Sun Pharma Advanced Research Company Limited (SPARC.NS) Earnings Call Transcript & Summary

Ladies and gentlemen, good day, and welcome to update on SPARC strategy and portfolio hosted by SPARC. [Operator Instructions] Please note that this conference is being recorded. I now hand the conference over to Mr. Jaydeep Issrani. Thank you and over to you, sir.

Thank you, Faizal. Good evening, ladies and gentlemen. I am Jaydeep Issrani. On behalf of SPARC, I thank you for joining today with us for SPARC's update on strategy and portfolio. On our call today will be CEO, Mr. Anil Raghavan; and members of SPARC's senior management team. The presentation that we will be using for today's discussion was sent out earlier. We hope you have received the slides. The slides are also available on our website at www.sparc.life. We will also upload the call transcript on SPARC's website soon. The format of the discussion will be similar to what we have followed in the past that is we will go through the presentation first and then open the call for questions. Before we start, I would like to remind you that our discussion today includes forward-looking statements that are subject to risks and uncertainties associated with our business that may cause actual results to differ from those projected in the presentation. I will now hand it over to Mr. Anil Raghavan for his presentation.

Thank you, Jaydeep, for the introduction. Hello, everybody. A very warm welcome to all of you to the 11th edition of SPARC's annual portfolio review. Thank you so much for joining us today and for your continued support and engagement. Always means a lot to us. We are delighted to welcome you back to this very important call. As usual as Jaydeep said, we have SPARC's management team on the call today with me. In the interest of time, we don't plan to do introductions. I request the presenters to briefly introduce themselves before beginning of their segments. By way of agenda for today. We will start with brief comments on our strategy and certain updates on important programs pertaining to late stage clinical assets and commercializations. Subsequently, we will dedicate most of our time in the rest of the call to provide more detailed updates on 5 important programs, which are 4 NCE clinical programs plus one important biologics platform with clinical visibility. Dr. Siu-Long Yao and Dr. Nitin Damle will provide those updates. We will conclude the presentation with brief comments on our cash flow situation and financial performance from Chetan, that's Chetan Rajpara, our Chief Financial Officer. So with that, let's get started with Slide 4, please. Slide 4. Here we are starting with a brief snapshot of SPARC, a bit of a state of the union. As regular participants in this call, most of you are aware of our pivot from a delivery system innovation focused group to an innovator with reasonable appetite for early stage risk. We have made significant progress in that journey. Given where we have reached, I want to highlight 5 key drivers of SPARC's value upfront without dwelling too much into each one. We can go over this in detail if there are questions during the Q&A. First is the portfolio itself. Four NCE clinical programs in the areas of considerable unmet medical needs, vodobatinib in neurodegenerative diseases and its companion program in late line chronic myelogenous leukemia for patients failing on ponatinib. Vibozilimod or SCD-044 in dermatology autoimmune conditions where S1PR1 target therapies are evolving into an important class alternative to JAK inhibitors. And finally, our selective estrogen degrader SC0-120. And we are adding a very high potential platform built around a set of novel antibodies against what we call as tumor associated antigen 1 to this mix. Including this one, on the preclinical side we have now around 10-plus programs with varied stages of the prosecution. So we believe our portfolio has enormous potential. Also, better balance in terms of risk and novelty. SPARC is clearly going beyond our initial niches of validated biology and small molecule follow-ons. That transition is very real now. We have in the process become a balanced risk taker with differentiated assets pursuing validated biology on one hand for example BCRA or S1PR1s. Our completely novel mechanisms such as c-Abl inhibition in neurodegeneration or targeting new tumor associated antigens with differentiated construct. So our intent is simple, go after good science wherever possible in a modality agnostic way when we have an opportunity to push the standards of care in difficult-to-treat diseases. So we are really proud to note that we have made important strides in that direction. Now the third point here is the operating model itself. At its core, SPARC proposition is translational engine forward on actual brick-and-mortar lab infrastructure not a virtual company and high quality human capital, which gave us substantially lower costs. We have now 350-plus scientists with an overall headcount touching 400-plus, 3 locations, 4 labs and a self-sufficient process which can take a program all the way from bench to bedside. With significant validation in place, we believe our translation can be a real differentiator for SPARC. And on the other end of the chain, we maintain substantial flexibility. In the last few years, we have converted many of our late stage assets from our legacy portfolio. Elepsia with Tripoint, Xelpros with Sun, PDP-716 and SDN-037 now with Visiox and phenobarbital hopefully coming sometime in 2022. These transactions and potential royalties will certainly give us access to some non-dilutive cash not really enough to make our operations cash neutral, but this can contribute in a meaningful way and make a difference. These cash flows with the recently raised preferential issue allows us to keep most of the higher value programs in-house for a little bit more for the next set of inflection points giving us a strategic flexibility to do something interesting hopefully in the future. And finally on this slide, the team. We have a truly global high quality talent pool both in the middle to senior level as well as at the entry level. Significant experience at the senior rungs allows us to develop raw talent, which is available in India. Add in a diversified and fairly accomplished advisory layer, we have the human capital to build a good quality operation and that's a significant strength and means everything in this industry. So the broad point I want to leave you with from this slide is simple. For investors with appropriate risk appetite looking for a bet in pharmaceutical innovation from India, SPARC also is a viable option with a high value portfolio and increasingly validated operating margin. Now allow me to add a little more color to a couple of these points in Slide 5, please. We have indicated in the past our operating model is getting built out fully with several important elements becoming more prominent now. Instead of talking through this whole slide, let me focus on few important components I want to highlight. Accessing early stage science is a do or die consideration for us. We have been building up our academic and small biotech outreach in a systematic manner in the last few years. We can now see the real impact of these relationships on our portfolio, both in our clinical portfolio as well as in the preclinical programs, particularly on the preclinical programs. We have structured relationships or ongoing collaborations with several Tier 1 academic systems globally or their biotech spinoffs like Wash U or University of Michigan or UCSF increasingly or Israeli University on the university side; and companies like Bio Proj or Biomodifying among academic spinoffs. These early stage strategic partnerships are going to be a key element of our operating model. Our go/no go decision making has become substantially more stringent with external participation in the form of reviews with our Scientific Advisory Board and also with external key opinion leaders. Ideas to kill unviable programs as early as possible and as completely as possible before it starts consuming significant discretionary spend during the costlier later stages of development. As we have spoken about many times in the past, our Indian footprint definitely offers significant cost arbitrage, but it goes beyond cost. There is certainly patient and data access advantages stemming from us being here, which can make our programs competitive. We are increasingly looking to leverage these data and patient advantages from India's additional opportunities to create value. And finally, on the commercial side, we now have several external commercial relationships as I have mentioned; Tripoint, Visiox and CMS with a bunch of our products in China. We are also reviewing additional external relationships for some of the other near-term licensing opportunities. These transactions offer important validations for our model in addition to giving us some space to take the more valuable asset to later stages of milestones, which can give us better yield and realizations. So more broadly on this slide, we couldn't have been able to do the portfolio pivot which we managed without significant adjustments and capability development in the operating model, which we have done. And we are confident that SPARC represents a possibility for higher returns on innovation capital as we can take significantly more shots on the goal for a given amount of invested capital. Now a quick look on the portfolio strategy on the next slide, please. Here we go. As you know, we are focused on 3 important niches within our identified therapeutic areas; neurodegenerative diseases within neurology, treatment resistance in certain tumors in oncology and some autoimmune disorders in the immunology space. Why? Neurodegenerative diseases haven't seen much by way of innovation in a decade or 2 making the standards of care there really stagnant. But we are seeing very attractive new science in this area giving us exciting new testable hypothesis. We have to see this also with the progress in this field on the biomarker side of these diseases, particularly imaging markers, which give us a lot of anticipation about diseases like Parkinson's, Alzheimer's and ALS. On oncology, oncology continues to be interesting for many reasons in spite of high competitive intensity. Regulatory support for accelerated approvals and potential for premium pricing has 2 really important factors and add in the mega basic science, that's what's going on in this space. Oncology is difficult to ignore for an early stage company trying to build a multi-therapeutic area portfolio like SPARC is. And finally, on immunology, several important opportunity areas. Localized immune sufficient or modulation in diseases like Crohn's and ulcerative colitis or effective oral options are missing in important dermatology autoimmune conditions where both the local options and more sophisticated biologics options are very strong or for that matter mechanistically synergistic combinations, which can actually take the efficacy to the next level are all opportunities in autoimmune spectrum worth chasing. And in terms of intent, we would like to have a multi-modality tool kit and we believe we now have a modular biologics platform, which allows us enough flexibility to go after specific targets using multiple strategies. We call it molecular engineering for precision medicine and we will talk a little bit about that later on when Nitin comes in. And we want to do that in short-cycle innovation; fast hypothesis generation, testing and going over and then repeating the cycles. So the key takeaway in this, the broader focus is on higher value ripe for innovation areas with an intent to engineer solutions, we're seeing a more bigger platform. Slide 7. This is the story of our pivot, which I spoke about a little while back. So I'm not planning to spend a lot of time here. Here are some highlights I want to leave you with. We are competing our legacy reformulation effort now. We have 3 NDAs planned for early part of 2022; that's PDP-716, SDN-037 and phenobar; and that completes our transition out of simple delivery system based programs. I already touched on the clinical stage NCEs so let me not go there. We are planning an important preclinical platform play with antibodies targeting differentially expressed tumor antigens. Here we have multiple possibilities to create ADCs, T cell engagers and other multi-specific entities. These are very important additions to the portfolio which can give us high impact, potentially first-in-class options going forward and we will do a deeper dive on this part later on in the presentation. Before we transition to NCEs and biologics based targeting, I guess it's important to talk about a few late stage programs quickly either in products in the market or going into submission in short order. So very briefly let me start with Elepsia on Slide 8. As you know, we have licensed Elepsia to an early stage US neurology specialty called Tripoint Therapeutics earlier this year and we have been working with Tripoint to launch Elepsia fin the U.S. We are very happy to note that Tripoint had a very good launch earlier this year and they are scaling fast. Tripoint has around 40 reps now promoting the product across U.S. and they plan to accelerate their roll out going into next year and already have their support from both Medicaid and also employer provided systems. And we are very hopeful about the trajectory of this product going into 2022 and beyond. Now on PDP-716 on Slide 9. PDP-716, as you may know, is a once-a-day formulation of a widely used second line glaucoma drug brimonidine, which is indicated thrice a day and we have had a successful Phase III readout earlier this year. You may remember we also had a successful Phase II study for this product. In these studies, we compared 0.35% brimonidine once-a-day formulation with tid Alphagan-P 0.1% IOP. And in the chart here, we have the data from the recently concluded Phase III study. As we can see, the study measures intraocular pressure at 3 time points; 8 a.m., 10 a.m., 4:00 p.m.; across 4 visits at baseline, weeks 2, 6, and 12. Across these time points on multiple visits, the once-a-day brimonidine demonstrated comparable IOP reduction to Alphagan-P thrice a day. The study also demonstrated comparability of safety profile, 38.8% on OD and 32.3% to be precise on Alphagan-P. These successful readouts at this stage for the submission early next year calendar 2022 and the Visiox transaction we announced earlier this week. Now let's also take a look at the other ophthalmic formulation SDN-037 in the next slide. Now SDN-037 is a twice-a-day formulation of an ophthalmic steroid used to treat the signs and symptoms of inflammation post cataract surgery. Here in this Phase III study, a statistically significant number of patients achieved an ACC 0 rating without having to take rescue medication compared to placebo, 68.3% on steady track versus 32.5% on placebo. SDN-037 formulation was very well tolerated and has an adverse event profile comparable to published difluprednate data. So as PDP-716, SDN-037 will also go into a submission in early 2022 calendar and forms part of the Visiox transaction, which I will touch on in the next slide. I'll start with the ophthalmology assets on the Visiox transaction. As we have announced yesterday, we've licensed PDP-716 and SDN-037 to a U.S. based ophthalmic focused startup called Visiox. In addition to the regular licensing components like an upfront payment, milestones and royalties and teams, this transaction also gets SPARC a 10% ownership of Visiox. That allows us an opportunity to get an additional slice of their success beyond the regular royalty structure. We are super excited about our partnership with Visiox and really looking forward to U.S. NDA submission in early 2022 and subsequent market authorization. Another important transaction we recently announced is our licensing of a number of antibodies against a unique cancer target from an Israeli company called Biomodifying. As we've been talking about, we have a growing interest in biologics and these antibodies will add to our ongoing efforts to leverage antibodies in oncology and also in inflammation either as standalone therapies or as part of multi-specific combinations. We believe these programs will add significant value to SPARC's portfolio in the medium term. Now let's move to the next slide to briefly discuss the ongoing impact of COVID-19 on our business on Slide 12, please. COVID has been a frustrating disruption for SPARC and also the companies in our ecosystem in many ways. The shutdowns and restrictions resulted in lost lab time, manufacturing and supply chain disruptions leading to delays in the supply of investigation products, in some cases even other study materials and also broadly clinical trial conduct across the board. The chart here on the right side of this slide summarizes the extent of disruption the clinical research ecosystem has taken in terms of delayed study starts, enrollment delays, even study cancellations and suspension, so on and so forth. Even though we've done reasonably well on many fronts, we cannot claim to be an exception here. We have done very well with our lab operations. We have come back to almost full capacity early on in the pandemic without having to go back and shut down again during the delta induced second wave. We have done all right with truck supply with significant support from our CMC partners including Sun. But we have been certainly impacted on the clinical trial execution both in terms of site initiation and involvement in ongoing contact. The impact has been more in studies which are reliant on a single country for patient accrual or relatively rare population. Vodobatinib in CML is an exception -- I mean is an example of such a setting and we have seen some delays in that program. Our first task was to ensure continuity of patients who are already on the trial both from an ethical and data conservation standpoint. We believe we've done well to ensure continuity of most patients in our trials through a fair amount of virtualization and also through a mix of hybrid techniques. We've also derisked our studies through significant geographic distribution, certain level of flexibility in our processes and direct-to-patient outreach, patient support services and providing extensive supply chain and logistics support to our sites. We are hopeful going into 2022 to reclaim some of the lost ground through aggressive execution and direct engagement with sites and patients. Before we move on from this slide, let me say this. It's obviously an understatement to say COVID has been a major disruption. While we may not have mitigated our risks fully, we feel good about the proactive measures taken to deal with the pandemic and minimize the overall impact on our portfolio. I believe a lot of these operational process adjustments we have made during this phase will become standard practices in our system with the potential to alleviate the overall quality of our operations going forward. Now before I transition, I want to briefly talk about our last fundraising round and plans for the future. I'll also briefly cover upcoming milestones. So let me go to the next slide, that's 13 please. Brief comments on the fund raising plan. Earlier this year we have concluded a preferential issue of warrants to the tune of INR 1,112 crores, that's roughly $148 million. More than 50% or more precisely around INR 600 crores came from our promoter and the rest from a group of generally marquee domestic investors and some foreign portfolio investors. I want to thank everyone on the call for their support and encouragement throughout this process. These warrants will be converted by the end of 2022. That will allow us cash to fund the development of programs like say vodobatinib current trials in CML and PV and SCO-120 proof-of-concept studies and our ongoing discovery operations. This will also allow us to make necessary investments to build the capabilities necessary for newer modalities such as biologics. But at the same time, our portfolio is expanding with multiple options for additional INDs in the medium term in addition to additional indication options for some of the existing programs, which need to be both preclinically and clinically prosecuted. We also need to plan the transition of current clinical programs to later stages of clinical development without taking major phase transition delays. With these considerations, we obtained shareholders' approval to raise up to INR 1,800 crores. We are in the process of evaluating our options for raising additional capital as we speak and we look forward to your continued support as we move forward with this intent. Now let's go to Slide 14 to take a look at SPARC's catalysts in the near future. On the legacy end here we expect to see Elepsia and Xelpros growing. We look forward to working with Visiox to ensure ANDA submission in the coming quarter for PDP-716 and SDN-037 setting the stage for ANDA approvals and launch hopefully by early 2023. And we are working on a similar clock for phenobarbital and we hope to see a licensing event for that product hopefully in 2022. Now on to NCEs on vodobatinib, PROSEEK and its companion trial in Lewy Body Dementia are both on track for data in 2023. Vodobatinib CML program is lagging our original schedule as I mentioned earlier and we hope to go into a submission in 2024 and trying hard to get back on some lost time as we see some normalcy post COVID. On vibozilimod, which is SCD-044, we hopefully have clinical proof of concept for both psoriasis and atopic dermatitis by 2023. And SCO-120, our selective estrogen receptor degrader, is ramping up from its first-in-human SAD/MAD studies to patient trials as we speak. We expect to have early PoC by the same time frame that's 2023. In addition, we are also working towards moving at least 2 more programs to a U.S. IND. We will review one of those programs later in this presentation and we hope to have at least one more IND in the same time frame. We will also stay in the hunt for additional assets from our external innovation pipeline. Slide #15 has a nice summary of our programs and pipeline. I've touched up on most of this material in my comments already so I don't plan to spend time on this slide. But this is a perfect segue to the next segment, that's Dr. Siu-Long Yao with updates on some clinical development programs. So I'll hand over the call now to Dr. Siu and he will talk you through these important programs and I look forward to seeing you on the other end of the call. Thank you for your time again. Over to you, Siu.

Thank you, Anil. My name is Siu Yao and I oversee clinical development. I also want to extend very warm welcome to all those who have supported us through the years as well as newer folks who may be on the line now. We truly appreciate all your support and faith in what we do. So Slide 17. Slide 17 presents some data that you've seen before in the past, but I've included here as a reminder to you. The diagram on the right is a kinome analysis that looks at potential targets of vodobatinib and shows that the activity of vodobatinib is specific against various related targets as opposed to many similar drugs where there is significant target activity. This allows us to hit the BCR-ABL target harder and potentially get more activity. The current plan is to study vodobatinib in the last line setting, that is patients failing greater than or equal to 3 lines of therapy. We believe that this setting in highly resistant disease will best demonstrate the benefit of the highly specific nature of vodobatinib. As opposed to other drugs in the class, there have not been any QT effects which can potentially lead to heart related diseases and death. Orphan Drug designation has been received from the FDA and EMA. And as you know, orphan designation can extend the exclusivity of an approved drug beyond the conventional patent line. Finally, we've been fortunate in that the results with vodobatinib have been selected for either oral or poster presentation at several major meetings now. Slide 18. This slide is meant to give you a flavor of some of the results we've seen so far. This is a so-called swimmer's plot where the lines represent the duration of response. There are some caveats when you look at this type of data that you should keep in mind. Perhaps the most important to note is that the data are only till when the patient's enrolled in the study. So for example, patients at the top of the figure enrolled most recently whereas patients at the bottom were enrolled much earlier during the study. As a consequence, patients at the bottom may have the potential to respond and stay on study the longest because they've had the potential to be treated the longest. Patients at the top of the figure again entered the study more recently so that less time has passed and of course the potential to have a long response is, therefore, not available to them. Nonetheless, you can see that there have been some marker responses, some of which have occurred at relatively low doses. For example if you look at the bottom line, that subject has been studied for over 4 years with a dose of 12 milligrams. The population summarized here is resistant or intolerant as we treat higher lines of therapy so observing that kind of a median duration on study of nearly 21 months is notable under these circumstances. Slide 19. This slide summarizes the design of the ongoing study in CML and [indiscernible]. The study consists of 3 parts. A single ascending dose healthy volunteer component, a multiple ascending dose in patients with CML and a pivotal efficacy part in patients who are refractory to greater than or equal to treatment, one of which includes ponatinib. That's shown in the yellow there. As we have previously discussed, there is general agreement between us and FDA that this population in the pivotal study represents an important unmet medical need and significant activity in this setting could provide the information needed for marketing authorization. We're most interested in the chronic space with success for the largest group of course and there are a variety of sites recruiting in a variety of sites -- in a variety of countries such as the U.S., Belgium, France, Italy, Spain, Romania, Hungary, Singapore, the U.K. and Korea and we're about a quarter of the way through for the pivotal data anticipated to read out in 2024. Next slide, please. The next few slides beginning with Slide 20 here provide some information on the use of vodobatinib for the treatment of Parkinson's disease. In particular we believe that vodobatinib has most, if not all, of the properties needed to make a meaningful impact against the effective c-Abl dysregulation in this disease. Vodobatinib has sub-nanomolar potency and exceptional and limited off-target activity giving a great potential to intensively limit c-Abl activity without causing unacceptable side effects. The ability of vodobatinib to penetrate brain with a brain/plasma ratio of approximately 0.9 further augments vodobatinib's potential in the target tissue. The net effect is augmentation of autophagic flux and prevention of partnering mediated mitochondrial control. All of this is technical scientific shop talk to basically tell you that vodobatinib is very specific for what needs to be done, has a unique ability to get to the place where the job needs to be done and then get the jobs done by removing the toxic alpha synucleins that is the clinically known hallmark of Parkinson's disease. Slide 21. This slide -- so in the past we have shared cellular data on the effect of vodobatinib in Parkinson's disease. This slide gives you an example of the effects we've seen on behavior. As many of you know, Parkinson's disease is practically associated with tremors due to the death of neurons in the substantial [ mitro ] part of the brain. This slide depicts the results of a pole test in an experimental model of Parkinson's disease. PFF or preformed fibros represent a method of inducing Parkinson's disease in mice. Mice that had Parkinson's disease due to PFF injection are on study and have difficulty in climbing down a pole shown on the left here. It takes them longer to descend the pole. The graph on the right summarizes the result of treatment with vodobatinib in this model. On the Y axis is time and seconds required to descend the pole. Going across the bottom on the X axis are various groups of mice. The first column in black there represents normal mice treated with placebo and the second column in green shows the results from mice treated with vodobatinib only. The purpose of these 2 control groups is to establish a baseline for normal mice and to show that vodobatinib does not affect normal mice. The next 3 columns consist of mice which have had Parkinson's disease artificially induced by the injection of PFF. You can see that increasing doses of vodobatinib results in shorter descending times. So by the time we get to the highest dose of vodobatinib denoted by the yellow or orange column there, the time required for the mice to make it down the pole is very similar to the time required for normal mice to descend. In past presentations, we showed you that vodobatinib protects against neuron loss in cellular studies. These data now show that the neuron protection afforded by vodobatinib can have behavioral results, which may be ultimately clinically meaningful. Next slide, please. Slide 22 goes over the preclinical studies that we've run to support clinical studies and increase our confidence in vodobatinib and its safety. We've demonstrated the compound safety and acute toxicity in single and multiple dose studies in mice, rats and dogs by oral and intraperitoneal route across a variety of exposure time frames. There was not any evidence of genotoxicity meaning that the likelihood that chronic use could be associated with the development of cancer in humans is low. Reproductive toxicity space has been completed across a variety of the species and as far as contact is concerned, there was only slight eye irritation and no skin irritation when the drug is applied to the surfaces. Finally, there is excellent cardiovascular safety in preclinical studies with minimal herd effects in vitro and no significant cardiovascular toxicity observed in monitored dogs. Slide 23. So one of the questions we've been running into recently concerns the results of a study that was performed with a similar c-Abl inhibitor drug called nilotinib, which is actually already approved and on the market for CML. In a study that was performed by the previously investigators, they evaluated 2 different doses of nilotinib against the placebo in patients with Parkinson's disease. The results of that study, as many of you may know, did not show much of a difference in outcomes between the 3 groups. In the conclusion file, the investigators specifically stated that the results do not refute the hypothesis of c-Abl inhibition as potentially important therapeutic target for Parkinson's disease modification interventions. Indeed there are a number of novel molecules targeting the c-Abl pathway in development that have a better therapeutic profile. The data in this slide summarizes the properties of vodobatinib and its better therapeutic profile and why it's a better drug than nilotinib. To start off, we took a very systematic approach and first determined the concentrations needed in the cerebral spinal fluid in order for the drug to work in the mouse PFF model that I showed you earlier. We then performed a clinical study to make sure we used the minimal dose that we needed to get to that same concentration in that cerebrospinal fluid of humans. What we can tell you is that ultimately we have a compound that is 22-fold more potent than nilotinib with which we are able to get tenfold more drug into the CNS compared to nilotinib. The net effect is that potency with vodobatinib is around 200-fold greater than nilotinib. As I mentioned, this is all able to occur without cardiac driven diseases or other toxicities that could limit vodobatinib administration. Part of this ability to intensely target c-Abl in the brain may relate to the fact that vodobatinib is not removed by drug pumps or [ epox ] transporters thus allowing it to cross the blood brain barrier compared to other compounds. Slide 24. This slide summarizes the design of the ongoing clinical study in Parkinson's disease. There are 2 doses of vodobatinib that you can see there and a placebo to which patients are randomized. Over the past year we've added an open-label extension shown in gray at the bottom there to obtain more information on the long-term effect of treatment and also to give patients an opportunity to continue to receive drug if they feel it's helping them. There are 84 sites involved in this setting and about 40% of the patients have been enrolled. Top line data are expected in 2023. Next slide, please. The endpoints of the study that I just mentioned, the PROSEEK study, are summarized on Slide 25. The primary endpoint is change in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale and the MDS UPDRS and secondary outcomes include the time to start asymptomatic medication. The EQ 5D score, this is a quality of life measure; the clinician global impression of severity score as well as other pharmacokinetic and pharmacodynamic measures. We're also evaluating a few exploratory endpoints such as change in dopamine activity in the brain measured by DaT-SPECT scanning along with skin biopsies looking at the amount of toxic synuclein and smartphone-based measures of motor performance and CSF cerebrospinal fluid markers. Slide 26. This slide is here to remind you that we are also collaborating with a Georgetown investigator to determine if vodobatinib might be used for lewy body dementia. This disease has a lot of overlap with Parkinson's disease and many suspect that the etiologies are actually similar. In this study, patients are randomized through either placebo or a low or high dose of vodobatinib. Treatment is for 12 weeks and about a third of the patients have already been randomized. Endpoints include safety and tolerability as well as a variety of biomarkers. A data readout is anticipated in 2023. Slide 27 moves on to vibozilimod, a S1PR1 agonist that is being developed by us for a couple of inflammatory diseases. This is a background slide to give you some context for some of the subsequent slides. There are multiple drugs either approved or in late stage studies in this class, including fingolimod, ozanimod and etrasimod. Fingolimod was the pioneer in the class, but it's been associated with serious cardiac side effects specifically due to its effect on the S1PR3 receptor in the family. Currently, vibozilimod is in early Phase II studies in atopic dermatitis and psoriasis with readouts expected in 2023. I'll provide you a little more detail about this in the next few slides. Next slide, please. Slide 28 provides a little more information on what we've seen with vibozilimod in humans. We initially studied vibozilimod in a 3-part study consisting of a single ascending dose part followed by a [indiscernible] part followed by a multiple ascending dose component. In general, vibozilimod has performed the way that we anticipated based on the preclinical data. In the single ascending dose portion of the study, 6 dose levels were studied in males and one in female. There was a 55% reduction in lymphocyte count following a 1 milligram single dose. You can see this in the figure on the right. This magnitude of effect is expected to be associated with efficacy that as has been observed in other drugs in the class. There's no lymphocyte reduction in the [ food ] effect portion of the study. Four dose levels were studied in the multiple ascending dose portion of the study. Approximately 60% reduction in lymphocyte counts were observed following 1 milligram doses and representative asymptomatic bradycardia was shown at the bottom right-hand side there with a half life just shy of 3 days. Slide 29. This slide summarizes the design of the ongoing Phase II study in psoriasis. In this study, 240 patients are randomized among 3 doses of vibozilimod and placebo and treated for 16 weeks to obtain results on PASI75, the primary endpoint of the study. This is shown in the pink and magenta color. There are a series of subsequent rerandomizations shown in yellow to provide insight into things like the durability of response on therapy and the durability of response following completion of therapy. This study was just started with approximately 10% of the subjects randomized. Next slide, please. Slide 30 goes over the design of the atopic dermatitis study. This is actually quite similar to the psoriasis study. This study also consists of 240 patients approximately randomized to 3 different doses of vibozilimod or placebo. The endpoint is slightly different. It's the EASI-75 instead of the PASI75, but it also occurs at week 16 and the study also recently started. Slide 31. This slide provides some background on our oral selective estrogen receptor degrader. As you may know, this is a substantial market. Approximately 200,000 women are diagnosed with estrogen receptor positive disease and as you can see on the right there, survival can be core in advanced disease. These women along with the 20% to 30% of them who acquire mutations will be eligible for treatment with SCO-120. Oral SCO-120 is designed to be a step above intramuscular process, which is both uncomfortable to receive as well as very poorly active or even inactive against estrogen receptor mutations at practical doses. We're in the midst of transitioning from healthy volunteer studies to patients at this point. In general, I can say that SCO-120 has been very well tolerated and has been no really notable AE. The multiple dose study in patients will be started soon and patent expiry is expected to be around 2040. Next slide, please. Slide 32 here summarizes some preclinical efficacy data with results in mice with brain metastasis. On the Y axis there, you have the proportion of mice with brain metastasis who survive. On the X axis is time and days. Treatment was started on day 7 and continued for 8 weeks. There are a lot of curves here so some of which can be difficult to distinguish, but I'm going to ask you to focus on the X axis and towards the end around 98, 84 and 77 days. Those are the light blue -- turquoise, orange and red curves that end around those days. Those groups of life you can see have the longest survival and those groups are the groups who have been treated with the high, middle and low doses of SCO-120. There's another curve in gray as well as another curve which is buried in there around 8 to 35 which are control groups and that grey curve is for Fulvestrant and the Radius compound and you can see that survival with Fulvestrant is not much better than the control group. In fact this is consistent with what we know clinically meaning that Fulvestrant does not penetrate well into the CNS or central nervous system and it's not a good treatment for patients with brain metastasis. In short, these results suggest that SCO-120 may have activity in patients with brain metastasis as well as tumors elsewhere in the body. The next slide, Slide 33 goes over our current clinical plan for SCO-120 in patients with breast cancer. We've completed dose escalation now in volunteers and are at or near exposures that we expect to be efficacious. We will confirm the tolerability of these doses in patients and see if we can escalate a bit more in part one of the study that's soon to start. Altogether, this will probably involve around 16 patients. The main focus will be to confirm the safety and pharmacokinetics we saw in volunteers in patients. Part 2 of the study will focus on obtaining preliminary efficacy information and pharmacodynamic confirmation of the dose to be used for later phase studies. There will be around 15 patients involved in this part of the study and the study will start shortly and will provide results in 2023. The next slide, Slide 34 goes over the last drug that I'll touch on in my portion of the presentation. Phenobarbital, as many of you may know, is a well-known existing drug for the treatment of seizures and previously have shown that its activities can be superior to that of existing anti-epileptic drug such as levetiracetam. However, its current formulation has some limitations especially when it's used for the treatment of seizures in neonatals. As noted in the second bullet here, the current formulation contains benzyl alcohol as a preservative. Unfortunately, benzyl alcohol is classic CDN8 and can cause a gasping syndrome, which can ultimately be fatal. There have been many guidances and advisers which warn against the administration of drugs containing benzyl alcohol in them. What we've done here is removed the benzyl alcohol so that this will no longer be an issue in the treatment of neonatal seizures. SPARC's formulation has been granted orphan drug designation by the FDA and we're anticipating filing for approval sometime in 2022. I hope I've been able to get you up to speed on some of the more important clinical stage programs in our pipeline. And at this point, I'd like to introduce my colleague, Dr. Nitin Damle, who will tell you about something perhaps even more exciting in the preclinical space. Nitin?

Thank you very much, Siu, and good evening to you all. I'm Nitin Damle and I look after the biologics R&D at SPARC. In the next 10 minutes or so, I would like to discuss our biologics space, which is a new dimension for our R&D activities within SPARC. We had noted in our presentation to this audience a year ago that we have been exploring development of a new biologics technology platform with the potential to yield multiple molecularly engineered and innovative precision medicines. This modular platform technology has evolved from the antibody engineering advances made over the last 20 years or so and leverages the applications of single chain FV as a unit for antigen recognition and binding as shown on Slide #36. Using such modularly assembled scFv immunofusions can be used as a substitute for a classical tetromeric IgG and can do almost everything that classical IgG antibodies can. This platform allows us to make use of any antigen specificity of choice and thereby create mono bi, tri or even tetra-specific immunofusions with the power of effecting functions of as many as 4 distinct antibodies. So we have -- we can incorporate in principle power of 4 different antibodies into one molecule. We have been able to create such multifunctional immunofusions with anti-tumor and anti- angiogenesis effects for use in cancer therapy and anti-inflammatory immunofusions for the use in inflammatory diseases. And these are currently being explored for therapeutic impact. What I would like to share with you here at this point is a glimpse of our very first biologic asset being developed as an antibody drug conjugate or ADC, targeted to as yet undisclosed Tumor Associated Antigen 1 or TAA-1. The concept of ADC is pretty straightforward. ADCs represent antibody targeted delivery of chemotherapy in which a potent cytotoxic drug is covalently linked to an antibody with a specificity for a tumor antigen that is often overexpressed on the surface of tumor cells and via which the cytotoxic agent can be preferentially delivered to the targeted tumor cells. Thus, delivered cytotoxic agent then kills the tumor cells, but spares the rest of the body from the toxicities of the drug. ADCs are rapidly becoming a staple in cancer therapy with the regulatory approval of at least 11 distinct ADCs in the U.S. and Europe over the last 20 years or so. In our very first ADC asset, we have made use of clinically and commercially validated drug linker combination to create our own ADC. The target of our ADCs in antigen here refer to as TAA-1, as I mentioned earlier, which is overexpressed on the cell surface of a wide variety of human carcinomas, including those that have relatively fewer treatment options. Additionally, when antibodies bind to TAA-1, they are rapidly internalized. Hence, TAA-1 can be an ideal tumor antigen for targeted delivery of potent cytotoxic payloads or other response modifiers. Here I would like to share with you a glimpse of in vitro as well as in vivo activities of the TAA targeted ADC. Next slide, please. Slide #37. Here, we show the in vitro growth inhibitory effect of the ADC against pancreatic cancer cell line that overexpresses TAA-1. The left side of the graph shows that TAA-1 targeted ADC in a concentration independent manner, inhibits the growth of this cancer cell. In the graph on the right side is the effect of a similar ADC made using a CD20 specific isotype-matched antibody [Technical Difficulty] carcinoma cells. This non-binder ADC is able to exit cytotoxic effect only at the highest concentration tested and is about 50 to 100-fold deeper than the TAA-1 specifically-targeted ADC. Similarly, although not shown here, TAA-1 specific ADCs unable to mediate differential cytotoxic effect against carcinomas that lacked the expression of TAA-1, indicating that the anti-tumor effect of TAA-1 specific ADC is specific and focused for TAA-1 expressing tumor cells. We have further evaluated TAA-targeted ADC in multiple human tumor carcinoma xenografts, established in immunodeficient mice. Next slide, Slide #38. Here, we have evaluated low, intermediate or high dose of anti-TAA-1 ADC in the pancreatic carcinoma xenograft that expresses high levels of TAA-1. In addition, we have also evaluated the same ADC in an ovarian carcinoma xenograft that expresses relatively low levels of [Technical Difficulty] of the graph shows the impact of the anti-tumor efficacy of this ADC against pancreatic high TAA-1 expressing carcinoma. On the right side, you have this same ADC being evaluated against low expressing -- low TAA-1 expressing carcinoma, ovarian carcinoma. In this evaluation, the putative therapeutic effects, therapeutics were administered in tumor-bearing animals once a week for 3 weeks, after which the growth of the tumor xenografts was monitored. The anti-TAA-1 ADC in a dose-dependent manner strongly inhibits the growth of both high and low TAA-1 expressing carcinoma xenografts. In contrast, neither the unconjugated cytotoxic drug used at the same concentration as that of the highest dose of the ADC nor the non-binding anti-CD20 ADC at the highest dose can exit meaningful growth suppressive effect against these carcinoma xenografts. We are presently evaluating the impact of TAA-1 targeted ADC against human carcinoma xenografts that expressed varying levels of TAA-1 to further establish the TAA-1 specificity of this ADC. Although not shown here, anti TAA-1 ADC can suppress the growth of TAA-1 expressing carcinomas irrespective of their size. So both large and small volume xenografts are subjected to therapeutic impact and have shown to be inhibited in similar evaluation. We are excited about these clinical results and hope to advance this ADC through preclinical development, with an eye on the IND submission targeted for 2023. Next slide please, Slide #39. We are exploring a number of distinct ADC opportunities that can benefit from the experience of developing anti-TAA-1 ADC. Our TAA-1 focused efforts are not limited to just the ADC platform. Using TAA-1 targeting as an anchor, we are also exploring biologic strategies to engage the immune system much more effectively for effective cancer treatment. In this regard, we are also exploring T cell engaging strategy using our bispecific immunofusions, in which one specificity can be targeted to the T cells and the other being TAA-1. Using such a T cell engager, tumor cells and T cells can be brought together, resulting in the activation of T cells and their subsequent attack on tumor cells. In another version of the same strategy, immunoenhancing cytokines or co-stimulatory ligands can be used as part of the bispecific or trispecific immunofusion assembly. However, these remain quite exploratory at this point for further elaboration. What we would like to emphasize here is that this immunofusion platform has the potential to represent multiple first-in-class biologic products for our near-term pipeline. Next slide, #40, please. While I have discussed so far the biologics aspect of our R&D, there are number of small molecule or NCE opportunities that we are pursuing. And there are 2 such opportunities that I'm going to mention in this presentation. The first is a synthetic targeted cytotoxic agent, in which the cytotoxic payload is linked to a small molecule ligand targeted to a tumor-associated antigen. So in similar when as ADCs, except in this case, instead of using antibody, we are using a small molecule ligand as a delivery vehicle. And an application of this is intended for a metastatic prostate carcinoma. The second small molecule opportunity that I would like to refer to here is an immunomodulatory agent that we would like to develop for the treatment of alopecia areata and possibly other immunoinflammatory disease indications as well. You may learn about these opportunities in our subsequent presentations in the years to come. I will stop here and would like to invite Chetan Rajpara, SPARC's CFO, to provide financial update. Chetan?

Thank you.

This is operator. Sir, we are not able to hear you.

Can you hear me now?

Yes, sir.

Good evening, everyone. This is Chetan Rajpara. I plan to go over SPARC's financial and cash position at a high level. Slide #42 please. During FY '21, total income was INR 258 crores, while total expenses were INR 410 crores, resulting into a net loss of INR 151 crores. I would like to mention that FY '21 income includes an upfront payment of US$ million from SCD-044 licensing deal, which is a non-recurring item. Let me update you on our financial results for the first half of FY '22. During the half year FY '22, first half year FY '22, total income was at INR 56 crores, while total expenses were at INR 173 crores, resulting into a net loss of INR 117 crores. Next slide please, Slide #43. As Anil mentioned earlier, the company has raised INR 1,112 crores in July '21 by way of a preferential issue of warrants in order to meet expenses over next 24 to 30 months. Of this, INR 600 crores were contributed by promoters and remaining INR 512 crores were from 30 external investors, including 8 FPIs. The company has received INR 278 crores upfront, being 25% payable by investors on application. The balance INR 834 crores is to be received upon the conversion of warrants by investors within 18 months from the date of allotment. Cash on hand as on 30 November 2021 was INR 12 crores. The company also has a line of credit for INR 250 crores from the parent company, in addition to the bank facilities for INR 218 crores. Of this facility, we have used INR 100 crores as on 30 November 2021. The company has obtained shareholders' approval for raising an additional sum up to INR 1,800 crores by the issuance of fresh equity or debt. The company is in process of licensing certain late-stage clinical assets in order to generate additional liquidity. For FY '22, approximately 40% of our expenses are budgeted for the clinical cost. However, we are aggressively managing our costs and working to control our non-clinical expenses tightly. The company has taken all possible measures to limit the impact of COVID in order to ensure business continuity with minimal disruption. The company will further evaluate and actively respond to minimize its impact on the financial performance. That's all from me today on the financial update. A big thanks to all for joining the call. I will now hand over the call to Jaydeep for facilitating the Q&A.

Thank you, Chetan. We will now open the call for a question-and-answer session.

[Operator Instructions] The first question is from the line of Ketan Gandhi from Gandhi Securities.

Sir, any guidance on PDP-716 and SDN-037 for peak sales potential? I believe it has reduced substantially since the last presentation.

Ketan, this is Anil. We have made a forecast projection for PDP-716 or SDN-037 even in the last presentation. So even in this edition, we are not making a forecast for the program. And we will -- we are working towards NDA submission sometime in early part of 2022 and subsequently launch in 2023. And as we work with the partner, we will try to give market guidance maybe towards the launch.

And any guidance for phenobarbital?

Phenobarbital also is early for us to make a guidance. We need to first go through the process of licensing, the program out, which we are hopeful we can complete in 2022 and then we will work with the partner to give the guidance to the market.

[Operator Instructions] The next question is from the line of Manish Jain from GormalOne.

First of all, congratulations to the entire team on such great progress despite COVID-led massive challenges. So my first question was on vodobatinib that what are the scenarios under which we can get maybe an accelerated approval ahead of the timelines that we have shared in the presentation where the kind of clinical results if they are far ahead of what we are budgeting, if you can give some scenarios that would be helpful?

Manish, on the question specifically on vodobatinib in terms of the possibility for an accelerated approval, I will be stepping into a speculative realm if I say specific scenarios. I mean, we are, as you can see, we're doing a fairly well powered clinical study. And the idea is to create a reproducible outcome from this PROSEEK program and also provide definitive proof-of-concept for the c-Abl hypothesis. And if we have what we hope to have, which is a positive outcome from this trial, at that point, we need to initiate a conversation with the agency. The agency has been fairly encouraging of neuroprotective intervention, as you have seen in the recent Biogen controversial that the Biogen approval, which also is leading to additional submissions in the data pathway in Alzheimer's. So we won't have a conversation in terms of where we can go with the results, and there are several possibilities. And classically, if you look at the pathway for approvals in these settings, it could require 2 additional Phase 3 studies. And the rest of it is a matter of negotiation in terms of whether there is a possibility of accelerated or conditional approval and then following it up with additional studies or getting an approval with one additional study. They're all in the speculative domain. And I, at this point, need to stay aware from that.

Great. No, that answers the question. And one -- Chetan, just one last clarification that you've mentioned a cash position as of 30th of November, '21. Has this been after the upfront payment receipt of Visiox and the upfront payment after -- paying to Biomodifying LLC? Has both of these been accounted for?

Manish, both these payments are yet to be processed. So this position is before making this payment.

I had few more questions. I'll join back the queue.

The next question comes from the line of Anubhav Aggarwal from Credit Suisse.

A couple of questions. First is on vibozilimod where we have partners and pharmas, so just a clarity there. On Phase 2 trials, is Sun Pharma going to fund the trial or you guys will fund it and then that will get reimbursed? Can you clarify that?

No, this program is the clinical program for vibozilimod for Phase 1 is funded by our licensing partner at Sun Pharmaceuticals.

So even Phase 2, which are going to start for all the immunology sites will be funded by Sun Pharma?

Already these studies are on. So it is not going to start. They're currently recruiting at the moment.

So if I see a pipeline, majority of spend for you, for SPARC will largely go towards vodobatinib. Would that be a right understanding?

We have 3 studies in vodobatinib, that is vodobatinib Parkinson's trial, which is a fairly large and global program. We have a smaller Phase 2 program, which is a single center study with Georgetown and a form of Parkinson's called Lewy Body Dementia. And then we have multiple studies on the -- a multi-part study for registration of vodobatinib chronic myeloid leukemia. And then we are also ramping up significantly on SC0-120, which is our estrogen receptive degrader study, which is moving now from healthy human volunteer SAD/MAD leg to actual patients, which is going to consume resources. In addition, as Nitin mentioned, we have potential to add 2 more programs to the clinical pipeline in the medium term.

One more question. When you see over next 4, 5 years, the spend for SPARC, you guys added biologic as a capability, you talked about how significant this can be for the company if all goes against TAA-1. Do you think that that would become the significant amount of focus for the company in future when you -- let's say, when vodobatinib is commercialized, let's say. Post that, when you see the pipeline between neurology, oncology and immunology areas that you are seeing it? Would that become the main focus area?

Well, I wouldn't characterize as main, but it's certainly a very important area for us. I mean, this whole space in which you can engineer in a modular way, multi-specific entities with biologics or a combination of biologics small molecules is something which we are very excited about. We believe that in several therapeutic areas that's going to be the future; whether it's going after treatment resistance in oncology or several autoimmune conditions where there is a need to move the efficacy bar beyond what the field has achieved with single-agent therapies. So in that sense, yes. I mean, that's a big platform player that we have and we have been investing in during the last few years. And now this is giving us visibility to actual tangible programs in addition to the one that we have disclosed today or once we have disclosed today. And there are also other possibilities, both on the biologics side as well as on this conjugated small molecule or small molecule antibody as a combination. So I feel that's something which we will focus on.

If I can ask one more question. The last question is on the in-licensing that you have done for Biomodifying, those antibodies or multi-specific antibodies. Where this will be more used? Will this be more used with your biologic program or -- what you're doing or this is something new completely, which will add to the capability of the company? I can understand what you have in-licensed, but I'm not able to understand how will you fit it in your portfolio?

So that is again going through the same story. If you can actually look at the platform, it becomes either a standalone antibody from the funds of antibodies that we have licensed or it can also become a more head or targeting in other multi-specific combinations using the same platform that we just described. So that's the play. It can actually happen with multiple antibodies and multiple small molecules. So it gives us the modular play to plug and play.

The next question is from the line of Sameer Baisiwala from Morgan Stanley.

A quick question, Anil, is who is your manufacturing partner for 716 and 037?

So 716 and 037 are different Sun entities at the moment. So we have 2 units supporting. For both 716 and 037, we have one in supporting from the Sun system.

Just curious, is it Halol or some other site where it's getting done? I asked this because obviously Halol has the warning letter.

It is not Halol.

And the second is for your NCE pipeline, vodo, vibo. Who is your manufacturing partner for the clinical quantities?

So currently in vodobatinib we have used both internal and external sources. And we will continue to -- as we go into commercialization, as we've committed in the past, we will create multiple options for that product. And in vibozilimod, it's a Sun program and that will continue to be on the Sun platform, and they get to choose the CMC strategy.

And for vodo when you say internal and external, can you qualify that?

Within the Sun network, I think we have used Sun as a manufacturing partner, and we have a relationship on the CMC side, which is spanning across multiple products. So that is the option that which I refer to as the internal option, and the external options are known Sun options.

Just a final one, I know someone -- this was asked the first question, but still coming back because that could be an important dollar inflow when you commercialize these 2 716 and 037 in 2023. So any guidance can you give? I'm assuming that your royalty would be mid-teens or high-teens around that. So in the following year or 2, can this be a substantial or meaningful cash for you to fund your research or any thoughts on this?

So let me say this. I think the structure is correct. I mean, we have upfront. We also have regulatory and approval milestones plus royalties in mid-teens. In addition to that, we also get the 10% equity with Visiox as part of this, which gives us access to an additional life value. But when I say this, we don't have an agreed target both in terms of revenue and revenue and peak sales with the commercial partner. And I would like to have that agreement, which we will hope to have during the course of this year before the launch, before we make a disclosure to the market. But let me go to the core of your question. Would that be sufficient to make a cash neutral from a funding the R&D process? No. If you look at many of these 505(b)(2) cash flows, they're not going to be substantial from a coverage of $50 million, $60 million of annual spend that we have. It will be a substantial contribution to the overall cost, but it is not enough to cover that. So these programs will give us some non-utility funding, but not enough to make us cash neutral.

The next question is from the line of Ketan Gandhi from Gandhi Securities.

Sir, I was looking at the corporate presentation presented in January '21 on the website of the company, where for all this molecule, you have peak sales potentials of $10 million. And in current presentation, we are mentioning $20 million. So I want to understand which molecules have led to this additional increase of $10 million?

So there are -- if you look at the main difference between the disclosure that we've made early part of 2021 and now is the disclosure of the ADC program. And that ADC program with a tumor antigen, which is getting expressed in multiple tumors has a substantial peak sales impact. And we also believe that there could be a potential rerating of the S1P1 class, but we haven't taken much from that. The big differences here is essentially coming from disclosure of an additional program which can have multiple legs.

The next question is from the line of Jayesh Gandhi from Harshad Gandhi Securities.

Sir, for our SCD-044 program, can you help me out in understanding the market opportunity for psoriasis and atopic dermatitis?

Well, again, with the carrier that I won't give you a specific number as a forecast given this is a program currently owned by our commercial partner, Sun Pharma. Let me offer some comments broadly in terms of the opportunity space that I see in dermatology, autoimmune conditions. If you take the indication like psoriasis, you have fairly mature set of options on the topical part of the treatment paradigm, that is the steroids and non-steroidal options, which are very mature. And psoriasis also have seen a substantial number of biologic entities with very high level of activities on the other end of the spectrum. But if you look at the middle part of the therapeutic continuum where patients and prescribers are looking for safe oral options. The option currently is only apremilast, apremilast which used to be a Celgene product, which is sold to Amgen for almost $13 billion. So there's a dearth of really good options on the oral end of both psoriasis and atopic dermatitis. And that's where the programs like the S1P1 programs also take 2 programs are trying to position themselves. And it also gets a significant boost because of what happened to JAK inhibitors, which is emerging as a class of choice in atopic dermatitis. I assume recently both Pfizer and Amgen and including inside topical JAK inhibitors got black box warning, creating significant safety concern around that class. So SCD-044 and S1P1 can evolve as a class alternative to JAK inhibitors in dermatology and beyond. So we believe that it's a substantial opportunity. But at the moment, I don't want to enter into giving a specific number, which I think should come from Sun at some point, at an appropriate time.

And last question from me. So can we envisage a year by which we will be self-funded for all our programs in the future?

So the answer is unfortunately no. We have a fairly robust clinical program, and the success of these clinical programs will decide how soon we can be cash neutral. Not just the success, it's also a function of how long we want to be keeping these ourselves. If you see the outcomes that we are projecting for 2023, if we are fortunate to realize those outcomes, they create cash events and significant cash events which can make the company cash neutral. But there is a strategic choice at that point, whether we raise additional capital to run the next leg and capture a substantial part of the value or you settle for encashing the program at this stage. So those are significant decisions that we need to take, particularly on vodobatinib and in some of these early-stage programs that we're talking about, and the timing of when we can become cash neutral is going to be a function of that. But at the same time, when you look at the way to look at the valuation of companies like SPARC or early-stage clinical portfolios, with every progressive validation clinically, the probability of success of the program goes up, and therefore, the discounting of the program should come down. So in that sense, even though it may not result in actual cash coming in if we decide to stay with the asset, we should re-rate based on the incremental value of lower discounting because of higher probability of success.

And sir, one more question, if I can, please. I mean, do you see any peer of Sun Pharma, Sun Pharma Advance Research globally? I mean, any company globally which is having a model like SPARC, business model like SPARC?

So yes, that's an interesting question. I think there are a lot of companies globally on innovation, and they are on a spectrum. In one another spectrum, we have a single product or a single platform company. This is a binary bet on a program. And if you look at most of the pre-money universe of biotech, the majority of those companies are single product or single platform binary bet. There are very few companies which are making a broader system play in terms of creating a translational development system, which can come up with a substantial number of products. There are companies, for example, you have in CNS, there are several companies now coming out which fee-back companies. Pfizer recently did their -- taken out their CNS portfolio. It has become main support company. And there are other companies with substantial number of programs. But if you want to look for a parallel, I think the Chinese pharmaceutical companies are at better parallel, because there are several elements of this SPARC story reflected in those companies, like for example, BeiGene. And if you look at BeiGene, they are probably ahead of us in terms of when they started and are in the U.S. market with their own innovation. But they have slightly different model in the sense they pursue the Chinese domestic opportunity more aggressivity for initial approvals and then take those products to the U.S. But they have created enormous level of value-based on that model, and there are other Chinese companies also in that structure. So these are -- ultimately, they just negotiate China-U.S., Corridor or China-Europe, corridor. And we believe that SPARC is probably the most invested in and mature vehicle from in the U.S. corridor standpoint. And so in that sense, they are somewhat of an appropriate comparison.

[Operator Instructions] The next question is from the line of Anubhav Aggarwal from Credit Suisse.

Couple of questions. One is on vibozilimod. So in Slide 28 you have talked about initial signs of efficacy for the molecule that you talked about 55% reduction in SAD and almost 60% reduction in MAD. So just trying to understand versus, let's say, apremilast or very early days, I understand, but just trying to understand the potential from this early efficacy data for let's say for BMS drug, which is going to get approved soon. How would this drug compared to other oral options in the space for psoriasis, let's say, and then for atopic dermatitis in the Phase 3 for example?

Let me unpack that question. If you look at what is being presented in that slide is that the lymphocytopenia for SCD-044 at certain safe doses goes up to 50% to 60% at therapeutic doses that we are proposing at this point. We cannot use that marker as a comparison with apremilast or TYK2 because mechanistically they are different drugs. This is a mechanistic pharmacodynamic marker for the S1P1 mechanism, which works in -- works through secreting T cells in the lymphatic system and then creates peripheral lymphopenia as in bringing down the circulating T cells. Compounds like apremilast or TYK2 then work through that mechanism. So if you want to have a direct clinical comparison, we need to wait for the Phase 2 to see how the lymphopenia translate into a PASI 75 score in a Phase 2 setting. If you look at apremilast's PASI 75 score is somewhere in the 30s which is a very average response. Our hope is that a 50% lymphopenia will translate into something better than or substantially better than the 30% PASI 75 score that sell cross -- I mean, apremilast has seen. Does that answer your question, Anubhav?

Yes, it does. And just the second question on this same molecule is, when you talk about Phase 2 readout in 2 years from now. So when you say 2023, are you referring to early CY '23, fiscal '23. Can you just -- or late '23, what you're talking about there?

No. I would say that's the disclosure that needs to come from Sun. At the moment, we can only say that we expect this to come in calendar 2023.

So then just -- it's a 240 patient trial, Phase 2, and if you start dosing then and the PASI 75 score should be clear in, let's say, 6 months. So certain time for recruiting patients and then dosing them. Just trying to understand why is it 2 years that you're talking about the timeline here?

So some of that is related to COVID and COVID has been a major disruption in terms of getting sites into the trial. And this is also a complex trial, in the sense, it's not just a topical product in dermatology. Here we have substantial cardiac monitoring that we need to do to ensure that clearly cardiac 50 advantage and profile from the study. So it requires both in terms of the conduct of the study and also COVID as a backdrop, we are conservative in terms of projecting our timeline at the moment.

And last question is on your 2 -- Visiox Pharma deal that you've done on 2 molecules. Just trying to understand, this is a new company for me, Visiox Pharma, can you -- want to talk about a little bit here that what kind of resources they are putting on the table that they can deploy behind these 2 products or target products? Secondly, if let's say in the agreement between you and Visiox, is there something that in 2 years after the launch of -- sort of time period, if the sales doesn't ramp-up after a certain point of time, you can take back molecules, et cetera. So it's a new company, I'm just trying to understand that you repose a lot of confidence there? Do you take any equity stake as well. So how is this partnership different from a normal partnership that we'll do with an established firm?

So a couple of things. One is they propose a fairly aggressive marketing plan for this program, and we are happy about the commitment and the sourcing that they are showing for the program. It's also the pedigree which is giving us confidence, and this group has done something similar and very impressive in the CNS side. And we will work very closely with them to ensure aggressive launch for this program and to realize the full potential. And we will review the performance of the collaboration on a regular basis as we usually do with other collaborators and see how it goes.

The next question is from the line of Sameer Baisiwala from Morgan Stanley.

Just wanted to check, maybe I missed your comment. In your next round of fundraising, INR 1,800 crores, is it just enabling or you are in the process of doing it at the moment?

At the moment, we have an enabling resolution. An enabling resolution allows us to explore our options, and we are in that phase, Sameer.

So safe to say it's something real and credible that if markets allow, you will execute over the next, whatever, 4, 6 months?

I will phrase it exactly like that, but we have a shareholder approval for going ahead with exploring this additional raise of INR 1,800 crores. And we have in that enabling that solution allows us to explore different modalities, not just equity, but also debt and other instruments. So at the moment, we are setting our options and we will take a call on what is the best way to move forward or whether to exercise this enabling resolution in the future. So I wouldn't frame it quite the way you framed it.

The next question is from the line of Manish Jain from GormalOne.

Quite exciting to see the kind of progress that we have made in ADCs. Just in terms of capability set required to take it from the current stage right through to the market with NDA approval, what are the missing capabilities that you need to create?

I think if I look at the broad spectrum of different phases that can lead or take this product to clinic and beyond, we have the developmental capabilities internally in exploring these effects and characterizing them preclinically and also preparing them for the IND and also taking it to clinic. Those are competencies that we built over the years. Where we currently do not have the internal competencies are in the CMC side. And we may have to work with external partners in terms of both scaling for IND-enabling studies as well as for clinical studies, and we are in the process of evaluating potential manufacturing options and partners for that. So if I were to look for key gaps in the process chain, I would put CMC as an area where we need to have a collaboration. And that's something which is strategic for us as we kind of scale up our intel in this space, we may have to kind of have multiple options there.

[Operator Instructions] As there are no further questions from the participants, I would now like to hand the conference over to Mr. Jaydeep Issrani for closing comments. Thank you. And over to you, sir.

Thank you, Faiza, and thank you, everyone for being on the call today. In case you have any follow-on questions, feel free to reach out to us. We will now close the call, and I thank you once again for joining with us for the call today. Thank you, everyone. Bye, bye.

Thank you. Ladies and gentlemen, on behalf of SPARC, that concludes this conference. Thank you for joining us, and you may now disconnect your lines.