Mark Day:
0:05
My thing was never to be in one box for seven years. Right? It was, what's the goals? How do I get them accomplished? How do we drive the science forward?
John Simboli:
0:17
That's the voice of Mark Day, Director, President and Chief Executive Officer of Bioasis Technologies. At the 2019 CEO and Investor Conference, Bioasis was named Buzz of Bio winner in the public therapeutic category. Listen in now to my conversation with mark. I'm John Simboli. You're listening to BioBoss. This afternoon I'm with Mark Day, President and CEO at Bioasis Technologies. Mark, how'd you find yourself here at Bioasis?
Mark Day:
0:48
I was looking for a disruptive enabling platform technology that could really turn around the probability of success and neuroscience. Something that was flexible enough to be able to deliver diverse sets of payloads—sRNAs, enzyme replacement therapies, small molecules, you know, varying antibodies of different sizes, et cetera. And the nucleus for that was because in every company I've worked at, it's been the same fate for neuroscience, clinical development programs. And specifically what I mean by that is that the drug typically makes its way through phase one and do the safety assessment. And you escalate your dose, single ascending or multiple ascending dosing. And on the face of it, neuroscience looks like a no-go area because of the high attrition of development compounds due to futility. And by that I mean the compound is deemed not to have worked in the patient population. In reality what was really happening across the board was that, not all companies do this, but some companies will keep the phase one dose low based on what they discovered in animal models. And you know, that almost guarantees success through phase one. But the real test for the patient comes in phase two, phase three, right? And that's really where you've done your phase one, you're now looking for proof of concept that your medicine actually works and the patient responds to that medicine. And literally, if you look at all of the programs where there's enough data on, right, in terms of did the drug cross the blood brain barrier, did it engage its target? And can be a receptor like histamine three, for example? Or it could be target tissues in the case of brain metastases where the cancer's actually, metastasized into the brain. And none of the available medicines can get across the blood brain barrier unaided. And so, around 2008, 2009, after seeing multiple failures at that point and realizing that, if you kind of took a money ball approach tradition, you know, the Brad Pitt movie, and look how he constructed these team, right? It's about what are the three things that predict the success of the drug. And that's missing in, I'd say, about 80% of the phase two/three's that failed. So just to be clear, that means the drug has to get across the blood brain barrier. It has to bind to its target. The target can be a receptor or it can be target tissue where the disease manifestation is. So in the case of brain mets, you will have brain metastases in the brain and you need your drug not just to get across to BBB but actually go to the target sites. So that's the target engagement piece. The third piece of this, and this is how we choose our programs, is how we advance programs. It's not enough to just get increased brain exposure. And this was part of my due diligence on looking for the right company. So it's not enough to get just the increased brain exposure. The brain exposure has to translate into the target engagement. The target engagement is meaningless unless it drives the biological effect that you're looking for. So in the case of brain mets for example, it's obviously a decrease in tumor size, the volume of the tumors. To date, there is no been no treatment options, other than drilling a hole in the head, that can get the drugs into the brain. And of course through direct delivery like that, you know, there's, obviously, you know, liabilities like infections, it's expensive. It's not something you want to do en masse, so you can't do that on lots of patients. And these are pretty sick patients. So they're the three predictors. The additional thing we look at is... so tumor shrinkages good obviously in that context, but what you really want to see is, because typically a cancer therapy, for example, is going to take several weeks to several months, sometimes it doesn't work at all, to manifest. So another way of looking at the kind of pharmacodynamic effect of the medicine and to get a sense of not just your dose, which you can do with PET imaging, but actually to show that you're starving the tumor out. In this case, in this example, glucose metabolism is a really easy, very routine thing to do. You know, cancer cells, they're hungry, right? They feed on arginase and other things, they'll consume anything that allows the cancer to grow. It's kind of an odd side of evolution. But that's what you're seeing in rapid time in cancer. So the glucose metabolism itself can not just indicate what dose is able to drive the biological facts. In this case, what you want to see is the tumor starved of glucose. So when I came across different BBB technologies, I came across this one that I never heard of before called Bioasis, and now you have to remember this back in 2008, 2009 so Bioasis was really only formed as an entity in 2008. And I looked at it and I was familiar with all the other BBB techs and a very top line of that is these guys were able to get into the brain really quickly, like super fast compared to competing technologies and the competing technologies were delivering in the region of 1 to 1.5% of the injected dose. So, for example, for our lead program in brain cancer, once you inject the drug, just intravenous, it's literally seconds for it to get to the blood brain barrier and across it. So that was one differentiation. The second that excited me was the abundance of targets that the technology was able to deliver. So, for example, it's delivered sRNA therapeutics in one example there, you know, the sRNA is there to knock down the Nox4 gene, which is a major factor in stroke, and really deliver cargo and you see really, really elegant data in those—that's under review right now in Science. But you see there's really elegant data there to show that not only can you deliver, sRNA and knock down the gene of interest and, at least in the preclinical models, be able to totally restore the neurological function. There were also other targets which were really large targets that you can get into the brain. And with that, you know, we have two antibodies, trastuzimab, which has never been brain penetrant before, and linking with our technology, gets into the brain, does all of the things that predict success and we're we're advancing towards development on that. But Medimmune did an independent validation where they're interleukin 1 antibody... again, it was in there, gangbusters, with a single dose, study around for just two weeks, then two weeks drug was still in the brain. When I looked at that set of diversity, it meant that this was really disruptive on the sense that, could be really disruptive, on the sense that if the competitive field is 1% to 1.5%, if the injected dose meant we could deliver four to six, that was a huge advantage. Right? The second was the diversity of the payloads. It's literally a small peptide, you'll link it onto a well known medicine like trastuzimab or cerezyme or any of the medicines that work peripherally. So, you know, breast cancer, et cetera, but they don't get across the blood brain barrier.
:
9:01
So one of the things that really kind of caught my attention was the enzyme replacement therapy space. Gene therapy and enzyme replacement therapies, the known medicines do a pretty good job on the periphery. So in, in certain diseases, like for you and me, we're healthy so what the body normally does is there's waste flowing around your body 24/7, but you don't know about it cause your body clears it out. In diseases like lysosomal storage, diseases, where there's a deficient enzyme, for example, it doesn't treat the brain symptoms, cause cerezyme is just one example. It doesn't get across the blood brain barrier. Now there were several neurological conditions associated with Gaucher's disease and in those diseases, we've been able to show, in the preclinical models, which I think mostly faithfully kind of recapitulate the human condition. So you'll see increased heparan sulfate in the liver and the spleen. Cerezyme can take most of that out. On the neurological side, we've been able to show in a couple of different knockout models that we can clear out heparan sulfate from the brain. And so that's a huge, huge advantage. So at that point, I started taking this seriously, as a diligent kind of individual. You know, I also pressure tested all the other technologies at the same time.
Mark Day:
10:41
So that's how I ended up here, to be honest. I got to know the company through the partnership that we had. And then at that point I just kept in touch with a company. And then, weirdly, to answer your question specifically, the previous CEO offered me the CEO job at JP Morgan in 2017 and I joined in April 20 of the same year.
John Simboli:
11:05
Did you know at some point, maybe when you were a young guy, maybe a young guy plus a couple years, that someday you thought you'd end up being a leader of a biopharma?
Mark Day:
11:15
Honestly, no. My early part of my career was really based around, really wasn't thinking about being a CEO at that point. It was more about learning all the different facets of the companies. Which I think is a skill set that you know, is fairly unique because you have to remember, in big pharma, if you don't stay in the job for five years, they think you're flighty. Right? And you know, my thing was never to be in one box for seven years. Right? It was, what's the goals? How do I get them accomplished? How do we drive the science forward? And so, it wasn't until Frank Walsh, who's the CEO of Ossianix, which is a competing technology based around the transferrin receptor. Frank had been a great mentor to me over the years and when I was at Wyeth, he was head of research and it was actually Frank that first said to me,"Have you thought about being a CEO?"
John Simboli:
12:21
And what did you say?
Mark Day:
12:23
I said, no, I said, it hasn't crossed my mind at all. Because, literally, when I'm all in on something I'm all in on it. So for me it's, you know, it's get the job done, go in, get it done, do it really well. If it's really good, scientifically, I'll end up in a really good journal. But you know, Frank and I, you know, continued talking to each other over a long period of time and he'd bring opportunities up to me that he thought would be good. And so started talking to a couple of companies, like to get a feel for it.. And then that was actually the seeding of the idea that yeah, I probably could run a company. Right. Knowing that there's a lot of learning along the way.
John Simboli:
13:08
When somebody asks you for the most basic level, an intelligent person though, says, what do you do for a living? What do you say?
Mark Day:
13:15
I'm responsible for the oversight of a public company. And the mission of that company is to deliver medicines that haven't been deliverable before. And we have an approach that we feel is very efficient in delivering those medicines. And we're going to take these drugs into development and then we're going to test what they can do. And I think that's really the top line of it. Making medicines.
John Simboli:
13:45
If you can remember what you wanted to be when you were a kid, and then if that had anything to do with the way your professional life worked out, what would you say?
Mark Day:
13:52
You know, I've wanted to be an A&R executive.
John Simboli:
13:56
Artists and repertoire?
Mark Day:
13:58
Yeah. I was always into music. I grew up in an environment where, I mean literally the Gallagher Brothers, from Oasis, which has no association with Biooasis, that was the name of the company when I took over. But a lot of a lot of folks actually go like, oh, did you name the after... No, it's got absolutely nothing to do it. But I was always interested in music. Factory Records, which was the big independent label... it was just, you know, we were in this kind of area where music was a big thing in Manchester. So I actually, my own ambitions, I was always interested in the brain, but not as much as I was interested in music, at that point. And that's been a constant trend through life, right? We're humans. I mean, that's an important thing. The CEO is the face of the company. But we're also people, right, and there are things that we like to listen to and go and see, whether it's a concert, whatever. My early ambition as a young man, is very different to once I got really involved in neuroscience and our, you know, drug development, I think I made the right choice.
John Simboli:
15:14
So what's new at Bioasis?
Mark Day:
15:15
So we've been executing on our internal strategy. So that is, on the one hand you heard me talk about, you know, Herceptin for example, in the brain and, breast cancer as an example. The advancement of those from having preclinical data. By that I mean good recapitulation of disease, but not in human, has been good and we've been driving that forward. in terms of where are we today that's different from last time we spoke, right. John, I'd say, the company's currently a small market cap company, right? So the company had never had, since 2008, a business development deal. So in 2018 one of the things we did was really knuckle down on the due diligence. The data room, as an example. Intellectual property, all the R&D data, etc. Got that organized. That was important because it enabled the execution of the Prothena licensing deal we did in October. And that's really exciting because, on the inside, you've got one kind of tranche, and that is wholly owned programs, which we have several, they're all well-established medicines. They're off patent. And by just linking our technology to those drugs, they're actually new medical entities and if they work in both the periphery and the brain, then you've got a new standard of care potentially. Right. And that's guidance we found from lots of consultants we have that really have cut their teeth in these FDA meetings. So that was, that was important. So you've got that tranche of well-established medicines, which means relatively low risk, well-known medicines to the FDA. On the other side is licensing xB3, our blood brain barrier delivery technology, which is a small 12 amino acid peptide. And you know, there's another company we did a deal with, it's not disclosed, the name of the company. So that's actually really an important agreement because in that case you've got your external kind of portfolio, so to speak, where you licensed the technology, is starting to be taken up and we actually do have a good number of terms you use to work through at this point. But in those cases, the two that I'm talking about here, is they're going to make advances with xB3 and then return the data to us, which we can then share with future investors. So the capital kind of constraints around the company on the interenal program are just specifically for the internal programs, all of the new exploratory experimental therapeutics that xB3 will be used with will be run by our partners. And so, it's a really productive relationship. The other things that are new to the company, considering it was founded in 2008, is we actually go into the FDA for brain cancer program in June, you know, it could be June or July, depending on the FDA turnaround times, which, have significantly improved in the last two years. So that's, that's a positive for sure. And then the next step after that would be actually the phase one start, which we anticipate to be probably the second quarter of 2020. And, that's really exciting because nobody's been able to deliver these types, like trastuzimab, across the blood brain barrier. So as I mentioned earlier, the only way you can really get medicine there, intrathecal doesn't work, you just don't get an exposure. The only other option is direct delivery, which involves drilling a hole in the head. So if we can show in a PET study, that xb3 delivers trastuzimab in a meaningful quantity to be able to actually impact the disease, it'll actually be the first demonstration of a noninvasive drug delivery system, taking a drug across the blood brain barrier and getting to it's target, hopefully having the desired therapeutic effect. Because, let's face it, it's a terrible, terrible disease and right now your options are, if you've got brain cancer, it's a really poor prognosis as anyone can imagine. So that's, that's a real shift for this company, is both on the business development side as well as actually advancing programs towards development
John Simboli:
19:59
Who is Bioasis?
Mark Day:
20:01
So it's personality, if you want to kind of describe it as a character is, it's a bit mischievous, right? It's disruptive, but it's enabling at the same time and, and it's got the potential to really change the probability of success in neuroscience and the, the whole aim of this, this goes back to an interview I did with you in 2017, right, and that is to make neuroscience a much higher probability success game. Cause right now if you look at the probability of success in neuroscience, and I've been on several companies where I'm responsible for BD, and the PTS is literally rounded up, b everything in Alzheimer's, it's like 0.06 probability of success rate, right? But that's not true. That's the whole market taken together. Now, you look at the base inhibitor that Merck ran, they did do a solid job on it. That that is the one failure where I can point to and go, that mechanism, in my mind, based on those data, that mechanism doesn't work in Alzheimer's. Right. The flip side of that is all the drugs that didn't have that kind of diligence around how the drug was selected, how the dose was chosen, what was the biomarker that actually was going to predict whether or not it could remove the disease. So Bioasis is there as a character to disrupt the other BBB companies, you need more than that percentage to get into the brain sensibly and compete. But at the same time, our mission is totally, solely, directed at the patients. The other kind of new news is, as you'll remember from the opening party, a celebration of the Bioasis U.S. headquarters, was Debra Rathjen came onboard as our chairman at that evening. Right. So that was, that was a big inflection point. Deb has been massively supportive of the management team. You know, she's got 18 years of experience at previous biotech. So Deborah is now Executive Chairman and she's absolutely been invaluable to me.
John Simboli:
22:13
How about on the level of platform versus drug development. Do, sometimes, people get it wrong? Do they think you're strictly a platform company versus you might want to do something with this platform?
Mark Day:
22:33
I think you have folks out there, actually a portion, who are only interested in platforms. When I was at BMS, Carl Decicco was also a great chap great to work with, he and another chap, Art Bertelsen, they just got it, right, a platform, could be enabling. In other places, depending on who you're talking to, the concept of platform may not be so important. It might be particular therapeutic. So even if you doing rare diseases if you're doing big diseases. And I think there are strategic considerations, but for us, most people react very positively to a disruptive enabling platform.
John Simboli:
23:16
We're sitting in your elegant brick space here in Guilford and this could be located any place. I can picture this being in Cambridge, I can picture this being a lot of different places, but it's here, it's here in Guilford. So, the obvious question is, how did you pick Guilford?
Mark Day:
23:35
You literally have an entire pharmaceutical workforce on your doorstep because, literally, everyone that works at BMS is within five square miles of this office. Right? So that's good. And so the other thing here is stability. It's a stable place to... it's a great place to live. It's great for families, the schools are great. So, you know, there's a lot of upside to being in Connecticut. Five minute walk from the office is the Metro North train station, which means you can get to Old Saybrook for the Boston train or you can actually get straight into New York. And so, you know, you put all those things together and it's a sensible place to be.
John Simboli:
24:22
In the tristate area, which people in organizations do you stay in touch with to help build the Biopharma community that you're part of here?
Mark Day:
24:30
I think the most proactive support we get locally is actually from BioCT. They've just been really good, you know, putting out press releases of ours and solicited through their network. So we do have a good network of folks just within BioCT. I think that stuff's really important, to have that. In terms of locally, as I mentioned, you know, we're all either ex BMS or Alexion at some point in this ecosystem. So, you know, I have lots of folks at disposal to run ideas by, to brainstorm and Deborah and I talk regularly. But you know, in terms of just getting out there and what might be going on that you don't know, Vlad Coric, CEO, at Biohaven, you know, worked with him at Bristol, he's a formidable individual, excellent professional, very entrepreneurial. Doug Manion, as I mentioned earlier, is a good mentor to me at Bristol, actually bumped into him at BioCEO, So I managed to catch up with him there, and you know, so each of these individuals has a whole different set of experiences and networks that at the right time, you can plug into and get additional guidance and feedback from. So that's been good. I've always had very strong relationship with MassBio in Boston.
John Simboli:
25:57
Mark, thanks for sitting down with me today and I appreciate your making time.
Mark Day:
26:01
It was a pleasure. Always, John. And, thank you very much.
John Simboli:
26:06
When Mark Day says,'We're humans too; the CEO is the face of the company, but we're also people," I picture the album covers from Factory Records that hang on the walls at Bioasis Technologies office in Guilford. Mark's connection to Factory Records in his native Manchester and his leadership at Bioasis seem to share a passion for new thinking. Check back each month for fresh CEO insights on BioBoss. And if you haven't heard my conversations with John Houston, CEO of Arvinas, Erika Smith, CEO of ReNetX Bio, and Jennifer Good, CEO of Trevi Therapeutics, check them out now. I'm John Simboli. You're listening to BioBoss.
