Oral Drug Delivery For Breast Cancer Prevention With Atossa Therapeutics' Steven Quay

In this episode of Sit and Deliver, host Tom von Gunden talks with Atossa Therapeutics CEO Steven Quay about oral drug delivery for early intervention in patients at high risk of breast cancer. The discussion covers formulations, coatings, and dosing for orally administered, cancer-preventative approaches to reducing breast density.

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Episode Transcript

Tom von Gunden, Chief Editor, Drug Delivery Leader:  

Welcome to another episode of Sit and Deliver, the series in which we hear from leading thinkers about drug delivery and routes of administration for drugs and therapeutics. My name is Tom von Gunden, chief editor at Drug Delivery Leader and your host for this series. Today I am joined by Dr. Steven Quay, CEO of Atossa Therapeutics, a company working on the oral administration of therapies targeting breast cancer.

Welcome, Steve.

Steven Quay, CEO, Atossa Therapeutics:

It's great to be here, Tom.

Well, it's great to have you here. Thanks for joining us for the episode today. Let's start by talking about the patient population that you think about and is front of mind for you as you work on developing orally administered therapies targeting breast cancer. So, who is out there and how do you think about the demographics of this segment of the population that you're working toward addressing?

Now that's a great question, Tom. It is important to narrow the scope for today's discussion. (Z)-endoxifin, which is the drug that we're developing, actually has activity in the prevention of breast cancer, in the early treatment, in the maintenance after surgery, and in salvaging people who have metastatic disease. So, sort of the A to Z or alpha omega of breast cancer. But, for its delivery properties and for its uniqueness, I think focusing on prevention is probably the most important setting.

What we have right now is a situation where there is a drug approved for prevention. It's called tamoxifen. It works. It reduces about 60% of breast cancers over five years, but 1% of women take it. Why? Because there are very, very serious side effects that it has.

So that was the drug delivery challenge that we had. Could we deliver something that didn't have that safety profile, in the prevention space? Great. You asked what's on the market today and what the current experience is like for women who want to address the potential for breast cancer or breast cancer. What's currently available? And what's the experience like for them today? Well, if you are looking at it from 30,000 feet, breast cancer is now treated at the time that it has occurred. We don't really look at trying to prevent it. For the most part, we find it usually by mammography or by physical exam.

Then we have what is euphemistically called “cut, burn, and poison,” which is to say that there is surgery, there’s radiation therapy, and there's usually some sort of chemical therapy given afterwards. So that is the landscape of most women's experience with breast cancer. And that's why I am so excited about the concept of being able to prevent it in the first place because that really is a whole different ballgame for women, for their families, et cetera.

Great. All right. Well, thanks for the background of the current landscape and treatments as you're working there to advance and improve on what's available. I'll ask you in a minute about the specific mechanism of action once the treatments are in someone's body. But, at just a little bit higher level, what's the general approach you're taking to delivering something through oral administration?

The key in any oral delivery is the frequency that you do it, which is how many times a day. And then what it does as it goes through the various compartments. So, basically, it is swallowed and there's not much happening there. But the first component, of course, is the acidic stomach. And then you go to the alkaline small bowel, and then you get absorbed into the circulation. And then you have first pass liver metabolism. So, with (Z)-endoxifin, because it has a double bond and because the Z form is one configuration and acid catalyzes, the conversion to the E form, happens pretty rapidly and is inert.

Our first challenge was to get it through the gastric compartment. So, we had to come up with an enteric coating that would both prevent the pill from dissolving in the stomach. And also, would it work with (Z)-endoxifin because there are some excipients that weren’t terribly successful, did not necessarily worked well with (Z)-endoxifin in terms of its stability over long-term shelf life.

Now that we’re into the realm of the mechanism of action: If there’s any more detail that would be helpful, if there’s more to say about what actually happens in the body once it’s there, and if you could add to that what the treatment regimen might look like for a typical patient …

Yes, so the concept is that you will identify, at mammography, not women who have cancer, but women who are at risk of having cancer. Very interesting history here. If I could just take a minute. In the late ‘80s or early ‘90s, we developed mammography that was used to find little granular findings that were typically pre-cancer or something like that. But a wonderful physician named Fisher at the University of Pittsburgh stood back and said that there's a background density difference between women. You can categorize them as low density or high density. And if you look out ten years, there's about an eight-fold difference in cancer in women with the high density compared to the low density. So, mammography is now gradually shifting from being a cancer-finding tool to a cancer prediction tool. And that's where we step in using the identification of women at high risk, which means they have high density, and then try to intervene in that process.

Gotcha. And for those folks who would take your therapy, what would that look like? What would the experience be like? How often? That sort of thing.

I imagine a woman sort of doesn't think about her breast health until she's 40, when she has her first mammogram. If she has a family history or something, maybe age 30, age 35, but generally at 40. She has her first mammogram, and she gets sort of a good news/bad news report. The good news is there's no cancer. There's nothing to biopsy. But the bad news is she has high density and, therefore, is at an eight-fold increased risk of breast cancer.

In our clinical trials, we're going to design them to find the women that have about a 3% risk over the next two years of getting breast cancer. That's  pretty high in a clinical trial setting. She will then go on a regimen where she would take our pill once a day. It had the same side effects as a sugar pill in the clinical trials that we did. There were no adverse events that we saw in that trial. We have to do further testing, of course, but she would take that. And then over, between six months and two years, we would reassess the mammogram. And in about 60 or 70 percent, the density would decrease. And we know that that means that she has a reduced five-year risk of breast cancer.

So, it's identifying the women at high risk, giving them a drug that has pretty benign background in terms of side effects, and efficacy is good. And then preventing breast cancer for, we think, a lifetime, maybe there's a reset in ten years. That's for some future research.

Gotcha, gotcha. So, you may have already covered the ground of what I'm about to ask to wrap up today, but I'll give you an opportunity to look out to the near or far horizon. If the advancements and improvements that you're working on take hold and have the effectiveness that you would hope for and that we assume will happen: How would you describe what you envision the landscape of breast cancer and the patients out there to look like? How would that differ from what today's landscape looks like?

Tom, while we have had this interview here, there have been about 30 women diagnosed in the world with breast cancer. That's the frequency of this condition. So, we think that we can greatly affect the estrogen-driven breast cancers, which are 75 to 80 percent of them. So, our aspiration is to cut that in half or maybe slightly more.

In the U.S., that would mean going from 250,000 cancers a year to maybe 100,00-125,000. I have invented seven other drugs in my career. An MRI helped about 80 million women, but this would be the capstone to a career for me of being able to prevent breast cancer in so many women.

Great. Well, I appreciate the work that you're doing there. It sounds extremely promising. Thank you for joining me, Steve, for today's episode of Sit and Deliver and sharing your perspective. And to our audience, thanks for joining us, and we'll see you next time.