Q2 2020 ChemoCentryx Inc Earnings Call

[music].

Welcome to the Chemocentryx.

Second quarter 2000, Chinese National results Conference call.

At this time all participants are in listen only mode. They tell me will conduct a question and answer session. As a reminder, this conference call will be recorded.

I'd now like to tend to call over to Bill Snyder Ya Man Mcclellan.

Last night. Please go ahead.

Thank you good afternoon, and welcome to the Chemocentryxs second quarter 2020 financial results Conference call.

Earlier this afternoon the company issued a press release, providing an overview of its financial results for the second quarter ended June Thirtyth 20 Twond.

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 Dot Chemocentryx Dot com.

Joining me on the call today is Dr., Thomas Schall, President and Chief Executive Officer, 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, Chemocentryx will provide an overview of the Companys financial highlights for the second quarter 2020, before turning the call back over to Tom for closing remarks.

During today's call, we will be making certain forward looking statements, which of those of you. Following the slides can see if you look at slide two.

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 could 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 filed on March 10, 2020, and its form 10-Q filed on May 11 2020.

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 August 10th 2020.

Chemocentryx undertakes no obligation to revise or update any forward looking statements to reflect events or circumstances. After the date of this last conference call.

With that if it's my pleasure to turn the call over to Tom Mitchell.

[music].

Thank you Bill and good afternoon to everyone listening. Thank you for joining us on our second quarter Twentytwenty Conference call.

I will report you today on what I believe its be impressive progress in executing on the 2020 goals that we laid out for you at the started the year.

But who could have guessed that.

Just how far and SAS this pandemic would spread or how long it might last.

Our Hearts go out to all of those affected to their friends and families into all the healthcare workers, who are fighting cobot 19.

The cobot crisis has affected this all.

Here are Chemocentryx me, we're already at or near full enrollment in our current cycle of clinical trials when the full force the pandemic struck and we expect to initiate our next cycle of clinical trials next year.

We have therefore been able to meet most of the milestones that we set out for ourselves this year with relatively little impact well taking actions to safeguard the health of our employees, we're continuing to make key hires and build out a team ahead of the anticipated commercial launch.

Avago Pan and 2021.

The Corona virus has led to heightened awareness of the importance of the bodys own defense mechanisms and to the crucial role that the immune system planes and as you can see from slide three our discovery and development efforts focus on small molecule therapeutics that.

Target specific chemoattractant receptors. These are the receptors that activate inflammatory cells in auto immune diseases. We started in renal disease, but have leveraged our science into dermatology as well and have now even branched out into a new era in oncology.

At the core of at all is the belief that a precise mechanism of action helps to achieve precision medicine.

Our drug candidates are designed for anti inflammatory properties without broad immuno suppression. So that's the immune system can remain fully focused on its mission to resist illness and disease.

This isn't important differentiating feature from other currently standard therapies for the diseases in which we at Chemocentryx are developing new medicines.

Our lead candidate Avago Pan selectively targets, the cfivea receptor switching off the inappropriate activation of harmful neutrophils in complement driven diseases.

In early July as shown on slide four we submitted our new drug application to the FDA for Avago pad in the treatment of patients with Anca associated vasculitis.

We expect to hear back from the FDA later this quarter with regard to next steps in the FDA review process.

We are working also intensively with our partner Vifor pharma as we as they gear up to the potential commercialization of a buck a pen outside of the U.S. Vifor will pay us royalties and the teams to the mid Twentys on net sales outside the United States Vifor plans to file them.

Marketing approval offer authorization with the European Medicines agency by the end of this year 2020.

We are working closely with them as they prepare their me using our core technical documents from the FDA preparations as the key source.

Our applications to regulatory agencies and our preparations for the anticipated commercialization of Avago Pan are built upon the key findings in the advocates pivotal trial.

As a reminder, ads compared our new targeted therapy Avago pad.

Gcgs against what has been the current standard of care, which contains high and chronic doses of glucocorticoids such as prednisone.

We looked at clinical effects in the of Bupropion therapy group in comparison to the prednisone austerity therapy group.

Steroid therapy group, rather in a randomized blinded controlled worldwide sales to be trial of Anca vasculitis patients.

We believe the advocate findings demonstrate a compelling value proposition in terms of out of ocho pads potential to meet the four major unmet needs of Anca vasculitis patients first stopping and cut vasculitis.

Equipping therapy was statistically superior and sustaining remission of Anca vasculitis at 52 weeks compared to the prednisone containing standard of care group.

Second eliminating the need for chronic stereo steroid therapy and the many illnesses associated with that current chronic steroid containing standard of care.

And the advocate trial Avago pen patients achieved a significant reduction in the toxicities and illnesses known to be related to steroids.

Sure.

Stopping the accumulated organ damage that comes with this deadly and debilitating disease Avago Pan therapy led to improved kidney function.

And its use produced a statistically significant improvement in the estimated glomerular filtration rate a key metrics of kidney function.

Fourth and improvement in quality of life.

Too many anchor patients.

Spirits poor quality of life.

Feeling listless ill and lacking in anything like normal vitality.

From advocate there was good news here to a statistically significant improvement in clinically validated measurements of quality of life on Novakov pain therapy.

And overall of off a pan also demonstrated to save favorable safety result in this serious and life threatening disease with fewer subjects, having fewer number some serious adverse events in the of Ocho pen group than than the steroids standard of care group.

[noise] results of the advocate trial were featured in oral plenary sessions during annual meetings of both the you lar or European lead against Rheumatism and E. R. H E. B T. A the European European Renal Association European dialysis and transplant assessed.

You should meetings.

Add DRA DTA for example, Dr., David Jade from Adam Brooks Hospital in Cambridge, England presented some remarkable data on EG, if our improvements from the advocate trial.

Slide five shows that 80% of advocate patients who entered the trial had defined renal impairment.

In this group their baseline fr, which was well balanced between the two groups was on average about 45 mill permit.

A backup in therapy and prove that Egypt bar by nearly eight milk for men over 52 weeks of therapy, which was significantly better than the prednisone containing active comparator group.

In fact, the graph on the right depicts a finding that something to route Nephrologists have described to me as remarkable.

In the lowest turtle obese patients.

Yes.

Those with DGF are less than 30 mill permitting that baseline.

And in fact these individuals their baseline EG fr was about 21 mill permit.

Yes.

Avago Pan by the way this baseline of the this tear tells only about five or six milk hermine away from being a dialysis candidate in this group Avago Pan therapy boosted their EG fr by almost 14 mill permanent over the 52 weeks.

This result shows that we have not only met our goal of stabilizing or preserving what kidney function remains in this disease state and in so doing potentially sparing patients from dialysis, but in fact, the data suggest that avago pad may actually improve renal function.

Overtime in a very significant way.

We believe that a buck of pain therapy offers new hope for patients suffering from Anca vasculitis, and importantly could read them of the toxic consequences of the use of up there I have a stair a therapy developed more than half a century ago steroids.

There are some other social but notable findings from the advocates study.

One of these for example is that patients on of occupancy therapy performed very well.

In the second six months of the trial.

During this period of Onco panel was essentially a monotherapy since the standard concomitant background therapies, such as cyclophosphamide, alright toxin Mad have ceased.

The data suggest that Avago Pan alone may suffice in controlling Anca vasculitis over time, perhaps without the need for repeated administrations of background immunosuppressant drugs, such as Writeups anymore.

While more clinical data may be needed to draw firmer conclusion.

Given the importance of preserving the immune function as we anticipate vaccines in the era of Cobot 19.

This could be a crucial benefit.

We are continuing to move forward with our plans for potential commercial launch as you will see on slide six.

Our aim is to be is to be ready to launch soon after FDA approval.

We have secured commercial batches of a buck a pen that we need for launch we continue to higher well qualified candidates for key positions expanding the capabilities of our commercial operation.

And weve broadened and deepened our knowledge of the structure and dynamics of the U.S. Anca vasculitis market through intensive market research.

We're also taking appropriate educational opportunities to present data on the disease and on the findings from the advocate study to clinicians can both nephrology rheumatology and other relevant disciplines.

And we've initiated discussions with key payers to raise their awareness of the current on met needs and burdens of Anca vasculitis.

We plan to field, especially force of approximately 60 to 75 people to launch of Ocho Pan and the U.S.

Anca vasculitis is a disease that is estimated in the published literature to ravage anywhere between 40000 and 100000 people of the U.S.

An estimated four to 9000 cases alone new cases are diagnosed each year in the United States.

Given the strong value proposition suggested by the advocate data, we believe that avago pads utility could extend beyond day to vasculitis, making up a pan a pipeline in a drug and with strong patent protection.

Given the strong kidney benefit finding an advocate we continue to refine our pipeline and expect to introduce of Opco pan into for lupus nephritis into clinical development in the first half of 2021.

And as you can see from slide seven we expect to report topline data from two more indications this year.

Indeed, the backup hands ability to stifle the activation of destructive neutrophils by jamming. The cfivea receptor represents a precision approach that is relevant not only in kidney diseases, but potentially outside the renal space as well.

In fact, the first topline data that will be report. This year is in hydrogen idas supra tivo, the disabling skin disorder.

Chess is driven by neutrophils that are thought to be activated by the cfivea receptor endovascular lightest complement dysregulation is almost universal NHS patients.

Our Aurora study depicted on slide eight is a double blinded placebo controlled phase to be or clinical trial of approximately 390 patients with moderate to severe hs.

With patients randomized to one of three arm <unk>.

The primary endpoint is the hydro Natus Super Tivo clinical response score or high score after 12 weeks of treatment.

We designed the trial to be power to a registration grade level and decided to slightly over enroll in order to provide some cushion for anticipated cobot related last patient follow up.

As I mentioned earlier the covered crisis has affected this all we add CCX IR no exception, but the impacts have been less grievous for us than for others.

Still while the majority of our subjects had already enrolled in the Aurora trial before the full impact of the Pandemics.

The summer resurgence of covered 19 has led to the renewed if temporary restrictions of some of the clinical sites.

It is therefore likely that this will impact somewhat the normal processes of data collection and verification that then lead to database blocking and subsequent data analysis these processes, which our routine to any clinical study are likely to going to be modestly delayed in Aurora Oh.

Into cobot.

Thus, we predict that the reporting of the 12 week topline results. Originally forecast for Q3 is now expected early in Q4.

To be clear no unblinded data are yet it has.

No unblinding or any other unblinded analyses have you had occurred in this trial, we are merely predicting a modest delay and reporting as a consequence of cobot delays.

I'm often asked how we are dealing with the placebo issue NHS.

The primary endpoint assessment known as high score has an unavoidable elements of subjectivity.

But it is the standard that the FDA expect sponsors to use in determining clinical effects NHS and ultimately the standard by which they will assess for approval of a new therapeutic agent.

We have been very careful to attempt to minimize subjectivity in high score.

For example.

We have carefully selected sites.

Which are all in the U.S., allowing a high touch approach and also in health care system, which tends to keep placebo responses in check.

We have engaged a training program of intensive training standardization and monitoring.

For example, first to train.

Suffices to say, we train train train and principal investigators had to pass the certification test on high score to qualify to enroll patients standardization.

Developed and mandated the use of standardize records and continuous worksheets across the clinical sites and finally monitoring during the blinded data collection takes our resident medical monitor scans nearly daily for anomalies in the data collection and isn't frequent contact with the investigator.

Were also who is also still blinded and they join me resolved Andy recording anomalies using our standard protocol.

In all of these ways and more we're scrupulously attempting to control what we can control to reduce variability and placebo response in the high score assessment.

Our other current uncle pen trial is in another kidney indication see three glum area Luckity.

C. GE is a rare and devastating kidney disease. There is no sta approved therapy Pricy threeg.

Accolade is a randomized blinded controlled trial the design of which is shown on slide nine.

The trial is unique in many ways, including that we will collect and carefully measure kidney biopsy data as a metric measure of efficacy and this will be coupled with other traditional markers of kidney function.

Many expert suggest that we are already in possession of the largest and most comprehensive data set, albeit still blinded.

For CTG, yet assembled for this life threatening illness.

We aim to announce top line data for the acolyte accolade trial by the end of this year.

[noise] innovation and life Sciences does not come up without it set backs and ours came with the disappointing topline results from our luminaire one trial of CCX 140 in focal segmental glomerulosclerosis.

We don't see a way forward for Ccxone hundred 40, NFS Jess and.

In the interests of bio medical innovation and completion, we will report more detailed luminal, one as well as the smaller alumina to datasets in due course.

On a brighter notes see slide 10.

And also in the second quarter, we announced that we have identified an orally administered checkpoint inhibitor ccxfive five nine formerly referred to as CCX 6559, which we plan to advanced into clinical development in the first half of this coming year 2021.

Data presented in June at the annual meeting of the American Association for cancer Research showed that our optimize checkpoint inhibitors led to a mark inhibition.

Of the PD, one PDL one interaction in vitro and importantly produced a potent anti tumor effects in vivo in pharmacological models.

We believe that Ccxfive fivenine has the potential to be used alone or in combination with anybody therapy or other oncology therapies.

Our small molecule checkpoint inhibitor is designed to address at least two limitations of current antibody checkpoint inhibitor therapy one.

Small molecule may achieve better penetration of the tumor in fire tumor micro environment, where some tumors are currently resistant to antibody therapy.

To.

A small molecule brings the convenience of a flexible dosing capability.

Before I turn the call over to Susan can I have for our attention financial results.

Let me add that during the quarter, we have further strengthened our balance sheet with a follow on offering that yielded net proceeds of almost $326 million.

We report today over a half a billion dollars.

In cash and cash equivalents on the balance sheet as of the end of the second quarter.

This financial strength.

Flies many important degrees of freedom.

Pursuing our ultimate mission.

We believe that we have the resources we need.

Potential commercial launch of Avago Pan and Anca vasculitis and beyond.

We can pursue the simultaneous further development of Avago Pan and other high need high value clinical indications as well as additional formulations.

Can we can follow the science and invest in other novel and highly innovative drug candidates such as our orally administered checkpoint inhibitor ccxfive five month.

[noise] My warmest thanks to all my colleagues at Chemocentryx, especially in these difficult times for their tireless work and advancing us to this stage.

And to the many clinicians involved in our clinical trials.

And I think especially.

The patients and their families who have devoted so much to our controlled blinded trials not knowing if an active agent was part of their personal plan, but doing so for the benefit of the community as a whole.

Susan.

Thank you Tom.

Our second quarter 2020 financial results were included in our press release today and are summarized on slide 11.

Revenue was 49.4 million second quarter compared to 7.2 million conditioning clearing in 2019.

Increase in total revenue was primarily due to the acceleration of revenue recognition associated with Tcs one for the agreement with Chrysler.

Following the decision to discontinue development CCX 140, and Ssds 47.2 million of deferred revenue was recognized as contract revenue.

Research and development expenses were 2.8 million because its second quarter 2020, compared to 17.6 million same quarter last year.

This increase was primarily due to patient enrollment fokko kind of a warmer trial in patients with hydrogen that is superior to them.

National fees associated with the preparation of Iraq apparent and doing.

So should we think that's can I just.

And higher drug development, 'cause discovering expenses, including those associated with Ccxfive fivenine.

Early administered small molecule PDL one inhibitor.

These increases were partly offset by our expenses due to the school enrollment CCX one point Illumina one trial in 2019.

General and administrative expenses were 10 point Threemillion card to second quarter compared to 5.6 million in the same quarter last year.

Increase was primarily due to higher employee did expenses, including those associated with a commercial planning efforts and higher concession offering.

Net income for the second quarter was 20.3 million compared to blame net loss of 16.2 million.

Same quarter 2019.

Total shares outstanding at June 30, 2020 were approximately 68.8 million shares.

Lastly, we closed the quarter like 504.6 million in reported cash cash equivalents and investments, including the 325.7 million net proceeds currently do 2020 equity follow on offering as our common stock.

Tom.

Thank you Susan.

To summarize as you can see in slide 12.

We have filed an N D a for a bako pan and Anca vasculitis.

And our partner Vifor expects to file an M.A. in Europe by the end of 2020.

We continue to build our commercial capability.

We are on track to release topline results from two further clinical trials of of Ocho pen in patients with Hs by early Q4, and we'll see three g. by the end of the year.

We are preparing far next cycle like pipeline advancements and we anticipate initiating a clinic clinical programs in the first half of 2021 for orally administered checkpoint inhibitors, ccxfive fivenine as well as for Avago pad in patients with lupus nephritis.

We have attracted the financial resources that we need with now over a half a billion dollars on the balance sheet at the end of Q2 Gendrive us to the next phase of our growth as we seek to become a fully integrated pharmaceutical enterprise that brings fundamentally new medicines.

To patients that need them most.

This chemocentryx enterprise is built on bio medical in innovation.

On determination.

On integrity and on purposeful resilience.

With science and data illuminating the path ahead, I look forward into a future based with the bright light of hope and prosperity.

With that I will now turn the call back over to the operator, and we look forward to your questions operator.

And ladies and gentlemen, as a reminder to ask a question you will need to fast Sarwan I must tell us on tinder dry a question Baskett founder hash key please standby long we compile the can't name Austin.

And our first question comes from the line. This scheme feed a house with Raymond James Your line is now open.

Good afternoon. Thank so much for taking my question. My question is on the analysis of Aurora given all the different moving parts you highlighted on the call. So I was hoping you could quantify the net impact of covert any discontinuations are patients missing their final visit.

Versus over enrolling the study.

And where where it leaves you really with respect to study power and also wondering is the.

Primary analysis here in IP analysis or a per protocol analysis on those patients that haven't deviated from protocol in the last.

How are you treating the patients who may have missed their final study visit because of cobot cobot impact or those responses imputed.

From prior measurements like Lpos or are there just the censored. Thank you yeah, great Great question Steve.

So it is.

All of our analyses are intended as I TT because as I said, we made this trial kind of a registration grade trial since it's a but even though it's a quote phase two or phase Twob trial. So our intention will be to report the status as intense treat.

We will obviously do and have in our stats plan pre specified various kinds of per protocol analyses. So those data will be informative and meaningful as well.

Currently we have been and obviously, we and others have been really careful in documenting the effects of cobot on patients, particularly for primary endpoint determination working very carefully with FDA and documenting and real time, what we're doing with those folks at the moment, we do not intend to last.

Observation carry forward.

Necessarily for those that Mr 12, we visit owing to cobot.

The.

Certainly will capture all of the data we can from those folks, particularly if there so in the trial.

And and.

Measured thereafter, so those might be eliminating data as well, but I think the good news is the first part of your question, which is the I think probably the most important part.

Although yes, it is clear that that dropouts and some loss data.

Owing to Cove, it is going to be higher than what we and others might have modeled.

The fortunate news is I don't think it's going to.

It's not going to.

Materially impair our ability to still have very good power in this trial. So that's I think for us the the the excellent news, we really made a big trial with big groups. It was very highly powered to detect the differences.

That historically, we might be led to expect and certainly highly powered to detect a statistical differences between the groups. So even you know a doubling if you will and I'm not saying thats the number but even if we add twice the number of dropouts or lost data at 12 weeks I think weve.

Oh got really good powered discrimination. So I fundamentally believe that we'll be able to return a meaningful and clean result from the 12 week data even with you know the fact that cobot has messed with some of that data a little bit and really the the biggest impact for us as a slight delay as we.

We get into the sites and do our data verification and collection process.

Appreciate the detailed answer that.

Thank you.

And our next question comes from the line has begun Khalid BP I do need your line is open.

Great. Good afternoon. Thanks for taking my question is and congrats on all the progress so.

Tom if we can go to or or a protocol I. Just wanted to ask can you remind us what the protocol allow us in terms of antibiotic usage on that because I mean, I guess pioneer one and two they did have a little bit of that antibiotic usage versus not antibiotic usage.

And as we look forward in terms of the regulatory front.

Can you update us on your latest thought process with regards to maybe orphan drug designation or conditional filings flash AA or accelerated approval based on or a data alone.

Sure. Thank you take on without going into all the details on the antibiotic use I can tell you that were much closer to the pioneer studies than we were to any other studies, we realize that concomitant antibiotic use can be a confounding feature in the short term.

In ascribing effects to the high score and so we were pretty careful about looking back at what has happened in pioneer one and two and trying to a tiered those guidelines and also making sure that to the extent possible. We didnt have imbalances in antibiotic usage between the group. So again I think we've been very cognizant of that as a complicate.

Feature and trying to avoid it as a complicating factor in our interpretation.

You know back to the regulatory strategy. So it's.

The history is clear on whats gone before.

We're experiment where we're.

Evaluating the early stage two three patient population as did the pioneer studies, which were the studies as people May know are the only phase three pivotal trials that led to so far the single loan registration of a drug in this space that's for Adimab, the anti TNF drug email humira.

And we want to.

We want to try to avail ourselves as much as we can from information from that precedent. So interestingly that sponsored got an orphan drug designation for early stage two three because that patient population is under 200000 people in the U.S. and that is still the case so we.

Have a leap in attempting a and continue to work on our orphan drug designation, we don't yet have that designation yet to chemocentryx, but there is precedent.

And we've been certainly working on that Oh continuously so we get to know if we get that orphan drug designation, but again there is precedent for it.

We fundamentally believe that early stage two three patients are still fewer than 200000, United States at this juncture.

So with all of that in mind getting back to the one of the main points the question.

We.

We set up this trial to be big enough and highly powered enough, where where we got really good data with a highly differentiated agent, particularly one which at that time was not yet in registration for another indication, but we had confidence that it wouldn't be and that's what that has come to past that.

We are filed we're actually have a filing under review for registration of Avago Pan and Anca Vasculitis. We were we had been helpful of that with strong data. We could have an interesting discussion with the FDA about potentially a conditional registration or at least how to get to an accelerated path to register.

Ration again with strong data, so again without going into a lot of details and certainly I I do not at all speak for the agency and the agency, we'll just have to see what data we have as we will and then we will will discuss from there I think it's really great news, though that theres a huge it seems to me a huge.

Demand not just for new therapy, NHS, but new orally active therapy.

And so.

Again, even even cobot, notwithstanding but certainly prior to covert.

We really enrolled the this study very rapidly and I think that again speaks to the eagerness.

Folks and this community to have a new new therapy options. So.

We'll see how strong the data is we'll have discussions with the agency and in the light. If date are positive we will do everything that we possibly can to bring the drug to registration in this indication as quickly as possible.

Great. Thanks for taking our questions look forward to the data.

Thank you Dan.

And our next question comes from the line. This masako something that the kind of Cowen. Your line is now open.

Hi, Tom Hanks, Thanks, and congratulations on the progress this quarter.

I was hoping you could extend or what are they on that what might be considered clinically significant result in nature or perhaps you know what is a strong enough.

Result that would give you confidence to the program for either two registration or two registration enabling studies.

And then could you also help us understand what you might report in the fourth quarter as far as data goes.

Maybe what per protocol and now it seems you might present.

And if you specifically will be breaking out humira failures.

And maybe remind us of the powering the study if you don't mind as well.

Sure. So its all of those are really excellent questions Michelle Thank you for them.

You know we have sold little precedent in the world of Hydrant at a super Tivo in controlled trials that are informative.

To really help us guides some of those cancers out I will take some guesses.

And certainly we have up again for lack of a better term an endpoint, which is a strong tool, but not a not a very sharp too precise tool and the element of variability in subjectivity again makes it a little bit difficult to always try to compare apples to apples, particularly.

When there's only been one or two apples in the been before so.

Let me say this that as a general rule.

Anything that gets me to a clear answer about it next step to me as a success so.

You know if we see clear separation between the groups.

And if some of the secondaries look also supportive and we say to ourselves while it's clear that we're having a clinical effect indeed, a clinical benefit.

Thats a good answer.

Hopefully we won't get the other kind of clear answer which is there's nothing here, but we've done our best but again, even a good clean answer on that side of the equation.

Just allows us to focus on other areas that we can put our our time effort and treasurer. So so getting back to you know we always like people always like to say will what would it what would an interesting difference be for me any statistical separation that significant I will say, let's look very carefully.

That and with this kind of instrument careful as we are to use it as carefully as we can that probably is meaningful. So we would we with minimum I'd like to see a statistical separation, obviously with the high score.

And you know the only precedent we have about what's good for registration what strong enough for registration is what we've seen before and the one drug thats been registered and you know somewhere you know a delta.

Between 20, and 30%, 25% to 30% with obviously the bigger number going to the new agent in that case as it was that a little bit map over the background therapy. That's the one regulatory precedent we have for registration. So I think it could be argued that something approaching that is pretty strong data since that's all.

We have so far.

And again, we'll just have to see how the agency thinks about these things it's pretty clear they like they want to stay with high score they've been very clear the community about that so that's what we're using we've we will report essentially be and you'll recall in this trial.

We've committed to talking about the 12 week primary endpoint data. We also have some additional.

Oh open it's open label, but blinded to dose of.

Continue dosing for 24 weeks. So we've got some special challenges here in trying to preserve the integrity of this dataset, while presenting topline data, which will essentially be aggregate data between the groups that will tell us whether there is a difference between.

You know any of the dose groups in the placebo.

So definitely we'll have that information that will be a valuable and if in fact will tell us whether we achieved the primary endpoint of a statistical separation between drug taking folks and placebo taking folks.

The powering on that is was established quite early on and I think we've talked a little bit about it. Originally we were powered to see about a 90, I'm, sorry, 90% powered or greater to see the historical standard of a 20% difference.

Again, I don't think even with all of the challenges of co bid, we probably have something pretty good still very good power in that way.

So I'm not worried about a material deep powering of the study in any way. So I think again, we'll get a clean answer.

But the whole point is if we get a nice strong resolved on the primary endpoint we want to have.

Dataset preserved integrity, so that when we take the follow up phase we can use the entirety of the data with the discussion with the FDA and again ask how could this support a registration or in former registration. So that's what we'll be talking about sometime in Q4, when we bring the data forward.

Okay. Thank you so much Tom.

You're welcome Michelle Thank you.

And our next question comes from the line of CAD bounce off My first handler. Your line is not open.

Well the.

Update some congrats correct successes, but we're really present here, so I'm couldn't understand sort of how the d. the I'm, hoping that it's positive because.

Or.

Q3, two could who.

The approval so there would be supplemental filings, but would you need to wait for the is the approval to file for the other indications or understand the sequence of that with respect to regulatory filings think summer.

Well Ted Thank you.

I.

I hesitate to a pine on regulatory details since my regulatory expert is not on the phone today, we have an excellent team at Chemocentryx, who does this work.

But my understanding is that probably while each filing and of course, the background materials and each filing.

Such as the manufacturing and chemistry controls et cetera, obviously, the cumulative databases and other ways safety et cetera, those support any individual filing that's probably each indication would be taken in its own turn so it and point of back from a pragmatic aspect.

Anca vasculitis filing will be moving along on the calendar already in its own way in its own pace.

And you know will we probably have that process well underway by the time the other filings got put in and again without.

Being entirely familiar with the details because each of these indications is also sector separate divisions within the FDA I presumed that those divisions, while obviously cooperating extensively.

On the on the materials would of course have their own process. So I think they're kind of quezada independent.

But again were supported by the core technical information.

Well again, it's a high quality problem, hopefully [laughter] well no. Thank you.

Thank you.

You are going to work or the guys paperwork.

Okay.

And our next question comes from the line. Its name names you have the Wells Fargo Dictating. Your line is not open.

Excuse me Andrew Your line is now open.

Sorry, I was on mute thank for taking the questions regarding the H S study design there is a 10 make the I'd.

Or maybe kind of the meet those arm just curious.

What.

Why was it because either the other studies didn't include any of those armed.

Oregon, 30 maker VIP, so, what's the reason of including that arm and what we might read or.

From that arm in the Hs study and also if you could.

Yes so.

I have a follow up after that sure of course.

Endpoint in fact in one of our phase two development programs. We did include a 10 megawatt 30 make dose against.

No about Japan.

All of which was on the background therapy of standard of care. So it was kind of every group got high dose glucocorticoids and daily setting.

In addition to the combination of either cyclophosphamide or Reitox amount. So the classical glucocorticoid, plus X protocol, where axis, either cyclophosphamide or or or Reitox men. So every individual in that phase two study got bats, and then we layered on.

Either 10 make dose or the 30 make dose.

And while that study was mostly a safety study to see if there would be any additional safety burdens that avago pan might impose on people should that drug be use not that we're seeking to use it that way, but should someone ever use of ocho penned in addition to what they've been doing for you know all these years.

Ears.

And thankfully there was no safety burden that about Copan brought to that party.

We were able to look at 10 30 Meg.

Again the powered this study was not powered for efficacy.

But there were hints.

That what we saw with the active effective 30 big dose in the other trials.

Was present, an apparent even in that setting where of course ciber. They were getting standard of care. So.

There was that to deal with an background, whereas the 10 make dose was not quite as Pope. So we do have some experience and of course, we have all of our calculations. Both from pharmacological studies that are off clinical and then the other healthy human volunteer studies to suggest that at low.

Lease where the target that we're going for a pharmacological coverage essentially pharmacological inertness. If you will have the receptor at trough levels of the drug the 10 make dose falls short of that so we put it into this study as one of the arms and essentially this being.

In India, a new indication.

You know outside the space that we were in before we wanted to be able to speak to any.

Questions that regulators or others might have.

That would be a along the lines of well we see that you have some effect at this 30 Mcdow is is that he is that really could you go lower and still see an effect in this indication. So we just built that in and if nothing else that will inform the dataset.

We don't think that 10, Meg dose in that way, we'll have the same pharmacological coverage at all and so I would be gratifying. If the dose response could be seen again, given the limitations of high score that's always a question.

But we wanted to be able to demonstrate to regulators that we had explore dosing at scale in this particular indication. So thats why we put it in the trial as as we did.

Got it that's very helpful. Thank you and then.

Remaining question is regarding any safety m- implications from the HF study.

More specifically I think before the end collapsed vasculitis study.

The economics.

Of ACO kind of used on top of.

Sacrifice that might or might have some AD. So it's.

The safety safety, why it's a little hard to see clearly.

If you profile.

Because of the background therapy here I think there is a very good opportunity to demonstrate safety and it's a large dataset.

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Could you share your thoughts on what in addition to efficacy what kind of the safety leverage will then provide too.

Hi, or lack of pain.

Pipeline. Thanks, Yes, very perceptive question and you're quite right in the anchor patient population there on background therapy for their disease. There on also an amazing number typically an amazing number of concomitant medications control other complications of the.

Therapy.

Our full access for Pneumocystis Jerre Vecchia as a consequence of being under high doses of glucocorticoids endorse cyclophosphamide and Rituximab.

So that has its own problem that that conmeds, they're trying to control their incipient diabetes and.

Some of the bone problems with Conmeds.

It really a challenge patient population and one hopes going back to a buck upended anca vasculitis by removing some of the need for these broadly immunosuppressive therapies. We also get rid of some of these nasty conmeds that give them. So many a ease in essays.

But even there and aimco, we could show, 40% fewer number of severe a ezenia backup and group versus the prednisone standard of care group. So areas seems to be at many levels very good safety advantages to using about copan, but again, we'll let to well that regulators and other.

You said through the datasets and I won't say anymore about that since its under a planning right now, but it is pretty clear to us that the that Hs population is by and large.

Handing the fact that they have this really debilitating illness and that causes them a lot of discomfort and pain in many areas of life physically and emotionally.

They are by and large not under the burden of quite so many concomitant medications and the safety database, although still blinded. The suggestion is that we have far far fewer across the board safety events just in this patient population full stop and.

Again, even in the blind the dataset nothing that seems out of the ordinary for this patient population. So I think when when the data come out it will certainly add too and fundamentally enhance the picture of safety around about Japan, which we believe based on evidence to date, both preclinical off clinical number of species and humans both.

Healthy and when they Anca vasculitis population.

We believe will be a very supportive data package on safety as well. So we hope it will just further enhance that package and if there are any outstanding questions that come out of Anca vasculitis, which in a complex patient population there always could be but if there are any we've got an equally large dataset and hydro not a super tivo to check whether.

Not any of those kind of answer evident NHS. So I think it's going to be a real benefit to our overall package profile.

Got it thanks very helpful.

Thank you and our next.

Our next question comes from the last two that's hard to ask median Leerink. Your line is now open.

Thanks, very much congrats on the progress as well.

I was wondering if you could categorize or characterize your pay pair interactions for us in terms of how well you're finding that they appreciate the various sources of value that of OCC upon could deliver in terms of the total cost of patient management Navy, including a lot of the safety liabilities that you were just.

Alluding to and the range of efficacy benefits are you finding that anything resonates more or less than you know how are you thinking about incorporating the feedback you've obtained from payers to date in your ultimate pricing decision.

Great question.

We.

Again without going into too many details and my commercial team are going to be presenting a lot of information that is health economics conferences, as we get closer to launch and.

And so those will be very interesting things to watch, but I'm going to say that these these interactions to date have been.

We've been very pleased with how much payers actually get it in this Oregon in this particular orphan indication.

They totally understand.

Maybe totally is a bit too strong, but let's just say that we've been impressed at how much understanding there is out there about the true cost of this kind of disease you know.

You can go out and to do that big Big ticket stuff like dialysis and so the kidney data with something that was again very pleasantly a factor in some of those conversations so far.

That's obvious right I mean end stage renal disease will bankrupt are our Medicare system that we don't do something about it overall.

About 9% of the total Medicare budget far more than the entirety of the NIH budget for all medical basic medical research or certainly more than than the NIH budget Jesper instate redundancies forget everything that leads up to it.

But payers, even if you take that out of the equation, which is not which is a big factor not to take out but they understand the hospitalizations art.

Richard just a fraction of this big pie of Anca vasculitis care, there's astonishing number of hospitalizations per year in the U.S. on the order of what to 13 or 14000.

They're not short it's not a day or so it's you know seven to 11 days and cost ranging just the just the cost associated with the anchor codes in the diagnosis and hospitalizations ranging from you know 100 250000. This is just part there's a fraction of the total cost they get that things like Google core.

Vertical AIDS.

Maybe our cheapened the bottle, but they are super expensive to use they get the the all the complications and the safety consequences and the absolute diminution of quality of life and the Pharmaco economics of having people out of work out of the you know in health care system. All the time, so I would say.

This is one of those things that.

You always go into a little bit fearful of the unknown, but so far hats off to the payers they've been a lot more knowledgeable.

And and you know and a lot more.

On message and very receptive to the data we're presenting so I think that's been an encouraging part of the of the journey. So far and we'll have more to say about those details a little bit later on in India and the process.

That's very helpful. Thanks for the Insightops.

Thank you very much Joe.

And our next question comes from the line. That's on your time ran out with JP Morgan. Your line is now open.

Hi, Tom in season, Mrs. Tough on asks on upon thank you for taking my question.

So one secretly d. and there is some competitive activity in the space what are your thoughts around differentiation here forever. Upon C. Five innovation kind of nationalistic pushed back then and then why didn't the latest thinking about academic epidemiology for CPG, where I think let me check can be somewhat variable.

Hi, Thanks, so much.

Yes, Indeed, colitis curious really Eric but I, we have a lot of discussions even within the enterprise about what is the most reliable.

Idea of both incidence and prevalence just in the U.S., let alone anywhere else in a world. It's a rare disease that much as true there's no question.

I don't know if it's quite as ultra rare as some of the literature suggests that my own inclination is maybe not so.

Yeah, I think that you know the the treatable patient population the United States is.

Certainly accessible between yes, probably in the low number of thousands.

Thats kind of what we're looking at but it's hard to know it it is hard to know.

Having said that since there is nothing available for these people and since they go through this really dismal progression of being young people, having end stage renal disease going in dialysis, maybe getting a transplant usually from mom or dad, but typically mom, having that transplant sale within a few short years.

From the same underlying condition and going back in dialysis I mean, this is a bidding a really bad grim cycle and very expensive obviously for the patients their families and then of course for the health care system. So it's definitely very worthwhile approaching this this problem and approaching it from.

A couple of different angles, I fundamentally hope that.

We can all find even in a rare disease like that I think any approach that wins or any couple of approaches that wins is real progress and it will help everybody because frankly see threeq luminary a lot the fee again, one of its mysteries since it's so rare isn't it really you know one disorder or how many.

He disorders is it I mean, we we keep collapsing different features of kidney disease with complement dysregulation under new titles and see Threeg is the latest one I just think of it.

Generally speaking as a complement regulated I'm, sorry complement dysregulated equal merial apathy, so as to differentiation no. One else is attacking what I think as the fundamental question is like why does the kidney.

Develop this massive inflammatory and eventually self destructive feature at the level of biopsy.

And it's not just that you have all of these protein deposits and in the part of C. Three g. that used to be called dense deposit disease, that's sort of gone keeping up the gloom area. I mean, there is active this production I think can sell.

No. We know that complement is dysregulated. There is ample evidence for cfivea receptor Sci Fi. They is more difficult in my opinion to detect either at the level of histochemistry or even with some soluble detection and the periphery, but Sci Fi be through nine this is definitely present in these patients.

Theres lots of evidence of terminal complement.

Activation, leading to what would be a C. A.

Presence and we believe it's there and the kidney as well.

Fundamentally so.

We're the only game in town for stopping what we think is neutrophil mediated destruction or other granular sites meeting some of this destruction.

Other approaches yes, there are some and then there's some in the complement intervention space I think that are orally active drug validated that the level of another very difficult and complicated disease involving the kidneys Anca vasculitis invalidated robustly has to de risk our approach somewhat at.

And the question will be we know it's all C. G. the same kind of disorder or are there going to be subsets that will be more amenable to.

Treatment with one modality versus another and that will play out I think over this next year, but make no mistake as you know some of these other approaches have been frustrated and it's really difficult to understand what's happening. This disorder. It's one of the reasons that when we set out we intentionally decided.

To do something different and we said look see three g. as you know you can that presumptive see three g. and then we do a lot of biopsy work in this area. So let's take biopsies lets confirmed that you have see threeg at the level of biopsy at least and then let's look again at six months, that's a real invest.

But on the part of patients and clinicians but.

Theres real good evidence that you can you know if you get a histological improvement in and around the globe aerialists that matters and that that may well ultimately them.

Fall into line with reduction in proteinuria, which is sustained as well as an improvement over time in each CFR.

And really by bringing all of these features together, including this biopsy endpoint, we think we'll be able for the first time in the history of this disorder to marry all these features together from a really good blinded data set collected blinded evaluated in the case, a histology by a central laboratory.

And this should be very powerful so I think we're going to have a lot to offer in terms of just knowledge and I hope I'm very sanguine and you need bullish about therapeutic benefit for some of these people where the Bakken.

Great. Thanks for taking my question. Thank.

Thank you test.

And our next question comes from the line of added like then H.C. Wainwright. Your line is now open.

Thank you Hi, Tom Hi, Susan.

Hello, Ed.

So just a couple of questions first on actively.

You are expecting the.

Topline data.

By the ended the year is that owning stratum, one or will you we think some striving to data as well.

That's a again a very insightful question. Thank you very much for bringing that up so I.

It's notable when we talk about.

The accolade trial design and I think we alluded to that on one of the slides.

Hi, I reminded people again of this biopsy, we originally you know.

There's no approved therapy, so theres no regulatory path here by the way and I think most people understand that when we set up this trial.

There was a some really good literature at the time.

And this is by way of stratum, one instead them to sort of people understand this little bit better.

There was good literature that suggested that if you had bona Fide C. Gholam aerial apathy I.E. active lesions and destruction in your kidney come area by.

You were probably likely also to have a buyer a bio marker of high levels of C. Fivea through nine or soluble Mac complex in your periphery in your blood your circulation and this was a biomarker that was a stable fairly easy to measure because C. B through nine is stable and there are good.

Good assets for it and so it would kind of make good sense right, you've got a complement dysregulated kidney disease and there's a nice biomarker in the blood. So maybe that's going to be helpful for diagnosis and knowing whether we're having a therapeutic benefit. So originally the trial was designed just for those people that had a relatively.

The high level of see by be through nine in the periphery.

Yes, we got the trial design launched and consulted with FDA. There were some other papers that came out that had an a kind of the opposite point of view it said.

Basically said you know actually all the actions and the kidney don't worry about what's happening the blood because you could have ceased see threeg and have fairly low levels of confident that complement activation markers and the blood, including Sci Fi be through nine so what we decided to do is actually get that second stratum, which is.

Low soluble Mac complex.

In the trial, so that in a way we can definitively answer the question and after all that we had this stratum one trial and got a great resolved. The next question would be will do another trial and people with low soluble Matt complex and see if you get the same result, and so we just thought we do it all in one now why do I tell you all these things.

The fact is when you have presumptive see threeg.

And you then and that's what we do we look for presumptive see Threeg. We screen people. We then next take we next take their measurements on on soluble Matt complex lower high and then the last step we do as biopsy Pru because that's the most invasive step and so by at least by the standards of this.

Trial design, which was done with consultation with the leading Nephrologist new World. This area. What we know is this it seems that the original hypothesis is more correct. If you have biopsy proven C. Glomerulopathy you are likely to present clinically with this marker of high soluble Matt complex.

And in fact, if you have low soluble back complex, even if you clinically at presumptive to the Hep C. G. You convert at the level of biopsy, which is the last step at a much smaller rate. So all of that is by way of saying that we will have virtually all of the target of the original stratum one and the strategy.

Two there will be less data only because far fewer people actually have see threeg when they have low seibel Mac complex. That's what our trial design data suggest so far we havent unblinded anything other than knowing that they simply don't come out on biopsy, we see threeg.

Anywhere near as frequently when they have low sizable amount. So we will put out all the data we have in the world, which again is probably the bulk of the data to be had from clinical trials on T. Threeg and we've already answered I think or at least provided new information on a fundamental clinical question, which was the key.

Controversy between soluble Mac higher LOE does that equate to see threeg and the kidney at a level a biopsy the level of biopsy. The high Seibel, Matt complex is much more correlated with see threeg.

Sorry, I think I won't give you the detailed numbers yet, but we'll have all the data when we talk about that at least for the six month primary endpoint.

Great Fantastic. Thanks for all the information and maybe just a far simpler question with a with a short answer.

So.

With the expectations of 60 to 75 specialties field sales force.

I'm, just wondering where you are in the hiring.

We're doing I think a great job of the hiring again, we've really got a great commercial organization young dynamic the quite experience and a lot of product experience and lunches under their belt. So the the infrastructure at the executive team level is very much in.

Place and now that now we're just bringing on a accordingly and the appropriate time, the actual sales reps and medical science liaisons.

No two to bring them in.

With the appropriate timing, but did the the whole hiring plan is is totally in effect and we're well on our way to bringing in many of those people that will be involved in that field force.

Great. Thanks, Tom.

Thank you Ed.

I am now showing no further questions on the ones like attend to call back if I must solve for closing remarks.

Oh, Thank you operator, and again I wish to think everyone who's been on the call today again, it's been a very exciting although challenging year for many of us in the industry.

But we're making good progress I very much look forward to updating you as we execute further on these 2020 plans and again. Thank you all for your time and attention today you may now disconnect abide.

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Good afternoon, and welcome to the Chemocentryx.

Second quarter 2020 financial results conference call at this time all participants are in the listen only mode. Later, we welcome that pay question and answer session. As a reminder, this conference call will be recorded.

I would now like to technical over to Bill's flatter yield rents Mcclellan.

So slight please go ahead.

Thank you good afternoon, and welcome to the Chemocentryx second quarter 2020 financial results Conference call.

Earlier this afternoon the company issued a press release, providing an overview of its financial results for the second quarter ended June Thirtyth 20 Twond.

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 Dot Chemocentryx dotcom.

Joining me on the call today is Dr., Thomas Shaw, President and Chief Executive Officer, 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 Companys financial highlights for the second quarter 2020, before turning the call back over to Tom for closing remarks.

During today's call, we will be making certain forward looking statements, which of those of you. Following the slides can see if you look at slide two.

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 filed on March 10th 2020, and its form 10-Q filed on May 11 2020.

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 August 10th 2020.

Chemocentryx undertakes no obligation to revise or update any forward looking statements to reflect events or circumstances. After the date of Thislife conference call.

With that and it's my pleasure to turn the call over to Tom Mitchell.

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Thank you Bill and good afternoon to everyone listening. Thank you for joining us on our second quarter Twentytwenty Conference call.

I will report to you today on what I believe it's the impressive progress in executing on the 2020 goals that we laid out for you at the started the year.

But who could have guessed that.

Just how far and fast this pandemic would spread or how long it might last.

Our Hearts go out to all of those affected to their friends and families and to all the healthcare workers, who are fighting cobot 19.

The cobot crisis has affected us all.

Here at Chemocentryx, we were already at or near full enrollment in our current cycle of clinical trials when the full force the pandemic structures and we expect to initiate our next cycle of clinical trials next year.

We have therefore been able to meet most of the milestones that we set out for ourselves this year with relatively little impact well taking actions to safeguard the health of our employees. We are continuing to make key hires and build out a team ahead of the anticipated commercial launch.

Of Avago Pan in 2021.

The Corona virus has led to heightened awareness of the importance of the bodys own defense mechanisms and to the crucial role that the immune system planes and as you can see from slide three our discovery and development efforts focus on small molecule therapeutics that.

Target specific chemoattractant receptors. These are the receptors that activate inflammatory cells in auto immune diseases. We started in renal disease, but have leveraged our science into dermatology as well and have now even branched out into a new era in oncology.

At the core of it all is the belief that a precise mechanism of action helps to achieve precision medicine.

Our drug candidates our design for anti inflammatory properties without broad immunosuppression. So that the immune system can remain fully focused on its mission to resist illness and disease.

This isn't important differentiating feature from other currently standard therapies for the diseases in which we at Chemocentryx are developing new medicines.

Our lead candidate Avago Pan selectively targets, the cfivea receptor switching off the inappropriate activation of harmful neutrophils in complement driven diseases.

In early July as shown on slide four we submitted our new drug application to the FDA for Avago pad in the treatment of patients with Anca associated vasculitis.

We expect to hear back from the FDA later this quarter with regard to next steps in the FDA review process.

We are working also intensively with our partner Vifor pharma as we as they gear up for the potential commercialization of of occupancy outside of the U.S. Vifor will pay us royalties in the teams to the mid Twentys on net sales outside the United States Vifor plans to file them.

Marketing approval offer authorization with the European Medicines agency by the end of this year 2020.

And we're working closely with them as they prepare their MAA using our core technical documents from the FDA preparations as the key source.

Our applications to regulatory agencies and our preparations for the anticipated commercialization of Avago Pan are built upon the key findings in the advocate pivotal trial.

As a reminder, advocate compared our new targeted therapy of Ocho pad a gun against what has been the current standard of care, which contains high and chronic doses of glucocorticoid such as predators zones.

We looked at clinical effects in the of Banco Pan therapy group in comparison to the prednisone austerity therapy group.

Steroid therapy group, rather in a randomized blinded controlled worldwide phase three trial of Anca vasculitis patients.

We believe the advocate findings demonstrate a compelling value proposition in terms of out of occupants potential to meet the four major unmet needs of Anca vasculitis patients first stopping anca vasculitis of.

Kopin therapy was statistically superior in sustaining remission of Anca vasculitis at 52 weeks compared to the prednisone containing standard of care group.

Second eliminating the need for chronic stereo steroid therapy and the many illnesses associated with that current chronic steroid containing standard of care.

In the advocate trial of Ocho Penn station achieved a significant reduction in the toxicities and illnesses known to be related to steroids.

Third.

Stopping the accumulated organ damage that comes with this deadly and debilitating disease of occupancy therapy led to improved kidney function.

And its use produced a statistically significant improvements in the estimated glomerular filtration rate a key metrics of kidney function.

Fourth and improvement in quality of life.

Too many anchor patients.

Experience poor quality of life.

Feeling listless ill and lacking in anything like normal vitality.

From advocate there was good news here to a statistically significant improvement in clinically validated measurements of quality of life on of occupancy therapy.

And overall Avago Pan also demonstrated a safe favorable safety result in this serious and life threatening disease with fewer subjects, having fewer numbers of serious adverse events in the avago can group than than the steroids standard of care group.

Results of the advocate trial were featured in oral plenary sessions during the annual meetings of both the you lar or European lesions rheumatism, and E.R.A. E DTA, the European European Renal Association European dialysis and transplant is.

So you should meetings.

Add DRA EBTDA for example, Dr., David Jain from Adam Brooks Hospital in Cambridge, England presented some remarkable data on fr improvements from the advocate trial.

Slide five shows that 80% of advocate patients who entered the trial had defined renal impairment.

In this group their baseline fr, which was well balanced between the two groups was on average about 45 mill permit.

Avago pen therapy improve that EG fr by nearly eight mill Permian over 52 weeks of therapy, which was significantly better than the prednisone containing active comparator group.

In fact, the graph on the right depicts the finding that Sumner Nephrologists have described to me as remarkable.

In the lowest turtle obese patients.

Yes.

Those with DGF are less than 30 mill permitted at baseline.

And in fact in these individuals their baseline EG fr was about 21 mill permits.

Yes.

Avago Pan by the way this baseline of this tells only about five or six milk hermine away from being a dialysis candidate in this group of Ocho Pan therapy boosted their EG fr by almost 14 mill Permian over the 52 weeks.

This result shows that we have not only met our goal of stabilizing or preserving what kidney function remains in this disease state and in so doing potentially sparing patients from dialysis, but in fact, the data suggests that avago Pan may actually improve renal function.

Overtime in a very significant way.

We believe that of occupant therapy offers new hope for patients suffering from Anca vasculitis.

And importantly could read them of the toxic consequences of the use of up there I have a stair a therapy developed more than half a century ago steroids.

There are some other settle but notable findings from the advocates study.

One of these for example is that patients on of occupant therapy performed very well.

In the second six months of the trial.

During this period of Onco panel was essentially a monotherapy since the standard concomitant background therapies, such as cyclophosphamide, alright, tux demand have ceased.

The data suggest that Avago Pan alone may suffice in controlling anca vasculitis overtime, perhaps without the need for repeated administrations of background immunosuppressant drugs, such as Writeups anymore.

While more clinical data may be needed to draw from our conclusion.

Given the importance of preserving the immune function as we anticipate vaccines in the era of covert 19.

This could be a crucial benefit.

We are continuing to move forward with our plans for potential commercial launch as you will see on slide six.

Our aim is be is to be ready to launch soon after FDA approval.

We have secured commercial batches of Avago Pan that we need for launch we continue to higher well qualified candidates for key positions expanding the capabilities of our commercial operation.

And we broadened and deepened our knowledge of the structure and dynamics of the U.S. Anca vasculitis market through intensive market research.

We're also taking appropriate educational opportunities to present data on the disease and on the findings from the advocate study to clinicians in both nephrology rheumatology and other relevant disciplines and we've initiated discussions with key payers to raise their awareness of the current and met needs.

And burdens of Anca vasculitis.

We plan to field, especially force of approximately 60 to 75 people to launch of occupancy in the U.S.

Anca vasculitis is a disease that is estimated in the published literature to ravage anywhere between 40000 and 100000 people in the U.S.

And estimated four to 9000 cases alone new cases are diagnosed each year in the United States.

Given the strong value proposition suggested by the advocate data, we believe that avago pads utility could extend beyond data vasculitis, making up a pan a pipeline in a drug and with strong patent protection.

Given the strong kidney benefit finding an advocate we continue to refine our pipeline and expect to introduce of ocho pan into for lupus nephritis into clinical development in the first half of 2021.

And as you can see from slide seven we expect to report topline data on tumor indications this year.

Indeed, devop kopins ability to stifle the activation of destructive neutrophils by jamming. The cfivea receptor represents a precision approach that is relevant not only in kidney diseases, but potentially outside the renal space as well.

In fact, the first topline data that will be report this year is in hydrogen Ida supra tivo, the disabling skin disorder.

Hs is driven by neutrophils that are thought to be activated by the cfivea receptor.

Endovascular lightest complement dysregulation is almost universal NHS patients.

Our Aurora study depicted on slide eight is a double blinded placebo controlled phase Twob clinical trial of approximately 390 patients with moderate to severe hs with patients randomized to one of three arm.

The primary endpoint is the hydro Natus Super Tivo clinical response score or high score after 12 weeks of treatment.

We designed the trial to be powered to a registration grade level and decided to slightly over enroll in order to provide some cushion for anticipated cobot related loss patient follow up.

As I mentioned earlier the covered crisis has affected us all.

We add CCX IR, no exception, but the impacts have been less grievous for us than for others.

Still while the majority of our subjects had already enrolled in the Aurora trial before the full impact of the Pandemics.

The summer resurgence of covered 19 has led to the renewed if temporary restrictions of some of the clinical sites.

It is therefore likely that this will impact somewhat the normal processes of data collection and verification that then lead to database locking and subsequent data analysis these processes, which our routine to any clinical study are likely to going to be modestly delayed in Aurora.

Into cobot.

Thus, we predict that the reporting of the 12 week topline results. Originally forecast for Q3 is now expected early in Q4.

To be clear no unblinded data are yet in hand.

No unblinding or any other unblinded analyses that we had occurred in this trial, we are merely predicting a modest delay and reporting as a consequence of cobot delays.

Hi, I'm often asked how we are dealing with the placebo issue NHS.

The primary endpoint assessment known as high score has an unavoidable elements of subjectivity.

But it is the standard that the FDA expect sponsors to use in determining clinical effects NHS and ultimately the standard by which they will assess Ford approval of a new therapeutic agent.

We have been very careful to attempt to minimize subjectivity in high score.

For example, we've carefully selected sites.

Which are all in the U.S., allowing a high touch approach and also in health care system, which tends to keep placebo responses in checked.

We have engaged in a training program of intensive training standardization and monitoring.

For example, first to train.

Suffice to say, we train train train and principal investigators had to pass the certification test on high score to qualify to enroll patients standardization, we developed and mandated the use of standardize records and continuous worksheets across the clinical sites and finally monitoring.

During the blinded data collection phase our resident medical monitor scans nearly daily for anomalies in the data collection and is in frequent contact with the investigator also who is also still blinded and they join the resolved Andy recording anomalies using our standard protocol.

In all of these ways and more we're scrupulously attempting to control what we can control to reduce variability and placebo response in the high score assessment.

Our other current Abaco Pan trial is in another kidney indication see Threeq glomerulopathy.

C. GE is a rare and devastating kidney disease. There is no sta approved therapy Pricy threeg.

Accolade is our randomized blinded controlled trial the design of which is shown on slide nine.

The trial is unique in many ways, including that we will collect and carefully measure kidney biopsy data as a metric measure of efficacy and this will be coupled with other traditional markers of kidney function.

Many experts suggest that we are already in possession of the largest and most comprehensive dataset, albeit still blinded.

Foresee threeg yet assembled for this life threatening illness.

We aim to announce topline data for the acolyte accolade trial by the end of this year.

Innovation in life Sciences does not come up without it setbacks and ours came with the disappointing topline results from our luminaire one trial of CCX 140 in focal segmental glomerulosclerosis.

We don't see a way forward for Ccxone hundred 40 NFS, yes.

In the interests of biomedical innovation and completion, we will report more detailed lumina, one as well as the smaller alumina to datasets in due course.

On a brighter notes see slide 10.

And also in the second quarter, we announced that we have identified an orally administered checkpoint inhibitor ccxfive five nine formerly referred to as CCX 60, 559, which we plan to advance into clinical development in the first half of this coming year 2021.

Data presented in June at the annual meeting of the American Association for Cancer Research showed that are optimized checkpoint inhibitors led to a marked inhibition.

Of the PD, one PDL one interaction in vitro and importantly produced a potent anti tumor effects in vivo in pharmacological models.

We believe that Ccxfive fivenine has the potential to be used alone or in combination with antibody therapy or other oncology therapies.

Our small molecule checkpoint inhibitor is designed to address at least two limitations of current antibody checkpoint inhibitor therapy one.

A small molecule may achieve better penetration of the tumor in fire tumor micro environment.

Where some tumors are currently resistant to antibody therapy.

To.

A small molecule brings the convenience of a flexible dosing capability.

Before I turn the call over to Susan can I have for our attention financial results.

Let me add that during the quarter, we have further strengthened our balance sheet with a follow on offering that yielded net proceeds of almost $326 million.

We report today over a half a billion dollars.

In cash and cash equivalents on the balance sheet as of the end of the second quarter.

This financial strength.

Flies many important degrees of freedom.

Pursuing our ultimate mission.

We believe that we have the resources, we need with potential commercial launch of Avago Pan and Anca vasculitis and beyond.

We can pursue the simultaneous further development of Avago Pan and other high need high value clinical indications as well as additional formulations.

And we can follow the science and invest in other novel and highly innovative drug candidates such as our orally administered checkpoint inhibitor ccxfive five months.

My Warmus, Thanks to all my colleagues at Chemocentryx, especially in these difficult times.

For their tireless work in advancing us to this stage.

And to the many clinicians involved in our clinical trials.

And I think especially.

The patients and their families who have devoted so much to our controlled blinded trials not knowing if an active agent was part of their personal plan, but doing so for the benefit of the community as a whole.

Susan.

Thank you can ask second quarter 2020 financial results were included in our press release today and are summarized on slide 11.

Revenue was 49.4 million for the second quarter compared to 7.2 million traditionally period in 2019.

Increase in total revenue was primarily due to the acceleration of revenue recognition associated with Ccxone hundred 40 agreement before.

Following the decision to discontinue development Ccxone hundred 40, and Ssds 47.2 million of deferred revenue was recognized as contract revenue.

Research and development expenses were 2.8 million for the second quarter of 2020 compared to 17.6 million and the same quarter last year.

This increase was primarily due to patient enrollment fokko, Pat a warmer trial in patients with high Goodnight is superior to them.

Yes, and no fees associated with the preparation.

Okay Indian.

So assuming baskin either.

And higher drug development contracts discovering expenses, including those associated with Ccxfive size nine.

Orally administered small molecule PDL one inhibitor.

These increases were partly offset.

<unk> expenses due to the school enrollment CCX, one point Illumina one trial in 2019.

General and administrative expenses were 10.3 million Curtis second quarter compared to 5.6 million in the same quarter last year.

The increase was primarily due to higher employee related expenses, including those associated with our commercial planning efforts and higher concession fees.

Net income for the second quarter was 20.3 million compared blame that loss assist key point 2 million same quarter of 2019.

Total shares outstanding at June 32020 were approximately 68.8 million shares.

Lastly, we closed the quarter with 504.6 million in reported cash cash equivalents and investments, including the 325.7 million net proceeds credit do 2020 equity follow on offering as our common stock.

Tom.

Thank you Susan.

To summarize as you can see in slide 12.

We have filed an end da for Avago Pan and Anca vasculitis, and our partner Vifor expects to file in EMEA in Europe by the end of 2020.

We continue to build our commercial capability.

We are on track to release topline results from two further clinical trials of of Ocho Pan in patients with Hs by early Q4, and we'll see threeg by the end of the year.

We are preparing far next cycle like pipeline advancements and we anticipate initiating a clinic clinical programs in the first half of 2021 for our orally administered checkpoint inhibitors, ccxfive fivenine as well as for a backup and in patients with lupus nephritis.

We have attracted the financial resources that we need with now over a half a billion dollars on the balance sheet at the end of Q2 Gendrive us to the next phase of our growth as we seek to become a fully integrated pharmaceutical enterprise that brings fundamentally new medicines.

To patients that need them most.

This chemocentryx enterprise is built on bio medical an innovation.

On determination.

On integrity and on purposeful resilience.

With science and data eliminating the path ahead, I look forward into a future based with the bright light of hope.

And prosperity.

With that I will now turn the call back over to the operator, and we look forward to your questions operator.

And ladies and gentlemen, as a reminder to ask a question you will need to fast Sarwan I meant dollarsone Kelly dryer questions Baskett founder hash key please stand by all the compiled it can have Austin.

And our first question comes from the line. This scheme feed house with Raymond James Your line is now open.

Good afternoon. Thanks, so much for taking my question. My question is on the analysis of Aurora given all the different moving parts you highlighted on the call. So I was hoping you could quantify the net impact of.

Over the any discontinuations are patients missing their final visit.

Versus over enrolling the study.

And where where it leaves you really with respect to study power.

And also wondering is the.

Primary analysis here in IP analysis.

Or a per protocol analysis on those patients that haven't deviated from protocol and then last how are you treating the patients who may have missed their final study visit because of cobot cobot impact or those responses imputed.

From prior measurement slick LCFS or are there just the censored. Thank you yeah, great Great question Steve.

So it is.

All of our analyses are intended as ITD because as I said, we made this trial kind of a registration grade trial since it's a but even though it's a quote phase two or phase Twob trial. So our intention will be to report the status as intense treat.

We will obviously do and have in our stats plan pre specified various kinds of per protocol analyses. So those data will be informative and meaningful as well.

Currently we have been and obviously, we and others have been really careful in documenting the effects of cobot on patients, particularly for primary endpoint determination working very carefully with FDIC and document in real time, what we're doing with those folks at the moment, we do not intend to last.

Observation carry forward.

Necessarily for those that Mr 12 week visit owing to cobot.

The.

Certainly will capture all the data we can from those folks, particularly if there so in the trial.

And and.

Measured thereafter, so those might be eliminating data as well, but I think the good news is the first part of your question, which is the and I think probably the most important part.

You know, although yes, it is clear that that dropouts and some loss data.

Owing to Cove, it is going to be higher than what we and others might have modeled.

The fortunate news is I don't think it's going to.

It's not going to.

Materially impair our ability to still have very good power in this trial. So that's I think for us the the the excellent news, we really made a big trial with big groups. It was very highly powered to detect the differences.

That.

Historically, we might be led to expect uncertainly highly powered to detect statistical differences between the groups. So even you know a doubling if you will and I'm not saying thats the number but even if we add twice the number of dropouts or loss data at 12 weeks I think we still got well.

Really good powered discrimination, so I fundamentally believe that we'll be able to return a meaningful unclean result from the 12 week data even with you know the fact that cobot has messed with some of that data a little bit and really the the the biggest impact for us as a slight delay as we get into.

The sites and do our data verification and collection process.

Appreciate the detailed answer but.

Thank you.

And our next question comes from the line has begun Hollywood BP I see your line is open.

Great. Good afternoon, Thanks for taking my questions and congrats on all the progress so.

Tom if we can go to or or a protocol I. Just wanted to ask can you remind us what the protocol allow us in terms of antibiotic usage on that because I mean, I guess pioneer one and two they did have a little bit of that antibiotic usage versus non antibiotic usage.

As we look forward in terms of the regulatory front.

Can you update us on your latest thought process with regards to maybe orphan drug designation or conditional filing slash AA or accelerated approval based on or a data alone.

Sure. Thank you take on.

Without going into all the details on the antibiotic use I can tell you that were much closer to the pioneer studies than we were to any other studies, we realize that can comment in antibiotic use can be a confounding feature in the short term.

In ascribing effects to the high score and so we were pretty careful about looking back at what had happened in pioneer one into and trying to adhere to those guidelines and also making sure that to the extent possible. We didnt have imbalances in antibiotic usage between the group. So again I think we've been very cognizant of that as a complicated.

Feature and trying to avoid it as a complicating factor in our interpretation.

You know back to the regulatory strategy sell its.

The history is clear on whats gone before.

Where experiment where we're.

Evaluating the early stage two three patient population as did the pioneer studies, which were the studies as people may know are the only phase III pivotal trials that led to so far the single loan registration of a drug in this space. That's four at a limit the anti TNF drug humira.

And we want to.

We want to try to avail ourselves as much as we can from information from that present, so interestingly that sponsor got an orphan drug designation for early stage two three because that patient population is under 200000 people in the U.S. and that is still the case so.

We have we been attempting and continue to work on our orphan drug designation, we don't yet have that designation yet to chemocentryx.

But there is precedent.

And we've been certainly working on that Oh continuously so we've yet to know if we get that orphan drug designation, but again there is precedent for.

We fundamentally believe that early stage two three patients are still fewer than 200000, United States at this juncture.

So with all of that in mind getting back to the one of the main points the question.

We.

We set up this trial to be big enough and highly powered enough aware, where we got really good data with a highly differentiated agent, particularly one which at that time was not yet in registration for another indication, but we had confidence that it would be and that's what that has come to pass that.

We are filed we are actually have a filing under review for registration of Avago Pan and Anca Vasculitis, we were we have been helpful.

That with strong data, we could have an interesting discussion with the FDA about potentially a conditional registration or at least how to get to an accelerated path to registration again with strong data.

So again without going into a lot of details and certainly I I do not at all speak for the agency in the agency, we'll just have to see what data we have as we will and then we will will discuss from there I think it's really great news, though that theres a huge it seems to me a huge demand not just for new therapy in H.

Yes, but new orally active therapy.

And so.

Again, even even cobot, notwithstanding but certainly prior to covert.

We really enrolled the this study very rapidly and I think that again speaks to the eagerness of folks in this community to have a new new therapy options. So.

We'll see how strong the data is we'll have discussions with the agency and in the light. If date are positive we will do everything that we possibly can to bring the drug to registration in this indication as quickly as possible.

Great. Thanks for taking our questions look forward to the data.

Thank you Dan.

And our next question comes from the line. This Michelle Gilson at Canaccord. Your line is now open.

Hi can high today, congratulations on the progress this quarter.

I was hoping you could extend over there on that what might be considered clinically significant result, and HX or perhaps you know what is a strong enough.

Result that would give you confidence to the program for either two registration or two registration enabling studies.

And then could you also help us understand what you might require in the fourth quarter as far as data goes.

No maybe what per protocol and now it seems you might present.

And if you specifically will be breaking out humira failures.

And maybe remind us of the powering of the study if you don't mind as well.

Sure so.

It's all of those are really excellent questions Michelle Thank you for them.

You know we have so little precedent in the world of Hydrant at a super Tivo in controlled trials that are informative.

To really help us guides some of those answers out I will take some guesses.

And certainly we have out again for lack of a better term an endpoint, which is a strong tool, but not a not a very sharp too precise tool and the element of variability in subjectivity again makes it a little bit difficult to always try to compare apples to apples protect.

Similarly, when there's only been one or two apples in the been before so.

Let me say this that as a general rule.

Anything that gets me to a clear answer about a next step to me as a success. So.

You know if we see clear separation between the groups.

And if some of the secondaries look also supportive and we say to ourselves while it's clear that we're having a clinical effect indeed, a clinical benefit.

That's a good answer.

Hopefully we won't get the other kinds of clear answer which is there is nothing here, but we've done our best but again, even a good clean answer on that side of the equation.

Just allows us to focus on other areas that we can put our our time effort and treasure. So.

So getting back to we always like people always like to say well what would it what would an interesting difference be for me any statistical separation that significant I will say, let's look very carefully at that and with this kind of instrument careful as we are to use it as carefully as we can that probably.

Finally, as meaningful so we would we with minimum I'd like to see a statistical separation, obviously with the high score.

And you know the only precedent we have about what's good for registration what strong enough for registration is what we've seen before and that one drug thats been registered and you know somewhere.

Delta.

Between 20, and 30%, 25% to 30% with the obviously the bigger number going to the new agents in that case as it was that a little bit mab over the background therapy.

That's the one regulatory precedent we have for registration. So I think it could be argued that something approaching that is pretty strong data since that's all we have so far.

And again, we'll just have to see how the agency thinks about these things it's pretty clear they like they want to stay with high score they've been very clear the community about that so that's what we're using we've.

We will report essentially be and you'll recall in this trial.

We've committed to talking about the 12 week primary endpoint data. We also have some additional.

Oh open it's open label, but blinded to dose.

A continued dosing for 24 weeks. So we've got some special challenges here in trying to preserve the integrity of this dataset, while presenting topline data, which will essentially be aggregate data between the groups that will tell us whether there is a difference.

Between.

No any of the dose groups in the placebo.

So definitely we'll have that information that will be a valuable and if in fact will tell us whether we achieved the primary endpoint of a statistical separation between drug taking folks and placebo taking folks.

The powering on that is was established quite early on I think we've talked a little bit about it. Originally we were powered to see about a 90, I'm sorry, 90% power to greater to see the historical standard of a 20% difference.

Again, I don't think even with all of the challenges of co bid, we probably have something pretty good still very good power in that way.

So I'm not worried about a material deep powering of the study in any way. So I think again, we'll get a clean answer.

But there's a whole pointers, if we get a nice strong result on the primary endpoint we want to have.

And dataset preserved integrity, so that when we take the follow up phase we can use the entirety of the data with the discussion with the FDA and again ask how could this support our registration or inform a registration. So that's what we'll be talking about sometime in Q4, when we bring the data forward.

Okay. Thank you so much time.

You're welcome Michelle Thank you.

And our next question comes from the line of Keds brand software My first handler. Your line is that open.

Well the.

Update some congrats on great successes, but we're really for the year, so I'm kind of understand sort of how the data.

Hopefully another positive.

And or.

Q3 two.

Could impact.

The approval so there would be supplemental filings, but would you need to wait for the is the approval to file for the other indications I'm just kind of sort of understand the sequence of that with respect to regulatory filings. Thanks. So much.

Well Ted Thank you.

I.

I hesitate to a pine on regulatory details since my regulatory expert is not on the phone today, we have an excellent team at Chemocentryx, who does this work.

But my understanding is that probably while each filing and of course, the background materials and each filing.

Such as the manufacturing and chemistry controls et cetera.

Obviously, the cumulative databases and other ways safety et cetera, those support any individual filing that's probably each indication would be taken in its own turn so it and point of fact from a pragmatic aspect.

Anca vasculitis filing will be moving along on the calendar already in its own way in its own pace.

And we'll probably have that process well underway by the time the other filings got put in and again without.

Being entirely familiar with the details because each of these indications is also suffer separate divisions within the FDA I presume that those divisions, while obviously cooperating extensively.

On the on the materials would of course have their own process. So I think they're kind of quezada independent.

But of course supported by the core technical information.

Well again that high quality problem hopefully.

Well no. Thank you.

Thank you.

Looking forward to the Derek I think somewhere.

Okay.

And our next question comes from the line if Mormons you with Wells Fargo, indicating your line is now open.

Excuse me Andrew Your line is now open.

Sorry, I was on mute thank for taking the questions regarding the HF study design. There is a 10 make the I'd.

Or maybe kind of a meet those arm just curious.

What.

Why was it because other the other studies didn't include any those armed.

Oregon.

30 maker.

So what's the reason of including that arm and what we might color.

From that arm in the Hs study and also if you could.

Yes.

I have a follow up after that sure of course.

Endpoint in fact in one of our phase two development programs. We did include a 10 makena 30 make dose against.

No about copan.

All of which was on the background therapy of standard of care. So it was kind of every group got high dose glucocorticoids and daily setting.

In addition to the combination of either cyclophosphamide or Reitox amount. So the classical glucocorticoid, plus X protocol or axis, either cyclophosphamide or or or a REIT tux, Matt. So every individual in that phase two study got bats, and then we layered on.

Either 10 make dose or the 30 Mcdonald's.

And while that study was mostly a safety study to see if there would be any additional safety burdens that avago pan might impose on people should that drug be use not that we're seeking to use it that way, but should someone ever use of ocho Pan in addition to what they've been doing for you know all these years.

Ears.

And then thankfully there was no safety burden that avago Pan brought to that party.

We were able to look at 10 30 Meg.

Again this study was not powered for efficacy.

But there were hints.

That what we saw with the active the effect of 30 big dose in the other trials.

Was present and apparent even in that setting where of course ciber. They were getting standard of care. So.

There was that to deal with an background, whereas the 10 make dose was not quite as Pope. So we do have some experience and of course, we have all of our calculations. Both from pharmacological studies that are off clinical and then the other healthy human volunteer studies to suggest that at least.

Piece, where the target that we're going for a pharmacological coverage essentially pharmacological inertness. If you will have the receptor at trough levels of the drug the 10 make dose falls short of that so we put it into this study.

As one of the arms and essentially this being in India, a new indication.

You know outside the space that we were in before we wanted to be able to speak to any.

Questions that regulators or others might have that would be a along the lines of.

Well, we see that you have some effect at this 30 make those.

Is that he is that really could you go lower and still see an effect in this indication. So we just built that in and if nothing else that will inform the dataset.

We don't think that 10, Meg dose in that way, we'll have the same pharmacological coverage at all and so I would be gratifying. If the dose response could be seen again, given the limitations of high score that's always a question.

But we wanted to be able to demonstrate to regulators that we had explore dosing at scale in this particular indication. So thats why we put it in the trial as as we did.

Got it that's very helpful. Thank you and then.

Remaining question is regarding any safety incident implications from the HF study.

More specifically I think.

For the income ask vasculitis study.

Of ACO kind of used on top of.

Cyclophosphamide or how come out so if.

The safety safety why its little hard to see clearly a safety profile.

Because of the background therapy here I think there is a very good opportunity.

To demonstrate safety and it's a large dataset.

Yeah.

Could you share your thoughts on what in addition to efficacy what kind of the safety leverage will then provide too.

The entire lack of Penn.

Pipeline. Thanks, Yes, very perceptive question and you're quite right in the anchor patient population there on background therapy for their disease. There on also an amazing number typically an amazing number of concomitant medications to control other complications.

Of the therapy.

Prophylactic CES for pneumocystis share of that Guy as a consequence of being under high doses of glucocorticoids endorse cyclophosphamide in Rituximab.

So that has its own problem that that conmeds theyre trying to control their incipient diabetes and.

Some of the bone problems with Conmeds, there really it's really a challenge patient population and one hopes going back to a buck upended anca vasculitis by removing some of the need for these broadly immunosuppressive therapies. We also get rid of some of these nasty conmeds that give them. So many a ease in essays.

But even there and aimco, we could show, 40% fewer number of severe a ezenia backup and group versus the prednisone standard of care group. So there is seems to be at many levels very good safety advantages to using about copan, but again, we'll let to well that regulators and other.

You said through the datasets and I won't say anymore about that since its under a filing right now, but it is pretty clear to us that the that Hs population is by and large nai.

Handing the fact that they have this really debilitating illness and that causes them a lot of discomfort and pain in many areas of life physically and emotionally.

They are by and large not under the burden of quite so many concomitant medications and the safety database, although still blinded. The suggestion is that we have far far fewer across the board safety events just in this patient population full stop and.

Again, even in the blind the dataset nothing that seems out of the ordinary for this patient population. So I think when when the data come out it will certainly add too and fundamentally enhance the picture of safety around about Copan, which we believe based on evidence today, both preclinical off clinical number of species and humans bolt.

Healthy and when they Anca vasculitis population, we believe will be a very supportive data package on safety as well. So we hope it will just further enhance that package and if there are any outstanding questions that come out of Anca vasculitis, which in a complex patient population there always could be but if there are any we've got an equally large dataset.

And hydro Natus supra Teva to check.