Building Value for Pipeline Assets with Mina Sooch

PODCAST EPISODE 275

Click here to watch the video version of this podcast.


Serial entrepreneur Mina Sooch, president and CEO at Ocuphire Pharma, talks with host Firas Rahhal, MD, about her experiences of “starting things, building things, and hopefully creating exits.”

She says, “An important quality in innovating is the desire to take an asset that’s under-appreciated, add value and showcase that, and bring that to patients.”

Because she’s held different roles over her career, Sooch is able to consider different points of view about what’s needed to build a company at each stage (i.e., gaining capital and finding the right talent). Lessons learned include bringing in the right KOLs, with appropriate experience to leverage; diversifying assets (two are better than one); and why the later the stage, the better.

Sooch also describes Ocuphire Pharma’s pipeline assets, including Nyxol, an ophthalmic drop that restricts the pupil, being targeted for three separate indications – reversal of mydriasis, presbyopia, and night vision disturbances; APX3330, an oral tablet targeting treatment of diabetic retinopathy and diabetic macular edema; and APX2009, an investigative agent for age-related macular degeneration.

Click “play” to hear Mina’s great insights!

Transcript:

Firas Rahhal: Welcome back, everyone to the OIS Retina Podcast. This is, again Firas Rahhal of Retina Vitreous Associates Medical Group in Los Angeles and of ExSight Ventures in New York City. And I have with me today as my guest, Mina Sooch, who is the current president and CEO of Ocuphire, I believe you’re the co-founder also, we’ll talk about that shortly. And before we ask you any questions, I want to just give a little background on you. And then I’d like to ask you a little bit about the background as well, if you don’t mind me.

Mina Sooch: Sure.

Firas Rahhal: Thank you. So you were previously Co-Founder and CEO of Gemphire, which is a public clinical Stage Company in the cardiovascular space. And that had had a successful IPO in 2016. And prior to that, you got a long record here, my dear CEO, Co-Founder of I’ll pronounce it ProNAi, is that correct?

Mina Sooch: That’s correct.

Firas Rahhal: Which is also a public clinical Stage Company in the oncology space. And I do see a lot of overlap between oncology and ophthalmology, as you know, and you were on the board there from its founding in 2004 till 2014. And then I’m very interested in this last piece, your managing partner, and we’re Co-founder of Apjohn Ventures, a VC firm that invests in early stage life science companies, which began in 2003. Does that still exist? And are you still participating in that?

Mina Sooch: It still exists, we’re in harvest mode. And so yes, I’m still managing out the some proceeds coming in from one of our partnerships on one of our portfolio company.

Firas Rahhal: The list was much longer than that, I honed it down to a few things, you’ve obviously had an unbelievably productive career in this space, and have been very busy and successful. How have all these very positions kind of led to your current position now with the occupier? And what are the similarities or differences between some of those previous posts in your current post?

Mina Sooch: Sure. So one is, I think, at heart, I’m a serial entrepreneur. So I’m a chemical engineer, as an undergrad at Harvard MBA and have been a strategy consultant, a venture capitalist, and an operating CEO and board member, of course, over the last 25 years in the pharma biotech world, so but the one thing that’s sort of common is starting things, building things, and hopefully creating exits, you know, where we can. So I really like, in particular, those last couple companies that you listed, you know, I think some of the themes are that there are a lot of I live here in Michigan, by the way, and for 20 years now, my kids have grown up and are in college and about to graduate in one case, but the point is that, you know, being able to find those under appreciated assets, those biotech drugs that have promised, but maybe ran out of steam, whether it’s financing steam, or talent, you know, to continue to advance it further into the clinic, depending on what stage it was. That is something that I think is the common thread between whether it’s prone I jump buyer, or occupier. And so all of those ideas all came out of the Midwest, whether it was a company like Pfizer, and their work here locally, or whether it was academic, or LASIK surgeon like Dr. Gerry Horn, in the case of Nick Sol, or Dr. Mark Kelly, in the case of APX 3330, so we really have that similarity that cuts across, but I think the balance, the glue, is just the ability to sort of want to take something that’s under appreciated, and add that value, and hopefully showcase that and bring it to patients. Of course, ultimately, in terms of the work that we do at the companies, I would also say maybe the other Yes, kind of what I’ve learned from those experiences, I think being a VC versus being an operator versus being an advisor consultant really allows me to sit 360 around a table. So I’m really I hope, being able to think about everyone’s point of view. And really thinking about what we need to do as we build the company at every stage, whether it’s gaining capital, whether it’s finding the right talent and the network that we’ve built out, really looking for advice, I have to say in every case, we’ve built out KOLs Firas. And so every time right away, bring the experts that I’ve had for 30 years in the industry space so that we can leverage that knowledge in history, which you can’t replicate. So we were fortunate very early on, for example, at Ocuphire to bring in, you know, Dr. Eliot Lazar, and Dr. Jay Pepose, Dr. David Boyer, your partner and others, you know, to really complement our skills and knowledge so that we could advance the programs in the right way, very quickly. So I would say those are some points but you also ask for differences. So what you learn, right, every startup, every company that you found, and then work through, there was ups and downs. And so I think three lessons learned that I would highlight one is two assets are a good thing to have, which is why we went searching for the second asset. And we really wanted to be diversified for ophthalmology and not just to front of the eye although we did look at other front of the eye assets. We looked at for 30 assets in 2019. And but having a back in the front really allows us to have conversations with many partners and many investors. So it’s really nice to have both but two assets as a portfolio. So you’ve got more than a binary sort of shot on goal. The second is the later and later the stage, the better, I’m getting older. So the only lesson learned is I have started stuff on a napkin as a VC with an idea and filed the patent with the inventor to now having 11 studies or 10 studies or 5 studies already in place, and really starting late Phase 2 and then interface 3 programs, which we are now so the later the stage, the less the risk, the more closer you are to the market, to the FDA process. regulatory approval process, I think, is the nice sort of change that we have here at Ocuphire. And the third, I have to say about the optometry or ocular sector. This is my first I’ve done cardiovascular and cancer and other diseases as a VC, this community is one it’s tight knit, you were just saying that earlier that you know, everyone knows everyone. So you’re one call away from the KOL, who can then get you in front of a site or in front of them ever, including the FDA. But the FDA is consistent, you know, Dr. Wylie Chambers has been consistent with everyone over his 30 years, which is really nice and sort of good number of approvals. On the drug side, you don’t see that there’s inconsistency, there’s a change in where the bar is. And that makes it really hard to be a company drug developer and trying to move things through if the if the bar is changing, and the other is just all the trials during COVID. On top of it, it’s just been unbelievable to see the productivity of the community of the sites, the investigators, the patients, and also fairly capital efficient relative to again, other disease areas, and trying to build value by adding clinical data as you march towards the FDA. So that’s a unique component is this disease area and working in the front. And then now in the back of the eye as well just really enjoy the community that I’ve been a part of for three years now.

Firas Rahhal: There’s so much in all that. And I agree with everything you said, and I haven’t sat at all of those chairs around the table that you mentioned, but in a couple of them as an early stage VC and as a Retina Ophthalmologist, myself who’s involved in a lot of trials. So I’ve been in a couple of those chairs. I couldn’t agree more, your broad experience and diverse experience really does give you the perspective of I think everyone if not almost everyone at that table, that’s a distinct advantage in your current spot as a CEO, do you find that to be part of the challenge is getting everyone on the same page when you’re trying to put the pieces together in the early stages?

Mina Sooch: Um, I think that’s a great question. I would say that with Ocuphire we’ve been very fortunate to have our board, our corporate board as we built it and added I think our latest addition was Susan Benton, which many of you know in the industry, when we went public in November, great add to give us that commercial kind of late stage development, long longevity perspective than the ocular space, really, to be honest. And then since I get to build every team, we sort of bring in folks that make sense that are focused on our goals and Ocuphire. Since we started, we had Nyxol we said we want to get in the clinic. When we got APX in, we want to get it into the clinic. I mean, that’s next day. But over the course of figuring out the right indication, the right protocol, make drug, get everything set up, broaden the patent states and every case before we start something, and then execute. And I think as long as right now we have four trials that were the focus since we’ve been public in November. And that is the focus. So what’s nice is we can use that to sort of create a commonality around everyone’s you know, past histories and what they need to contribute to the company. So again, four trials deliver on those four trials. And hopefully the data comes with that execution success as well.

Firas Rahhal: Thank you, you also mentioned something that caught my ear as a commonality of some of those posts, which is you know, I’m a starter maybe I’m paraphrasing, and you clearly are and early stage, biotech. I know the ophthalmology space and not the others, but there’s obviously similarities. I sometimes think those of us who are in it, and the VC I’m associated with is in early stage, it’s somewhat masochistic. And one time Emmett Cunningham said to me at a meeting and he’s helped me a lot in this space, said, Oh, you guys that ExSight you know, this is high risk area where you live. And so and then now you’re seeing some of the later stage stuff as you brought companies to IPO and, and late stage clinical trials and commercialization. It’s all fun, but the early part is really challenging. Which part do you like the most is there, what are you what do you see if you’re going more, you said something about age, which I got then just

Mina Sooch: I get to color mine. So we’re all good,

Firas Rahhal: Is that more fun for you now, because you feel like the timelines are better or what do you think?

Mina Sooch: Yeah, no, I think, again, as an early stage VC, and we started, you know, preclinical stage three out of I think nine companies or four were all preclinical. I think it’s harder now for me to look at just animal data, and say, I believe in the mechanism and the data, whereas having human safety, and then some human efficacy data, and mechanistic data, really goes a long way to reducing the risk. So I would say that my comfort and joy in doing clinical work, and having all three of these last companies be at the clinical stage, is it’s very rewarding, because we’re actually seeing the impact republishing on it, we’re getting discussions with the FDA, we’re having interface to meetings. And we’re working towards an NDA, which is really fun, actually, right to think now, for one of our indications, we’ll talk about that, that we’re going to march down a path towards an NDA. And that’s what we do drug development for is to bring drugs to patients. So I’m going to say that my early stage years are gone. And I like you can come over to the dark side later, Firas.

Firas Rahhal: And then, at the end of all that, it’s also now for you less masochistic, so congratulations.

Mina Sooch: Pretty much! Probably the main thing.

Firas Rahhal: Let’s, let’s talk a little bit a lot about Ocuphire. That’s what we’re here to talk about also of course. And the first indication I want to talk about even though this is OIS Retina, I want to hear about the first indication is it pronounced Nyxol,

Mina Sooch: Yup.

Firas Rahhal: Nyxol, an ophthalmic drop, it seems to me that this is based in phentolamine, a drug that’s well known to ophthalmology 0.75%. And it constricts the pupil. And there’s a number of different programs that you have, I want to I want to hear your thoughts on the different programs. But in particular, in this area for the retina community, we’re kind of interested in fascinated by the idea that we might again have reversal drops for the 1000s of patients we make suffer with dilation every year. So tell us about Nyxol what the programs are, and then maybe more elaborately or detailed about these, the dyadic reversal part of it.

Mina Sooch: Yeah, perfect. Thank you. So first, Phentolamine Mesylate? Yep, an existing drug approved over 60 years ago for reversing, lowering blood pressure in a surgical setting. And then about 10 years ago to reverse anesthesia. Those were both injectable formats. And we are the first ever proprietary drop formulation, which is also preservative free, no EDTA and stable. And I say all those things, because those are good underlying characteristics tip for a commercial product. And we’ve also got over eight clinical studies done now on it, of which one of them is our latest Phase 3 in reversal of mydriasis, which we’ll talk about in a second, which was the Phase 3 registration trial that we just read out on March 15. And but the other two programs real quick before I come back to Rm is we have a phase two and presbyopia which we initiated in mid February. And we know 2021 is the year of presbyopia, I think is probably the best way to characterize the anterior segment focus in that area. And so we’re proud to have sort of built it into our plan two years ago and really be in the middle of you know, Allergan filing their NDA and that space, and others finishing are starting Phase 3s and are starting a Phase 2, that we’ve guided that we’d read out at the end of this quarter, the second quarter, and we just started it in mid February. So it’s really nice to see the availability and productivity of the patients and the sites. What I want to say about presbyopia, and what’s unique about Nyxol the one minute point I would make to the audience is unlike the other approaches that yes use either pilocarpine or a cholinergic agonist that works on the sphincter muscle to constrict it pretty severely to get to below two millimeters which what you need with the pinhole, we actually use Nyxol to get you one millimeter because it’s a works on the iris dilator muscle and reduces it moderately, and then we use low dose pilot point 4% to get the other one millimeter or more that we need. So you’re sort of getting to moderate meiotic mechanisms using both muscles to then achieved the pinhole and I think that’s what makes us unique. So we think the safety tolerability, durability, distance vision being maintained all have no headache, no brooch. Things like that will be very positive, we hope to continue to showcase in our phase two study. So that’s the point of differentiation, but there is room for many presbyopic options as a drop, since it’s the first time that community will have such an option. And I think 100 million subjects out there just in the US. So I think it is the Star of the Year, I think and we look forward to doing more data readouts in the field, including ours and just being a part of that field and then continue to progress the program and to Phase 3 if we have successful phase two data, this.

Firas Rahhal: Just for clarity for the presbyopia indication. It’s going to be the Nyxol plus pilocarpine in some percentage and some dosing frequency.

Mina Sooch: Yeah, 0.4% is the dose that we selected, actually, that’s on Clintrials.gov. And it’ll be a kit sort of commercial option, which we tested the concept in our end to phase two meeting. And we do need to show that the components contribute to the total package. And I’ve just showed you why Nyxol alone, again, Iris dilator, has a certain sort of rethink elasticity. So we think that moderate meiotic is sort of the extent to which you can use that to reduce the pupil size, which is nice because you never overshoot. And you do not create too small of a pupil, which is a really important safety issue to consider with meiotic drugs. And with the low dose pile of that 0.4%, we think is just that right dose below where you’re going to see the side effects, but just enough to get not 2 1/2 – 3 millimeters of reduction, but that one millimeter of reduction, and alone, each cannot get you three lines of improvement, because each alone do not contribute to the pinhole that you can’t get to the pinhole with just one you need. One plus one equals the pinhole. And that’s how we can get the 3 lines of improvement on the primary endpoint and show the contributions of the components in our phase three. So for right now, our phase two is the two together compared to placebo. And we’re studying the components of secondary endpoints.

Firas Rahhal: How will that putatively How will the patient use this? Will they use it on a regular basis as needed basis planning? To be doing a lot of reading in a few hours? I’m going to put my medicine and I will it be used?

Mina Sooch: Yeah, I think the industry probably hasn’t figured that out yet for us. So I don’t know that I can have the answer. But I would say the following that for Nyxol at least what I didn’t mention about the product profile earlier. Besides it’s got a very nice safety profile in these eight trials that are completed and it’s partly due to be active until I mean, it’s just a really nice alpha one antagonist, Alpha 1 – Alpha 2 antagonist is that it’s durable. So unlike other eyedrops, there are some that are also 24 hour durability, but not any of the colon nergic agonist. So we have the uniqueness again, to bring one component that will maintain one line of vision improvement, near 24 hours, maybe even one line of distance, as well, for 24 hours. So you take it at night, every night before you go to bed, which is going to be similar to the night vision disturbance indication. And then in the morning, or whenever you want to start reading about 30 minutes before, take take a drop of the low dose pile. And if you need another one, if it wears off that for six, eight hours, we don’t know till we run the study, then you take a second drop. And I think that’s how all the drops will work. There’s not a single drop out there that’s claiming more than eight hours for us. So if you want more than, you know, six or eight hours, you’re gonna need to take a second drop, but you’re my reading glasses and I don’t mind getting up once or twice during the day to use a drop instead of putting having my glasses on all day. So. So I think that’s how some will think and others will just use it PRN you know, if you just decide every once in a while you want to you can take our two drugs, you know, five minutes apart. That’s not a problem either. It’s just again, we think there’s a goodness to a routine. And just having that slightly smaller people actually enhances your everyday vision. So we think that’s a good thing. And patients might actually like taking exalt, but that’s for presbyopia, which then has parallels to I got sidetracked. So RM presbyopia night vision disturbance. So we’re the only ones working in the clinic, where it’s presbyopia there are multiple players, which we think validates the sector. For night vision, we are kind of pioneering it and the prior sponsor that we brought the asset in from was doing the same. So we’re running a phase three at over 15 sites here in the United States. It’s actively recruiting. And we’re looking to take care of patients that have sort of moderate to severe night vision disturbance, the halos, the glare of the starker’s, either caused surgically by the LASIK surgeons, or maybe by IoL implants or aging, dry as well that’s imperfections on the edges. And if you can get that people again, moderately, from seven down to six, or six down to five, which is where the higher order aberrations are, then you can dial out in your frame, that the light scatter that’s coming in and really improve that night vision. In some of our market research, we learned that 25% of people avoid driving and over 100 patients that we surveyed with night vision disturbance, so it is a real quality of life concern. In our discussions with the FDA, we agreed on the endpoint, we’re running our Phase 3 with that endpoint. And we have some proof of concept data from our Phase 2. And we’re excited again to see how that reads out which will be around the end of the third quarter of this calendar year. So that’s our other program and I’m going to come back to Rm so I’m at which is to

Firas Rahhal: the retina guys.

Mina Sooch: Yeah. And so we were we were focused right now on RM to go after the routine eye exam just in terms of the study design is healthy subjects. And we just completed 185 subjects Phase 3 registration trial, it was one day in length, and we tried 3 on mydriatic agents we had then on that friend or phenylephrine tropicamide, and a combo pyramid. So we again on the end, we had light eyes and dark eyes. And we tried we had two drops in the study eye right eye and we had one drop in the non steady eye and our results were very positive and exceeded our expectation. To summarize, we found that we more rapidly reversed the primary endpoint was to return percent of responders back to their normal baseline pupil diameter, within point two millimeters. And we had about 50% compared to 7%, at 90 minutes, which was the kind of agreed upon endpoint with the FDA. But it turns out, we also hit it at 16 minutes. And then we hit that separation and statistics, P values less than 0001 across the entire time elements up to six hours, we had that same effects in light eyes and dark eyes, all the light eyes responded faster, as expected, and we had the effects across three agents, again, phenylephrine responded faster. But we had nice effects and separation between tropicamide and pyramid. So this is and then two drops in one drop didn’t have as much difference as we thought. But where it did have a difference. If your darker eyes are using your pika might or have a trick might in the combo, you may want to use two drops, because it really helped the reversal a bit more than the one drop, but we had activity with in statistics with both. So we’re really happy with the results. And it sets the stage to do a second Phase 3, do a Pete study because it’s actually the active ingredient phentolamine has been approved for three years and up in the dental as the anesthesia application that I may forgotten to mention earlier and also just get our manufacturing program ready for submission in terms of making commercial batches with one year stability. So it’s a pretty clear path. And so the work that we’re doing for we’ll call it the routine eye exams in the optometrist office or the ophthalmologist office can come to the retina. So I didn’t forget that this group wants to talk about post surgical, you know, mydriasis recovery, and we definitely and believe 100% that that should be used in the specialty settings as well. And we would love to be able to offer something like Rev-Eyes, but a much better version of it that was available long ago, to patients today, in a very simple single use, you know, vial that the physicians can give as soon as the surgery and the procedure is over. So there’s no reason it’s only for routine, it’s definitely for both just our study design is around healthy subjects. going in for a dilation.

Firas Rahhal: I’m glad you mentioned the name because I was struggling to remember the name of the Rev-Eyes and ask you about it had the impression and for no other reason than intuition. So please correct me if I’m wrong. I’ve had the impression that that went away based on a business model rather than maybe efficacy or, need and people’s desire to have this because, as we mentioned earlier, the patients ask for it all the time after our retina exams, of course, they’re all dilated, so they go home and they’re frustrated and driving home is difficult, etc. And then it just sort of disappeared. Although there’s one practitioner in town here in LA, that my patients always say, hey, can’t you give me the reversal? Like, you know, the referring doctor? And I have there isn’t any. But I guess they’re using Pilo in some institutions, maybe as a replacement. We don’t do that. What happened to the previous and what was the problem with the business model? if any? And if that is the right reason, if I’m guessing, what are you going to do differently? If anything?

Mina Sooch: Yeah, we get that a lot, obviously, because Rev-Eyes are a direct result was also an alpha one antagonist in terms of the class. So it’s in the same class, which is actually what gave us the idea to go after it two years ago, in addition to night vision and presbyopia that there was a precedent already laid forward, it was not taken off the market for efficacy reasons or technically not safety, however, from the FDA has benefit risk analysis. But I think from a patient perspective, and physician perspective, the safety profile was not very attractive, there were beet red eyes you needed for drops, there was burning and stinging associated as well, and ptosis and a few other side effects. So it was a fairly long list in order to save those hours, over the course of you know, three, six or eight hours of, you know, faster dilation return. So, in our minds, what we’re offering is a very tolerable or we have no burning or stinging in our data to date, very mild redness that when we do get redness, and no ptosis and no other brauerei getting because again, we’re working just on the iris deserter muscle, we’re using their one drop or two drop, not four drops. And so that whole safety tolerability side we think is improved. Having said that Firas, you’re not the first doctor to tell us people come in and ask for it. So we think that’s positive. So even with those side effects, people were still wanting a reversal drop. That’s the message I think we want the community to kind of hear. And so on the business model side what was wrong back then it was 19 you know, the 90s for the most part, and they were only charging the doctor to have a multi-use bottle and it would only last for three weeks. That’s what the label said. So and yet to mix it, you know, as the doctor and I don’t know, any drug you use today that you mix at the chair, or at the bedside, outside of an ICU setting, or in the hospital setting. So it’s not a practical model, it’s not something that the doctors and offices want to handle. So we’re going to have preservative free blow fill, seal, single use vials, use it on the patient, throw it away. And you know, our business model is either the doctors can just buy it from us at a reasonable, you know, price per unit, or we actually think we did market research on this, that patients are going to be willing to pay $5to $20. And that’s the price range that we surveyed. And there really wasn’t any sensitivity in that range. So you kick the number, and we’ll do more homework. Now that we’re thinking commercial, pre commercial. So you know, we think that the business model now is private cash pay maybe $10, I’ll just take the middle number for a moment. And the doctors can either charge the patient or they can absorb it, it is up to the doctors, because they make it more patients in the routine setting to dilate their eyes, to be honest, because there are many patients, your patients can’t say no Firas, but but their routine eye exam patient can and we found some market research to to get the makeup to increase that by 30%. So again, you know, we’re here to help everyone who’s dilating the eyes, the physicians and the patients get back to their normal, faster and not dread getting dilated. Right. That’s the other part of it. So I think there’s the business model is different in a couple meaningful ways. But the product, commercial product is also different in various ways. We think our efficacy is probably similar with less drops, and we’ve looked at some comparative data. So you know, we feel the benefit risk is looks promising. And we’ll do the second registration trial. And this will be available, you know, hopefully for a label to reverse it using phenylephrine tropicamide, or a combo thereof, you know, to reverse pharma logically and use my dresses. So that’s what we’re going for.

Firas Rahhal: I think there’s no question to put a cap that the demand is there, we hear it all the time in our clinics. And I think the business model works, I think the majority of patients who asked for now, which seemed to be a lot would likely be the ones to feel that 10 bucks or some you know, small fee is well worth it because they’re shortening their time out of work and their time out of being able to be functional. It’s a it sounds like a winner. That makes sense to me.

Mina Sooch: Yeah. And you mentioned Pilo, just real quick before we get to the retina which of course we need to get to. Although this is obviously applicable to be the retinal and Dr. Eliot Lazar, we really happy that you brought up postmitotic recovery because we’ve been talking about that is that is a nice place to start to really be begin to emphasize this product profile. Pilo has issues I’m a little concerned with the docs who might be using Pilo off label because working on the sphincter muscle to constrict it back. In order to get back to your your normal pupil size has a lot of side effects that are well known whether it on the extreme retinal tear in the middle other issues related to using the ciliary muscle as well, which is, you know, gets affected whenever you use pilot you affect the sphincter muscle and the ciliary muscle. And there’s just a whole series of well documented side effects in using pilocarpine. As a reversal agent. It’s been studied in the 90s. But there’s really been a few very few papers in the last two decades that focus on Pilo, to reverse mydriasis. And I think this the consensus for most was it’s not the safest muscle to use to reverse the dilation and the iris dilator muscle is a sort of a good muscle to use. And so we’re excited again, that we’re the only ones with an alpha one blocker in clinic in development, patent coverage. So we look forward to hopefully being a single solution if we continue down the path towards the NDA. So

Firas Rahhal: I agree 100% for it for whatever it’s worth, I don’t think pilocarpine we use for reversal madrasas makes any sense. And we have it in our office, and we don’t do that. And I think it’s pretty few and far between, but I have heard of it. And I’m glad you brought it up. And we talked about it, because that doesn’t make sense that way too large a side effect profile for such an indication.

Mina Sooch: Right, right. I think it also might cause narrow angle closure. There’s not many I sort of only listed one or two but there’s a series of side effects. Okay, so let’s move to the retina.

Firas Rahhal: Let us move to diabetic I know my retina viewers are gonna, you know, fascinated by the diabetic retinopathy. I am actually whenever you start talking about oral medication, that’s there’s a newness to that. It’s been it’s been talked about many times before. There’s obviously pros and cons to everything but let’s start with the beginning. It’s the product is called APX 3330. If I’m not mistaken, it is an oral tablet, and it would be treating diabetic retinopathy and diabetic macular edema, which are somewhat separate entities but you get the idea. Tell us the mechanism. Some of this drug and I read that it’s a dual action compound, maybe you can tell us a little bit about the compound itself.

Mina Sooch: Yeah, so it is a small molecule first, first of all, and it therefore is very easy, obviously to make world. And it hits a novel target called ref one that Dr. Mark Kelly discovered over two decades ago, which is redox oxidation factor. And essentially, it’s a transcription factor regulator, and it regulates to downstream and important into the two different pathways both F1-a down the VEGF pathway, and NF-kB, down the TNF-a and the aisle six and the other side, you know, other cytokine inflammatory markers. And what it does is it basically doesn’t allow those transcription factors to then activate and create their downstream products. So it inhibits Ref-1, which is otherwise an activator of those two downstream pathways. And so we basically have an anti-VEGF mechanism and an anti-inflammatory mechanism to bring it back to how the retinal you know, community sees the two options of steroids that are injected, or obviously, you know, EyeLea, Lucentis Avastin and other anti-VEGF in development that are used on the anti-VEGF pathway, so we’re upstream and we add inflammation in a safe way, as opposed to potentially having to use steroids that then cause some of the IoP and, and glaucoma and other issues for patients. So we’re really excited to have oral as our novel or innovation and the dual pathways.

Firas Rahhal: If you can’t talk about it, and I assume you can, because this small molecule, is there a history on this what is the history of this campaign? If you’re able to share with us I know there was some previous safety data from perhaps another indication? Can you share any of that previous history with us of this drug?

Mina Sooch: Yeah, I mean, as a public company, there’s a lot more data in our SEC filings as well. And our website, lot of publications, the history is that APC 3330 was originally E 3330. being developed in with over 10 trials and a lot of preclinical work as well by a site in Japan. So large pharma in Japan was interested in the anti inflammatory properties, and indication so they’re going after hepatitis A, B, C, and D, an alcoholic steatosis. So various Phase 1 and Phase 2, again, collectively 10 trials, they actually saw some signals of efficacy, positively on the on the liver and inflammation, but they ended up licensing in Humira and another agent over a course of a few years. And so about 15 years ago, or so they basically put it on the shelf. And Dr. Marchelli, at that time, was working on his target, and realize that that small molecule would interact with the target and was beautifully interacting with the target, not specifically TNF-a, which was the hypothesis of the ACI team. So good took a couple years, but they were able to bring the asset into a spin out of Indiana, and then they worked in cancer. So you’ve got a history and the inflammation hepatic space of patients, three, almost 320 patients, they’re treated with the drug. And then there are just under 20 patients in the oncology study solid tumor kind of folks unfortunately, on their last leg that were given APX3330 to see what it would do to help both on target engagement PK-PD, as well as obviously any efficacy. And it turned out that there were several patients that went up to 600. Meg’s per day dose, oral tablet, and had out to one year and had a very nice safety profile, there was actually three, one or two that were passed a year and one just close to a year, and a few others that were many, many months, and ACI, there was also a whole handful that were two to three months. So we have a very large body of safety, human data, showcasing that this mechanism, given systemically as an oral tablet, had very little organ toxicities or other side effects, except two things we saw, which was slight, less than 10%. We actually think it’s less than 5%, mild diarrhea, and mild rash. So and so we think for an oral chronic option for the retinal space, that this is the best profile, I think that seen to date. And again, our diligence in an oral option when before we brought it in with our KOLs was safety, safety, safety and then safety, safety safety again, because we know that that’s been the issue for those that have come before that had been oral and in general, what’s important to all of you, because treating locally versus treating systemically is sort of a paradigm change. So we’re looking forward to offering 4-DR the study design is in end PDR and some early PDR patients 43 to 60 On the DRS s score, and evaluating a two step improvement as our primary endpoint in diabetic retinopathy specifically, and we’re gleaning the DME data is we’re allowing in the, in the non steady eye for them to have centrally involved DME. And so because of systemic, we’ll be able to see what some of the other fluid and revision improvements might be, as well in both eyes, but specifically in DME patients. So I think Firas, our focus is definitely dr is the first. But while we’re at it, we’re going to get some additional information for DME that can then set us up to do a second study in DME, specifically under wet-AMD, which we’ll talk about, but I think the key is diabetic retinopathy is an unmet need. And we think we have an oral option that at its core has a unique mechanism. And it has just a significant amount of safety data, as well as its mechanism also imparts good reason to believe you shouldn’t expect to see too many untoward side effects with it.

Firas Rahhal: This is amazing, because what you said about the indication and your plan to study, and I think this is becoming now more and more normative, I for a long time, have felt that we should be more formally studying the effect on the overall diabetic retinopathy of some of these great drugs that we’re now getting that were originally intended for DME and we’re finding out they’re amazing for proliferative disease and for reversal of advanced non proliferative disease, the panorama data from Eyelea is very impressive. It’s actually really robust and compelling data. And I’m glad that others now yourself included are interested in studying formerly the effect on diabetic retinopathy, not just the DME, because ultimately, that’s the more widespread part of this problem is

Mina Sooch: Sometimes more of them. But obviously, the severity of the disease is more in DME patients, of course, you want to treat them first, obviously.

Firas Rahhal: And I applaud you for studying it this way. I think that’s the right approach. And I think I’m looking forward to hearing how you do at this dose of 600 milligrams that you mentioned, how much do you know about the penetration of the drug into the eye or into the spaces in the eye that we need them to get to at that level?

Mina Sooch: Yeah, so we actually have PK data from both ACI and Pepsi on phase one PK data, and both very similar curves. And what we found is in a C and lcnv model that had very similar 50% fluid reduction, as Eyelea and others have been that model that that dose when carried forward and looked at it on a concentration between our human concentration and the animal concentration to reach efficacy, there was a 50 to 100 fold, larger amount of drug we’re giving it 600. Meg’s and that’s the dose that we can give safely. So we’re actually going after our phase two zeta one trial, which just this morning, we announced a screening of our first patient at many sites, including yours. And so call out to any Doc’s out there, feel free to, you know, come find us. For the diabetic retinopathy patients, we are basically giving the most drug we can safely to see if we can maximize the effect in this phase two trial, which is a double mass randomized placebo controlled study. It is not an open label study, because we already have 10-11 trials behind us. And we feel pretty confident of our ability to see an effect and therefore didn’t want to do an open label study. And so we wanted to do it right, we wanted to get the data points. So we can move into Phase 3, on Dr. And then expand into DME or wet-AMD or GA, where we would complement and anti-VEGF treatments and not of course, go at it alone. But this is a single agent study. And we’re pretty excited that we have more drug probably than we need, and therefore have a good chance of seeing in effect. Having said that we could dos de escalate, if there are any safety signals of concern, if we see in this phase to that maybe we hadn’t seen previously. But the other is, we’re actually at arvo next month or is it April, we will be presenting some PK PD data on the modeling in the retina for us. So stay tuned. And we have exact numbers of what we think the predicted amount of our drug is. Dr. Mark Kelly, and his staff will be presenting that data. So

Firas Rahhal: perfectly fair answer and I will look for that that’s going to be of some interest and good for you. You’re going to publish that. Let’s talk briefly in our final couple of minutes here on the wet-MD prospect that you mentioned. I’d read that you’re that would be the next logical step. Certainly everyone in these spaces recognizes the similarity of the disease’s VEGF etc. that then the APX 2009. Is that just an intravitreal version of this drug that we were just talking about? Or is this a completely different drug?

Mina Sooch: Yeah, no, it’s a completely different drugs. So Dr. Mark Kelly has a whole series of chemical compounds that he designed around APX 3330 to kind of capture the space so we actually have composition of matter on Tuesdays are 92014. And others of the group choosers are a nine has multiple publications in ophthalmic models, as well as in vitro mechanistic papers as well, again, you can find some of those on our website. So we were thinking that what we found from conversations with the doctors, and again, I want to shout out to four of our KOLs for the back of the ISO Dr. Boyer, Dr. Allingham, Dr. Kaiser and Dr. Heier. We’re invaluable in that design that you were crediting us on. So you need to thank them for helping us all summer. Yeah, yeah, all summer and early until we submitted the protocol and in the fourth quarter. And it turns out that the target is really exciting and important and interesting to many folks. And so, but systemic delivery versus local delivery was sort of the input and feedback that we kept getting. So we said, well, our second generation product should be a local delivered version of the molecule. And whether that’s intravital, or maybe some other, you know, proven local delivery is where we have 2009 APX users or a nine sort of your marked because 3330 has so much human data, that it didn’t make any sense to take a step back and not offer the market, and patients an oral option, and not to be scared because others had failed before. When you look back, and we’ve analyzed those, those failures, which is just a handful, not that that many, you know, most of them were because liver toxicity, cardiovascular blood pressure toxicities at doses, where they never could achieve the dose they wanted for the translation from animal models. And when you put all those together, we don’t have any of those issues that we’re observing or seeing. And oral isn’t novel, there are two nutraceuticals that have been used for, I don’t know, decades, I’m sold by your two largest player in players in the eye space for general eye health, and their oral tablets that you take for general eye health. So the idea that something that you take orally, can get to the retina, it pretty similar concentrations to what’s in the blood is sort of out there and established for decades. And it was really finding a retinal product that you could have a mechanism that could be safely given. But coming back to 009 we’re looking at we’re about a year away from an ind. And we would love to work on that with a partner who says excited and having a local delivered a rough one inhibition molecule, or with future funding, you know, doing another calendar year, we could also see ourselves developing it ourselves. So I think we’re excited to provide a local and a systemic opportunity around the ref one target. So that’s our thinking around 2009. And that, therefore wet-AMD made a lot of sense to think about it, you’re already taking an injection, so you would just be adding, you know, another injection, in that case.

Firas Rahhal: So was the age of the patients with wet-AMD a factor in the decision to stay in the intravital space for that one or not really?

Mina Sooch: No, I don’t, I’m gonna just say we haven’t gotten that far into the thinking on, you know, tablets versus intravital, or other delivery mechanisms. So I think that is an area of work for the company. Again, we were sort of focused on these four trials and getting them launched. But I have to say that many folks on the team are excited to continue to explore how do we develop to 009 in a local way. And I think, again, leaning on partners and delivery formats that have been proven is our thinking because we don’t want to reinvent, we want to borrow and use what the industry is de risking for that molecule. But you know, we’re excited to pursue that as well. It just won’t be right this moment. But again, timing wise, when we do start working on it, we’d be about a year away from an ind so.

Firas Rahhal: One final question about that. When would you project if you can clinical trials in the wet-AMD space with the product we were just speaking up?

Mina Sooch: So 2009 or APX 3330? Not yet. So there’s actually two things for choosers or a nine. I mean, I think so probably 2023 because we’re already starting in 2021. And sort of thinking about when you’d launch a trial. So I think that would be reasonable to expect a and it probably be a phase one to right out of the gate. But I was gonna say for APX 3330 on the systemic side, not the local side, our thinking is with positive dr data that we would want to expand as an adjunct therapy and do a DME study, a wet-AMD study kind of similar to Kodiak and others that sort of you know, start to, you know, go after in parallel the different indications. And in that case, we would want to have the anti-VEGF and you know either the initiations and then start APX 3330 once you achieve you know that the primer sequence I guess we’ll call it that you do to get the patient to your target goal. And then see if we could extend treatment if we can increase response rates with adding APX 3330 which in my mind, the best benefit is you’re going to see saw less because you’re gonna have constant exposure to the back of the retina to reduce the inflammation reduce the vessel formation. In the fluid leakage. And you know, that’s what we’re hopeful for. So I think we actually could envision APX 3330 starting a wet-AMD study before a local delivery APX 2009, if things went well Firas, so.

Firas Rahhal: Make sense at I’m very excited by this, I look forward to seeing data as it comes out as well. And I can tell you, the patients will be excited by the idea of taking a pill rather than taking a shot. So that you know more to come on that. But thank you. And I do think you’re, again, you’re kind of going to where the patients I think would like us to go?

Mina Sooch: Well, it might be the first time the patients will lead the retinal docs into a new era. But I think at the bottom end of all of this is, you know, we’ve got two exciting products front in the back. Lots of data readouts come in presbyopia in the second quarter night vision in the third quarter sometime early next year, hopefully with recruitment for the Dr Study goes as planned, have that readout as well. And, and then every time we have a positive data readout, then we’ll start planning for the next evolution towards an NDA. So you know, we’re excited. Hopefully, we’re bringing some new treatment options, where there aren’t any today. So I think that was part of our goal and building Ocuphire. And that was the other common theme of all of my companies was big problems, want to try to solve them and maybe go after a little bit differently than everyone else. But with derisking kind of all along the way, not taking sort of big binary risks, but trying to look for areas where we’ve said we’ve shown certain risks are off the table so we can focus on, you know, those risks that we can’t control and can only, you know, figure out with clinical trial design and execution. So,

Firas Rahhal: Thank you, Mina, thank you very much. Mina Sooch, President – CEO of Ocuphire just for everyone again, if they caught in towards the end, thanks a lot for taking the time. fascinating discussion. Really cool concepts and good luck in your continued clinical trials.

Mina Sooch: Thank you Firas. Thank you for having me.

Firas Rahhal: You’re welcome.

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