was a very big difference from being at a law firm, where essentially you’re being rated on the quality of the work but also how many hours you bill. So, now, you’re working as part of a team that is ultimately being judged on the quality of the drugs you get to market and how well they do in the marketplace.

I worked at Bristol for about eight years and learned every aspect of the business I could. I had some great mentors at Bristol-Myers Squibb who gave me some stretch assignments and opportunities to work on some really important projects. My wife used to joke that when I was at cocktail parties and I was dispensing advice about high cholesterol and other things—she was like, “you’re not a doctor!” I said, “well, it’s true, but in narrow areas I think I know as much as anyone does.” And, we really did. The drugs that we worked on that I helped work with the regulatory filings, I helped worked with the promotion of those drugs—to really be effective, I had to learn as much about the drugs as anyone did. I had to really understand how doctors were going to prescribe it, the conditions that patients were living with, and how it was going to help them. I tried to learn as much as I could about the science. I am most definitely not a scientist, but I learned just enough probably to be dangerous.

I really enjoyed my time at Bristol-Myers Squibb, but it was a very large organization when I was there—about 50,000 employees. It had some ups and downs. Some of those downs for me personally were very big opportunities, because I got to work on a number of crises that the company was going through, and crises can be great learning experiences. I look back on that time very fondly because it really did give me a broad knowledge base and broad exposure to all different issues, both domestically and internationally.


EDWIN WARFIELD: Tell us about your most recent acquisition. How did you find Onapristone, and what are its potential implications for cancer patients?

SCOTT APPLEBAUM: When we acquired Onapristone in December of 2017, we bought it from a company that was winding down. We acquired this asset and everything that came along with it, including all the data that had been generated, all the regulatory filings, and all of their clinical drug supply that’s still in existence. The drug had been studied for a number of different types of cancer. Initially, it was studied a while ago in the mid-1990s by a company called Schering AG. It was being developed as an oral contraceptive. At the time, there was some research being published that talked about the role of the progesterone receptor in breast cancer, and it was thought that if you were able to slow or shut that down with an agent, that you may be able to slow down or reverse the effect of breast cancer. (Schering conducted two studies with Onapristone). Onapristone is a pure antiprogestin. There are other antiprogestins that are combination agonist or antagonist, but Onapristone is the only pure antagonist.

It was studied in two different trials in the mid 90s. One trial had 19 patients, the other had 101 patients. Out of these two trials, the 120 patients, they showed really positive and interesting clinical benefits for these women who had breast cancer, and these are patients who had metastatic breast cancer. The results were really positive. Schering, however, as a company, made some strategic decisions to not advance it as an oral contraceptive, and with that all of the funding went for the breast cancer studies as well. Basically, they just left it behind.

We were stunned talking to the people who were involved at the time. We’ve spoken to the person who was the lead investigator on the breast cancer trials—he’s now a rather prominent breast cancer researcher in the U.K., his name is John Robertson. He said he was really disappointed and stunned that Schering discontinued development, rather rapidly and without much of an explanation when he was studying the drug. We’ve now reconnected with him and he wants to work with us to resurrect the drug and get it back into the clinic in breast cancer trials.

An important piece of the story is the initial studies that were don in the mid-1990s. The second piece of the story is how the drug was picked up by the company from which we acquired the drug. That company was called Arno Therapeutics. They had taken a look at the data that was out there and said “there’s something interesting here—we want to pursue this.” A couple of hurdles in their way were that they had no drug supply. They had to find a way to manufacture it, and it was difficult to manufacture it. They spent a fair amount of money, came up with a better manufacturing process, and, as a result, were actually able to create a slightly different version of the drug. It was a more pure form of the drug and it was an extended release version of the drug. This action becomes pretty important, because people have learned over the last 20 or 25 years, as the progesterone receptor impacts breast cancer, the goal is to shut it down for a 24-hour cycle and keep it shut down. The drug that was studied by Schering initially was an immediate release version of the drug, and it had a short half-life. That meant that by the end of maybe four or six hours, they weren’t getting full coverage on the receptor. Arno reformulated the drug into extended release, and decided to dose it twice a day, which effectively shuts down and covers that progesterone receptor for 24 hours. So, with a lower dose given twice a day and an extended release version, they were able to get full coverage. From a pharmacokinetic aspect, this is important and we think will lead to even better results than the ones we saw Schering had from the mid-1990s.

The other thing Arno did was they did Phase 1 studies in multiple tumor types and then they started a Phase 2 study in prostate cancer. That’s where their story ends because, they had a difficult time enrolling the study in prostate cancer based on requirements for the study including taking bone biopsies, which are difficult and painful, and patients were not really willing to undergo it. And the science wasn’t really leading them to prostate cancer. There were other reasons where they had hypotheses, but we think they would have been more successful had they stuck to breast cancer.


EDWIN WARFIELD: You spend a lot of your time giving back to the community. Can you tell us about some of your nonprofit work?

SCOTT APPLEBAUM: When I’m not at work, I spend as much time as I can with my family. I’ve got, at this point, three grown daughters, so no one’s home right now. My oldest daughter is getting married next month, which is very exciting, and I have two other daughters who are in college. When I’m not with them or my wife, I spend as much time as I can involved with a few different nonprofits that are really meaningful and near and dear to me.

One of those is the Boys & Girls Club of Philadelphia. I’ve been on the board there for a number of years. The work that they do in the community is really outstanding. These are kids who generally don’t have the types of opportunities I did when I was growing up, and it’s great to see that they have a place to go after school—a place where they can do their homework, a place where they can get a hot meal, because I’m not always sure that they know where that next meal is coming from or where that place is going to be to get their homework done in a quiet place. The impact that we make in the community through the Boys & Girls Club is really tremendous, and I wish we could spend more time with the clubs, more time with education, but we have a great leadership of the club here in Philadelphia. About five years ago, Joseph and Lisabeth Marziello came in. They had turned around a few other underperforming Boys & Girls Clubs, and they showed up here, and within a year or two at most, just turned around the work that we’re doing here in Philadelphia. They really ramped up the fundraising and renovated most of the clubs. We’re now in the process of trying to build a new club in Germantown. And, again, as I mentioned earlier about the impact that you make on patients and their lives, well, you see that when you go to these clubs and when you talk to these kids. You see kids who have graduated and going on to college, where I don’t know that would have happened without these clubs being there. So, I try to spend time with them whenever I can.

I’m also on the board of another nonprofit called the DEFY Foundation. This one’s a little more personal to me. One of my close colleagues and a great leader at Shire when I was there, whose name was Mike Yasick, died of a very rare disease—one that fortunately none of us had ever heard of before—it’s that rare—but it had just a devastating impact on his family. The condition is called vascular Ehlers-Danlos syndrome. And, he, his two brothers, and his father all passed away. Mike was a leader of our ADHD business at Shire, and one of the most beloved people, and he died suddenly one day while at work. And, then six months later, his 24-year-old son died of the same condition, suddenly. And, then about a year after that, his, at the time, 21-year-old daughter was diagnosed with the condition. It’s just a devastating illness. But, Emma Yasick, Mike’s daughter, she’s tough—she’s a fighter—and she said, “We need to do something. We need to take control of this disease.” So, she and her fiancé started a nonprofit foundation called The DEFY Foundation—Defeating Ehlers-Danlos for Yasick. We’ve been active in the community, raising funds and raising awareness. Over the last few years, we’ve done 5Ks, we’ve done golf outings, we’ve done newsletters. We’ve raised about $80,000. We’ve made a $25,000 grant to one of the few researchers in the field who is actually down at Hopkins.

We have a really exciting event coming up in May. We are hosting an international symposium of researchers from around the world who specialize in vascular Ehlers-Danlos. There’s not too many of them, but there’s been some exciting developments. There’s actually a company that is developing a drug for it now called Acer Therapeutics, and they’ve provided a sponsorship to us. We’re very grateful for that. I have a very close personal relationship with the family, and they’re just the most terrific people you’ve ever met, and I’m just so inspired by their spirit and how they carry on and how they continue to fight this disease and fight for a cure, and I’m optimistic we’ll get there. Whenever I spend time with them, it’s very rewarding time.

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