Ocugen, Inc. (OCGN) Earnings Call Transcript & Summary

Good afternoon, everyone, and welcome to Citi's BioPharma Virtual Conference. My name is Max Riso. I'm a Director within Citi's Healthcare Investment Banking team. It is my pleasure today to introduce you to Ocugen. Ocugen's mission is to develop gene therapies to cure blindness and to develop a vaccine to save lives from COVID-19. Joining us today from the company is CEO Shankar Musunuri, who will be walking us through the company's presentation. On a brief housekeeping note, we kindly ask to reserve all questions for Q&A at the end of the presentation. And with that, Shankar, I'll turn it over to you. Thank you.

Thank you, Max. Good afternoon, everyone. Thank you for tuning into Ocugen presentation today. Forward-looking statement. We are a biotech company, strong diversified portfolio in many areas, starting with vaccines and the breakthrough gene therapies and novel biologicals. Our first program vaccine, COVID-19 vaccine, it's going through approval process in Health Canada. It's currently under review. And on the modified gene therapy platform, we have a breakthrough -- we believe is a breakthrough gene therapy platform, which can target rare diseases as well as diseases that target millions. And our novel biologic is targeting back-of-the-eye retinal diseases very broad in nature, such as diabetic macular edema, diabetic retinopathy and wet age-related macular degeneration. Once we built an integrated capabilities based on biotech platform so that we can more innovations to the market efficiently. And we do have a healthy balance sheet to support all our programs. Coming to our pipeline. Starting with our vaccine, COVAXIN, which is a whole virion inactivated vaccine, which we licensed from Bharat Biotech in India for North American market, for U.S. and Canada. And this vaccine has been authorized in many countries, including India, it has the EUA. It has been -- so far, they have administered over 75 million doses. And currently, it's -- we have completed our rolling submission to Health Canada. And we are working with FDA for a regulatory pathway. Coming to our modified gene therapy platform, which is very unique and game-changing technology platform in the ophthalmology space. And that's starting with OCU400. It's based on NR2E3 gene. It has got 4 different orphan drug designations for different mutations from FDA and NR2E3, rhodopsin, CEP290, and PDE6B. We also have a broad orphan designations for this product from EU EMA for RP, retinitis pigmentosa as well as leber congenital amaurosis. And the second program in the gene therapy platform is OCU410 based on the RORA gene that's targeting dry age-related macular degeneration, which is a significant unmet medical need globally, 9 million to 10 million patients, U.S. alone struggle with this disease. Currently, there are no approved therapies. And our novel biologic, which is also in the preclinical stage, targeting DME, DR and wet age-related macular degeneration is going through the preclinical. Now I'm going to spend some time on our key programs, starting with COVAXIN, which is BBV152. This vaccine has been licensed from Bharat Biotech of India. It's a large vaccine company. They developed many innovative vaccines. Currently, they are commercializing over 16 vaccines and they supplied over 4 billion doses for the global use. And we have licensed this product for U.S. and Canadian markets. So moving on to COVAXIN. Where are they today? COVAXIN, our partners have completed large Phase III clinical studies, demonstrating safety and efficacy and also demonstrated efficacy for the variants of concern specifically Delta variant in the clinical trial. In a bit, I'm going to share the data. And also from our perspective, we have completed a rolling submission to Health Canada, the review is ongoing. And our partner, Bharat Biotech, they have completed submission to WHO. It's going through a review. They're expecting EUL. And we're also in discussions with FDA for our regulatory pathway for the U.S. We have also announced this year that we are partnering with Jubilant Hollister in Spokane, Washington to produce the product in the U.S. So currently, we're in -- the technology transfer to Jubilant is in progress. COVAXIN product profile. This vaccine has 2 adjuvants in addition to inactivated whole virus vaccine as the aluminum hydroxide, Algel and IMDG. IMDG is the novel adjuvant Bharat Biotech licensed from U.S., from a company called ViroVax. And ViroVax developed this novel adjuvant in collaboration with NIH. And the target population based on the current studies, they have completed is 18 and up. Our partner is also doing pediatric trials. Currently, they're in progress to age 2 and up. And again, this is given in 2 doses, 0 and 28 days. And currently, it's being supplied in multi-dose vials, which is relatively easier and also good for mass immunizations. And expect the shelf life of this vaccine, which distinguishes from other vaccines currently available in the U.S., has got approximately 2 years of shelf life and also stable at room temperature for 25 degrees which will be terrific for mass immunizations, stockpiling as well as international distribution. Why do we need COVAXIN when you have so many vaccines, at least 3 are available in the U.S. with millions of doses. This is a differentiated vaccine. We believe strongly this is needed in our arsenal in the U.S. and Canada. And the reason is, this is designed based on the broad spectrum immunoresponse. Humeral, which is antibody response as well as a theatral response, which is really needed for long-term memory for the vaccine to work. Specifically, this vaccine because of the novel adjuvant induces a theatral response which can be vital for durable and -- duration and long protection for the vaccine. And also in Phase III clinical trials, our partner has shown -- the vaccine is effective against Delta variant. And this is the only product with the controlled Phase III clinical trial data -- efficacy data. That's very important, that's what is very prominent in the U.S. today. And this is responsible for many hospitalizations. And the safety profile looks very solid. And this is similar to placebo. And if you look at the vaccine platform itself, this is similar to polio vaccine, influenza and other inactivated viral vaccines in the past, we're all used to. And the transportation and storage, I already mentioned it, it has significant advantages compared to the vaccines, which are currently available in the U.S. with their long-term potential storage at 28 degrees. And also stable at room temperature, which could be very easy to deploy in the mass immunizations and stockpile and global distribution. So coming to this, why this elicits a broad spectrum immune responses. On the left side on this slide, if you look at the cold virus, it has got a spike. It has got analogue proteins. It has got membrane. It has got nucleic acid protein which are integral part, which are conserved portions. And so all 3 vaccines which are being used in the U.S., they're all including mRNA vaccines, they're based on the spike protein. The spike is the one which is mutating. And that's why the vaccine efficacy starts going down. However, COVAXIN used the entire virus inactivated with adjuvants. Therefore, it elicits broad immune response, not only against the spike, they've got analogue proteins and nucleic acid protein, which is very important, because when you have the mutations, I think CDC stated few weeks ago, we are very close to getting the viral escape with the current vaccines. However, if you have a broad protective vaccine, as is shown in this picture, if you have multi-antigens, even though one part of the virus is mutating, it will have ability to neutralize the vaccine -- the vaccine can neutralize the virus compared to single part-based like spike-based protein or mRNA or any other vaccines, which are focused on one part of the virus. That's very important. So now here, this is the Phase III results are summarized here in this slide. The overall efficacy for this vaccine is 77.8%. Once again, in a bit, I'm going to share during the clinical trial, many cases or 90% are variants. So keeping that in mind, this is -- this data is solid. And efficacy against severe disease, which is important because severe disease includes hospitalizations is 93.4%. And as I mentioned before, this is the only vaccine which has the data from controlled clinical trials on Delta variant, which is very, very prevalent in the U.S. today, 65.2%. And the adverse events, again, they're similar to placebo, 12.4%. And if you look at any inactivated viral vaccines hepatitis vaccine, which has an aluminum adjuvant, you see about 15% adverse events, which is pretty nominal, and that's what you see here in a similar range. And the serious adverse events are less than 0.5%. Once again, this is a large study, about 26,000 patients. And continuing the efficacy and safety results from the Phase III clinical trials. Once again, on the top, you're comparing, there is the symptomatic, that means just as other efficacy results from other vaccine trials, there are 130 cases in this case. And based on that, overall efficacy is 77.8%. And again, severe cases such as including hospitalization, the efficacy is 93.4%. Again, I'm going to focus on asymptomatic, the third line on the top table, which has a 63.6%. That means in this clinical trial, they monitored the patients who have asymptomatic disease. That means they don't have any symptoms. However, they show positiveness for RT-PCR. And that's important because if you have efficacy on asymptomatic patients that has potential to reduce transmission. That's important. That's why 63.6% is a very important number to notice. And also adverse events I talked about, again, you have BBV152 and the placebo, they're compatible, and the overall adverse events are very similar, around 12%. And the serious adverse event in both the cases are less than 0.5%. So what is the role of adjuvant in COVAXIN? That's the adjuvant Bharat Biotech licensed from U.S., which was developed -- codeveloped in collaboration with NIAID or NIH. And this adjuvant, the aluminum hydroxide and IMDG, it's a combination. It's safe and immunogenic and that boost the T-cell response, specifically TH1, which is very important for long-term immunity and durability of any vaccine. And again, this data coming out of the clinical trials specifically showing the T-cell response, the TH1, looking at on the right side graph, significant increase with the current vaccine dosage 6 micrograms with aluminum hydroxide and IMDG showing pre-vaccination versus vaccination, significant increase in IFN-gamma and TFN-alpha, which is very evident from this slide. So I mentioned before, during the clinical trial, there are many, many cases of variants. So what they have done, the cases which are confirmed with RT-PCR, they took many of these patients, and they did the genomic sequencing. And in that, they found out over 90% of the cases of variants. And again, on the right side, you can see 59% or Delta variants. And there is additional 13%, which is Kappa, which is another Delta variant lineage. That means you can tell from this, the majority of the variants they found during the clinical trial are in this case are Delta, Delta variant lineage. That's very important to note. And coming back to the efficacy against variants. Again, with the Delta, they showed 65.2%. And another Delta lineage, 617.1 Kappa, they showed 91% efficacy from this trial. Overall, other variants, it's around 72%. So once again, this trial was done in the middle of emerging variants, and they have shown solid efficacy and demonstrated in the controlled clinical trial, which is very rare. And going back to another important aspect they monitored from the clinical trial is the viral load. In this slide, again, are showing against the Delta variant, looking at all the cases. And again, the vaccine case, which is BBV152 in the center and the placebo. So these are CTL values. That means the higher the CTL value, lower the viral load. So in this case, in these patients, the viral load for COVAXIN patients is 154 lower compared to unvaccinated for the breakthrough cases. So there is a lot of literature available for mRNA vaccines. The viral load doesn't go down. Why is this important? Just like I talked about asymptomatic efficacy here, if you have a lower viral load to vaccination, the potential for you to transmit the disease goes down. That's very important. So once again, our partners, the collaborative vaccine. They collaborated with Indian Council of Medical Research developed this vaccine. So that's equivalent of our NIH. So they have extensive publications in highly credible journals, including Lancet Science and everything so far, they have published it. And in fact, the Phase III results are going to come out in another medical journal shortly. So with that, I'm going to now shift gears and move on to our modifier gene therapy platform, which we believe is a game changer in ophthalmology space. So where are we with this? We have successfully completed our manufacturing at our partner, CanSino Bio, a strategic partnership on the manufacturing, CanSino Bio is a large biotech company, about $15 billion market cap. They have large facilities. And they have successfully manufactured collaborating with us at a 200-liter scale. That's a commercial scale for a Phase I/II supplies. And currently, we're finishing up the preclinical tox studies. And as soon as we're done with that by the end of the year, in the fourth quarter, we're getting ready to file the IND to initiate at least 2 parallel Phase I/II trials this year. So now why we believe this is a game-changing technology platform compared to traditional gene therapy? On the left side, again, this demonstrates -- you have a GenX, it has a mutation. So that mutating gene, it is a defective gene. It keeps producing the defective protein. And here, what you do is in the traditional gene therapy, you give a functioning gene. That functioning gene produces relevant protein, which will start controlling the disease progression. However, if you take diseases like retinitis pigmentosa, I talked about, there are about 150 mutations in that. So that means you have to come up with 150 products. And there are about 2 million patients globally struggling with it. And many of them legally have potential to become blind and they're in mid-40s. Just imagine being a family member or a person suffering from this disease. I mean it's almost impossible to develop so many products. This is where we come into the -- our platform technology on the right side. We've got modifier genes, oral modifier genes. These genes are -- they control gene networks within the retina and control the expression -- underlined expressed on mini genes like up regulating good genes and bringing the retina. So they have ability to target mini mutations. So same product. That's very important to note. So that means once you make the product, it's the same product, the manufacturing part is done, you go to the clinic, you get safety on 2 or 3 mutations. This can be applied to many mutations. So it has potential to treat entire RP. So this could be a game changer from the patient perspective because they cannot wait for people to develop so many products. And again, I'm going to demonstrate the data which got published in Nature shortly, why we believe this has potential to treat many diseases with a single product. So again, this is based on nuclear hormone receptor genes. These are like master genes in the retina. So their ability to reset the homeostasis and regulate the function of many networks, some of them are noted here on the right side, like, for example, photoreceptor development, inflammation, cone cell development metabolism. Again, this modifier concept is not new, and its impact on clinical phenotypes is well known in disease areas such as cystic fibrosis and spinal muscular atrophy. And we are the first company to introduce this in ophthalmology space. And again, our proof-of-concept is published Nature of Gene Therapy. And by a collaborator, Dr. Neena Haider, lab at Harvard Medical School. And this again shows same product, OCU400, tested in multiple animal diseases, representing multiple human disease mutations and is showing with multiple end points, showing significant risk view, demonstrating this therapy can be used for many orphan diseases. And I'm going to share some highlights from this publication. And again, at the bottom of the screen, the article link is there and people who want to look at it a lot more details, you can click the link and go to the publication. So here, you're looking at early stage of the disease and advanced stage of the disease. There are 4 different mutations here. Again, the green bars represent treated animals and untreated is dark bars. Again, here, what you're looking at is outer nuclear layer. As the retinal disease progresses, the degenerates -- outer nuclear layer actually degenerates. So in the treated versus untreated you can see a significant difference even in the early stage of the disease, the significant rescue from the treatment. Again, the same product is used in all these different animal models. On the right side in the advanced stage, in many cases, in fact, you're missing the outer nuclear layer for untreated, they're gone. So again, showing the significant risk view in any stage of the disease using this therapy. Coming into -- this is a functional endpoint looking at ERG signal, electroretinogram and looking at scotopic on the top left and photopic at the bottom. Scotopic is a dim condition, low light. And photopic means it's a bright daylight. And in both the cases, you can see the ERG signal is significantly protected and preserved in the treated animals. Again, looking it from the function perspective, the rescue works very well with the treated animals, the same product in multiple animal models, again, demonstrating the ability for broad stroke therapy. And now one would ask if you can apply this for many mutations, are there any off-target effects? So in this, looking at multiple endpoints, again, looking at fundus imaging and histology in the center, looking at retinal layers and the immunochemistry, at the bottom looking at ERG, again, when you give you over expression of NR2E3 in healthy animals, there is no, again, a difference in the end points when you look at it and showing the therapy works well with no off-target effects, which is very important for safety. So here, this is our regulatory strategy. Again, we are planning to initiate 2 Phase I/II trials this year with NR2E3 and rhodopsin. And again, we also want to get into CEP290 at a later point so that our goal is to do at least 3 parallel Phase III trials, and these are very small trials because it's orphan disease. And then moving to approval path. I mean we believe with some Phase IV commitments, if you prove the therapy is effective -- safe and effective in multiple mutations, our goal is eventually get the broad RP and LCA indications at FDA and EMA and eventually globally. And we're really excited about initiating the clinical trials this year. And once again, just to sum it up and competitive overview, we talked about many features of our therapy. It's a broad-stroke, and it will also help in the time and the cost, and the same product is going up for multiple mutations, and you can eventually potentially get the broad therapy. However, the traditional gene therapy, even though platform is proven, there's a product in the marketplace. However, you have to develop multiple products. You have to develop a product again and again for every mutation, which almost is almost impractical for 150 mutations for RP. Cell therapies are coming out. They don't have any approved products. They are in the clinical trials. Again, they can go broader than a traditional therapy, but you can only limit it to specific cell types like RP cells. There are multiple cell types within the retina. So at least cell therapies are broader than traditional gene therapies. However, our modifier platform is very broad. And now shifting gears. The second product in the pipeline is OCU410. It's based on the RORA gene. And again, dry age-related macular degeneration is a very complex disease. And there are many factors which can impact acculturative stress, inflammation, lipid metabolism issues. And targeting simultaneously all these things to control may be an answer for it. And we believe RORA gene, another master gene, which has ability to control these functional networks is an answer for this. And we are -- again, this is going through the preclinical studies right now and we'll eventually bring this to the clinic for the benefit of this patient. So again, OCU400 targets all the rare diseases, and this is going after large population. I mean, think about it, in the U.S. itself, we have 9 million to 10 million patients with a single injection gene therapy. If you have a potential controlling the disease burden, that will be big, and we're very excited about this program. And now I'm going to shift gears, spend the last few minutes on our biologic OCU200. It's a fusion protein. It's targeting many retinal diseases, which are broad in nature, such as diabetic macular edema, diabetic retinopathy and wet age-related macular degeneration. And again, the population size is high with these diseases in the U.S. itself. And you're talking about 9 million to 10 million patients. And this is based on a fusion protein, transferrin-tumstatin. Tumstatin targets only integrin receptors, which are present on the active endothelial cells. And this is very targeted. And the transferrin improves the uptake and improves the efficacy of tumstatin. And again, because of the distinct mechanism of action, we believe this has potential to be a disease-modifying drug, unlike currently available anti-VEGF therapies in the marketplace. And again, there are many patients who are nonresponders to existing therapies. That's why it's very important to work on this and bring this therapy to the patients globally who are really in need. So in this slide, we compare head-to-head with the current anti-VEGF therapies. On the left side, it's a diabetic macular edema model. And here, you're comparing 10-microgram dose of OCU200, shows a significant equal results with Eylea, which is 20-microgram dose. Eylea is currently a gold standard in the anti-VEGF market. And on the center, you have wet-AMD model, looking at OCU200, head to head with Avastin, and it shows, again, reducing the lesions, shows statistically superior efficacy in this model. On the right side, again, you have Eylea and OCU200 as well as a combination in the wet-AMD model showing OCU200 works well compared to Eylea. And the combination, of course, is superior to individual. So once again, summing up this has a good potential to treat many of those patients struggling from this broad disease burden globally. So now to close out, I'm going to talk about our leadership team, and we have a very experienced team, a lot of experience in developing, launching and managing life cycle of many, many biological products that is a tracker of success. And many of us, including myself, Bruce and Mike and J. P., we all actually worked at Wyeth and Pfizer large pharma, managed many vaccine programs successfully, including Prevenar and Prevenar 13. And so with that, we also have a very strong scientific advisory boards on the retina side, many of them very well known, including a lot of gene therapy expertise. And on the vaccine side, we got the 3 renowned people from University of Pennsylvania, along with industry experts, such as Satish who used to be Biotherapeutics CSO for Pfizer at one point and Cathy though individually known in model vaccine development. So we have a strong leadership team along with scientific advisory boards, which are helping to move these programs ahead. And to close out, again, summing up, we are extremely working hard to bring COVAXIN into U.S. and Canadian markets, which is much needed in our arsenal to control this pandemic. And again, COVAXIN has significant data and including Phase III results came out showing solid efficacy and safety. And we have completed a rolling submission to Health Canada. It's currently going through active review for approval. And we are working with the FDA on regulatory pathway to bring this vaccine into U.S. market. And as I mentioned before, we are actually working on technology transfer and our goal is to target at least 100 million doses a year in the U.S. with our manufacturing capabilities. With OCU400, we have successfully completed manufacturing at a commercial scale. We are completing our toxicology studies. And as soon as they're done in fourth quarter, we will file the IND and we are going to get into the clinic with 2 parallel Phase I/II trials. Thank you.

Great. Thank you, Shankar for that. Just a couple of quick questions here that have come in. Just on COVAXIN, do you foresee a need for a booster approach down the line once it's come to market?

Yes. We are considering all those options absolutely. Because of the broad protective nature and also it has -- it elicits good antibody responses as well as T-cell responses, which is very important. If you look at other inactivated viral vaccines, such as Polio, you give a few shots and they work for long term. And that's a concept. And also this has the ability to neutralize other current variants as well as future emerging variants. So this could be a very good vaccine for looking at a booster option too.

Great. Thank you. And in terms of additional studies, do you anticipate any -- running any -- the need to run any additional studies for your BLA filing for COVAXIN?

Yes. We are working with FDA right now on the regulatory pathway and if and when we have to do any studies to get the BLA. And as soon as we reach an agreement, we're going to announce it and we're going to initiate the trials, whatever is needed for the BLA path.

Got it. Another question. Can you talk a little bit about where you stand on the manufacturing front and scale up on both programs?

Yes. On the COVAXIN side, again, our manufacturing is going well. Our partners in India have scaled up. They're continuously scaling up every day. And so they're trying to target between 500 million to 1 billion doses a year capacity. And here in U.S., again, we're transferring to a CMO Jubilant, tech transfer. That process is ongoing. And we're trying to target like 100 million doses capacity per year. Once again, if there is a significant need in future, we need more doses, as I mentioned, our partners have large capacity, and we'll try to accommodate whatever is needed in North America. That's our goal. And again, the second product, again, OCU400, as I mentioned, we have a partnership -- manufacturing partnership with a large biotech, CanSino Bio, and they got excellent expertise and also large facilities. So that's why even for early stage, we scaled up what you call it gene therapy in our commercial scale like 200-liter scale. We successfully manufactured it. And so that's what is going into the clinic. So we have a very good process, and we're very confident on our manufacturing.

Great. Thank you. I think that was it on the question front, but thank you for taking the time to present today. We appreciate you joining our conference and for those online, thank you for dialing in.

Thank you for having me. Thank you. Bye.

Thank you. Have a good one. Thanks. Bye.