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Michele Garufi, co-founder, chairman, and CEO of Nicox, has done whatever has been needed to get the company to where it is today – that is, with two promising product candidates in the advanced pipeline as well as two out-licensed products.
When it was time for Garufi to launch Nicox, there was no venture capital presence in the healthcare sector in his home country of Italy. So he and his Nicox co-founders looked outside the country, and found financing in France. They kept their research center in the Milan area, and now have a development center in the US.
In this episode of the OIS Podcast, Garufi tells host Rob Rothman, MD, that Nicox will continue to become more US-centered, and completely focused on ophthalmology. The company was founded on Garufi’s interest in nitric oxide (NO) donation, trying to apply NO properties to different therapeutic areas.
Garufi credits some of his ability to overcome obstacles to his competitive swimming days. “When I was young,” he said, “for seven or eight years I was on the national Italian swimming team, and went to the world championship. I had a great experience, but with great sacrifice and a lot of resilience.”
He pointed out that in a sport like swimming one trains for a long time, with one goal, perhaps a major championship. It may or may not end well. This isn’t unlike pharmaceutical research, where after years of effort, a drug may not work. This was part of the story of Nicox.
Click “play” to hear Michele Garufi tell the whole story!
Rob Rothman: Hello OIS Podcast audience. This is Rob Rothman here with another episode of the OIS podcast. For those of you who don’t know me, I am a glaucoma specialist practicing clinically in New York spend about half of my time seeing patients. The other half of my time I spend running InFocus Capital Partners, which is an ophthalmic focused venture capital fund, and we are nearing the end of our investment lifecycle with 13 early stage assets in ophthalmology, you have one or two later things, but we don’t invest in the public space at all. And for those of you who have listened some of my other podcasts, you know that I have elected to interview interesting people in ophthalmology to try and dive in a little bit towards the background of those people who’ve been responsible for making companies what they are today and with that as a backdrop, it’s my pleasure to introduce Michele Garufi, who is the co-founder, Chairman and CEO of NicOx. NicOx has a long history of involvement in ophthalmology. And we’re going to get into most of that with Michele in a few minutes. And it’s my pleasure to have you on the podcast today, Michele. So thank you for joining us.
Michele Garufi: Thank you, Rob, for your invitation. And good morning to you and everybody.
Rob Rothman: So I think I’d like to start this one off by having you tell everybody a little bit about your personal background. So some very interesting things about you that I think some people inside of ophthalmology know but others, others don’t. And sort of go into a little bit about, you know, sort of where you grew up and your education and sort of give us you know, overview as to how you entered the world of pharma and specifically, what led up to the formation of NicOx. I think that’s an interesting way to sort of segue into the company. So fire away and let us know.
Michele Garufi: Thank you Rob, yeah, actually, my life has been well unique, being Italian in this world of R&D public company. And I graduated from University of Milano in Medicinal Chemistry and then I got my degree of pharmacist as well. And I started working in the pharma industry since day one after my graduation and degree in pharmacy, and up to record that, which is a very well known company, in Italy, and in Europe and public company as well with a presence in US, and then I ended it, the virus of the independency to create my own company, but actually, in 1995. At the time, there were no venture capital in the healthcare sector in Italy. So at the time, I had to go abroad, and I had the chance to meet while in record it Elizabeth Robinson she was the Director of Product Development of Recordati and together we just became friends I was mentioning this idea together with a friend of mine pharmacologist too. To have a start up around the annual donating technology, nitric oxide donating technology. And as she helped me to find out the right way, because actually before joining Recordati Italy, she was one of the first employees of Genzyme. She has a PhD from MIT. And so she knew the world of course of the venture capitalists for me to do it and but unfortunately, we could not found the company in United States for personal reasons. So we looked for local money. But as I said, in Italy, there were no venture capital at the time in the healthcare sector. So we found money with the French venture capitalists, among them, the famous Sofinnova. And we create the NicOx in 1996. The three co founder being in Italy to Italian and one American back with a French company. That’s the reason why NicOx is French that water in South of France in the software and the police what they call, it wouldn’t be San Diego friends. And but we always kept the Research Center in the Milano area. And that’s the reason why all the new molecules have been let’s say a screen day in the Milano labs of NicOx but today since many years, we are more and more American I would say with the US Development Center in North Carolina a named RTB area.
Rob Rothman: So let’s go back for a minute. So you work in pharma directly out of college, where did the interest in nitric oxide donation sort of come from is that based on your education? Or is there something specific that you came across during your work where you decided that this was an important area that needed to be developed and had really not been developed at that time?
Michele Garufi: Good question Rob, when I was more working in business development and their licensing and marketing, but during my time in pharma, I was exposed to nitric oxide in the cardiovascular field. And together with the pharmacology, which I have pharmacology at the time was my colleague, we had the idea to apply the nitric oxide in a different way, rather than the conventional cardiovascular application that are well known since many many years as of as of eight or so, we thought of this nitric oxide donation that we implemented with a specific let’s say chemical a modification of existing molecule trying to apply the nitric oxide properties in different therapeutic areas among which ophthalmology and actually when we started the NicOx we were not really an ophthalmic company we started with an application in the inflammation field for inflammation cardiovascular only in 2005 success with collaboration with Pfizer at the time, we started to apply our ideas to ophthalmology and namely to prostaglandin for glaucoma and then we generated the first idea which was transformed and invites all that as you know, is the first drug based on our research platform, which has been approved by FDA a few years ago.
Rob Rothman: Fascinating. So you have basically had an idea and built a company around it. And that’s ultimately. Okay, I want to get back to this in a minute. But tell me about the swimming. Because some factoids about swimming, that I think are incredibly important to the attitude that you have towards NicOx. And I think it comes from your background as a swimmer. I don’t think a lot of people know this about you, but tell me about tell everybody about the swimming cuz it’s really, really interesting.
Michele Garufi: Well Rob, my friends know, because actually, I am teaching my swimming experience when I was younger. Every time I had to have a lot of resilience, like everybody in our sector, and yes, it’s true when I was younger for several years, I was in the National Italian Swimming team and went to the World Championship and I had great experience, but with great sacrifice and a lot of resilience. Because, you know, swimming is a tough sport, you need to train a lot and many times you have just to train with one goal that it could be the major event of major championship, which is a little similar to what we do your research where you work for years, years, and maybe when you get near to the wall, you lose because the drug doesn’t work and that’s what happened to NicOx. So I keep saying that my resilience, I think it’s coming from my sporting background. So I’m very, very happy I’m still following the Italian team and part of the of the world of swimming sail, but that’s taught me a lot and I think it’s for everybody in general sport, this kind of sport is very formative.
Rob Rothman: That’s fascinating. I come across a lot of people who are you know successful who have been competitive athletes and there’s clearly a connection between you know, the competitive drive and the ability to you know, propagate you know, your business in some way. So, I know you swam with Mark Spitz. Weren’t you?
Michele Garufi: At the time, Yes, yes. Yes. The famous in their early 70s. Training a lot as a swimmer, some of them I met them as well afterwards in US. So it’s nice to be in touch with your world when you are young.
Rob Rothman: Well, it’s not I think it’s nice for the audience to know that you know, Italy isn’t just famous for you know, fast cars and delicious wine and fantastic food. We also have pharmaceutical entrepreneurs in you know, world class swimming there too. So, changing the whole perception of Italy, Michele. Thank you for doing that. But anyway, okay, so let’s go back so here you are, you’ve entered the world of pharma, you’ve decided that nitric oxide diagnose donation is the area that you want to focus on. You formed a partnership with another smart person. You go out and build NicOx and what happens?
Michele Garufi: Well, what happens happen to me? What is happening, I guess to 99% of the CEO, a co founder of the r&d and biotech company up and down, up and down, especially after the listing on the French stock exchange market in ’99. We went through of course, that the beginning of the new millennium, you remember very well what happened at the end, as I said at the beginning of the company was focused on a very interesting approach of our era donating technology, but for several reasons that I’m not going to explain not related to ophthalmology, we had a setback as a last meter with FDA and at this point was around 2010-11. At this point, the board were very good board member, I still have very good board member, most of them are American sexually. At the time, we had Frank Baldino was a friend of mine was a CEO Stefan passed away, unfortunately 10 years ago, and Vonca Yen was the CEO of core therapeutics, and they suggested me to give up on this project was too difficult to get approval to focus in ophthalmology. Ophthalmology, as I said, we started in 2005-6, at the beginning was this ideas to develop new and alternative prostaglandin. And since then, really, the company was refocused just in ophthalmology. So we started to sync what we had in our labs in our pocket. We went out and we acquired a few years later a smaller research company is spinoff of Ora in a Massachusetts, Essex and we acquired two patents. One we approve it and the other one is in Phase 2 for blepharitis. And since then we had in 2017, in December, the approval by our partner Bausch + Lomb, of Vyzulta. But at the same time, we decided, because we became more experts in ophthalmology, we had a great team. And we have a great team, as I said in RTB, North Carolina, to develop our own drug for glaucoma that we believe is a superior to any other single agent on the marketing glaucoma which is silicone and NCX 470. And we are in the last phase because it’s in advanced Phase 3, and we have a lot of hopes on this track.
Rob Rothman: So hold on, let me go back again just for the audience. So NicOx has two significant out licensing for use in ophthalmology. The first is Vyzulta, right, which is a, an agreement with Bausch & Lomb and the second is Zerviate. Right?
Michele Garufi: Correct. Correct. But that’s true and while we license out. And we didn’t keep for us this right? Very simple. Vyzulta was licensed to Bausch & Lomb in 2010. When we’re still focused on the other therapeutic area, they said inflammation and cardiovascular and at the time we didn’t have in mind to become in of the company. So we couldn’t develop both the project in another area and in ophthalmology at the same time. So we decided to license out to Bausch & Lomb, Bausch & Lomb developers up to pro approval in December ’17. Zerviate, on the contrary, when we acquired the spattered in 2014, from Essex, we did the last part of development and the approval process. We got the approval but it was not enough only Zerviate to transform NicOx into a commercial company with a direct presence in US. It’s not a product as you can imagine anti-allergic you need other products in your bag is not a niche product, you need a strong feel for, so we decided to license out. And actually, we licensed out two islands, which has been acquired by my friend Jerry St. Peter, who was acquired by Santen and I think it’s a great deal. But now with 470 and 4251 in blepharitis. We think with these two drugs, they are sufficient water is sufficient to transform NicOx in the future in us in a different company with a complete fully fledged the organization and launch our own drugs.
Rob Rothman: So let’s go back just again for briefly. So tell me about the products that NicOx currently has in development that are in the clinical and preclinical stage and then we’re going to talk a little bit just as a segue in case you get into it directly about how or what challenges you’re facing as a European company that is building its own US presence now.
Michele Garufi: Absolutely.
Rob Rothman: And I think that by discussing the product pipeline that you have in development, which some people are not aware of, and how you intend to then transform NicOx from a European company with an out licensing portfolio to a company with a US presence launching its own products.
Michele Garufi: Correct, Rob. It’s a challenge. It will be another race for me but, yeah, well 470 as I said, is the second compound of our annual meeting prostaglandin family. And as I said, we hope and were convinced that this drug could be even better than Vysulta. And all the other single compounds as single agents treating iop lowering pressure. Why because, well, we have very strong signal from the Phase 2 where we reach a statistically significant superiority, versus latanoprost. So and after 28 days of treatment, but we realized that we were not at the top of the efficacy dose while we were more or less at the plateau of the side effects, which were mighty Perea in a range of about 20%. So very, very average, I would say the side effects. So we decided to start the phase 3 was a innovative adaptive design, where we tested not only the highest dose of the phase 2, which was already statistically superior to latanoprost. But with an even higher dose 0.1% of our drug, because as I said, we realized that 0065, we were not at the top of the dose. And there was an independent advisory board that after a certain period of time on a certain white, important group of patient number of patients, they look into the data, of course, agreed with FDA, when we go out for penalty, and they decided based on the guidelines, we gave them that 0.1% were definitely the dose to go for for the rest of the phase rate, because probably they saw they perceive the seasonality strong signal of the better efficacy without any increase of side effects. So, we are even more confident now that the end of the phase three will be able to show even a much broader wider superiority over latanoprost of 470. And in this case, you know, we know that if we reach if we hit this statistical superiority will be the only single agent having developing phase three a prostaglandin versus in other prostaglandin in a head void comparison, so it will be very important. So we’re very anxious, we went a little bit of delay with COVID. But now, I think the face we should be completed in the second quarter of next year. So we are working hard to where much more than 50% of enrollments. So, we are very confident that is the first compound and the second the 4251 one of the two products together with surveyed that we acquired in 2014 from asecs. We developed this formulation with an applicator where you use this suspension of nanocrystal of fluticasone to treat the eyelid to treat the blepharitis all kind of blepharitis and I know there are some competitors vying for specific kind of blepharitis our drug is suppose being a steroid to treat all the kinds of blepharitis and especially the sinus symptom of blepharitis. And by minimizing the exposure of the eye to fluticasone because so far, there are eyedrops and ointment which are used for blepharitis. But while you know you put the drug in the eye, blepharitis is eyelid disease so you don’t need to put the drug in the eyes, so we had a very nice phase way. trial with very good results on the three main sinus symptom blepharitis, which FDA recognized as the basis for approval which are rather nice ocular discomfort and debris. We got very good results. So we started in December of phase 2b on 200 patients study exactly the same endpoints and the primary endpoint is a percentage of patient which will go down to zero in each of the three signs symptom versus a percentage of patients which will go down to Zero with placebo and let’s hope to meet the primary point but, you know, anyways, the face still we want to see an indication of how father developed this drug that these two drug could be a good basis for, for, for nitric for the transformation that you were asking.
Rob Rothman: Right. So and just just to for the audience for those people who don’t know, the reason why the comparison of your clinical stage glaucoma compound as a comparative study versus latanoprost is that most, almost every study in the US has been compared to timolol, which for some reason is still the FDA surrendered, whereas most ophthalmologists and optometrists in the United States use prostaglandin analogs as first line therapy. Most of the clinical trials still make comparisons timolol comparison to latanoprost would obviously be significant that hasn’t been done to my knowledge in phase 3 study at this point. So that is a big deal. So you have these two products planned, and they are both later stage clinical assets in trials as we speak. How is Nicox gonna execute now what is the plan for you? It’s not, it’s great. It can be seen this before and ophthalmology, where you have a great product. And, you know, transforming that into a viable commercial entity, with its own sales force and its own marketing plans is more complicated. And I know that you have a plan. So tell us how that’s been for you in terms of development and in struggles, challenges and successes that you’ve had so far.
Michele Garufi: So the first challenge, I’ve seen the NicOx will have to become a more and more US centered, we are already a lot of US center in terms of, you know, shareholders as well, and especially the Wellness Center, they said all our clinical CMC manufacturing team and 90% of it is in US, in North Carolina. But as well, this will imply that we need at the appropriate time probably could be after the results of our maintain trial to be listed on NASDAQ, and clearly to be financed, and hopefully at the right valuation that NASDAQ will recognize the NicOx wants it, or clinical results will be out to find the company for the last step and for the transformation. I am hard believer of their rollout strategy. So I know there are other products and other companies out. And clearly, I think that the management of the company, including probably with the top management, I’m talking about myself, will be American because clearly, I have a good experience in Europe, I was marketing products in Europe, I never did it in the US so I don’t pretend that my time my age. Also, I feel a young swimmer to be the number one guy launch in the driving US. But that is not the problem. I know a lot of good professional in US would be very excited to transform the company. And we have exchanged a lot of ideas how to do it, how to put together a pipeline of products, either by acquisition license or even merger with other small companies to create around NicOx which should have the most important products I think for 470 and 4251, even with the most prudent sales estimate should be really big catalysts to attract other small companies or other products to create a new specialty pharma company in US.
Rob Rothman: And I would assume that you have a timeline in mind for this as your clinical trials are beginning. So is there any you have any ability to discuss that timeline? Or is that information you’d rather not distribute?
Michele Garufi: I would not distribute but you know, well, I’m talking to professionals, they know that the phase 3 will take especially from 470 is time I think that to sync that in a couple of years we’ll be very close to an NDA submission for 470 into diva not disclosing any single confidential so and they know that when you start preparing an NDA submission, you must have started your pre marketing your pre commercial activity. So these are indicative guidelines, but they’re very intuitive. They’re considering the state of the 470.
Rob Rothman: So if you could look into the into the future, however many years you want to go forward five years down the road 10 years down the road. How do you view NicOx? What do you think the company looks like? I think if somebody asked you to describe the company today, you would have a description that you could give as to you know the summary of what NicOx is how does that differ from the way you think NicOx will be described, you know down the road.
Michele Garufi: Oh without being a dreamer because poor people are not dreamer very usually they’re very, very concrete. And I was not a dreamer when I was thinking, to succeed in getting an idea of our company of my company approved by FDA, and I did it, I think it was one of the few, probably the first French company having a new chemical entity approved by FDA among the R&D biotech company. I’m not talking about Sanofi or the Big Pharma. Of course, I’m thinking that NicOx unless you know, someone is coming in and taking us over, which can always add in a public company, as I said, could be the catalyst to agglomerate, around our Pipeline, in your specialty pharma company, and in growing, but to do this, we have to be in the States, our commercial head and in future CEO has to be in the States. And we have to be more and more present in this market. We have a large collaboration in OcuMension, which is a great Chinese specialty pharma company focusing ophthalmology, we are licensing tirely, our pipeline in this region to OcuMension, they are listed on the Hong Kong Stock Market. And they have to say that the license needed as well a compound from another important of the company in a public company in the US in their market cap base, we send times and hours just to show that probably the value of NicOx has not been recognized yet, but I’m patient, I’m resilient. So I do hope the NicOx maybe merging or acquiring products, changing the name changing the management will survive as a guide catalyst for a new ophthal company.
Rob Rothman: Yeah, I think that and again, this is coming from the clinical side of my world that there is this general sort of perception or sort of fear of dread that a lot of the specialty ophthalmology companies in the US have had either changes in ownership or changes in focus that have left a lot of early companies feeling as though the strategic marketplace has become very thin, where many larger, previous ophthalmic partners are not as focused on the future of ophthalmology as they used to be. And, you know, we have, you know, welcomed new specialty pharmaceutical companies with open arms and hearing that you have plans to pursue that pathway in the US, I think, is a very welcome statement for entrepreneurs, people with early stage assets, who I’m sure would love to talk to you about, you know, potential partnerships as you grow. And it’s a reversal of a trend that I hope will continue where we see more and more entities looking to become larger players in the ophthalmology market in the United States. So it’s great to hear that and I think that your strategy of partnering with someone in China is obviously critical, as we know that the growth of ophthalmic disease in China is probably going to drive most of the growth outside of the US going forward. So these are things that I believe, make up make a lot of sense. So
Michele Garufi: Yeah, yeah, no, I will just say, I heard from several people that they wished were new player in ophthalmology, actually, especially in the States, but in the world or in the Western world, because in many companies where either disappeared or changed their focus, and that’s exactly what they want to do with the advantage of coming from Europe and knowing that the opportunities in the States mainly, and second is Europe, but first, the first market of a focus of NicOx will be US definitely.
Rob Rothman: Yeah, it’s fascinating to see how it’s changed over the years. And, you know, as a, somebody who is actively involved in running a venture capital fund, we’ve come across some really fantastic companies with incredible assets. And our process in terms of figuring out where to invest also involves an assessment of where the exit would be, and what the strategic partnership potential looks like. And it’s become more challenging. It’s become more challenging as companies I think, have tried to figure out you know, where their places some of the larger acquisitions even Bausch and Lomb and Alcon and Allergan sort of roll ups and rollouts. And it’s difficult to, I think, identify you know, where some of these high-quality early assets will end up and we think companies like NicOx, you know, companies like Eyevance and with Santen, and then companies like Aerie who are you know, growing in this space will be critical to the development of ophthalmic innovation in the United States. So thank you for having that dream and for pursuing it for NicOx. I keep going back to the thought of you swimming competitively for the Italian national team and a swimming to me is incredibly intense physical activity. And I can I sort of envision you know, sort of the path of NicOx so far as a I guess, a swimming race that’s, you know, just made the turn right. You got another half a lap to go here. But I think that the products that you’re developing now, and your outlook are great and sort of encouraging for United States ophthalmologists, and I’m sure ophthalmologists around the world. Anything you want to share with us before we wrap up you know, it’s a fascinating development to hear about a company that you started and have grown to this stage. Anything you want to share with us before we before we sign off.
Michele Garufi: Just say, hey, just want to say that I miss US physically as well, because I was used to come 10 times a year, in the last 20 years, probably. And I was thinking the family for vacation. So it may get my wife saying I want to go back to the States. Of course, I was coming for work. They were enjoying the US. So they and I’m missing as you know, piano being a more a US character always optimistic looking for challenge zone, I miss the US environment, which is very different from the European one. And I think that we all learn a lot, at least in the biotech sector from US and so I don’t want to stay away too long.
Rob Rothman: Well, I think the most of us here in the US are thinking the exact opposite, that he was very much like to get to Italy right now. almost anywhere else. Anytime you want to flip flop just let me know. I can’t wait to get back to Italy in five years.
Michele Garufi: Tourism and vacation and see. And while it’s a wonderful country, you have to see that for my business. US is the number one still so
Rob Rothman: Well I think that we both agreed and I think we discussed this briefly that I hope and I think that at the American Academy of Ophthalmology meeting this year, we’re going to be at a place where most people will be coming anything travel restrictions will be easier. I think people are planning on being there. I sort of feel like that’s going to be the first real post COVID breakout where we all are able to get together in a similar way face to face. And I’m looking forward to that. I’ll be looking forward to seeing you know, continued development and press releases from NicOx economic development. So just want to thank Michele Garufi again for taking the time to speak to us today. It was pleasure and a privilege and I’m looking forward to seeing you in person. Hopefully in New Orleans this year. Very Sure.
Michele Garufi: For sure! Will not miss. Thank you, Rob and thank you OIS.
Rob Rothman: Absolutely. Thank you again OIS audience again looking forward to future podcasts with you.