Please note that this conference is being recorded. I now hand the conference over to Mr. Jaydeep Issrani from SPARC. Thank you, and over to you, Mr. Issrani. Thank you, Neil. Good evening, ladies and gentlemen. My name is Jaydeep Issrani, and I head the Business Development and Investor Relations at SPARC. On behalf of SPARC, I welcome you to SPARC's yearly update on strategy and program updates. I'm joined by our CEO, Mr. Anil Raghavan, and members of SPARC senior management team for the call today. As we have done in the past, we will be using similar format for our discussion today. That is, the presenters will walk you through the slides, after which the call will be open for questions and discussion. The presentation for today's discussion was shared earlier. If you have not received, you can download the presentation from our website, which is www.sparc.life. Before we start today's discussion, 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, and actual results may be different from those projected in today's presentation. I will now hand it over to Mr. Anil Raghavan for his presentation. Over to you. Thank you very much, Jaydeep, for kicking us off. Hello, everyone. It's my pleasure to welcome you to SPARC 13th Annual Portfolio Update. As always, we are immensely grateful for your continued engagement and support. That means a lot to us. Thank you for taking the time to be with us today. I'm sure most of you have been regulars on this call, so you know the routine. We have the SPARC management team with us today on the call. Most of us are on these calls for some time, but we have a new addition, that's Dr. Venkat Palle, who joined us as the head of Drug Discovery and Preclinical Development late last year. Dr. Pallei comes with an impressive trail of achievement, and we are very lucky to have him leading charge in discovery and preclinical development. In terms of our agenda today, we will begin by covering certain important elements of our strategy. I will also give a bit of the lay of the land of our late-stage portfolio and provide some guidance on what to expect in the short to medium term. After which, we will spend much of our time today on three things. Dr. Siu-Long Yao will talk to us about the clinical programs, that's vodobatinib in PD and CML, and vipafoslin in atopic dermatitis and psoriasis. Dr. Vikram Ramanathan and Dr. Nitin Damle will provide updates on the programs of, update on the progress of two important programs, which we introduced you last year as SCD-153 and SBO-154. We will conclude the presentation with brief comments on our financial situation and cash burn from our CFO, Chetan Rajpara. With that, let's go to slide 5, please. Here we have a recap of the shifts that we have taken in the last few years, from being a primarily delivery system-focused company to an approach which embraced the risk profile of the modern biotech fully. In a sense, towards the portfolio of assets holding significant promises, improving the standards of care, and making an impact on the lives of patients we hope to serve, while carrying multiple layers of risk. But our model differs from the contemporary biotech business model on many fronts, and we have spoken about some of these differentiating factors at length in the past. Our capture operation is one of them, and low cost of failure, breadth of our portfolio, compelling founder's vision, and the founder group's willingness to back it up with appropriate financial commitment, and so on. We've also spoken about our efforts to narrow our therapeutic focus and sharpen our execution. So I don't plan to go over these foundational elements of our pivot in more detail today. But I would like to highlight two other points before we go into the rest of the presentation. In the last few years, we have made a significant push towards strategic partnerships with tier-one academic research systems globally to access high-quality early science. We can clearly see the impact of that sustained effort in terms of collaborative programs moving to clinic now. That is an important validation for a very important tenet of our strategy. We also have additional early-stage, undisclosed preclinical programs in collaboration with some of the marquee institutions around the world. A productive bridge to external science has always been part of our vision and differentiation strategy, and we hope also that the bonds and competencies that we built in establishing these structures are going to be extremely useful in further building out our portfolio. We really look forward to that. I also want to touch upon an element which is not specifically called out in this slide. That's our changing modalities mix and the maturation of our biologics group. We've completely moved out of the NDDS programs, which was our mainstay in years past. Traditional small molecules, though, is a significant share of our effort and will continue to be so.... We think small molecules will remain an important part of the therapeutic toolkit because of the larger swath of intracellular targets that we can address with appropriately designed small molecules. We have made exploratory investments in building an in-house biologics capability, almost ground up under Dr. Nitin Damle's leadership. Those efforts are now turning real with this first asset, an antibody-drug conjugate, approaching its clinical entry in 2024. But more importantly, we have built a competitive competency which can engineer antibody therapeutic constructs, be it traditional naked antibodies, drug conjugates, or bispecific or multispecific antibodies, and scale them to clinic. We are also leveraging our understanding from the ADP effort to create small molecule drug conjugates, which is emerging as an important therapeutic class. Additionally, we have several exploratory efforts in newer modalities and have taken some really meaningful bets around pushing our modalities even further. We look forward to bringing additional programs from the biologics basket for sure, and hopefully even from newer modalities in the short to medium term. So, in recap, I want to emphasize the one point I made during our call last year. For investors with an appropriate risk appetite and an ability to grapple with translational risks in pharmaceutical development, SPARC offers a contemporary story and a compelling one at that. And that story is getting more real now than, than probably at any point in the past, and we have several important catalyst, catalytic events coming up in 2024. So let's go to the next slide, it's slide six. I want to go over some of that. This slide has a, a straightforward listing of the series of data and phase transition events set up for the portfolio in the calendar year coming up, that's 2024. Some of them will have the ability to move the SPARC valuation substantially based on data, of course, either way. So let's go over the list. First up is PROSEEK interim analysis. We are doing an administrative interim analysis, which will give us the primary endpoint and secondary endpoint trends for 442 patients, plus additional biomarker trends. The important business objectives of this administrative process is twofold. First, to initiate potential licensing discussions before the public release of the full data set, and secondly, to initiate planning and setup activities for the regulatory interactions and potential phase III trials of vodobatinib in neurodegenerative disorders. We plan to maintain the study blind for everyone outside of a small group covered under a very strict confidentiality commitment. We expect two more important program milestones in quarter two of 2024. SCD-153 will have its first data read out, which will help us develop an initial understanding of potential safety profile of the product. Also, more importantly, an ability to move to mass steady-state patients, which can give us a lot of information regarding target engagement and efficacy markers, plus some early indication of potential therapeutic dose. We will also cross out the patient enrollment for our atopic dermatitis program, which we'll talk a bit more in the Q2. In the Q3 of 2024, we will have PROSEEK fully read out. As you can see, that is probably the most important data catalyst for the company currently, and certainly most clearly was. That will lead to setting up the end of phase II meeting with the FDA to agree on the registrational path for vodobatinib. We will look to initiate the phase III program in Q4 and start exploring the fuller opportunity, which I will touch upon in a moment in the rest of the slide set. We will also look to conclude our partnership strategy for the asset. PROSEEK will also give us clarity in terms of our resourcing requirements and options. So that is a big data event. We have three significant milestones coming up in the last quarter of the calendar. Our first biologics IND, our antibody-drug conjugate program, is currently tracking to that plan for an IND in Q4. We will then have phase II data from atopic dermatitis study, and from a SPARC standpoint, that will set the stage for additional milestone payments from our licensee, plus we can initiate a PA consultation and pivotal trial planning for atopic dermatitis. And finally, we will also have the multiple ascending dose studies started in Q4 of 2024 for SCD-153. We've only listed the data and milestone events from our larger programs, here in this thing. We will also have additional milestones like the refiling of dronedarone and potential progress in enforcing our exclusivity for Sezaby. I'll come back to those programs, towards the end of my comments. Before we go to the next slide, I want to summarize all this very briefly. So 2024, we'll see several big moments with SPARC, including opening the lid on a potentially game-changing program for the company and hopefully for the field.... I can't overstate the significance, so I want to spend the next few slides, next couple of slides, to fully unpack the true meaning of these milestones with SPARC and shareholders. Slide seven, please. First, the big news from last week, PROSEEK achieved its recruitment target late last month. We set out to recruit 504 evaluable patients. We ended up with 513. Su will give you more color on both the state of the study and expectations going forward. But I want to recognize the team and the effort that went into completing the accrual of the study. This is one of the largest phase IIB programs currently active in early-stage Parkinson's disease globally. We started this trial in full swing when health systems around the world, unfortunately, began to shut down because of the pandemic. COVID created enormous challenges in prosecuting this program. So we're genuinely happy to be here and want to thank patients, their families, our investigators, and site staff around the world, including some really passionate physicians in India, who supported this program wholeheartedly, and our execution partners and the large team here in SPARC, who drove this drive program with enormous skill. As I mentioned in the previous slide, we expect the interim analysis completion by end of Q1 2024, and the full readout and phase III initiation soon thereafter. That indeed is something we look forward to. So why are we so excited? PROSEEK will give us probably the most definitive proof of concept for one of the most important hypotheses in the neurodegenerative diseases field, that is, c-Abl inhibition as, approach for neuroprotection. The role of excessive reactive oxygen species and the redox imbalance it creates in triggering a cascade of events that results in neuronal toxicity and death, has been identified as a potentially intervenable pathway across the neurodegenerative spectrum for some time now. Dr. Ted Dawson of Johns Hopkins and several other groups around the world provided compelling mechanistic and pharmacological evidence supporting the Abl story. But this hypothesis has never been fully tested, as the field lacked an appropriately specific agent with the relevant pharmacological properties, particularly good blood-brain barrier penetration and safe dose. That is the promise of vodobatinib. A sub-nanomolar inhibitor of c-Abl, ultra-specific to Abl1 and Abl2, and that crosses the blood-brain barrier sufficiently to ensure adequate coverage with a peripheral safety profile, which makes clinical exploration in neurodegenerative diseases feasible. And importantly, that promise was delivered by vodobatinib in preclinical and early clinical studies. The totality of evidence we have from everything we have done so far in this program was directionally consistent and supported translation. So in that sense, PROSEEK promises the first real validation for the c-Abl pathway in a sufficiently trial-sized global trial. With the right patient setting, that's pre-L-DOPA patients with a DaT confirmed diagnosis, and the right duration to see an effect beyond the placebo impact. 40 weeks in Part One in our case, followed by a long-term extension period of another 40 weeks without L-DOPA. I want to talk about the broader implications of the positive outcome in terms of the opportunities it presents. But before that, from an operational standpoint, our immediate priority coming out of PROSEEK is the finalization of the late-stage development plan, including closure of our partnership strategy and getting regulatory clearances, FDA and other agencies around the world, and initiation of this first registration program. And those will be the most important execution priorities of SPARC next year, if you see the data that we hope to see in PROSEEK. So now let's go to slide eight. For a little bit of big picture on vodobatinib. The way to look at the opportunity PROSEEK validates is to look at various layers of the hypothesis and see the context in which it is tested. At its core, PROSEEK gives direct validation to the relevance of c-Abl inhibition and oxidative stress response modulation in Parkinson's disease. So if inhibition of c-Abl means bending of the degenerative curve in a significant manner, that not only slows the progression during the initial symptomatic therapy phase of that PROSEEK target, but it can also extend the period of effective management under dopamine therapy. And at the starting phase of the spectrum, the other end of the spectrum, biological understanding of prodromal PD and precursor conditions like constipation and REM sleep behavior disorder, can offer additional opportunities to intervene early and intervene proactively. So the inner core of opportunity for vodobatinib, and maybe for other selected brain-penetrant Abl inhibitors, is to become a background therapy across the PD treatment continuum. The next layer comprises a set of diseases characterized by alpha-synuclein aggregation, like the multiple system atrophy or Lewy body dementia. In these indications, several pathological hallmarks of PD are at play. but also some important differences, like the area of the brain that gets affected. We believe that a compound like vodobatinib, which can modulate or moderate oxidative stress response and get distributed uniformly across the brain, is an agent worthy of testing in the immediate adjacent disease. That aspect, from an epidemiological and inadequate standard of care standpoint, offers some really large opportunities. Then there is an outer ring of possibilities driven by other culprits, like activated Tau or A-beta or SORD in diseases like Alzheimer's and ALS. Our early studies in iPSC-derived neurons indicated some of those possibilities, and we plan to continue studying vodobatinib and its promising backup theories in these conditions. So summarizing the last two slides, we have reached a significant and important milestone with the completion of the enrollment targets for PROSEEK. We expect substantial data flow, which not only validates our hypothesis, but has the potential to teach us a lot more in terms of the disease biology and maybe the heterogeneity of the disease and its response, correlation of several important candidate biomarkers, and so on. That sets up multiple patient settings, which can potentially make vodobatinib the backbone of standard of care across the neurodegenerative continuum. And that's a huge deal, and, and we are understandably super excited about it. Now, let's move on and examine the key watered question, which I'm sure all of you have in your mind. So let's go, go to that, and slide nine, please. Slide nine. Much of the current biotech landscape, if I can step back for a minute, consists of companies created to test 1 interesting hypothesis. Investors and teams move on, either cash out on success or move into something else on failure, to the next shop. That's the typical biotech story. But we are architected somewhat differently with a substantial internal discovery, translational and clinical development capabilities with a cost to failure advantage. We're designed to spread the risk across an actively managed portfolio, learn from our successes and failures, strive to improve the quality of our competencies, and deliberately build optionality as we come to critical decision points like the one that we are approaching now. And we believe we have meaningful optionality. Let me take a minute to explain. SPARC optionality has two coordinates: at a program level and at a competency level. At program level, we have multiple options and combinations to pivot to, if we need to. Immunology offers two high-value options in vipafoslin and SCD-153, and we expect to see additional value unlocking data from vipafoslin in the coming years. We will also see the data building up for SCD-153. We have a broader set of options to go to in oncology, where the highest value bet probably is the MAC-1 platform, which can generate multiple products using the ADC and bispecific construct. Vodobatinib CML, of course, offers a relatively lower value, but significantly surer option to leverage the asset if we unfortunately fall short in neuro. But I think it is also equally important to consider the optionality provided by other, other part of value creation, which is our competencies. SPARC represents one of the most or one of the most sophisticated translational engines out of India, attempting to innovate for the world. Across the value chain, from the ability to develop assets in multiple modalities, to self-sufficiency in various pieces of translational development, back to in multiple therapeutic areas, and the ability to design and execute clinical programs globally. We have had substantial learnings from our successes and failures, and that is one of our biggest assets differentiating the program. I'll go over a few specific points on our program here in the next couple of slides, but let me say this in summary. Investors evaluating SPARC should look at it, our, our portfolio, as one substantial opportunity to, move the standard of care in a very large medical unmet area. That's vodobatinib, backed up by a larger number of different hedges across immunology and oncology, with many of them reaching important developmental milestones in the near future. Now, let's go to slide 10 to take a look at the immunology program. I've already spoken about these two programs in my earlier comments. Just to highlight a few points, I have a couple of observations. One, vipafoslin, proof of mechanism for S1P1R agonist exists from competing clinical programs in dermatology and a wider swath of indications outside of dermatology, like IBD and Crohn's. As previously disclosed, we have reached target pharmacodynamic levels at safe doses, which is well correlated with efficacy of this class. We've completed a pooled analysis of safety data from 125 patients across our atopic dermatitis and psoriasis protocols, and managed to remove most of the extensive cardiac monitoring initially required in this trial. We will go over this in a little bit more detail during the clinical presentation from Siu. And we are now aggressively scaling this program with significant expansion to Europe and Canada, and we are also adding a substantial number of new sites in the U.S. From a competitive positioning standpoint, both in atopic dermatitis and alopecia areata, the current standard of care, the oral standard of care, I mean, consists mainly of JAK inhibitors, which carry a black box warning and significant safety complexities. Both vipafoslin and SCD-153 has the potential to be much safer options in alopecia areata and atopic dermatitis. And on a separate note, both these programs offer excellent examples of our SPARC strategic partnering process. Vipafoslin, as you may know, was developed originally in partnership with a French biotech company called Biocystex, and SCD-153 is an ongoing collaboration with two very accomplished groups, one from the U.S. and one from Czech Republic. We started our collaboration with these groups as a joint development program with an option to license the IP, and I'm really happy to announce that SPARC exercised that option to license the intellectual property supporting this program. You may have seen this, press release earlier today announcing the definitive licensing agreement, and that allows us to move forward with SCD-153 as a fully owned SPARC program. So, let's move to slide 11 now for oncology efforts. CML component of vodobatinib was always meant as a backup for the Parkinson's program. And we have had significant regulatory interactions recently about the nature of the data package the agency would like to see for registration. In line with FDA's broader strategic shift towards encouraging companies to explore marketing approval in earlier settings, FDA suggested a comparative trial in two line failed patients up against the last line, that is, the post-ponatinib settings. We will go over additional details on the emerging design of the expected clinical study in the clinical segment. We are also reexamining the cost and timelines before deciding to go it alone or partner at this stage. So vodobatinib in CML, as I said earlier, is a surer hedge. Surer because of the clinical validation and alignment with FDA on a path to registration, and we will have clarity and readiness to move forward when we reach that decision point pause to proceed. We've discussed the ADC program earlier, and Nitin will do a deeper dive later. But let me say this, we see enormous opportunities in antibody or small molecule-targeted preferential delivery to cancer cells. These platforms can be leveraged for the delivery of a wide set of payloads, ranging from small molecule, traditional cytotoxins, highly potent targeted therapies with limited safety margins, and even RNA therapeutics. MAC-1 give us a differentiated platform, which can open up multiple product opportunities. Our oncology effort also carries additionally some significant interest in certain other target classes, like new, synthetic vitality pairs or exploring ways to intervene in the RNA process more broadly with other agents and other modalities. But, before I look to summarize, I want to talk briefly about how our competency has evolved and how it offers another level of risk mitigation. Please go to slide 12. As I said, we don't look at SPARC just as a portfolio program, though they are the key drivers of the current value. A significant part of our proposition is our process, which is refined over a long period of time, involving learning from our successes and failures. We believe that SPARC development process, in terms of the targets we seek to address, validations that we insist, developability considerations around the nomination of an asset, clinical strategy and execution, and adoption of biomarkers, and our overall development toolkit, all have come a long way since we spun out of SPARC, I mean, SPARC, spun out of SPARC. Equally importantly, our portfolio management process evolved into a rigorous, objective methodology, which puts a premium on establishing and enforcing smart data scale gate, which allow us to kill unviable programs early and cheap and completely. So SPARC is not just a bet on a high-value portfolio, but on a system and competency which has been evolving and invested into over a long period of time. I hope you share our excitement and confidence beyond the here and now, which is certainly exciting, but also for the long run. Let's go to slide 13, please. We will have some additional comments on our cash flow and bond from Chetan later on in this presentation. But want to make a few observations on additional cash movements outside of vorapaxin and our early-stage programs we've talked about here. Our partners have successfully launched Elyxyb, Xelpros and Sezaby as current commercial products in the U.S. Elyxyb is commercially commercialized by our partner, TriLine, and we've achieved early run rates indicative of a fairly robust growth trajectory. Unfortunately, we have had supply disruptions from the Halol import alert. We've managed to find an alternative vendor and are in the process of finalizing our plans to relaunch the product in the US. Certainly, that's the benzyl alcohol-free formulation of phenobarbital got approval in the US last November. Sun is our commercialization partner, and Sun has launched it again in the US during Q1 2023. As you may know, this product has a seven-year exclusivity, and enforcement of that exclusivity is a key value driver for the growth of this asset. We are working diligently to make the case for the agency and other stakeholders to enforce this exclusivity and also remove unsafe options from the market. Let me not go to the specifics of the numerous initiatives that we are undertaking here, and some of them are listed on this slide. On PDP-716, we have completed the submission of the NDA. As I indicated earlier, we received a complete response letter from the FDA indicating certain deficiencies in the external API manufacturing plant. There were no additional clinical data requirements indicated at this time. We have already identified an alternative API source and are in the process of planning a resubmission in 2024. And finally, as we mentioned earlier, we expect the topline of phase II and initiation of phase III program in atopic dermatitis will be out a little more. That triggers additional cash milestone for SPARC. Plus, we believe that there may be opportunities to commute future revenues from this program to generate additional cash to support the development programs that's required for us to seek readout. In the next two slides, at 15, 14, and 15, we have summarized the portfolio and key milestone expectations. I don't plan to go over them in detail, except for one program, which is our oral dexamethasone strand. We took the program into dose escalations in patients. Based on data from competing programs, it is becoming clear that effective clinical differentiation for this class as a whole is becoming a challenge. With small effect sizes, the program needed very large clinical studies and may not be the best use of capital for SPARC. Our portfolio review late last year, and as we disclosed earlier, down prioritized this program, and we can go into additional detail if required during the Q&A. With that, let me now transition the call to Dr. Siu-Long Yao, who heads our Clinical Development Group, for the next leg of the presentation. He will cover the clinical programs in much more detail, and I look forward to seeing you back during the Q&A. Thank you for your time. Over to you, Sul. Thank you, Anil. As Anil mentioned, my name is Siu-Long Yao, and I'd like to add my warm welcome, especially to the many who have been accompanying us over the years. Sorry, I can't hear you well. I'm coming more clear. Okay. How about now? Uh, yes. Is that better? Yes. Okay. I oversee clinical development, and I'll walk you through our major clinical programs. So slide 17. The first program I'll describe is vodobatinib, our c-Abl inhibitor for Parkinson's disease. Slide 18. Okay, thank you. This slide gives you some basic background on Parkinson's disease. There are a lot of people affected, approximately 7 million across the world, and the prevalence is growing. There are anticipated to be 14 million infected by 2040, actually. So in fact, the growth of the disease is outpacing total population growth, meaning that the market is enlarging. The therapy we have is one where we believe we can modify the disease and actually change its trajectory or course, rather than just treating its symptoms. So the pictorial at the bottom of the slide gives you an overview of the disease and what we're talking about. I'd like you to focus on the middle row first here. There you have the disease starting from a prodromal stage on the left and progressing to diagnosis, maintenance treatment, complex treatment, and finally, palliative treatment. On the other rows, both above and below the middle row, there are major clinical events depicted that need to be managed in the care of these patients. As Anil mentioned, we're initially studying vodobatinib in the prodromal, diagnose/diagnosis stage, but if it works, there's potential to extend it to all stages of the disease. So next slide, please. On slide 19, this is a reminder of the design of the phase II proof of concept study named PROSEEK, Anil alluded to. The study consists of three arms of placebo, a high dose of vodobatinib, and a low dose of vodobatinib. Part one is the key part of the study, where subjects are treated for 40 weeks, and the effects of treatment on the primary endpoint of part three of the UPDRS scale is assessed. The study is fully enrolled, as Anil mentioned, and we anticipate having some initial interim data in March 2024. Part two of the study is a long-term extension, where subjects who initially received placebo, along with subjects initially treated with 384 milligrams, receive more treatment with 384 milligrams for an additional nine months. Subjects randomized to 192 milligrams continue at that dose during the extension. So right now, approximately 87% of the eligible Part One patients have rolled over into Part Two, and completion of the overall study is anticipated in May 2025. So next slide, please. Slide 20 gives you an idea of the distribution of patients across the world. On the Y-axis is the number of patients from each region, and going across the bottom on the X-axis is the region. Over 40% of the patients have come from the U.S., as you can see. Some additional detail about what we've seen so far is summarized in the other bullets on the right there. There were grade 3, 4 events in about 6% of the patients, and GI events and rash were the most common in EE. We do have a data safety and monitoring board, which is unblinded to treatment allocation and reviews all safety data in an ongoing fashion, and they've not recommended any changes in the conduct of the study following 6 interim reviews. Next slide, please. So slide 21 summarizes some of our biomarker plans for the study. The biomarker subgroup in the study consists of over 150 of the 500 course, patients in the study, which translates into over 50 patients per arm that will have biomarker data. What I just told— You know, what I just said there is a, in fact, a simplification, however. In fact, some of the biomarkers will be obtained in all subjects, but in general, we are targeting to get 50 subjects in each arm with all biomarkers. The biomarkers that will be obtained upon study entry and exit include dopamine transporter scanning, skin out and skin alpha-synuclein content. Target engagement will be assessed by c-Abl and CSF status, and neuronal death will be assessed through neurofilament light. Pharmacodynamics will be assessed through various downstream targets that you can see listed there, and we have smartphone-based measures of patient functional status. Slide 22. This slide summarizes, provides a summary of the concomitant studies in the program. There is an ongoing cost density study, and we plan to perform a relative bioavailability study, along with some drug-drug interaction studies to support the phase III plans. A human ADME study is also planned. Next slide, please. In slide 23, there is a summary of some other related alpha-synuclein-based disorders that could benefit. There are the other classical synucleinopathies, such as dementia with Lewy bodies and multiple system atrophy, along with the prodromal synucleinopathies, such as primary autonomic failure and REM sleep behavior disorder. On the right is a western blot that summarizes the activity of vodobatinib in a model of Alzheimer's disease. Molecular weight is depicted on the Y-axis, and treatments used are displayed as columns, as columns. In this case, treatments were done in duplicate, so there are two columns for treatment with controlled DMFO and two columns for treatment with vodobatinib. As you may know, tau is the protein of interest in Alzheimer's disease, so I'll ask you to focus on the phospho-tau and total tau rows in the middle of the block. As you can see, treatment with vodobatinib significantly diminishes both, suggesting that treatment with vodobatinib may be effective for Alzheimer's disease. Slide 24. So this slide, transitions to our program with vodobatinib in chronic myelogenous leukemia. Next slide. On slide 25 is a summary of the commercial landscape for CML. The graph on the left consists of rate per 100,000 on the Y-axis and year going across the X-axis. The top curve is the incidence of the disease, and you can see that it's steadily increasing over time. At the same time, the death, the rate of death from CML is decreasing, so that overall, the prevalence of the disease or patient population is actually increasing. In fact, the current market is valued at $3.5 billion, and you can see on the graph on the right, the graph on the right gives you an idea of the major drugs used in the treatment of CML and their, and their respective market shares. The next slide. Slide 26 summarizes more recent data we've seen with vodobatinib in CML. The, the figure you see is a summary of all the patients that we have efficacy data on. The rows represent the disease status of the patient population, either at baseline in the top row or following treatment with vodobatinib in the second row. The percent of the population is represented on the X-axis. As you can see, most patients were not in response at baseline, but following treatment, over 40% of the patients have achieved responses, which is really remarkable in this patient population, many of whom were resistant to ponatinib. Responses were very durable, as you can see in the last bullet, where median time on drug was over 32 months. Next slide. Slide 27 provides some preclinical data that supports our plan to do an earlier life study with a larger market potential. On the Y-axis, you have tumor volume in mouse xenograft, and on the X-axis is time and days. The top curve represents results obtained with vehicle control. The line below that is the tumor size following treatment with nilotinib, a representative second-generation tyrosine kinase inhibitor for CML. You can see that there is some control of tumor size, but treatment with vodobatinib, either at a lower or higher dose in the bottom two curves, is much, much better. This, along with other data, suggests that we can beat existing second-generation treatments in earlier lines of therapy and capture a larger market share. In slide 28, we've had discussions with FDA, and they are actually quite supportive of getting an initial approval on an earlier line of therapy. This is consistent, as Anil mentioned, with their Project Frontrunner initiative. Our plans are summarized in the diagram below there, and we're planning to do a randomized study against one of the second-generation treatments for CML, with a primary endpoint of major molecular response. So slide 29. The remaining slides summarize vipafoslin, a sigma-1 agonist for the treatment of psoriasis and atopic dermatitis. Slide 30, please. As I mentioned, the two initial indications we're targeting for vipafoslin are psoriasis and atopic dermatitis. The prevalence of psoriasis in the U.S. is approximately 8 million, and the market is dominated by biologics. Though there are biosimilars, penetration has been limited to date. For atopic dermatitis, the U.S. prevalence is even higher, approaching 18 million. Though JAK inhibitors are available, as Anil mentioned, they're associated with several black box warnings, such as thromboembolism, cancer, major adverse cardiac events, and even death. On slide 31, summarizes the design of the phase II dose-ranging study for psoriasis. There are four arms consisting of placebo and various doses of vipafoslin. The primary endpoint is at 16 weeks, which is part one of the study. In part two, we're evaluating the effectiveness of switching to higher doses if efficacy is suboptimal, and part three is a safety extension. Currently, there are 15 sites are active in the U.S., and three sites are active in Europe. Slide 32 summarizes the atopic dermatitis study. Again, there are the same four arms, but this time we've eliminated some of the re-randomization. The primary endpoint is also at week 16, and there are 18 U.S. sites and 15 European sites that are currently active. Finally, slide 33 summarizes the major events for the atopic dermatitis study, consisting of a futility analysis in the Q2 of 2024, an interim analysis for the primary endpoint in the Q4 of 2024, and study completion in the Q2 of 2025. So this is my last slide. At this point, I'd like to hand you over to my colleague, Vikram, who will walk you through some very nice preclinical data with one of our up-and-coming drugs. Vikram? Thank you, Siu, and good evening to everyone. My name is Vikram Ramanathan, and I oversee preclinical development at SPARC. In the next few minutes, I'll be giving you an update on our compound SCD-153, which we are developing for alopecia areata. We are happy to share that the IND was filed in India recently, and we have approval from the DCGI for phase I clinical studies. Slide 35, please. Alopecia areata is a disease where the body's own immune system attacks the hair follicles and thereby causes hair loss. There is a large patient population that suffers from the disease, and current treatments are inadequate. JAK inhibitors have recently been approved, but they carry an FDA black box warning for cancer, stroke, and death. The other alternative is steroids, but these are also not preferred because they require intradermal injections in the scalp and have serious side effects. The pictures show how the disease manifests. It disproportionately afflicts the younger population, less than 30 years of age, and causes them significant psychological stress. There is clearly an unmet medical need. Slide 36, please. So slide 36 gives some background on the compound SCD-153, which is being developed as a topical therapy for alopecia areata. On the left is shown a healthy hair follicle. The hair follicle has so-called immune privilege, which means that it is shielded from the immune cells in the nearby vicinity. The alopecia areata diseased follicle is represented on the right. In this case, the immune privilege is lost, and there are now disease-causing T cells present at the base of the hair follicle in what is called a swarm of bees phenomenon. These T cells secrete inflammatory cytokines and damage the follicle, and so hair falls out. SCD-153 inhibits this inflammatory process and can counter the disease. Importantly, SCD-153 has been designed as a topical agent, and so systemic exposure and systemic side effects would be minimized. Slide 37. So, so this slide shows preclinical data in an immune cell-driven mouse model of alopecia areata that spontaneously develops hair loss.... The disease here is caused by the CD8+ cytotoxic T-cells, which is also the culprit in the human disease. The graph on the left shows the hair growth index on the Y-axis, and the time of treatment of SCD-153 on the X-axis. Applying SCD-153 on the skin three times a week results in the animals recovering hair growth compared to the vehicle-treated animals. We have also studied other dose strengths and regimens of SCD-153, and have seen meaningful hair growth in those cases as well. The hair growth can be visualized in the photographs on the right. The hair growth index is derived from a software-based analysis of these photographs. The animals start out at a similar level of disease at week zero. The animals in the top row on the right received vehicle for 16 weeks and show continued disease with no hair growth. Animals in the bottom row on the right received SCD-153 applied to the skin for 16 weeks and showed good hair growth. We have also examined the skin samples under a microscope and found that the disease-causing T-cells are reduced after SCD-153 treatment. So these data demonstrate good single agent therapy. Importantly, there is room now to look for combination therapies with SCD-153 for hair growth as well, and we have initiated combination studies with low-dose JAK inhibitors. Slide 38, please. So this slide shows quantitative PCR-based measurement of gene expression of inflammatory markers in the skin of the alopecia areata diseased mice. These are interferon signature genes associated with alopecia areata in humans as well. The Y-axis shows the relative fold increase in the mRNA gene transcript levels above the baseline. In each set, the first bar is the level in healthy mice. These are all very low because they lack disease. The second black bar in each case is a fold increase in the disease mice, and the difference between the first and second bar is the disease-associated change. In each set, the last two bars are from the diseased mice, but which have this time received SCD-153 treatment on the skin, and a reduction in the transcript levels of these genes is evident. These data provide a mechanistic basis for how SCD-153 causes hair growth in this disease models. The markers shown here attract the disease-causing T-cell to the site, and these then initiate the disease. We should particularly note the increase in chemokines, CXCL9, CXCL10, and CXCL11 in this slide, and we'll come back to the same CXCL9, CXCL10, and CXCL11 after a couple of slides. Slide 39, please. So slide 39 summarizes the current status. Following toxicology and safety pharmacology testing, the IND was recently filed with the DCGI. We now have approval for the phase... First-in-human phase I study, and the phase I study has been initiated now in India. The single ascending dose study will be a randomized, double-blind, vehicle-controlled study. As shown in the figure, we will have 5 ascending dose cohorts. As usual, there'll be in-house assessments up to 48 hours post-dose and subsequent follow-up. The primary objective, of course, is safety and tolerability, and plasma PK will also be studied. This will be followed by a multiple ascending dose study. Slide 40, please. Slide 40 is the last slide on SCD-153. We are now evaluating the potential of SCD-153 in another autoimmune skin disease, vitiligo. Vitiligo is a condition where skin pigment is lost and white patches develop. The chemokine CXCL9, 10, and 11, which we did discuss just a couple of minutes ago, also attract the vitiligo, causing immune T-cells to the site in the epidermis. These then secrete inflammatory cytokines that target and destroy the melanocytes, which are the pigment cells. Inhibition of this cycle by SCD-153 suggests that the drug has potential in this disease as well. Vitiligo also causes a large psychological burden for the patient, and available options are few. So we are in the process of testing this possibility in preclinical models. To recap then, we have shown that topically applied SCD-153 promotes hair growth in a spontaneous immune mouse cell model of alopecia areata, and SCD-153 inhibits inflammatory cytokine gene expression in the underlying skin of these mice. An IND has been filed with the DCGI, and the phase I study has commenced in India. I will now hand over to my colleague, Dr. Nitin Damle, who will share an update on our work in the antibody-drug conjugates area. Nitin? Thank you, Vikram, and a very good afternoon to you all. I'm Nitin Damle, and I oversee the biologics function at SPARC, and I'll be providing update on SPARC's first antibody drug conjugate, SBO-154. Antibody drug conjugate field has exploded in the last six years, during which 12 novel ADCs were approved by the U.S. FDA as treatment options for cancer patients. As a result, the ADC strategy has blossomed into a commercially viable therapeutic strategy for strategic investments, and the ADC market is projected to cross $25 billion in sales by 2028, with 24% increase in the compound annual growth rate during the next five years, as shown on slide 42. During the last investors call, we had introduced SBO-154 as the first biologic therapeutic from SPARC, and described preclinically its anti-tumor therapeutic potential. SBO-154 is a humanized antibody-drug conjugate of microtubule-disrupting cytotoxic payload, capable of potently inhibiting growth of actively dividing tumor cells. SBO-154 is designed to bind with high affinity to a broadly expressed tumor-associated antigen, MUC1 or Mucin 1. Both the cytotoxic payload and its linker have been clinically validated and are represented in already, or in some of the already marketed ADCs. Let me say a few words about MUC1 as a tumor antigen. MUC1 tumor antigen, that's the target of SBO-154, as shown on slide 43. It's synthesized as a single protein that undergoes autocatalytic proteolysis into two subunits, MUC1 alpha and MUC1 beta, prior to its display on the cell surface. And when it's expressed on a cell surface, it's expressed as a heterodimer of MUC1 alpha and MUC1 beta. While MUC1 alpha is entirely extracellular in its display, it is tightly but not covalently bound to the transmembrane MUC1 beta subunit that holds the entire MUC1 protein on the cell surface. The region of MUC1, where MUC1 alpha binds to MUC1 beta, is recognized as the SEA domain, identified in the MUC1 cartoon on slide 43. MUC1 alpha subunit includes a variable number of tandem repeats, VNTRs, of about 20 amino acid long peptide sequences, against which a large number of monoclonal antibodies had been made and evaluated as therapeutics, as naked antibodies, radioimmunotherapeutics, or even ADCs during the past 25 years. None of these therapeutics managed to provide meaningful clinical benefit in cancer patient, in large part believed to be due to the presence of cell-free or shed MUC1 alpha antigen, both in circulation and also in the intratumoral compartment, where it could effectively compete with MUC1 antigen on the tumor cell surface. Intercept anti-MUC1 antibody therapeutics, and thus deny them the opportunity to target tumor-associated MUC1 to cause therapeutic benefit. Our ADC one, SBO-154, is a high-affinity binder to the cell surface membrane proximal SEA domain of MUC1. And as shown as circled in the MUC1 cartoon on slide 43. Unlike MUC1 alpha domain that contains VNTRs, the SEA domain of MUC1 is not actively shed or shed in very small quantities, so as not to be able to compete with cellular MUC1 SEA and intercept the SEA-targeted therapeutic entities, such as SBO-154. We have further confirmed that the sera from cancer patients show minimal presence of MUC1 SEA, while continuing to show the sizable presence of MUC1 VNTR antigens. Hence, the shed MUC1 SEA is far less likely to interfere with the binding and activity of SBO-154 against MUC1-expressing cancer cells. The next slide, slide 44, shows the relative strength of anti-tumor activity of SBO-154, evaluated against large xenografts of human carcinomas expressing different levels of MUC1 SEA on their cell surface. Whenever the expression of MUC1 SEA is high, SBO-154 is able to cause regression of preexisting tumor xenografts. On the other hand, low MUC1 SEA-expressing xenografts, although showed appreciable growth inhibition or disease stabilization, these xenografts failed to regress upon treatment with SBO-154. In contrast, an isotype-matched non-binding control ADC of CD20-specific rituximab, failed to show any growth inhibition in any of these evaluations. Thus, the anti-tumor benefit conferred by SBO-154 is preferential towards high MUC1 SEA antigen-expressing tumors. Our own immunohistochemical assessment of the expression of MUC1 SEA in patient-derived tumor biopsies and human tumor tissue microarrays suggest high level expression of MUC1 SEA in a wide variety of carcinomas, and thus, given opportunity, SBO-154 may be able to provide meaningful therapeutic activity in cancers with high expression of MUC1 SEA. The SBO-154 program is currently in the preclinical development phase, with the focus on manufacturing of the targeting antibody and the payload linker, and further, the assembly of the ADC SBO-154. We hope to file the IND with the U.S. FDA in the second half of the calendar year 2024. While we advance this program through its preclinical development, as shown on slide 45, we have engaged the U.S. FDA via the INTERACT meeting to seek guidance for various IND-enabling preclinical development activities, which serves as a prelude to our formal pre-IND meeting sometime in 2024, ahead of the IND submission. We are looking forward to the FDA response from the INTERACT meeting sometime before the end of this month. I'll stop here and hand over the discussion to SPARC CFO, Chetan Rajpara. Chetan? Thank you, Dr. Damle. Good evening, everyone. This is Chetan Rajpara, CFO at SPARC. I plan to go over SPARC's financials and cash position at a high level. Slide number 47. During FY 2023, total income was at INR 250 crores, equal to $31.1 million, while total expenses were at INR 472 crores, equal to $58.8 million, resulting into a net loss of INR 223 crores, equal to $27.7 million. Financially, at 2023, income was higher as compared to FY 2022, on account of upfront and milestone payments received for outlicensing phase III, and higher royalties on certain products. Let me update you on our financial results for the Q1 of FY 2024. For Q1 FY 2024, total income was at INR 34 crores, equal to $4.2 million, while total expenses were at INR 129 crores, equal to $15.8 million, resulting into a net loss of INR 95 crores, equal to $11.6 million. Next slide, please. So as you may be aware, the company had raised INR 1,112 crores, equivalent to $148 million, in July 2021, by way of a preferential issue of convertible warrants. The company has received INR 703 crores in January 2023, against the conversion of all warrants by investors. With this, entire process of the preferential issue stands received. Cash and cash equivalent as of 30th September 2023, was INR 363 crores, equivalent to $44 million. The company has sanctioned bank facilities for INR 175 crore, equivalent to $21 million in place, in addition to a line of credit for INR 250 crore, equivalent to $30 million from the parent company. The utilization of this limit as on 30th September 2023, is 0. The company has obtained shareholders' approval at the last AGM for raising a sum up to INR 1,800 crore, equivalent to $220 million, by way of a fresh issuance of securities. For FY 2024, approximately 30% of our expenses are budgeted for the clinical costs. We are aggressively managing our costs and working to control non-clinical expenses. That's all from me today on financial update. A big thanks to all of you for joining the call. I will now hand over the call to Jaydeep for facilitating the Q&A. Thank you, Chetan. Thank you everyone for patiently listening. We will now open the call for question and answer, and discussions. Thank you very much. We'll now begin the question and answer session. Anyone who wishes to ask a question may press star and one on their touch-tone telephone. If you wish to remove yourself from the question queue, you may press star and two. Participants are requested to use handsets while asking a question. Ladies and gentlemen, we'll wait for a moment while the question queue assembles. Participants, you may press star and one to ask the question. The first question is from the line of Ketan Gandhi from Gandhi Securities. Please go ahead. Yeah. So on slide nine, can you please help us understand, what about CML recalibrating to a changing regulatory and market landscape? Thanks, Ketan, for the question. I think what this refers to is a couple of significant changes in the way FDA is oncology, that, clinical programs in oncology. I mean, if you go back to, the prevailing paradigm in oncology for many years, the first registration, window for a program is usually the last line setting. You have to basically test a compound in the last line setting. And FDA is now, for many classes, actively encouraging sponsors to go to earlier settings through comparative trials as against, an open-label study in the last line setting. And this initiative is called the Project Frontrunner. So that is one important, regulatory, change, which, has consequences or implications for our program. The second, change, a significant paradigm shift, is the way in which the agency look at, acceptable doses. In the earlier setting, in earlier paradigm, FDA always allowed, you know, going up to the maximum tolerated dose and then, you know, coming down a step, from maximum tolerated dose and using that as a dose for clinical exploration of the program... but now, there's been at least some randomized data, to identify the minimally efficacious dose. And this is coming from recent experience across several classes where, you know, approved products then manifesting significant level of toxicity in clinical practice. Both these has implications for us in terms of, you know, the path that we are following based on earlier set of recommendations from the agency in our prior consultation, and what the agency would like us to do at this point, and that is the reset that we are alluding to. So, to understand it better way, it will cost us more, and it will cost us more time also. Is my understanding right? That is right. I mean, See, Okay, let me take a step back. See, what happens, I mean, the current expectation for a registration program in vodobatinib is completing a last line study. And that last line study may require fewer patients, but they are far more difficult to recruit patients, right? And this would require more patients, but they are in an earlier setting, and therefore, may be an easier to recruit cohort. As I said in my comments, you know, we are evaluating the cost and timeline implications, and that will become a decision point post PROSEEK, right? Once we have results from PROSEEK, whether we will pursue a CML is a strategic decision that we need to take. We will also decide whether we pursue this alone, as in ourselves or in partnership. You know, I also want to highlight one other aspect of this change. That is, this will be a comparative study, as in there will be an active comparator in this program, as against an open label study where there is no comparator in the earlier setting. So in that sense, you know, there is an opportunity for the cost to go up for sure. The timeline implications will need to be case based on the design. Thank you, sir. I have more question. I'll join back the queue. Sure. Thank you. Participants, you may press star and one to ask a question. Next question is from the line of Ishita Jain from Ashika Stock Broking. Please go ahead. Hi. Thank you for the opportunity. So, my first question is on the PROSEEK trial. In terms of the primary endpoint, we're measuring change in baseline, on the MDS-UPDRS scale. Can you quantify that? Can you quantify? Can you explain? Can you give- How many points of change would take us successfully to the finish line? I think Dr. Siu Long Yao can give a little bit more detail on the MDS-UPDRS part three. But if the question is about the design of the trial and what would be a meaningful change from a clinical perspective- Yes. The original study was designed against natural history data that we have from multiple natural history studies, particularly the MDS and the Michael J. Fox Foundation study. In that setting, if you take part two plus part three together, it's a 6.5-point deterioration over a nine-month period, which is the baseline deterioration that we assume. A 35% improvement of all of that is deemed clinically significant. That is proportionately split between part three and part two, even though a larger component of that part two, part three aggregate is actually part three. In that sense, from points perspective, it's 4+ points in part three and, you know, around 2+ in, or 2 in part two. So we still look for a 30% or 35% improvement on that trajectory, which is, from our consultations with care, deemed clinically significant, if that's the question that you're asking. Yes, absolutely. Thank you. My second question is, so, such a broad-based question on PROSEEK. Inhibikase Therapeutics, for their drug, risvodetinib, unblinded a part of their trial two weeks ago, and there seems to be signs of efficacy, I think only for their highest dose, is 200 mg. And they also got orphan drug designation for MSA, which, you know, is also an alpha-synucleinopathy. So I do understand that you perhaps cannot comment on a competitor, but strictly from a proof of concept point of view, can you draw some parallels with our c-Abl innovator, vodobatinib? I mean, they clearly, you know, claim a positive trend line for their study- Mm-hmm. Especially in the higher dose, and that all goes well for our program. But we will, you know, take that with not just a pinch of salt, with a lot of apprehension. Because the sample sizes there are very, very low, and this is almost 11 patient data. And it's also, if you look at the duration of treatment, it is a 12-week duration, and it is a known fact in the Parkinson's space that the placebo response data go only up to six months, right? So you're expected to see some level of, you know, moderation of the trajectory in that earlier phase. So we think that the overall treatment window and the patient size is inadequate to make, to make the claims that they're making. And also, the lower dose did not have an effect, but that is to be expected to a certain level because the blood-brain penetration requires substantial peripheral concentrations. In that sense, you know, that's reasonable. But if you look at the window for treatment and also the number of patients involved, I think, you know, it's too early to kind of have mission accomplished there. Makes sense. If I could just squeeze in one more, so perhaps a little far-fetched. What, post our phase II readout, what are we thinking in terms of phase III? What would the how big would phase III be? We have about INR 300 crore cash on books. Will there also be an agency meeting before we initiate protocols for phase III? And finally, will phase III include L-DOPA MAO inhibitors patients as well, which is slightly more advanced stages of PD, or are you sticking to only PD? So that is not an easy small question to squeeze in. There are many things to unpack there. So let me take out the most of this. Our registration program for the initial registration will not have the baseline L-DOPA or L-DOPA. We are allowing MAO-B for a constant stable dose of MAO-B allowed in the protocol currently. Right? Now, we will have an end of phase II discussion sometime, October 2024 timeframe, based on our current projections. And that end of phase II, you know, we are going into multiple possibilities. Some of them are really possible, and some of them, the worst case, we may require two more phase III to get this into a registration, depending on the data that we see and depending on the view the agency takes. But our final form, our registrational trial design can happen only after we have a consultation with the agency, with the data from the full data readout in August. We will have to wait till that to see, you know, how soon we can get to market. But we will not be going into, you know, additional settings, because if we introduce L-DOPA as a background therapy into this, that introduces a significant level of variability of response. That is, you know, certainly an avenue for us to explore and pursue at an appropriate time, because if we are bending the trajectory for the disease, we will definitely have an impact on later stages of disease. But that's a different program, and our most important priority would be to replicate what we've done in ProSiC and get this product to registration as soon as possible. Fair enough. If you could just give an update on phase II for Lewy body dementia, and I will join back the queue. Thank you. Lewy body dementia program is a single-center trial out of Georgetown. You know, that's a very small trial with, again, some of the issues that I spoke about in the previous program, in terms the treatment rate is small and also very few number of patients. We are looking at that trial for a biomarker guidance, and we will have data around the same time. Mm. Because Georgetown shut down their trial activity for almost couple of years during COVID, and so there was significant delays in that program. But from a proof of concept standpoint, for even Lewy body dementia, we think ProSiC is a more relevant proof of concept because of both the mechanisms involved in both diseases and also the number of patients involved in ProSiC trial. So we will consider ProSiC readout as a trigger point or a stage gate for deciding on an LBD. Got it. Thank you. I'll join back the queue. Thank you. Other participants, you may press star and one to ask a question. Next question is from the name of Chan Pal Singh, individual investor. Please go ahead. Hello? Hello. Hello. Go ahead. Am I audible? Yes, you are audible. I have just first one question regarding vodobatinib for Parkinson's. That, are we eligible for the disease-modifying therapy, drug under the disease-modifying therapy? So disease modifying therapy designation in the label is one thing, and actual disease modification is, you know, from a clinical experience standpoint, different. It's different. It's very common on both. So a disease modification or disease-modifying therapy designation on the label may require like a different design, in the sense that you may probably need to have a delayed start design, which will further delay the program. So that is something which we may not explore on day one, and we may try to, you know, add to that later. And we will also have a consultation with the agency in terms of what we are seeing. And we will have significant endpoints here. If you look at the nature of data that we will have, both in terms of the actual trajectory of deterioration and also the time to introduction of symptomatic therapy, will give a practical data and guidance on whether the drug is modifying the disease trajectory life. So we hope to have a conversation with the agency in terms of the disease-modifying nature of the program and make the case for including disease modification designation in our label with this design. But if FDA has different views on that, then we will go ahead with the registration as a therapy in this disease before we pursue the disease modification tag. ... Okay, sir. Thank you. That's from my side. Thank you. Thank you. Next question is from the line of Jigar Valia from OHM Group. Please go ahead. Yeah, thank you for this opportunity. My question pertains to vodobatinib. We have this catalyst events coming up in Q1, Q3. Just a clarification that this certainly would not affect any optionalities on LBD or or even further on CML? So I didn't fully follow the question, Jigar. Can you repeat the question, please? Yeah. So with regards to the catalyst events coming up for vodobatinib, vodobatinib for PD, that shouldn't affect the optionalities with regards to the LBD indications or even with regards to the CML, which is again with regards to the same vodobatinib. Well, it will, in the sense that, I'm going back to my earlier response, to Ishita. The MSA and LBD essentially will depend on a successful completion of PROSEEK, in the sense that we're looking at PROSEEK as a definitive proof of concept for diseases driven by alpha-synuclein. So if there is a negative readout on PROSEEK, then it is a negative proof of concept for not only Parkinson's disease, but also for the mechanism more broadly, and that means across the diseases like MS, I mean, MSA and Lewy body dementia. It is not going to affect CML, because in CML, we already have clinical proof of concept, as Siu explained, in this slide deck. And we see CML as a hedge, even though a lower value hedge, against the failure of the hypothesis. Perfect. Very helpful, sir. Also, similarly with regards to SCD-044, would psoriasis or atopic dermatitis be in either-or scenarios and psoriasis as a hedge for dermatitis? No, these will be driven by the data from the phase II programs. And you know, we will have to ask them, our commercialization partner, they have, and Sun Pharma is our commercialization partner, and Sun has the rights to take those decisions. And I'm pretty sure, you know, they will take appropriate decisions based on the data that they're seeing in these programs and the competitive landscape of these areas. So I don't think, you know, we can give a generic response about the way it is going to be either or at this point, without actually seeing the outcome from the phase II programs, which will be coming soon. Got it. Very helpful, sir. And, so lastly, in terms of, if you can, I mean, I know if I missed, in terms of the, incremental burn down rate, for the coming year, $60 million could be more? So you see, next year, I mean, calendar year 2024 or financial year 2025 will be a true discontinuity from a trending standpoint for the burn rate, because we have been having a consistent burn rate for the last few years, because we have been pursuing, you know, certain number of clinical programs and certain number of clinical programs, and there is a certain level of predictability to that spend. But depending on, you know, what we do with Vorapaxar, and depending on how some of these early programs scale, and also depending on the partnering strategy in terms of how much development is retained within SPARC, you know, there is a potential for a bigger swing in bigger swing in development spend, next year. So unfortunately, I'm not in a, you know, position to give you a trend guidance on operating costs for next year, because we are going to have, you know, significant dependence and variability on some of the data readouts. I totally understood. Thank you so much. If I can just squeeze in one more, any timelines for the site transfer for Elyxyb, XELPROS? Both, both Elyxyb and XELPROS, in the case with Elyxyb, we are looking for a site transfer in the coming year, in the next financial year. XELPROS hasn't gone out of supply at this point. So we are still, you know, waiting for a natural grant from some in terms of transitioning that to a different plant. So we don't have a definitive guidance on XELPROS. But, in Elyxyb, we are looking at... Just one second. Thank you. Participant, you may press star and one to ask the question. Just wanted to go back. As I confirmed earlier, we are looking at financial year 2025, I mean financial year 2025 as a target for tech transfer of... Thank you. Thank you. Next question is from the line of Manish Jain from Gormal One. Please go ahead. Yeah, hi. Really delighted to see the kind of biologics capabilities that have been built up. And, ADC already really gunning for our NE. So I would say hats off to the team. And, I had three questions. The first one was, at what point can't we pursue vodobatinib both for PD and CML, if we license it to two different separate people altogether? Hi, Manish. Thank you for, thank you for your comments on the ADC space and the scale of the biology. You want me to wait for all the three questions, or you want me to- I would do it one by one. Okay, cool. So, you know, this is an interesting question in terms of pursuing PD and CML together. There are two or three complicating factors here. One is obviously the commercial landscape and the price implications. If you take late-stage cancer, and the price ranges are, you know, usually runs to several hundred thousand dollars per year per patient. But Parkinson's and the neurodegenerative disease section being, you know, significantly large disease burden, with significantly larger number of patients under management, the per patient per year pricing tends to be significantly lower, right? So if you have a product, even at a high dose, as in the Parkinson's dose is going to be higher than the CML dose, with much lower price, then the substitution risk for someone who is commercializing CML is quite high. Two, there are, you know, safety profile implications, in the sense the patients who are going to come to CML with this drug are significantly sicker than patients who you see in early-stage Parkinson's. So a lot of commercial partners really have trouble reconciling the fact that they have to deal with a complex safety profile, which carries some of the encumbrances of late-stage disease in cancer in trying to market a drug in early-stage Parkinson's disease, and in competing with programs which are not really encumbered with that kind of issues in leukemia. So there are some practical issues in terms of doing it both in terms of the cannibalization risk and also the risk of, you know, safety profiles getting initiated in Parkinson's. Got it. Got it. My second question was pertaining to Phase B, that is, phenobarbital. Where are we going to manufacture it? So we are in the process of, you know, inducting one more manufacturing plant. Currently, it's supplied out of one of the current facilities. And this second facility that we are now, as my partner is now inducting in, is a third-party vendor outside of the Sun network. So as we kind of, you know, work towards enforcing market exclusivity, we will have two providers for facility, one from the Sun network and one from outside. And that, we believe will give sufficient robustness to the supply chain. Excellent. Excellent. And, last question before I join back the queue was related to PDP-716. So in terms of alternate API partner, in, how much time do we think before we can respond to the CRL? So we have already identified an alternative manufacturing partner, and we are in the process of, you know, initiating the specific batches with the alternative partner, the API. It will require significant stability data, which is from a timeline standpoint a killer, and we expect it to happen towards the end of the second half of next financial year. Okay. I actually have a few more questions. I'll join back with you. Sure, Dinesh. Thank you. Operator, you may press star and one to ask a question. Next question is from the line of Ishita Jain, from Ashika Stock Broking... Sorry, from Ashika Stock Broking. Please go ahead. Thank you for the opportunity once again. So moving away from PROSEEK, on PDP-716, the one with Visiox, what is the I think that you already answered the timeline. So Visiox also in-licensed Omlonti, which is for the same indication as PDP-716. And since SPARC is a shareholder of Visiox, can you give some color on how has the ramp-up or the scale-up been for Omlonti? No, we cannot comment on that program in this call. We would like to stay with the SPARC program. Not qualified or equipped to comment on Visiox's other program. Sorry, Ishita. Got it. No problem. So on with the amiselimod, which is with Sun, I have a feeling you won't be able to answer this question either, but can you give us some color on, just to better understand the color on the terms of contract, so we can understand what is the payout, you know, especially in, calendar year 2024, which is, we're expecting a clinical proof of concept? No, unfortunately, we are anticipated, you know, we are not in a position to... We haven't disclosed this. Mm-hmm. What I can say at this point is, you know, the phase 2 readout is a milestone event for us, and we also have, you know, substantial royalties expected from this program once we cross the data threshold in phase 3 into a registration. ... The line for the participant dropped. Participants, you may press star and one to ask the question. Next follow-up question is from the line of Manish Jain from Gormal One. Please go ahead. Yeah, on the ADCs, I just wanted to know, we have highlighted 1 or 2 indications. At what stage post IND can we look at running 3, 4 or 5, 6 multiple indications? I think the early stage clinical program, or the early stage dose escalations in a program like antibody-drug conjugates would have patients from multiple indications. So we will look for, you know, clearly looking ahead here, because these are matters which are under discussion and finalization at this point. But we will look for certain threshold of expression of MUC1, and we will have a cutoff range, and we think that we can get patients from across 3, 4 tumor types. We have positive breast cancer, lung cancer, and a few other things. There is a possibility to do this more as a basket trial as against going up in one program or one entity. Very, very exciting. Very exciting. Thank you. Great. Thank you, Manish. Thank you so much. Thank you. Next follow-up question is from the line of Ishita Jain from Ashika Stock Broking. Please go ahead. Sorry, apologies. I think I got cut off. Sure. So just one last question on PROSEEK. I think I'm just asking this, we have had six DSMB meetings. Were they all 100% green light to go ahead on both dosages? Yes. Well, we specifically asked if they would like us to change anything in terms of the dosage used or the design or inclusion/exclusion criteria. They didn't want to change anything about the design or the dosages used. Okay, fantastic. And, I also noticed that, I think last month we set up a wholly-owned subsidiary called SPARC Life in the U.S. Can you comment on goal to create this? I mean, apart from monitoring clinical trials in the U.S., can this, subsidiary someday become, somewhat of a front end? Well, I don't want to go ahead and get ahead of myself here. I mean, we have, you know, a operation in the U.S., including Dr. Siu and others, who spearhead our clinical activity. And I think from a regulatory and governance standpoint, it's cleaner to have them in a subsidiary. And we also have a brand structure. At the moment, it is a part of a cleanup process, but that would become an operating entity for us in the U.S. And that, you know, we, if we scale into a late-stage development program for vodobatinib, that would become meaningful arm for us. Great. Thank you so much for giving me time. Appreciate it. Thank you. Thank you. Next question is from the line of Tushar Vora from MK Ventures. Please go ahead. Yeah, thanks for the opportunity. I must congratulate the management, very, very comprehensive review and lot of exciting developments for sure. Sir, just regarding the PROSEEK outcomes, you know, we mentioned that we are in touch with the, you know, potential for potential collaborations or out-licensing opportunities or something on those lines. If you can highlight a bit more details, what are the players we are approaching, what kind of interest we are seeing, and, you know, anything around that would be useful. So I won't be able to discuss who are the players that we are talking to because, you know, we are run by fairly strict confidentiality commitments on these conversations. But what I can say is that, you know, right through the phase II program, there have been consistently interest from large pharmaceutical companies, and we will initiate the process as we go towards, you know, data flow from this program to see what kind of partnership structures are possible. And we will also explore, you know, what is probably a smart way to split the value between us and a potential partner, depending on where we actually land with the data. But I'm not able to give you a specific answer in terms of names that we're looking for. I was looking for a number of players and the kind of players we are discussing with, what kind of companies or, you know, whether you- So we are looking at large commercial players, I mean, bigger pharma companies with a commercial footprint in the CNS space, or larger companies with a strategic intent in the CNS space. And we have a fairly significant field which is interested. Sure. Second, if we were to proceed to a full-fledged phase III clinical trial, assuming that we need one more trial for this, after PROSEEK, is there a range of, you know, an estimate as to how much, you know, resources we would need, and what could be the timelines possibly for this? So it's clearly a function of, you know, what we, what is the extent of pursuit that we can have, right? And what is the regulatory expectation. If we're going to have one clinical program, then one more clinical program, I mean, then we are talking about something in the range of $50-$60 million, to do that, one more clinical trial. And, if you need to have, you know, two more, then we are talking in the range of something in excess of $100 million. But these are all really exploratory numbers. But the larger question, and probably a driver for collaboration, is, you know, pursuing this program more fully. I mean, we, you know, gone to some length to describe some of the possibilities, both in late-stage disease and also to autoimmune disease, all the possibilities in the next string of opportunities, which is MSA and things like Lewy body dementia. So if you keep PROSEEK as a proof of concept for similar therapies, then how aggressively you pursue this, both the inner core of opportunity and also the, the peripheral set of opportunities is going to determine, you know, what is the kind of partnership or resourcing that is required. And that will be a major strategic consideration going into next year. Got it, sir. And, on the, you know, you mentioned that, in the most, conservative case, you could maybe need two more trials. But, what about the most optimistic scenario, given the safety profile of vodobatinib, which is clearly, at least, as per the data up to now, clearly very, very strong, as well as the efficacy part. What, what is the most optimistic scenario that, that you guys are hoping for or are building in as one of the probabilistic scenarios? I mean, so I don't... I think we will be getting into a speculative realm at that point. I don't want to get into that issue with this group. Because at this point, we did not have any substantive conversation with the agency about the future of this program. So anything that I say is going to be based on my read of what is possible and what is not possible, and that could be misleading. I don't want to be misled by, you know, what I can say at this point. No. Fair enough, sir. Maybe I'll rephrase the question. What are the possible scenarios after PROSEEK? Depending on the data, what are the pathways available from a regulatory standpoint, and whichever one may happen? You should look at, if you PROSEEK is an unusually large phase 2 program, you know, you have 504 patients and 504 evaluated patients. You have a clinical endpoint, which is what FDA has advocated for this disease indication for a long time. You will also have, you know, some biomarker data, significant biomarker data. Depending on the nature of the biomarker, like CSF or biopsies or blood, you know, we will have, you know, fairly large numbers in some cases and smaller numbers in some cases. This is a substantial data set. How FDA would actually look at this and how FDA would look at the disease is, you know, to be seen, because we don't have too many precedents in Parkinson's disease for neuroprotective therapies coming to a registration path. FDA, CNS division has been, you know, fairly progressive in dealing with indications like Alzheimer's and ALS. If you want to look for the most optimistic scenario, my guidance would be to take a look at what happened in ALS and in AD recently. There were three approvals in AD and ALS. In the most optimistic scenario, that can become a guiding benchmark for us with the agency. But I'm not saying that, because there's no precedence, and the conduct with this disease is somewhat different to like ALS and AD. So I think, you know, any speculation on what is possible is of limited value because of these differences in my mind. Got it, sir. And one last, if I may quickly squeeze in. If you can highlight some of the newer drugs that you are, you know, either looking to in-license or are at early stages of development. You said in the beginning of the call that you're looking at multiple modalities, you know, extending into newer modalities. Maybe if you can just highlight a little bit more around that. Yeah. So I think if I look at our project here, we have a historical focus in small molecules, and we have added biologics as a competency in the last couple of years, last two, three years. And there are, you know, different possibilities with that broader area, antibodies. Both conjugates, which has traditional cytotoxin, which is essentially much of the ADC field at this point. But we think that ADC will shift substantially with other kinds of payloads, like other targeted therapies, and even other modalities. I don't want to speculate there, but even things like RNA therapeutics are all possibilities coming from the ADC kind of constructs. Plus, you will see bispecific or multispecific structures, both bispecific or multispecific standalone antibodies, plus, bispecific or multispecific ADC constructs, try to, you know, improve target expression by adding an another specificity. So there are different possibilities there. And clearly, one other possibility, given our strength in small molecules, small molecules directed on cytotoxicity. In a sense, you can use a small molecule, a synthetic ligand to target to specific cancer cells, and that's something, you know, which we are definitely doing. And we have a program in consultation with UCSF. I think one of the slides has a reference to that. We already have a program in fairly late stage, preclinical program, and we will have news flow from that program going forward. Thank you so much, sir. That is very helpful. I'll join back in queue. Right. Thank you. Thank you. A reminder to all the participants, you may press star and one to ask a question. A reminder to all the participants, you may press star and one to ask a question. As there are no further questions, I now hand the conference over to Mr. Jaydeep Issrani for closing comments. Thank you, Nirav, and thank you, everyone, for being on the call today. In case you have any additional questions, feel free to reach out to us. We'll be available to answer your questions over email or through discussion. Thank you again for being on the call today. Thank you very much. Thanks much. On behalf of SPARC, that concludes this conference. Thank you for joining us. You may now disconnect your lines. Thank you.