Prometheon Phama's website splash page stakes out a bold claim: "Eliminating needle injections. Improving global health."
The Florida-based pharmaceutical company is, at this point, a fledgling operation, launched and housed in University of Florida's Sid Martin Biotech Incubator since 2012. It has a four-person executive team and four-person Board of Managers. But CEO/CSO Dr. Stephen Hsu and his colleagues aren't letting their firm's small size stymie the breadth of their ambitions.
Prometheon is in the early developmental stages of a transdermal patch technology called Topicon. The company hopes this tech can one day be used as an ultra-convenient vessel for administering large molecule therapies ranging from consumer products like hair growth meds to even drugs like insulin, vaccines, and infectious disease drugs in developing nations. The insulin technology development, in particular, could hold major promise and presents obvious partnering potential with leading diabetes firms, some of which have experimented with alternate methods of administration, including Eli Lilly, Sanofi, or Novo Nordisk.
BioPharma Dive had an extended conversation with Prometheon's Director of Business Development, Devon Grimmé, about what sets the company and its technology apart from competitors, the firm's development timeline and launch hopes, and what issues still need to be addressed in order to ensure that the product succeeds. Note: This interview has been edited for clarity.
The fight for patient convenience and busting the 'Rule of 500'
BioPharma Dive: Who do you see as Prometheon's main competitors? What other patches and technologies out there are you competing against?
Devon Grimmé: The race right now is for patient convenience. Part of that is because patients will prefer more convenient tech. But it's also a function of the patent life cycle of a lot of these companies and their medications, because they need new newer products to keep their portfolios and their sales up. You look at the different pre-fill syringes and they last, 20 days, maybe 40 days. They have Marvel comic book characters on them, whatever—it's all about trying to get to the patient for convenience. You have all these [other alternatives to needle injection] that are starting to come out, you've got Afrezza, the inhaled insulin [from Sanofi and MannKind].
We compete with everybody and we could be a great partner for one of the pharma companies that wants to interact with us because, we win on the patient convenience side. There's nothing more simple and less invasive than a completely passive, multi-day transdermal patch. 3M is doing a lot with their micro-needle platform. But the cost to manufacture [those], and the inconsistencies of administration, there's potential for, what my boss kind of came up with a term for, he thinks in the next couple of years we're going to see a rash of "micro-needle infection incidences."
So really, we compete with anybody that's trying to get a patient to comply with their medication, and we win because we're the least invasive and most convenient.
BD: From a technical standpoint, what is it that makes this specific tech work that sets it apart from others? We talked about the convenience factor as a marketing tool for reaching patients and doctors. What, in the guts of this, makes it different from other transdermal patches?
Grimmé: The biggest thing is that it's completely passive and that it's for very large molecules—so far, up to [more than] 22,000 daltons [for human growth hormone]. That's the biggest we've tried, but we've never tried anything we couldn't get across the patch.
We were very surprised to learn that the definitive atomic structure of the skin was only published in 2012, and so we're working with that investigator to understand exactly what's happening when our formulation is applied. That investigator said that our formulation perfectly anticipated his structure. We formulated this in 2010, but the structure wasn't published until 2012. It's creating pores and/or loosening up the tight junctions between skin cells and allowing these large molecules to pass through.
Something that's completely unique about it is that all of our ingredients are either Generally Recognized As Safe (GRAS) or are FDA-approved for other indications. The chosen ingredients, by design, were picked to solve the problem of thermosensitivty (having everything solid at room temperature and locked into a stable matrix), and it just so happens that by choosing some of those qualities, these ingredients had secondary and tertiary properties of being very effective chemical penetration enhancers. They'd all been studied as enhancers individually, but never together. And the reason we tried them together was for the thermosensitivity aspect of it, thinking about sub-Saharan Africa and equatorial regions that aren't as cold.
BD: So the large molecule entities used with this tech seem impressive. What is the size of the entities that can be used right now in current patches?
Grimmé: The patches that are on the market, like the birth control patch, estrogen patch, nicotine patch, pain patch, those are all around 250 daltons or so. And back in 2000, there was an NIH paper written about the "Rule of 500," saying that no molecule greater than 500 daltons could get across skin because the skin was just too effective a barrier.
So, we have shattered the Rule of 500 so far by about 50 times—22,500 daltons—and we don't know the upper limit yet. And once we understand the mechanism of action a bit better, what Dr. Hsu hypothesizes is that it's a bell-shaped curve distribution in the skins. There's different holes of different sizes, so if we can understand that, then we could shift that curve to the right with more holes of greater sizes.
Marketing timelines and getting patients to a 'yes'
BD: You mentioned Afrezza earlier. It's been kind of difficult for these guys to get their prescription numbers up with that product, they haven't exactly been mind boggling. Do you anticipate having some of the same problems? Or do you think that those problems are simply a consequence of the inhaled option not catching on with patients?
Grimmé: I think it's more [the latter]. There's a couple of factors with all of this that are at play there. One is, because [Afrezza's] a rapid-acting mechanism, there's a lot of patient and patient-psychology factors at play.
One thing we discovered when we did our initial Indiegogo campaign, we really started to dialog with the diabetes online community. We were really surprised by how passionate they are, and we found that, essentially, Afrezza is going to be largely a type 1 product. And what we found with type 1s is that, by and large, if they have a regimen that works pretty well for them, they're very hesitant to change it.
I think that's a major factor in it. I think inhaling the insulin and dialing up the dose, in some ways - it's certainly less invasive, but I don't think it's that much more convenient than dialing up on a pump or counting out your vials and getting a dose that way. And I think it's a new learning curve which people are hesitant to do in any scenario, whether that's a consumer product or healthcare product.
BD: Let's talk a little bit about your guys' manufacturing and trial and development timeline. Where are you in that process with various product lines that you're testing? When do you hope to move in to later stage trials and the market?
Grimmé: From a manufacturing standpoint, all of our ingredients and processes are already available at industrial scale. There's already a well-established patch manufacturing industry that we can use as an outsource. In terms of development and testing, we're basically raising or awaiting funding right now to begin large animal studies, pig studies. And that data, which takes about 6 to 9 months to gather, will allow us to apply to the FDA for human trials. Because we're applying under a 505(b)(2) pathway (since insulin is already approved), we anticipate being on the market by 2019. That's what we're shooting for, which is relatively quick as pharma goes.
BD: And which product is furthest along?
Grimmé: Definitely the insulin. There's a caveat to that, which is that our hair growth product may be on the market this year. That, we're getting ready to start human clinical trials on, and should be on the market this year. Insulin is further along in development, we've tested it a little bit more, but hair growth may be a much shorter path to the market.
Dosing questions and global ambitions for public health
BD: What are the safety concerns you're concentrating on most with this technology? Are there safety issues that might arise?
Grimmé: Well, again, the ingredients that we're using are completely passive and are GRAS or FDA-approved for other indications. So the [main] thing that we really have to show in terms of a 505(b) pathway is that our formulation is non-toxic [to the skin]. And it was designed to not be, so our risk there is minimized. The next thing is that we have to show non-inferiority. We're not worried about that because of how effective it is in our initial studies.
Probably our greatest challenge—and still a small one, because of how efficient it is—is we just have to understand the dosing implications. For example, with the insulin in our initial studies, we were able to deliver the equivalent of 140 units in a week-long cycle—so 140 units a week—we were able to deliver that with the equivalent of just six units of insulin in the patch. So it's very, very efficient, so that's something that we'll have to understand, is the dosing
BD: Using this technology in really hot places—why is that a concern? What hopes do you have your products in emerging markets and developing nations down the line?
Grimmé: This whole company was started around improving global health. This is really, truly a social enterprise. And it's Dr. Hsu's absolute mission—he left an endowed chair position at almost 50 to start a company. He was really thinking about, how do we get better treatments to people in areas that the main challenge is refrigeration and access to healthcare? What kind of simple products can we give them?
This kind of designed serendipity of discovering that these huge molecules can get across while using a thermosensitive matrix—once we get the funding or partnering for someone to test vaccines, or anti-malarials, imagine a 7-day antimalarial patch or vaccine patch that's totally temperature stable, that doesn't require needles, doesn't have syringes that are having to be disposed of and ruining the environment, or endangering people from needle sticks or reuse. We have a pretty compelling possibility there once that starts taking shape.