Good afternoon, and welcome to the ChemoCentryx Fourth Quarter and Full-Year 2018 Financial Results Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session. As a reminder, this conference will be recorded. I would now like to turn the call over to your host Bill Slattery of Burns McClellan. Mr. Slattery, please go ahead.

Thank you, operator. Good afternoon, and welcome to the ChemoCentryx fourth quarter and full-year 2018 financial results conference call. Earlier this afternoon, the Company issued a press release providing an overview of its financial results for the fourth quarter and full-year ended December 31, 2018. This press release, along with a few slides that you may find helpful while you listen to this call, are available on the Investor Relations section of the Company's website at www.chemocentryx.com. Joining me on today’s call is Dr. Thomas Schall, President and Chief Executive Officer of ChemoCentryx, who will review the Company's recent business and clinical progress. Following his comments, Susan Kanaya, Executive Vice President, Chief Financial and Administrative Officer of ChemoCentryx, will provide an overview of the Company's financial highlights for the fourth quarter and full-year 2018 before turning the call back over to Tom for closing remarks. During today's call, we will be making certain forward-looking statements, which those of you following the slides can see if you look at Slide 2. These forward-looking statements are based on current information, assumptions and expectations that are subject to change and involve a number of risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements. These risks are described in the Company's filings made with the Securities and Exchange Commission, including the Company's Annual Report on Form 10-K to be filed on March 11, 2019. You are cautioned not to place undue reliance on these forward-looking statements, and ChemoCentryx disclaims any obligation to update such statements. In addition, this conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, March 11, 2019. ChemoCentryx undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this live conference call. At this time, it is my pleasure to turn the call over to Tom Schall. Tom?

Thank you, Bill, and good afternoon to everyone listening. Thank you for joining us on our fourth quarter and full-year 2018 conference call. For those of you, who are following on the slide, Slide 3 shows that in 2018, we demonstrated our ability to execute across multiple clinical trials, giving us confidence that we will continue to deliver on our 2019 goals and indeed beyond. I am proud of our accomplishments in 2018. Among others, we achieved the following four notable milestones. One, we completed the enrollment of the ADVOCATE Phase III pivotal trial of our C5a receptor inhibitor of avacopan in ANCA or anti-neutrophil cytoplasmic auto-antibody-associated vasculitis on schedule, indeed and what some have called record-tying. Two, in Q4 of last year, we dosed the first patient in our large AURORA trial of avacopan for patients with Hidradenitis Suppurativa. This is a historic moment for ChemoCentryx as we go beyond kidney disease into dermatological diseases. Three, we made excellent progress in our clinical trials of avacopan in C3 glomerulopathy and also in the trial of our second unique asset, the CCR2 inhibitor CCX140 in Focal Segmental Glomerulosclerosis. Four, we are now looking forward to a cascade of catalysts over the next 18 months in which we expect multiple topline data readouts starting of course with ADVOCATE data in Q4 of this year. And let's not forget the very strong execution on our plan has enabled us to attract the capital we need to move forward on these major and data rich trials simultaneously while planning for commercialization in the U.S. Let's talk about this March progress that CCXI has made through our late-stage clinical trials. I will start with the ADVOCATE trial as referenced in Slide 4. A trial that we believe represents the largest randomized controlled clinical trial…

Thank you, Tom. Our fourth quarter and full-year 2018 financial results are included in our press release today and are summarized on Slide 14. Revenue was $9.3 million for the fourth quarter compared to $56.3 million for the same period in 2017. For the full-year ended December 31, 2018, revenue was $42.9 million compared to $82.5 million in the previous year. The decrease in revenue reflected the adoption of the new revenue accounting standard ASC 606. Research and development expenses were $15.1 million for the fourth quarter of 2018, compared to $12.9 million for the same period in 2017. For 2018 as a whole, R&D expenses rose to $62.7 million from $49.5 million in 2017, primarily due to the advancement and enrollment completion of our Phase III ADVOCATE trial and the initiation and patient enrollment of our avacopan Phase II clinical trials in patients with C3G and HS, and the CCX140 Phase II LUMINA trials in patients with FSGS. General and administrative expenses were $5.6 million for the fourth quarter compared to $4.1 million recorded in the fourth quarter of 2017. Full-year 2018 G&A expenses increased to $20.4 million from $16.5 million in 2017, primarily due to higher employee related expenses, including those associated with our commercialization efforts and higher professional fees. We recorded a net loss for the fourth quarter of $10.8 million compared to net income of $39.7 million in the fourth quarter of 2017. Our full-year 2018 net loss was $38 million compared to net income of $17.9 million in 2017. Total shares outstanding at December 31, 2018 were approximately 50.7 million shares. As Tom stated, we ended 2018 with $177 million in reported cash and investment. Additionally, in January, 2019, we added another $20 million to our reserves through the issuance of common stock from our equity distribution agreement. Lastly, we expect to utilize cash and investments in the range of $75 million to $85 million in 2019. Tom?

Thank you, Susan. To summarize, as you can see from Slide 15, 2018 was an outstanding year of execution on ambitious goals, completing enrollments in ADVOCATE, making great progress in our trials of avacopan in C3G, and CCX140 and FSGS, and launching our AURORA trial of avacopan in HS. Our track record of execution makes us very confident that we will continue to achieve on our 2019 goals and start a wonderful sequence of topline data readouts in no fewer than four late stage clinical trials. Our financial strength also gives us the fuel we need to run these trials simultaneously and to work on full licensing submissions in the Europe and United States for avacopan in ANCA-associated vasculitis as we continue to plan for commercialization of these products in the United States. In short, we are entering an unprecedented era of opportunity, full of potential for patients, clinicians, and the investors that we serve. With that, I will now turn the call back over to the operator and look forward to your questions. Operator?

Thank you. [Operator Instructions] Our first question comes from Michelle Gilson of Canaccord Genuity. Your line is open.

Thank you. Hi, congrats on the progress. This is Lina here on for Michelle. So maybe the first question, maybe you can talk a little bit about the PK/PD profile that avacopan has demonstrated in clinical trials in ANCA and in healthy volunteers? And then maybe you can dig a little bit and specifically into the PD data and biomarkers that suggest there’s an effect on neutrophils and whether you see – if you can also basically relate these data to what we know about Hidradenitis Suppurativa pathogenesis and whether you believe that these biomarker data are enough to suggest that you can see a read through to your Phase II trials from clinical data of an anti-C5a approach in HS? And then I have a follow-on.

Sure, of course. All very relevant questions, really great question. So we know from our data when we measure the pharmacokinetic/pharmacodynamic relationship of avacopan that essentially we're achieving a target which we set out long ago, which was to make C5a receptor bearing sales particularly blood neutrophils, which are the most abundant and probably the easiest to measure and probably it's the neutrophil driving most of the damage processes in the diseases that we're interested in as they respond to C5a through the C5a receptor. So we've done a lot of work to make those cells essentially pharmacologically inert to C5a in the body even when the drug avacopan is at its lowest levels throughout the day. We started those studies in healthy volunteers, where we perfected certain methodologies to look in whole blood, which is quite difficult to do it actually. Whole blood functions of neutrophils and their ability to change in response to the drug, that's the pharmacodynamic part. So those changes include the ability of those neutrophils to migrate in response to C5a, the ability of those cells to adhere and up regulate their adhesion molecule notably CD11b for those of you, who are aficionados of this area. And the ability of the neutrophils to spit out disruptive mediators reactive oxygen intermediates, as well as other enzymes from the granules of neutrophil, so neutrophil degranulation. If a neutrophil is inhibited in any of those functions and certainly all of those functions, it will be inhibited in the body from finding its target and therefore damaging its target in the real world. So our PK-PD relationship assessments beginning first in animals but then going to humans, first healthy volunteers where some of the data has been published, and then later data in patients, where the are data yet…

No. This is great. I was just also wondering in terms of HS landscape, maybe you can talk a little bit about where do you think avacopan would fit in based on the profile that you described and based on what you've seen with the C5a and C5 mechanisms?

Sure. Thank you. We've only – the world is only seen a little bit of data on C5a in this disease and that data is compelling. So far we have essentially 14 patients at a single site. The proof-of-concept there was with an antibody, a chimeric antibody meaning it's got a lot of mouse content apparently, and it's a once-a-week infusion antibody. So there are some things to deal with there going forward for development. The contrast for us is we are an orally active molecule were taken in a capsule form, can take it at home and you take it daily. So there maybe – there's already differences in the mechanism – the mode of administration, the mechanism of action again is an antibody versus a small molecule. And the other approach takes away C5a from the C5L2, which we believe and others believe is actually a beneficial pathway. We don't know what readout that might have in Hidradenitis Suppurativa. In models of ANCA vasculitis, it’s very clear that C5L2 disruption leads to worse disease, C5aR inhibition including with avacopan virtually eliminates the disease in ANCA vasculitis models, which have been done very carefully. So not all those differences notwithstanding, I think there's great enthusiasm for the idea of C5a’s involvement in HS, since you're asking specifically about HS, and the fact again that it is probably being driven through neutrophils, which are driven through the C5a receptor, the proinflammatory part of C5a pathway. So we believe again that should these data hold up in larger controlled trials including our trial, the AURORA trial, then having an orally active drug should be a big advantage in that patient population. I know there's another sponsor using that antibody who will be reading out some Phase II data in the first controlled setting, I believe fairly shortly. So we all wait eagerly what that data will tell us. Assuming they find a dose and a response from that study that will be interesting. We believe we already have a dose for complement-activated neutrophil-driven diseases, that's how we've designed the AURORA trial. So our trial is very large randomized controlled trial and powered to be of registration grade. So that's where we are. How all this will ultimately fit together? Believe me, there's plenty of opportunity in this landscape across these diseases and I believe there's room for all innovations. I happen to believe that we have the most differentiated and advantageous approach ultimately.

Thank you. May I ask another one, promise last one. Maybe you can talk a little bit about ADVOCATE trial specifically about the baseline characteristics? And are you seeing any trends that can indicate that some patients would be less likely to respond to standard of care? And how are you accounting for discontinuation in the study? And maybe a little bit about the powering of the study?

I can comment on some of that. First I'm going to say that obviously ADVOCATE is ongoing. We have still patients that are being dosed in ADVOCATE. It is all still blinded. So I really have intentionally not looked even at the blinded data to find out if there seem to be any ideas coming out of baseline data characteristics even in blinded trends. So I simply don't have that data. I will say this though, from what I do know about baseline characteristics, it appears to represent the patient population around the world, which I think is not unexpected since it's a global trial. And in terms of how this drug works, remember what we're trying to do here. We are inhibiting the neutrophil from doing its ultimate destruction. So in ANCA vasculitis, you have auto-antibodies against your neutrophils, and in our view the auto-antibodies themselves are not necessarily the problem. They do get the neutrophils sort of semi activated or primed. But it's clear, again from very careful genetic and model data, at least in animals that the ultimate culprit is C5a receptor. It is both necessary and sufficient. It seems to be the lethal agents in this cascade. That's what we're blocking. So irrespective of ideas, and there are some ideas in the world that one form of ANCA vasculitis is a little bit more difficult to treat than another form and may relapse more frequently, et cetera, et cetera. Frankly, a priori, we don't really much care about that because we're targeting how the neutrophil actually inflames the blood vessel and eventually destroys it. So I personally did not in our model take into account, whether or not you have one form or the other, so called MPO, GPA versus MPA disease for example. So to me, our mechanism should work equivalently on both. We're representing the population of ANCA in our trial and we should be able to determine, I think quite definitively if the drug has activity across this patient population as well as of course looking at the pre-specified subgroup analyses that take into account some of these other factors. So – but there should be no surprises in the distribution of the patient population in ADVOCATE. And to the extent that in Phase II, we had a representative patient population and I believe we did between the CLEAR and the CLASSIC trial. Again, we didn't see anything that stood out dramatically from those data as we've reported before in terms of responses. In terms of differences in efficacy I should say.

Thank you so much. Thank you for answering my questions and congrats again on great quarter and great progress of the year.

Thank you, Lina. Appreciate your questions.

Thank you. Our next question comes from Steven Seedhouse of Raymond James. Your line is open.

Yes. Thank you. Good afternoon. First thing I wanted to ask about was just the importance of impacting pain in Hidradenitis Suppurativa. So Humira improved pain in only one of their two Phase III studies and there's some evidence now that IL-1 alpha antagonism can reduce pain as well. When you look at complement inhibition in this disease with avacopan, does it make sense mechanistically that you would reduce pain? And do you think that pain reduction is just a secondary result of improving the lesions or is it a different ideology I guess in and off itself?

Yes, that's a beautiful question, and it starts to eliminate some beautiful and intricate biology I think. So what we do know is this, all of these mediators seem to ultimately talk to each other to some degree. So for example, we and others have shown certainly in vitro experiments that inhibition of C5a receptor can diminish the production of TNF and IL-1 in cell culture experiments and that’s not a new observation. I think this has been shown in one form or another for a long time. And it used to be thought that IL-1 and TNF were upstream of some of these other mediators, but I think it's more of a network. So the mechanism of the pain reduction is simply not entirely clear at the direct level. To the extent that it will occur, and I believe it will occur as it exemplified by TNF and IL-1 results today. I do think there's a good chance that this will read through with C5a receptor. And in fact, we know that C5a interestingly does have some effects on nervous system tissue directly. There's plenty of results in the literature that suggest that. So let's just say this, whenever you do a clinical trial, while it's important to build models, so you can build the right endpoints, I think you have to be open-minded. But to the extent that it would not surprise me, if we saw a reduction in pain, maybe both directly with C5a receptor antagonism, but certainly indirectly as the inflammatory cascade gets damped down and we go from a smoldering fire to maybe some embers that are just banking, that wouldn't surprise me in the least. And I think that we should definitely look very carefully at that parameter as we come out of the trial. It's built into the HS secondary endpoints that we're looking at.

Okay. Thank you. And this recent IL-1 alpha antibody bermekimab, this HS study was in 42 patients, but I guess eight patients dropped out before completing the study and the protocol used on Last Observation Carried Forward or LOCF analysis to handle those dropouts. And when you look back at a Humira Phase III, I mean they use that, but it was a sensitivity analysis. The primary analysis there was a non-response imputation. So can you just clarify in your Phase II are you using LOCF in the primary analysis? Or will the dropouts be considered non-responders obviously it could affect the response rates.

Yes. Steve, it doesn't surprise me that some of the anti-L1 folks dropped out. There's a long history of some issues with the approach with anti IL-1 as you know, or IL-1 receptor antagonists. So yes, it can be a pretty dicey thing. Let me say this, we haven't talked about all the details of how we're going to analyze HS. But as I mentioned before, it's a 390 patients study. We designed it with the both statistical power and other approaches to be essentially a registration grade trial. So I think you can infer from that information that we will use the appropriate statistical analysis to make sure that we are sort of the Phase III grade analysis. And I think obviously with that amount of – and we will certainly have the power to detect the signals we need to.

Okay, thanks. And just last thing quickly on enrollment velocity of that study. Can you say how many centers are online and how many patients you've treated so far in HS?

Well, let me put it this way, we have patients randomized in this study. We're still getting our sites up and running. I'm going to report on more details on that next quarter. But these trials – there's a lot of pent-up demand in this patient population and these trials, as you may know, can enroll very rapidly. So we're seeing – let's just say we're seeing a significant amount of enthusiasm. So when I mentioned that our aspirational goal is to get the trial enrolled or certainly largely enrolled this year, it's certainly based on some data that we have. So I'll fill in some more numbers as we go into the next quarter and get more sites up and running.

Okay. Thank you. Appreciate it. Thanks for taking my questions.

Thank you, Steve.

Thank you. Our next question comes from Dae Gon Ha of SVB Leerink. Your line is open.

Yes. Hi, good afternoon. Thanks for taking our questions. So just wanted to follow-up on the HS, the AURORA trial question. Tom, just wanted to get your take on, given the pent-up demand and obviously your colleagues are about to get done with their trial. So I would imagine there's even more of an influx of interest. How are you thinking about and how are you planning about balancing rapidity of enrollment, but also quality of output? Specifically, can you comment on maybe site overlap between the SHINE study and the AURORA study that's going on with yours? And then the other question with regards to HS, can you also remind us on what the estimated breakdown is within the prevalence of moderate to severe HS, how early stages two and three take up? And then I have a follow-up. Thanks.

Yes. So I can certainly address some of those items Dae Gon. Thank you for the questions. Again, without going into too many specific details, clearly there is some overlap in sites between SHINE and AURORA. That would only be expected. But there's actually quite a large number of sites and qualified sites that won't overlap, and you'll see that again as we go forward through the trial, but particularly as we start reading out the information. What I will say is this, the investigator community in HS has become – they're amazingly aligned and their desire to come up with new therapies. They became very much coalesced around the previous PIONEER result and how PIONEER was done. They've contributed greatly to understanding and all becoming as standardized as possible in how trial readouts and trial assessments need to be done with such things as the HiSCR or high score. They've also contributed fundamentally to quality of life indices and in a very meaningful way. So the HiSQOL for example is something that really has come out of a marvelous community effort in the HS investigator community. I think all of that's by way of saying that because there hasn't been that much for this patient population for a long time, these folks are really focused and they're all plugged in and trying to make sure that they do standardized their assessments across their field. We go beyond that of course, and some of these folks have contributed in our trial, have been in PIONEER, they’ve been in SHINE. So they know fundamentally what they're doing. And obviously there even in a new field, there is a cadre of KOLs and we all appeal to them. Beyond that, we've been very careful in this trial as we have with many other trials. And one advantage of ChemoCentryx is we've been in the clinical trials business for quite some years. So we've run big trials all over the world and we've learned a lot of good lessons from that experience in different indications. So we're really taking a lot of time for training, standardization, centralized assessments, and even adjudications were appropriate in some of these metrics. So we fundamentally believe we'll get high quality data, even though we will have not inconsiderable number of sites in this trial. But this is a switched on community. They're highly trained. They're all focused on how to get good readouts for HS. It's not trivial as you know, but I think that we're getting the advantage of some other efforts and we're right there on the riding the crest of that wave. So I believe that we'll be able to really get very good quality data. So that's essentially how we're controlling for the variability. You had a second question, which I've forgotten now. Sorry about that.

Yes. No problem. So it's just the breakdown of early stages two and three within the moderate to severe patient?

Yes. Thank you. So the data for HS is staggeringly inconsistent, somewhat confusing. But I think we and others can speak with some authority at least generally. If we don't go to breaking down the categories that discreetly, but we can certainly speak with some confidence about Hurley II and III as a category of moderate to severe. And so I think the data are pretty good. And as you know, here in the U.S., orphan drug designation has been given to for Humira, adalimumab for Hurley II, III. So I worked on that because we're also keen on getting that designation. We've been very successful in orphan drug designations with avacopan and other indications. We've done a lot of work on this. So suffice it to say, I'm pretty convinced that moderate to severe Hurley II, III in the U.S. is an orphan designation. It's probably fewer – it is fewer than 200,000. And the numbers between 150,000 and 180,000 are not unmeaningful based on the very best data to-date that we can glean from a variety of sources. So that's the prevalence data. It's harder to breakdown farther than that I think with any credibility. So I won't do so here. And then the question is how many patients will you be able to capture in that prevalent population? The answer is no one yet knows. But suffice it to say that again, when you look into the data for Humira, it's actually quite surprising how few scripts are written for that indication. And yet, as I mentioned, I think everyone's best estimate is about $1 billion worldwide for HS. So maybe the answer there is you don't need to – you don't need to get, but a reasonable fraction, not a huge fraction of that that prevalent population to still make a great return for that drug. Our goal obviously is to get patient relief in the broadest number we can. So we're going to definitely take a hard look at that 150,000 and 180,000 in the U.S. and figure out how to do that.

Okay. And then just quickly my last question is on FSGS LUMINA trials. Just given the cadence of events and I guess the pace of enrollment seems to be quicker in LUMINA-1, I just wanted to get your take on, is the next trial contingent on both trials completing? And what are your thoughts on maybe looking at some other podocytopathies or proteinuric renal diseases? Thanks again.

Yes. Thank you, Dae Gon. So those trials are independent entities, neither of them depend really on the other to move forward. The nephrotic syndrome was attractive to us because the FDA has given pretty clear guidance, guidance with a small G anyway, that if one can really significantly reduced the proteinuria in that population even in a fairly small number of people because their prognosis is so bad. There's really a great and serious discussion to be had about a registration in nephrotic syndrome. They have been a little more circumspect around what it would take beyond proteinuria, if anything, to get a registration in the sub-nephrotic population. So that's our LUMINA-1 population, nephrotic populations LUMINA-2. But if regulators and therefore the rest of us treat these as kind of two separate labels or two separate indications, so either can go forward on its own. And probably – well nephrotic syndrome is obviously a lot, lot more rare. So that's why the numbers is aimed for quite a bit smaller. Podocytopathy, I love the general idea of podocytopathy. As you may recall, and I alluded to it in my remarks, we ran a successful one-year long trial of CCX140 in diabetic chronic kidney disease. We showed a fairly rapid and durable lowering of proteinuria with CCR2 inhibition by CCX140 above and beyond what could be achieved just with standard of care alone. We added it on top of standard of care and showed a delta that was robust and consistent. So then we just pivoted to FSGS is another form of chronic kidney disease, one which was more tractable and one for which proteinuria lowering could conceivably result in at least a conditional license, and certainly a discussion with regulators about how to get the drug approved based on…

Great. Thanks again for taking the questions and congrats on the progress.

Thank you, Dae Gon.

Thank you. Our next question comes from Ted Tenthoff of Piper Jaffray. Your line is open.

Thank you very much for taking my questions. Tom, I always learn at least two or three things when I listen to you talk about this topic, really fascinating, and I love how you described the discovery engine as a well-oiled machine. So I'm excited to see what comes out of that well-oiled machine. Question if I may on – actually two, one housekeeping for Susan. With respect to the shares that were issued, can you give a sense of what number that was or what's the average price was during the offering in January? Thank you.

Of course. Thank you, Ted. So the $20 million that we issued was roughly 1.6 million, 1.7 million shares at $12 a share.

Great. And then Tom for you, so looking forward, obviously a lot of clinical updates coming, really exciting time next year as a company kind of such a transition into a commercial company. What really has to be done, obviously dependent on data, obviously dependent on regulatory outcome, but what really are sort of the steps you start to make to think about the commercial opportunity in the U.S.? Thanks very much for taking the questions.

Thank you, Ted. Those steps are already well underway here. And as you know, we’re really becoming aware of what the market is. We are doing a lot of with professional organizations and through the team that we've hired here to do this work in house, looking a lot into how these patients are actually treated, where they actually present. I'm talking about ANCA vasculitis now for the moment. Really what are the metrics that patient – behind how the patients are treated and what's the patient journey look like. So that whole buying process is a big thing. We're laying out – then from that we start to conclude whoever going to need to actually sell this drug actively. Clearly, we went into this. I often talk about our renal franchise. Some people correctly point out to me and they asked me, its ANCA vasculitis, it doesn't have renal in the name of the disease. Absolutely, true, it's a systemic vasculitis. It happens to be that the kidney is acquisitively sensitive. So anywhere up to 75% or 80% of people over the history of their disease will manifest renal consequences. And those tend to be very expensive, obviously if they go into end stage renal disease, et cetera, and even deadly. So we do think of it as a renal disease, but in addition to nephrologist, this is treated by rheumatologists and frequently lung manifestations are the other big problems. So we're learning more and more about ANCA vasculitis, where it presents? How it presents? I won't go into all the details today, but it's kind of eye opening. So that whole research process and the data it's yielding is telling us about how we need to think about fielding the correct type of salesforce, the right mix of…

Perfect, and of course, I don't mean to put the cart in front of the horse here. The regulatory, the clinical data and the regulatory will come first. One other quick question, if I may. I know you retain rights in China. What are your high level thinking about how to bridge that large, but difficult market? Thanks.

Yes. No, that's great. Probably when we last talked about that we had retained the rights in China, since then Ted, what we've done is our friends at Vifor International were so keen on getting those China rights. I mean we were in discussion with the number of players to really figure out what to do in China. Ultimately, we gave Vifor the China rights to avacopan and CCX140. We got some money upfront for those rights, about $21.5 million or $22 million as I recall. But more important than that – and that was fine, but more important than that was the sales on those two assets will now accrue to the aggregate or cumulative sales in the Vifor territories. And as you know, we get really lovely royalties off the topline of aggregate sales from their territories, as I mentioned in my remarks, ranging from the teens to the mid-20s based on sales tiers. So China could contribute when – so now you have to ask the question of Vifor, but eventual sales in China will contribute to reaching different sales goals in aggregate and their territory is conceivably taking us into other tiers. And so the cumulative effect of that deal I think in the end was spectacular for us. And I know that was meaningful for Vifor who’re very keen to be able to start thinking about how they're going to establish themselves in that part of the world as well.

Cool. Thanks for [indiscernible] missed that. Thanks for the update guys.

Thank you, Ted.

Thank you. Our next question comes from Ed White of H.C. Wainwright. Your line is open.

Hi. Thanks for taking my questions guys. So just a couple of quick things on the AURORA trial. First of all with the topline data expected in the middle of 2020, is that going to include only the 12-week data or will we see some of the follow-up data on the patients for those additional 24 weeks? And then also, Tom, you mentioned in the past many times that you have had the HS study is powered to be registrational grade study, but have you actually had discussions with the FDA regarding this study as registrational in nature? And I just have a follow-up for Susan later.

Sure. So what we're committing to on the topline data is the 12-week data right now. So we'll commit to that topline primary endpoint data. And again we aspire to get there in 2020, if we can get this trial mostly enrolled in 2019, and hopefully or earlier the better. But again, we'll keep you on taste with updates on that through this year based on enrollment. But yes, that's our commitment right now is the 12-week topline data. Obviously the follow-up data will be in process as well around the same time, but we want to make sure we talk about the 12-week as soon as we can. This conversations with the agency, we have had certain conversations. Let's just say for the moment we're trying to first get our orphan drug application approved. And so once we have that application, I think I'll be willing to say a lot more about where we may or may not be with the discussion with regulators. I suffice it to say that this trial is big. It's a very mature asset. Obviously it's a Phase III asset in other indications. So all of that up the benefits of the experience and the safety database and so on and so forth, certainly are not – they are certainly not harming our cause in that respect. But we just need to – it remains to be seen. And of course, I think the agency will be hesitant to commit to any study of being a Phase III prior to seeing the data and of course, prior to ascertaining whether or not we're in an orphan space with this particular asset. So I'll have more to say about that as we go through that process this year.

Okay, great. Thanks Tom. And then just for Susan, considering the $177 million, again the year with plus the $20 million raise in January. Maybe you can talk a little bit about the cash runway. Is this enough to get to launch with the potential Vifor milestones?

Sure. So I think that's a great question, Ed. I mean I think $177 million before the $20 million put this in very strong position. We've been consistent in providing guidance that it gets us through the multiple data readouts, including ADVOCATE, C3G, HS as well as the FSGS programs. So with anticipated filing in 2021 that wouldn't be too unreasonable, but that's about as far as we're actually projecting at the moment.

Okay, great. Thanks Susan.

Sure. Anytime.

Thank you. Our next question comes from Anupam Rama of JPMorgan. Your line is open.

Hi. This is Tessa filling in for Anupam this evening. Thanks for taking the questions and for the updates here. Maybe as we look towards the Phase III ADVOCATE readout later this year, perhaps a housekeeping question. Can you guide us to what we will see in the topline in 4Q? And what we will have to wait for in follow-up presentations? And then secondly, one on AURORA, apologies if I missed this earlier, but can you remind us of what type of reduction in high score you are looking for at 12 weeks both on a relative and an absolute basis? Thanks so much guys.

Certainly. So with the ADVOCATE data, obviously we'll be looking at the topline data from the primary endpoint of BVAS. So you'll hear the BVAS scores and the comparison between the standard of care arm and the avacopan arm for both week-26 and week-52. We hope to be able also to release the topline data on the quality of life assessments using the validated instruments that we employed similarly in the Phase II CLEAR trial. We will be giving readout on parameters that read to the preservation of organ function, including renal parameters. So we used to look for things like proteinuria values, proteinuria reduction over the course of the trial. Look for eGFR, look for things like the shedding of kidney inflammatory markers in the urine such as MCP-1 to creatinine ratios. Again, those were presented in the Phase II study and we've similarly built our plan to analyze them here. And then we will hope to be able to talk about vascular damage index and glucocorticoid toxicity and the delta between the groups. So that's a pretty ambitious slate. We hope to be able to achieve most of it, but at minimum you should look to BVAS scores and some of the objective lab readouts, which we'll be able to analyze I think in the time period that we've assessed. And certainly we'll speak to the overall efficacy of the drug and whether the data mirror what we saw in the Phase II study. In terms of the HiSCR score, we did a lot of modeling based on the TNF studies before. I think that we've been looking again to be able to at least detect the kind of signal at 12 weeks that was manifest in the largest spread for adalimumab in the PIONEER studies, and that should be handily achieved I think with the power that we have in our HS study. So you could use that as a sort of benchmark, and again, we'll have more details as we go forward on those readouts, but we should very handily be able to see those kinds of deltas.

Okay. Thanks very much Tom.

Thank you, Tessa.

Thank you. [Operator Instructions] We have a question from Harshita Polishetty. Your line is open.

Hey, Tom and Susan. Congrats on the progress and thank you for the detailed update on the late-stage programs. Most of my questions have been answered, but I have a quick one on your small molecule PD-1 inhibitor program, if I may. I understand it's very early on in the process, but could you provide some color on CCX4503 and how that addresses the challenges seen with developing small molecule antagonists, I guess with regard to targeting the highly hydrophobic PD-1/PD-L1 interaction surface? Thank you.

Yes, that's great. Thank you, Harshita. It's been a while since we had questions about that beautiful discovery engine we have. Our medicinal chemistry here is so excellent. I love to tell the world that, and this is another example. So as you know, antibodies are clearly ruling the risk with the PD-1/PD-L1 area as with many of the other checkpoint inhibitors. And for good reasons, these are fairly large protein interactions, and you're right, certain challenges like some of these hydrophobic packets and so on that get in the way of trying to really mediate disruptive interaction with small molecule have been daunting. Our guys have cracked this, at least, at certain levels, and our ultimate goal is to crack it in fact with orally active compounds. And we have made great progress. As you know, we published some data on the 4503 molecule or, at least, presented some at a meeting last autumn. I think it was very well received and certainly got a lot of people interested. And now we've even take – we've taken some steps further. We hope to be able to talk about those this year. Ultimately, as a business, we’ll probably need to take forward some of these oncology assets in the context of a partnership for a variety of reasons. We're still fairly focused in terms of size obviously and focused on inflammatory disease. But this is really a thrilling set of developments here. And if one could truly get useful small molecules, and frankly 4503 is pretty good molecule, but I think we've got even some better ones now. Clearly some of the liabilities of protein-based checkpoint inhibitors might be overcome. And as you well know, as good as the checkpoint inhibitors are right now, they have liabilities or difficult to…

Great. Thanks, Tom. That's very helpful, and once again congrats on the progress.

Thank you so much, Harshita.

Thank you. At this time, I'm showing no further questions. I'd like to turn the call back over to Tom Schall for any closing remarks.

Well, I just want to thank everyone for joining our call today. The discussion was very, very interesting and the questions were insightful, and I really look forward to updating you further as we go forward and then in weeks to come, and I very much look forward to talking with you at minimum at the next quarterly call. Thank you very much and have a great afternoon and evening.

Thank you. Ladies and gentlemen, this does conclude today's conference. Thank you for your participation and have a wonderful day. You may all disconnect.