Inotek’s Southwell & McVicar Have Designs on Treating Glaucoma

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Inotek CEO David Southwell and William K. McVicar PhD Executive Vice President, Chief Scientific Officer, share Inotek’s plan to bring to market a new first-line for glaucoma sufferers.

Podcast Guest

Transcript:

Tom Salemi: Hi, welcome back to the OIS Podcast. This is your host, Tom Salemi. Thank you for joining us for another tale of innovation. Today we’re working with Inotek Pharmaceuticals. You may have seen Inotek at OIS@AAO. David Southwell gave a great presentation there, an update on the company’s like of glaucoma. We sort of expanded on that conversation here today, visiting with the company, not only David Southwell, but very happy to be joined by Chief Scientific Officer, Bill McVicar. They gave a little bit of a history of the company, an update on Trabodenoson, their first line, front line treatment for glaucoma that’s currently in pivotal phase 3. Glaucoma obviously is an area that is desperately in need of new drug treatments, new eye treatments. We’re seeing some advances on the MIGS space that’s addressing sort of later stage glaucoma sufferers, but something on the early side certainly is necessary as well. So I hope you enjoy this very personal visit with David Southwell and Bill McVicar of Inotek Pharmaceuticals.

TS: Hi, welcome to the OIS Podcast, David Southwell and Bill McVicar of Inotek

David Southwell: Thank you very much. I’m President and CEO, and Bill McVicar here is our Chief Scientific Officer.

William McVicar: Hello, Tom.

TS: Great. Hello. Thank you for taking the time to talk about glaucoma. We’re excited to have had you at OIS. I know you’ve presented before. And glaucoma clearly is a huge disease that we talk about there, and it’s been a tricky one. No new drug has been approved for its treatment for close to 20 years. I’m sure as a drug company, you see that and see a huge opportunity. But is there also a red flag? I know we’ve talked about this in the past, but what are the unique challenges in glaucoma, and why do you feel we’re closer to overcoming them? David, maybe you can kick that one off.

DS: Yeah, this is David. I think the challenge with glaucoma is that the first line therapy is eye drops, and the existing eye drops that have been on the markets, and the last one, the last mechanism was approved in 1999, is that they’ve been relatively effective, but the all have a number of side effective that are associated with them. So the majority of them – well, 50% of the market is prostaglandin analogs. Those drugs have a number of side effects, including red eye and reduction in the adipose tissue, and darkening of the eyelids. And then the primary second line therapy is the beta blockers, which have the systemic side effects. And then the alpha agonists and the carbonic anhydrates inhibitors which have their own. So our approach was very much to develop a drug that targeted a natural mechanism with the objective of having both a good IOP lowering and working in the back of the eye without adding any side effects. One of the real issues in glaucoma, and I think what has really been a problem for developing drugs, is that the pathology of glaucoma is associated with the disruptive relay in the visual signal to the brain. So it’s the gradual destruction of the optic nerve. And the primary way that’s known to treat that is the reduction of intraocular pressure. But there’s a real need for a drug that works both by reducing IOP and by potentially protecting the nerves. And companies that have tried to develop neuroprotective drugs have not seen a great deal of success. So our product, Trabodenoson, works to lower IOP, and it also has some – it also appears to have some effect on the nerves on the back of the eye. And that’s a lot further out, but we’re doing work on that as well.

TS: Bill, can you get a bit into how Trabodenoson is able to do that, or at least why you believe it’s able to do that and why it’s being tested against glaucoma?

WM: Yes, absolutely. Yeah. I agree with David. We’ve had, I think, in the past suffered from a number of repurposed systemic drugs for the eye rather than purpose-built drugs to treat the problem, which is a tough problem in glaucoma. And I think we’re making some progress here because we’re getting a better understanding of the function of the trabecular meshwork. This obviously is the tissue that David referred to that is responsible for managing the appropriate pressure inside of a healthy eye. And out of that is some new targets, for example, TGF beta and in our case, adenosine. And adenosine, the natural or endogenous molecule is actually a cytoprotective molecule. So it’s built to protect the tissues in the body. And the challenge with making adenosine itself a drug has been that it exerts its biological action through a series of some receptors – four of them have been described – and so you get a wide range of biology, and it’s hard to focus or become selective and just achieve the biology that you want. The second issue with adenosine is that, you may remember from your high school science that ATP or adenosine triphosphate is how cells store energy. And so adenosine, the natural molecule put into the blood stream has a half-life of about ten seconds. So what we’ve been able to do is to take the biology of adenosine and deconstruct it, if you will. And when I say we, I mean with the help of some very good scientists that have published in the literature in the last 15 years, including Ted Acot and Craig Crosson and Mort Siven and Paul Kaufman. And what they’ve been able to show is that if you isolate the one A1 receptor that adenosine targets and avoid the others, therefore building a selective adenosine mimetic, what you can do is lower pressure in the eye. And moreover, from the work of Dr. Acot we’ve been able to see that what it does in fact is it stimulates a natural process that takes place in a healthy trabecular meshwork; that is, the production of proteases. And these proteases, specifically MMP2, clean out fluid outflow paths and then outflow can increase and IOP decreases. But importantly, you get the eye back to functioning the way it did when it was a little younger and healthier.

TS: How is the drug delivered, and when is it delivered? At what stage of the disease?

DS: So our drug is an eye drop. So it’s delivered much like the prostaglandins and the beta blockers as an eye drop. We’ve demonstrated in our phase 2 studies that we can give it once a day, which is important, because one of the forms of Trabodenoson that we plan to develop is a fixed dose combination with latanoprost. And latanoprost is a once a day drug. So if you’re going to coformulate it, it’s important to have another once a day drug. So ours is an eye drop. It’s a suspension. It will be administered either with a prostaglandin or, in the case of a fixed dose combination, in a combination with a PG. So this is for patients that typically that first present with glaucoma. There are patients that are too severe really for any eye drops. They have very severe disease, and those are the ones that tend to wind up on a device of some sort, whether it’s a shunt or a trabeculectomy or a laser treatment. But what we’re targeting is really first line therapy.

TS: I was curious about that. We do talk so much about MIGS at OIS and on this Podcast. There’s a lot of exciting transactions and some clinical success there. But you don’t see that as a competitor; this is more or less a complimentary technology or treatment?

DS: Well, I think it’s a progressive. The treatment of glaucoma is progressive. So when you present with glaucoma, you’re first put on an eye drop, which doesn’t require any invasive surgery at all. You just take the eye drop. And typically the first drug that’s given now is latanoprost. We’re going to offer another option for those patients either to be given as first line or second line therapy. The shunts, the trabeculectomies, those won’t typically be – they’re surgical alternatives that are expensive as well as being surgical. So typically those are second and third line therapies. So those would be on people who, for whatever reason, find that their IOP is not adequately controlled with any eye drop.

TS: Does the success of MIGS, though, does it influence or shape or reshape the market for therapeutics in glaucoma?

DS: Well, what it does is it raises – what we like about MIGS is that they raise the profile of glaucoma treatments. And so from that perspective, they’re a good thing. But we will not be competing against that market. We will compete against other eye drops.

WM: I think when we think about the MIGS as an alternative, it seems more likely positioned to cannibalize some of the other surgeries like the ALTs and SLTs, the laser trabeculectomies. And remember that these devices are typically, at least for now, only installed in a patient that’s already undergoing a cataract operation that also is at risk of glaucoma or has developed high intraocular pressure. So that somewhat limits the patient population for now, and I think if the data that I’ve seen is correct, that concern is about the duration of the effect of those treatments. So David is correct in that they are classically, at least at this point, still reserved for those patients that have failed multiple glaucoma drugs. So sort of competing in a different part of the population, the end stage patient.

TS: We’ll take a quick break right here to remind you that if you missed Inotek’s presentation at OIS, perhaps you were networking in the hallway, you’ll be able to see every presentation that we’ve had at OIS, as well as our panel discussions and our presentations at OIS.net. So go to OIS.net for a complete inventory of presentations and discussions coming from OIS@AAO. Now back to this conversation.

TS: And while we’re talking about successful clinical trials, Inotek had some great news of late regarding your Matrix 1 trial. Bill, can you fill us in on that?

WM: Absolutely. We were able to report this summer that we reached agreement with the FDA at our end of phase 2 meeting on the final design and endpoints of that study, and then have recently announced its initiation. So patients are enrolling now. And you may recall that that study is going to have several different of Trabodenoson which will allow us to sort of further fine tune and optimize its profile. And those doses will be compared statistically and clinically to placebo, and the trial will have in addition to placebo, a timolol control more or less to validate the sensitivity of the patient population. Other than that, it will be a fairly standard phase 3 program, 12 weeks of continuous treatment. The patients that will enroll in that will have glaucoma or ocular hypertension. This is the exact same patient population we used in our successful phase 2 trial, giving us a better degree of confidence about the predictability of the results moving forward.

TS: Looking at the trial design, I see you’re measuring the patients at 8 a.m., 10 a.m., noon, 4 p.m. on days 14, 28, 42 and 84. How is that done? I’m just curious as to the trial design. Do patients spend the entire day there? Is there a device that they bring home with them to do those measurements? Has testing IOP become easier and therefore made these sort of clinical trials easier to conduct?

WM: Sadly, testing IOP has not gotten that much better. So in fact what we use is the gold standards, which is Goldman applanometry. And so that has to be done in the clinic, so unfortunately, those folks will have to spend the day to get their serial IOP measurements. And we use a very rigorous protocol in which the applanometer is adjusted by one person and, if you will, read by a second masked person that therefore doesn’t enter any bias into the reading of the pressure of the eye. And we measure it of course several times at each of those time points.

TS: Fascinating. Looking at the business side of things, let’s talk about your financing. How much had you raised privately? And you were successful in going public recently. What made you decide to give that a go and to find your way onto the public markets?

DS: Well, this is David, Inotek is about 12 years old, and it was working on some very different businesses for a lot of those 12 years. And so we moved into ophthalmology several years ago with a goal to develop what became Trabodenoson. And the markets were pretty good late last year, and we wanted to go public really to fund our phase 3 program. Most companies go public as they’re heading into phase 3 to raise the money to do that. So we did an IPO in February, and we actually did the first ever equity and convertible IPO. And we raised about $65 million in that deal, which funded us through our first phase 3 trial. And then in July, we announced our phase 3 program and how we were doing it, and the market received that very well. Our stock actually tripled in one day. And we ended up doing a secondary which raised about $75 million in equity. So at this point we’re certainly well-funded to conduct our clinical trials in the monotherapy.

TS: And how is life as a public company? Having your stock price triple in one day certainly accounts for a good day, but what are the challenges you’re managing now that you didn’t have to manage as a private company? Of course dealing with investors would be the primary one. But does it affect your dealings with clinicians, patients, employees? How is managing the entire company different?

DS: Well, it’s interesting. When you have a public company, your stock trades every day, so people can see how you’re doing. You know that you have access to capital, so in many ways it’s much easier for an employee to be working for a public company because they know that you have access to capital. From a clinician perspective, they also know that we can fund our phase 3 clinical trials, which is very important. They don’t want to start a trial with a company that may not be able to fund it. The challenge is, and I’ve spent most of my life in public companies, that the challenge is of course in dealing with investors, and that’s why we hired Claudine Prowse, who runs our investor relations effort. And she came to us through Biogen. So and Claudine and I worked together back at Human Genome Sciences. One of the keys with Inotek on the inside of it is that many of us have worked together before. So our Chief Scientific Officer, Bill, and our Chief Medical Officer have worked together for well over 20 years. And I worked with them at Sepracor, which was two companies ago in my iteration. So we knew each other very well when we started working together. And Claudine and I worked together at Human Genome Sciences. So we’re a company that has worked together for a long time, and that really makes a difference because you can hit the ground running, and we know how another person is going to react to what we do. And it makes things much easier.

TS: That’s fantastic. And I worked for the Boston Business Journal for a time, and I covered all of those companies, so it’s great to hear those names again. It’s like a walk down memory lane. Well, we’re very –

DS: Well, it’s interesting. I mean you go up and down, and the process of working together during the ups and downs of biotech swings either brings you closer together or makes you determined not to work together ever again. Obviously, we were the former.

TS: Well, that’s good news for everyone at Inotek. And we’re very happy to have you as part of OIS, and I thank you very much for taking time for this Podcast today.

DS: All right, thanks so much.

TS: Thanks, David Southwell and Bill McVicar for joining us on the OIS Podcast. Happy to hear the progress Inotek is making. Glaucoma clearly needs new first line therapies, so we’ll continue to follow your story at future OIS’s, and of course you’re always welcome back here on the OIS Podcast. Speaking of the OIS Podcast, this is the last Podcast of 2015. I really have enjoyed this format, this way, this forum of bringing you the tales of innovation in ophthalmology. I’ve talked to some really impressive and astounding entrepreneurs, investors and executives in this space. It’s been a wild ride and one I can’t wait to continue in 2016. If you want to join us here on the program, email me at tom@healthegy.com . That’s tom@healthegy.com . Tell us a bit about yourselves, and we’d love to have you on the Podcast so you can share the story with our listeners. We hope you have a wonderful holiday season and a happy new year, and we’ll see you in 2016. Thanks very much for listening.