Q1 2020 Earnings Call

[music].

The day and welcome to the protagonists therapeutic speedy G.P. on get development update call.

Please note that the days conferences being recorded.

This time I would like to introduce Don <unk> protagonists, Chief Financial Officer, you go ahead.

Thank you operator.

Printing everyone. Please note that requires today's call will be available at the investors section of our website and protagonists dash C. Dot com.

We begin I'd like to remind me to today's discussion will include statements about the company's future expectations plans and prospects that constitute forward looking statements for the purposes of the same visions under the private Securities litigation Reformat 1995 actual results may differ materially from those indicated by these boards on.

<unk>.

The result of various important factors, including those discussed in that respect or section of our quarterly annual reports on forms 10, Q. and 10, K., which aren't file with the L.C.C.

While we may elect update these forward looking statements at some point in the future we specifically to.

Any obligation to do so even if I've you should change.

With that I <unk> over to the Nash Patel Presidents and C.E.O. two provided an update on the company's progress today.

<unk>.

Thank you all by joining us today.

<unk> well you'd also hear from Samuel effects of a chief Medical officer and up to run out of <unk>. Okay set off my descending methodology medical oncology at the model Sinai Hospital in New York City.

<unk> has been involved in the face to political study 50, 345 female where and he was sort of light a buddy full wouldn't be off the disease and his perspectives on C.D. 300, and its potential benefits as the <unk> or Phoebe.

Also present for the fall today I gave it a little of a cheap scientific off your soul right and D.

<unk>.

Yeah pleased to have all the isn't even just available to address question during that U.N. days session. After this call.

So they started slide number three.

You got to well aware went back and I started the 2020, but it's pretty clinical assets.

<unk> have been discovered so they use up all the technology platform in six different clinical proof of concept studies.

The three yes, that's fall into brought category.

304, <unk>, let the photos most often each are rare disease and older G. I just looked at target, except I.B.D.J. 200, and D.N. line for pretty quiet and it's so much about diseases R.I.V.D.

All these s. I have a multibillion dollar potential in multiple indication.

B.D. 300.

Type by that they got <unk> that sounds as a master regulator of I inform yesterday's stone age at a distribution I'm in the body was being pursued in face to open label proof of concept studies in <unk> or beat the Hell <unk> R.P.Z. heading to didn't come up with with those they saw that.

<unk> and then investigate a sponsored study in model just plastic syndrome or M.D. yet.

As you might recall it match your major objecting for 2020, <unk> indication for P.D.D. 300, that'd be kind of <unk> with a study in 2021.

Today.

We are pleased to announce initial like you have to weddings robust clinical data from a police I came up I program and the <unk>.

First indication for you, but those study that study.

This decision is based on three criteria.

Transcends consistency of the clinical data.

Favorable regulate the back far away and the commercial opportunity.

This is the color matched announcement today and vital most stuff over discussion will be around 345, P.M.L., where let me off the big this opportunity to talk briefly about about older restricted I.B.D.S.S. largely in the context of color update them cash runs with the.

<unk> face do studies of these agence, namely the old old I'll <unk> for three four others that I think <unk>.

And the old into liquid 2030 to step that antagonists B.D.D. 200 folklore disease.

Understandably going to be influenced by the thought I'd go read 19 situation.

That fall.

Why this study's up continuing they believe it is appropriate to the mall future guidance on the timeline sparked off line data from these studies.

In addition to the decision to focus on what efforts to what is rapidly advancing 340, psych email that I indication.

We are continuing the ongoing proof of concept study of 300 in how did did did he came up with them with doses as a potential second indication.

And also deciding do now discontinue for the Devil up myself study hundred or beat us how that same yeah.

<unk>.

On the financial side.

We ended the first caught up this year with about 170 million in cash sending west wing.

By factor they gained the delay in enrollment and the associated the clinical development costs, coupled with a reduction in operational need some expenditures Vietnam extending about <unk> at least six months to the middle of 2022.

No.

Let's go to slide number four and let me turn to P.D.G., putting hungry matches high load up to this call and to provide the rationale for why we are pursuing what decided female that as far as syndication.

First and foremost, it's a robust inconsistent plenty called responses.

We have seen it about ongoing pleased to see me try it.

Although small the data that is <unk> bellingham consistent.

Six also six those compliant patients treated fought up to 28 weeks with 300, a flat bucked on me flee.

As of today.

These are where do you know what what did he sells keeping in mind that prior to entering of a study this subjects what a savings frequent suboptimal in the weeks leading up to N. dog.

We are obviously very at that age by diseases, and then brought up and get the study continues with eight patients enrolled they.

And the whole also decided to now expand that got on study.

<unk> 50 patients.

The second factor is that <unk> for the Devil up <unk> 345, P.M.L. wet I indication.

As you know a pro drug <unk> falling through the <unk> designation <unk> by virtue of it being go Red is is in the U.S.N. deal.

And often state us put away certain benefits to the <unk> encoding 70 or stuff like that exclusivity up on F.D. up through <unk> use of the T.V. voters and tax credits for qualified cynical taught.

That's hard factor.

Besides the data that I <unk> is the very significant commercial opportunity that lies I hit off of based on the significant unmet need that exists today for these patients and specifically by let you off the digits 300 being <unk> <unk>.

Class non site totally debt to nature <unk> action.

Well be visa red disease that I've talked about 300000 people in the U.S. living with this disease and this number is unfortunately expected to grow as the population ages.

The majority of the patient subjected to <unk> to set up is that a combination of those pick but <unk>.

<unk>, the only F.D. up from side to read up to pet happy and Phoebe and despite having a limited indication in patients who have had any inadequate response to bet on Twitter fine Chicopee is expected to each almost 2 billion in status and 2020 and the largest person <unk> in the P.B. population 90 per cent.

<unk> 40 years based on data, mostly simply quarterly updates.

P.D.D. 300 has the potential to address a significant unmet need in this category, where that he's a lack of and you'll cycle through agence endeavor.

300 offers the potential of keeping patients flip out on me free without causing by definition.

So to summarize <unk>, <unk>, <unk>, but strong and consistent data and therefore are electing to focus on what resources on x., but I did that with the man of 345 P.M.L. <unk>.

Speak more about this I would now like to introduce of a chief medical office or stuff to say I'm, Middlesex them banks them as as good as mentioned we are really encouraged by the results. We've seen in the ongoing proves to study of P.D.T. 300 in patients with Paul He started to me up there.

Dr. Hoffman's Gonna walk you through the study results in detail, but one of the highlight why I believe the state of this problem for those to focus on the the first indication for 300.

Majority of P.B. patients today are treated with full bother me or for bother me in combination with fighter reductive therapies to control, a reprieve psychosis and keep them adequate levels below 45% as indicated in many treatment guidelines. There was a large body of evidence to show is emerging from another critters challenging and regardless of best available.

Therapy, there was substantial portion the patient segments that poorly controlled amount of grid, and therefore, a higher mortality rate compared to age matched controls.

The dreaming paradigm of P.B. allows patients to enter what I call the dangers on before they get the next treatment. So even those people were considered well controlled doesn't increase from adequate leading up to their for bother me.

Self administered 300 may reduce doctor visits me anxiety associated with you on certain beautiful bother me at that time.

Bother me because those are donated blood know is associated with acute symptoms and difficulties, but the real problem in these patients the potential for chronic symptoms related iron deficiency in four bottom line is patient.

P.G. 300 offers the possibility of putting the control of the amount of crude and the patients hands with a weekly soap injected the medic over the Dodgers hormone medic with a clear decision to focus P.G. 300 development in P.B.. We're expanding the current study do include additional patients will be also hosting a scientific planning.

Eating leaders in the field Milo proliferation neoplasms, we will also be working with patient advocates to discuss <unk> and future studies do holidays like the new girl.

I will close by saying that wall further follow data from additional patients will be needed to confirm the continuity of the robust quite uncle responses observed today.

We believe the study provides like I'm, calling rationale to initially planning for a pivotal program and P.B.

In the near term we're expanding the current study to include additional pace with patients as we focus on these encouraging results.

Finally, I want to express all pry them or the entire clinical development team of protagonists and all that protagonists employees would help us to get where we are today with this program.

With that I would like to turn over the Doctor Hoffman, who needs. No introduction is recognized expert in the field of my little proliferative disorders. In this director of the <unk> disease program with the icons school of medicine at Mount Sinai investigator in the 300 study Dr. Huh.

Yes, Thank you very much Sam thanks.

Opportunity.

Really exciting data.

So we can go to slide seven or you can educate the audience.

On what public <unk>. So that you can have a better understanding or the <unk>.

Potential for 300 and put this in Concord.

So you can see here the slide isn't part of what it was <unk>.

<unk> is a member of a group of chronic <unk> malignancies, My look for look for viewpoint awesome.

And these neoplasms or unusual in that patients frequently live several decades.

And these neoplasms occur at the level.

I'm still.

Normally unlike leukemia.

Characterize increase production.

Mature.

Mm.

Bureau is so.

Destructive to the patients are really the increase production of red blood cells, and that's the term roof roof psychosis.

Her previously <unk> subsequently.

No. The interesting thing about this disease is that there were 100000 cases of beer.

<unk>.

United States.

Do you use occurs.

Across races and age groups.

The critical diagnostic warning sign is better than the elevator no adequate.

Which is the homework z.

I think the importance of those drugs because although there was 100000 cases of these patients. These patients as I mentioned live for several decades.

The uses a drug would be quite warmed over that period of time.

The disease occurs primarily individuals or 50 to 70 years.

There is however, higher incidence and young females, who present with whites threatening form bother components.

The thrombotic events, though the current <unk> Bureau includes strokes as well as like Britain from Boces arteries.

Or beans within the agreements within the abdominal cavity.

It's a very high incidence and keep my courtroom barks and cerebral vascular incidents in strokes.

The women that we've talked about the young women they are particularly prone to develop mambo sous within the abdominal cavity, especially we had a thing not leads to a life threatening condition cold, but you already syndrome and is most of your forms.

Hmm requires liver transplantation.

Over the last 15 years, there's been tremendous understanding new understanding of this this group of my look look for the video plugs ones.

And they've been shown to be characterized by mutations in jeans that are associated with my lawyer with my Lloyd Woodfill production.

So the Marlow deliberately <unk> are associated with three driver mutations.

One involving track to the other team called Calreticulin and the other <unk>, which was a receptor or the hormone quote.

Virtually 99% occasions <unk> Bureau.

Probably mutation in shock to.

Most commonly who's a mutation that occurs that x. on 14, which is the job to be 617 up mutation.

A smaller group of patients huh.

<unk> excellent well and those are referred to was X. on 12 patients.

They have a similar phenotype again elevated amount of Chris increased Grumbos cities <unk> shorter lifespan do these thrombotic events.

Severe a ruthless psychosis next slide please.

Yeah.

We're going to talk now about the diagnosis symptoms and treatment and Polish like you Bureau.

So that you can get an understanding of the rules were P.T. potential with P.P.G. 300.

The diagnosis would probably say T.V. is triggered.

Finding an elevator the amount of Chris Serendipitously.

<unk> Oh by the event and that initiate.

The position looking for the diagnosis. So for instance, pacing <unk> per cent, we're going to keep my record on <unk> and from be found huh.

Mmm.

This these warning signs then blood tests to be performed but look for the presence of the truck to be 617 mutation.

The X. on 12 mutation object to be 617 up is my present.

And sometimes a bone marrow.

Bone marrow examination is required to <unk> to perform Cisco pathological confirmation that the diagnosis.

This diseases Nataline complicated boy Bonach episodes, but it's also complicated by burdensome systemic symptoms, including fatigue.

Visual symptoms mm night sweats neutrinos, <unk> extremists characteristically occurs on exposure to water.

It was turned awkward Reuters.

This might seem like a trivial symptom, but I could <unk>. So severe that patients were unable to shower for months or can lead to such stress that occasionally we've unfortunately.

Patients who have succumbed to suicide.

<unk> is the greatest risk the patience with <unk>.

These from <unk> as I mentioned, a heart attack strokes.

<unk> from both of us are pulmonary embolism.

Or the book two hours from.

The Cardinal feature of treatment and reduction or this from product risk is to reduce the amount of <unk> below 45%.

Again, the amount of credits just the measure that we use the number red blood cells from the degree or refer psychosis.

Not sure that essentially the viscosity either <unk>.

<unk>, thereby reducing <unk> from both.

So normalization of the amount of quit using therapeutic for bother me is very common.

And it is really the first treatment newly diagnosed patience would probably so it'd be a room.

Unfortunately therapeutic what bothers me leads to the removal red blood cells, which contain iron and leads to more severe iron deficiency contributing to many of the exacerbation that many of us to spend like symptoms. So they refer to previously.

And those patients that require frequent four bodies.

We're we're half or or advanced stage that is over six years, the beach or have from boces prior from Boces.

It is the recommend stations are the standard of care that those patients all be treated with hydroxy real interfere on <unk>.

It is in this situation but.

300 is especially attractive drug.

It'd be <unk> be used to treat patients who are not recording.

My looks suppressant agents or it could be a replacement for those model is supposed to be agents.

<unk> reductive agents or attraction interferon.

Or use in combination with four bomb and meet with supplemental poor bother me.

Or an alternative drug is <unk>.

Which is the only U.S.F.D.A. approved product for football.

Each of these drugs and I can go into that in detail. During the question and answer period are associated with significant adverse effects and have a question with.

Questionable.

Oh surrounding nor Tolerability.

Significant evidence as I've mentioned shows that controlling the amount of quit below 45% is the most important factor and minimizing boces cardiovascular events.

Death from bonuses.

Let's go to the next slide.

So we're going to talk a little bit about four bottomley, which many of you probably experience when you donate blood.

So most patients <unk> initially.

Phlebotomy is basically the removal of a unit of blood to reduce the amount of <unk> below 45%.

So our target is to keep those patients always below 45% cause it's been well demonstrated in literature that that reduces significantly incidence of thrombosis.

And the incidents with current Boces has been shown to be reduced.

When the degree of time with them adequate 45% is is is maximized.

In addition, these patients receive lodos aspirin.

To paralyzed.

There are platelets and there.

For all further augment this anti Colombo, Janice Colombo Genesis impatience with pop Polish Europe.

Patients, who undergo football unusable, often report feeling tired or dizzy after the full bother me.

And especially in the elderly this is a major factor.

Many of these patients become hypertensive <unk>.

Require a long stays in narrow patient facility or require a fluid infusions.

Or go into congestive heart failure, because there were fluids balance.

Furthermore, regular football enemy results in the iron deficiency.

<unk> well implementation of iron deficiency that may have a debilitating familiar debilitating symptoms.

<unk>, particularly severe fatigue weakness in <unk> cognitive impairments.

This cognitive impairment is a really big deal.

Because many of the patients complain of having a fuzzy brain syndrome.

And they cannot concentrate and do their their their jobs.

In addition, some of the patients have craving for unusual substances, such as ice for clay, which is term <unk>.

And then unfortunately, some of the patients have a restless leg syndrome, which prevents them from going to sleep.

Three or more for the bottom you use in the year in those patients receiving hydroxy area is is associated with an inferior prognosis and higher incidence of thrombotic.

Events.

So you can also thinks that in those in that situation, even in a patient who's receiving hydroxy Ria the combination therapy with 300 could eliminate those frequent lobotomies.

Further improve the <unk> the treatment regimen for these patients.

I think the most important part that you'll see about this drug or the real hot.

The aspect of it is.

But we see these patients, let's say three or four months intervals.

Three or four months interval.

We see that they have an elevator them out of <unk> not triggers us to do well bother me.

But in reality, we got no way to monitor them during the interval between their visits and it's likely that for significant periods of time. They have an elevated inadequate that's only detected at the time or their visit to work clinic.

So as you'll see the really cool part about <unk> 300 is is that there's a sustained inadequate control, which we really never been able to achieve with any of the other agents were but we're with football to be alone Cisco's out onto slide number 10.

Which is P.G.T. 300, and non <unk>, it's mechanism of action. So how does this drug really work well have cited hormone has been established recently in the last couple decades displaying a primary role in promoting the <unk>.

Iron and macrophages.

And decreasing aren't availability for the production of Red blood cells.

So macrophages or type of wipe what so and they are present not only in the bone marrow, but they're also present in all other body tissues.

But the macrophages in in the marrow or turn nursing sells because they're they're activity is essentially to eat iron to red blood cells in the metro and to alter to allow them to produce additional <unk> red cells. This process is this regulated by the track to mutation.

Leading to a reprise psychosis.

So P.T.T. 300 is believed to limit the excess production red cells and polished you mean Bureau.

Essentially allowing that iron to remain in the in the macrophages. Therefore, preventing is transfer into the report precursors.

In addition, it blocks the iron that's present in the <unk> in the tissues outside of the Metro.

Therefore, we believe alleviates many of the systemic symptoms that are associated with color. So you Bureau.

Let's not go on to slide 11, which is the phase to study design.

This is a really interesting manner in which this study has been constructed you can see there are three phases part one is that those findings pureed, which is over 28 days in there too <unk>.

<unk> well those affected those finding phase, where we essentially those as Scully patients.

Meet the amount of quit requirements 10 to 12 to 14 week period, where we essentially have ever see about <unk>.

That is to maintain the patients amount of crypt below 45%.

And then there's part to as a blinded withdrawal, where the patience or randomized to receive either the fixed acted those or placebo goes for up to 12 weeks.

And then I'm sure the patients will be happy about that those that go on placebo. They will then allow it then we will be allowed to put them onto an open label extensions babies <unk> up to 52 weeks will the will will again be able to roost receive.

<unk>.

If the patience inadequate succeed 45% bigots supplemental football enemies, let's go on slide number 12.

This is essentially the responses that we've seen in the seven patients that have been described that are being evaluated.

The red triangles indicate before bottom easily and you can see a lot of them to the left of the solid line and that's the 32 weeks prior to treatment.

And you can see that each of these patients and these were entry quick criteria had at least three lobotomies during that period.

And then you can see this dotted line and that's the time at which the doses. The drug was started in the first thing that strikes you is that they're a lot of red triangles. So the last.

And only one red triangle to the right and that's one of our patients who missed one goes due to the unfortunately due to the pandemic.

And the numbers indicate the doses that were administered over that period of time. So for instance, you can see inpatient put you know two or one there was a dose escalation and then de escalation withdrawal scars on the subsequent slide.

So this really this slide really summarizes and probably as are most important slide and it basically shows that with the administration or this or drug and careful iteration. That's what bothers me is almost virtually eliminated.

Next slide.

Let's focus on two patients one is the top patients which is the blue line.

And you can see that this patient. This is the the individual who missed the ghosts because of the covert infection and you can see that that she was started.

10 milligrams, then went up to 20 milligrams.

And on 20 will milligrams she had a a medical to 47.5.

He was unable to come in at that time because of the coping infection. So we increased as those 240 milligrams as a matter <unk> dropped but it was still above 45, you came and we for bottom I asked him and we've kept him now on 40 milligrams and you've seen on Wednesday, and he did not require a football team.

Amount of group was.

Was below 45.

If you look at the bottom patients who is.

And bright Red you can see that that patient started.

At times here on 10, then was increased the 20.

Then on week seven was got 40 milligrams and then on week, well <unk> 80 milligrams and you can see that that led to her maddox were dropping to 37.5.

We could her dose for 40 milligrams and you can see that over that period of time excuse remained we're bottomley free we saw her on Wednesday, and she can remains.

Hello, I'm adequate or 45.

So there's a dose adjustments that you can easily do the drugs are being administered at home by the patience, giving them a lot of freedom and also empowering them to control their own to see.

If we go to slide 14.

This addresses how do we know.

P.D.G. 300 is really hitting its target.

And what we're measuring here a serum ferrets and and if you were can recall third and there's a molecule that reflects storage on iron.

And you can see these.

Numbers and the vertical column and if you're below 25 that indicates that one as iron deficient.

And you can see with the administration of the drug at subsequent doses over time the <unk> the third in levels increase in each of these patients except for the bottom line for a patient receives extremely had her inadequate control wouldn't extremely low dose of.

Of 300, so these data indicate that the drugs is acting on target.

What about the adverse suspense because this is a chronic disease was one must anticipate that patients will be treated over decades.

This is a small samples that you can see that we had no serious adverse events and the <unk>. The adverse events that were recorded were essentially just irritation.

Essentially at the injection site.

That's slowly resolve in one of the patients had a bruise added 10 milligrams those.

Let's go on now to pay 16, which is our summary.

So just to start this off I think for bother me is use has probably been use for almost.

100 years.

For for at least since I've been in the school, which is from the seventies. There's been great debate about what is the optimal myelosuppressive agent, there's great concern about chemotherapy being used in these patients perhaps increasing the incidence of evolution to keep my leukemia.

We never really anticipated that hormone therapy might be used for this type of disease. So I think this really represents this trial really represents a paradigm shift has great importance for patients with <unk>.

So I think we can easily conclude that the additional data demonstrates the potential of this drug.

Almost entirely avoid the need for bottoming the treatment of Polish <unk>.

Those complaints patients were four bottom <unk>.

Persistent control from adequate levels I think that's really one of the most important issues is that the patients or <unk>.

How to sustain controller or a matter <unk>, which we anticipate will lead to a sustained alleviation other systemic Simpsons and elimination Oaklawn Baltic episodes.

And again as you as I.

Tried to indicate you. These elevator to map occurred levels are associated with significant cardiovascular events, such as heart attack <unk>.

This drug also offers the possibility of weekly administration without the up and down excursions and her inheritance, where bobby therapy or any other toxicities associated with.

Me therapy that I discussed with you.

Also this reduction in poor bother me.

<unk> be available systemically to avoid symptoms that we know that are related aren't efficiency.

So.

P.D.G. 300 has the potential as the first non side or a doctor therapy for P.V.

Destroyed was well tolerated and has a safety profile similar with results. Prior studies. So as you can see from my presentation on extremely enthusiastic about the strong and its future. Thank you for your time.

And get up to how fine.

I would like to not that there is that they have discussed today.

Address the study day that as of May 1st and the study continues to handle.

<unk> Blondin pizza sub make the present additional data <unk>.

Upcoming medical to make it.

So <unk> yeah, not working on for clinical programs, we have like Teddy Kennedy that's all it gets collect two other technology platform.

Priorities are one.

Advancing.

<unk> as well as in <unk>.

Two advancing be at 940 to what face taste, hey, studying at a set of things like this and three.

<unk> <unk> <unk> <unk>.

As a result of holiday ability to let me tell her focus like 300, they'll be neat and <unk> edge.

So what assets to extend out with cash.

<unk>.

Have taken steps to manage and Lola about operating costs, a lot and align our associates that out with God I'm studies.

As a consequence, we now have adequate financial resources, the fine line up but I think on capital expenditures totally they made a lot 2022.

Finally, yeah mindful of they in fact at the current current all at S. outbreak may have on our local operations on global activated.

As we disclose they'd have a financially they sales to the less today, we have suspending guidance fluffy at 940 face still initiation and feeding it 200 access to data and the activity of what's going to minimize impact on timeline and <unk> as quickly as conditions would permit.

I would priority is maintaining the health and safety off of it employees and those are what participating in our study.

Even continued to monitor changing conditions ghastly and satellite update set that up again.

They said that they would like to now open up the cause fuck questions operator.

Ladies and gentlemen, if you have a question that that's fine. Please press the star and then the number one key on your thoughts down down at selling.

If your question has been answered are you wish to remove yourself from the kills me suppress the bounty.

I first question comes from the line as Chris <unk>. Yeah line is now open.

Hi, this attack Chris <unk>. Thank you for taking the question maybe the first one is for that position on the line care so much for.

The overview P.V. I was curious you know how you look at a therapeutic like P.T. <unk> 300.

Killing in in terms of clinical practice on stripping everyday basis S.C.C.P.V. patient.

How you think it may set you know assuming this profile remains consistent.

Huh and sort of said treating I find the P.C., how how how are you may see you know excuse hitch in particular relative to trucks like check a fine. Thank you.

Okay. I think that's really terrific question I I think it's use would be quite wise wide.

I think virtually.

All patients with P.B. would be candidates were destroyed we've as you can see.

We have treated young patients and also older patients with this drugs who's been well tolerated.

Think the advantage again.

Especially with young patients those individuals we do not want to get a life long.

<unk> therapy or interfere on or geography, because on anticipated.

Potential for on <unk> on anticipated adverse effects. So if they have an increase school bonomy requirement. This would be an ideal treatment for those folks.

Because basically with free them up from returning to the clinic as frequently as they do and requiring repeated smoke put bodies.

When we risk ratify these patients those patients that go on the three treatments that I've discussed before frequently they still require from a bond movies and it's been shown by European investigators. If you have additional <unk> during the year during your administration of these.

Drugs that you're an increase <unk>.

So.

And that's sitting destroyed could be in a chunk the agent that would eliminate the knees <unk>.

Well Turner's ugly and I I could see this developing quite quickly patients are frequently.

Unwilling to take any of these agents, especially I drugs Maria and then interfere on because of the.

Potential we can pretend of potential Oh, hi, <unk> and the concern about interfere on essentially have x. systemic symptoms.

Problems with individuals aboard immune disease and also it's it's effect to to exasperated depression patients. So when those individuals I could see and even those high risk patients. If we could could controlled or matter quits with this drug which I think we can easily doom we've demonstrated that.

But this drug would be a real competitor for for any of those agents.

I I think it could be essentially utilize potentially for.

Oh, the broad swath patients would probably set the bureau, so I think and for long periods of time, that's the issue that I'd like to really emphasized to you for instance, like young females, who but you already syndrome, and we usually put those young females on model is supposed to therapy or interfere on.

For life long periods of time, when they come with several decades, there was far prefer being on a a non chemotherapy and on biologic pigeon like interfere on it would really liberate them.

Actually from the adverse effects.

Okay. That's that's very helpful. And then I was wondering if we could touch upon that data for for a minute you know talk traffic and could you elaborate on some of the effects of <unk> and the trial. If any you know like your yeah hope to see their on it and point like that Oh, yeah yeah.

Thank you.

Yeah. So in this situation, which you have to understand is this was <unk> so in reality.

Most patients with <unk>, all patients Oh say most.

The overwhelming majority patience with patience with color so either don't have symptomatic splenomegaly.

So the end points that have been used in the past, let's say for <unk> for reduction of spleen, Sars or minimal important. So these patients even though some of them at high risk disease really didn't have.

[laughter] minimal splenomegaly splenomegaly at all owned 40% of patients who color. So do we have splenomegaly knowing for advanced disease. It's is it symptomatic so the sample sizes too small.

An animal model wouldn't have side in the medics were given those are.

<unk> Bureau animal models administration.

A different cup signed a medic, Italy to reductions fundamentally, but we really were not not able to access this because none of these patients really had significant splenomegaly. So we await treating patients like that to see the the data in the mice recapitulates humans as it relates to the <unk>.

<unk>.

Very helpful. Thank you.

Our next question comes from the line as George Farmer as being though your line is now okay.

Hi, everyone. This is coping thing on for adored congrats on <unk> or <unk>.

We had two buckets and <unk> the first two maybe <unk>.

I know you guys are thinking about once weekly those same possibly twice weekly <unk> I was wondering if maybe.

Going forward at least for T.V.. You think you might you look we have quite weak weak or nothing at all and I was wondering since we are moving past yeah. That's the only an N.T.S. if you'd be willing to comments at all.

What kind of data what scene and those indication.

And I'll have to follow up production Hoffman, if that's okay.

Yeah, the government that for the question and I would have Sam sex C.M., all I'm set the first question.

Sure. So you know with respect to.

The use of 300, and we think that you know it's going to be used wisely.

You you were asking me about the one sneakily Oh, the once weekly and <unk>, we don't anticipate that we'll need to go to twice weekly based on this data the patients are having a robust responds to once weekly therapy, we can always consider that in patients who maxed out with respect to the effect, but at least so far once weekly dozing in the.

Range that we're studying is inadequate which is why we're confident about moving forward into a pivotal study because it looks like we're in the active range and we understand how to tie trade for drunk.

<unk> that that in in and they beat up how the data defenses independence day that they <unk> Laylaz [noise].

Hundred per cent near saturation, so that was I'd like a fish populations that demanded hi delays and twice weekly dozing to get that the SEC, let let us into the <unk> range is income bodies enter that diseases like at church, and especially E.V. The peace at third on is emphatically Lola.

So.

He had always hypothesize that.

<unk> logically one but.

<unk> all these other indications you may know lonardo, there and lower frequency off building. So all the data that the house into dad that is once weekly dollar thing and you can't see the I'll say that <unk> here.

And studied glove in Kenya, they pick a.

That's the second question for about the Hoffman.

Sure Yeah, I didn't say it but it'd be great Doctor hobbies, I know you mentioned that the screen sizes is not something you guys. Typically look out I believe in the protocol you guys are looking at A.P.V. specific kind of symptoms score because when you could maybe you'd be willing to comment to how maybe the trend is looking in the pace.

Let's say you've seen so far and then I guess the second part of that question was.

I, especially since during the blind it pays the blindly component to this trial how.

How are you guys using hydroxy uria or Jack pie, and whether it's past history or some combination or what what's the protocol for how people can give these other medications and in addition to P.T.V. 300.

Oh, Okay I couldn't speak to these questions. One is let's take the second question then mental probably ask you to repeat the first one but in the second question. If let's say for instance, we have one position in the protocol and then I think this guy is emblematic.

The <unk> this callers on maximal doses with a drunk Syria.

If we put them on higher doses of hydroxy area.

Would make them from beside opinion can put them at risk.

Having a bleeding event. So we've done with him as we've kept them on a fix those drunk to Reno and to that fix those hydroxy area.

Added 300, and that's eliminated the poor bottom new requirement.

Many of the patients who are on the clinical trials have been reluctant to go on my list of course, there will be.

So a lot of patients are not that interested in going on my list for some therapy because of the toxicities and <unk> associated with mom was supposed to therapy or interfere on there's also concern with some of the patience about <unk> about sacrifice about secondary malignancies.

Also increased incidence of shingles that is associated with that drugs and so.

That's <unk>, that's the context that we've been administering the drawn we've not had somebody.

Who are we are concurrently treated with interferon we've only had a patient we've been treated concurrently into small sample with on drugs too.

This is part of our goal and expanding the study is to open it up too crude additional patients with a wide variety approaches are used in these patients but.

But it's too early for the symptoms score just to come out in the symptoms score.

Score is really really well established it's been used in the registration of Jack by it's really well accepted by the field, we're using the standard scoring system and we'll be able to report that out later when we have more data.

Yeah, Let me comment on the symptoms score I mean, the symptoms scores of value.

You know in the patients with Paul This I think we've done <unk> I have.

Or a program project group Nancy Oughta, we've used.

Some score for instance to.

Since the advocacy of interfere on and also <unk> and it is useful but it's not as robust as it is in my love fibrosis anecdotally I can tell you that they're they're one of the patients in or.

<unk> had intractable pride is which was a limited by the use of destroyed and.

That was very satisfactory, but again, it's only one Google.

Indication the patients do a experiences sense of wellbeing, but that's really just the global <unk> I think to really get a good feeling of the results of the symptoms score would require a much more so much greater group of patients being study.

With a tool.

Cool.

That's that's perfect really helpful and start the nice I might have message is there and you are you guys can you comments at all about any data that you've seen with P.T.D. 300, and I think it was an I.S. team <unk>.

So that study has been discontinued we decided not to begin that study with the focus on T.V.. We've had such a strong reactions are the positive date in P.B.R. feeling was that we wanted to focus our efforts, where we saw such great results.

That's <unk>. Thank thank you very much appreciate that.

Congrats again.

Thank you.

Hi next question comes from the line as if they chose Schwartz. Your line is now often.

Joey can't hear you if you're on.

[noise], maybe offer that that'd be good that they <unk>, but unless they into them.

Hello.

Yeah.

<unk>.

Hello, Julia breaking up that our technical difficulties.

Mm.

Yeah.

Well.

Why don't they.

Well, then that's totally <unk>, Oh, no I never <unk> nearing.

We are having yeah technical difficulties.

Yup.

Are you guys able to hear me.

Yes, yes, yes.

Oh, Okay, great not sure what happened there. So I was just wondering if you could talk at all about any of the other blood compartment components like leukocytes ridiculous sites, whether you know there were on any you know notable changes there and whether you know you.

Can tie any of that to the targeted mechanism of action.

Okay. If we go back.

Go ahead.

Go ahead dot com.

Yeah, I mean, we have some appendix slides, which if you can go to slow it.

Depending starts starts on slide 18.

And the next slide basically, which I guess the slide.

19 is essentially the platelets and you can see that they're they've been essentially study in response to the in in those patients receiving the drawing to the <unk> the kindness not gone dramatically all.

I'd like to emphasize to you that although many clinicians huh use platelet numbers as a trigger to treat patients with probably so I think a litter sure well testifies.

Basically does not the Cleveland numbers, there's not correlate with the thrombotic risk inadequate mix.

The biggest the biggest difference so we <unk> those people who are sort of aficionados, a treating patients who college.

Essentially don't go after the platelet count.

Not had people who have had platelet counts over 1.5 million, while you're developing <unk>.

So as you can see they remain level. If you go to the next slide which is the ridiculous sites.

That's not what you're interested in you're interested in the next slide which shows Lucas sites and you can see that those levels of also remained steady during the.

During the treatment period.

I should also emphasized to you that none of the patients that receive the drug.

Had any thrombotic episodes during the administration or the drug Randy evidence of evolution or the disease to my look like Roses or two two leukemia and that's the reason why mentioning that to you is because frequently patients have elevated Lucas like counts when that occurred so the other linear just.

Remains stable during the period of the administration.

Oh, great. That's helpful. Thanks, and then for the company.

What.

Oh, the next updates we should look for from this trial and how quickly and you'd think you can get hey, pivotal trial onto the ongoing and what would the.

Design and and point analysis that you're.

Target there look like.

So thanks for that that question and I would have Sam sex elaborate on the the answer to the question sure. So we're currently in the process of working with thought leaders to design a pivotal studies. So we can't say much more about that until we get that design, we're going to move forward them to.

Discuss it with F.D.A. as soon as we finalize that the current study is going to continue and expand we expect it to the first part of its course open label. So we'll be aware of the data is it involves the randomize portion will be starting and we expect that there'll be further data updates in the last half of the.

Here at the various medical meetings in this field that occur that people are well aware.

And what I would like to add is that clearly you by name that difficult time, the <unk> satisfied.

Right off hand automatic David showed your data on seven eight tends to be also mentioned that now that I eight patients that are <unk> and the data speaks for itself. So the <unk> 10, 10 and they come in <unk>.

Chatter that data and and a shad as much information as as as they gather from this expand that study one of the things that Doctor Hoffman mentioned is these patients have to be full bottom eyes to we have to seek medical care. They can't just stay in their house and hunker down. So that's one of the things that's a damaged US is we actually give them.

Possibility of administering at home. So that's working in our favor. These patients can't just avoid care altogether or they run the risk of like won't bother to bounce and then <unk> getting the call.

Obviously, the next step status getting together with the <unk>.

And then collect more data and and have a good that up at the F.D.A. still finalize the the next favorite to study.

<unk>. Thanks.

<unk>.

Again that is far want to ask a question on your touch tone telephone.

Our next question comes from the line as Dot less Chow of H.C.W. Your line is how often.

Oh, Hey, How're, you doing <unk> sound for our dog child, Congrats on the data and I was just wondering if you guys could give a little more color about what you saw in the bay. The Palestinian trial that made you decide to discontinue.

So.

<unk> how about guidance has banned that we are doing multiple open label profile concepts that is that they intend help picking up Dana.

Today.

We have picked up in our huge margin and and that is like the AD habit to share as far as beat that pilots kinda sad, obviously be dot <unk>.

Safety data in 50, plus space <unk>, plus injections V. got excellent Pharmacodynamic data as you know they call that they shed.

Getting to that last December call and we are first cannot shad anybody and fought information right now because we had on that embargo and that but <unk>. They present things beat that Pal at an upcoming medical confidence in this corpus.

<unk> impression this is not a matter of us reacting to sell this as a matter of us reacting to the fact that P.B. is so outstanding.

We we really want to emphasize that you know it's very sad we were invested in these four things in parallel they're open label, we get to see the data all the time when we saw this day. There was no question in our mind that this needs to be the focus of the company. So I just wanted to make sure you understood that that we were really reacting to.

The positive there.

I see Oh, thank you.

In addition, they would like to thank for bag and a sample those the the patients to participate in over studies and the investigators to support this studies.

In this difficult times I want to specifically emphasize.

I'll thankful and proud I am up the protagonist employees that have brought us to where we are today.

Thank you all for joining us.

Ladies and gentlemen dates concludes today's conference call. Thank you all for joining you may now disconnect.

Goodbye.

[music].

Mmm.

Uh-huh.

[music].

[laughter].

[laughter].

[laughter].

[music].

[music].

[music].