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Prothena Corporation PLC (NASDAQ:PRTA)

NEOD001 Interim Phase 1 Data Call

May 2, 2014 4:30 PM ET

Executives

Dale B. Schenk – President, Chief Executive Officer and Director

Martin Koller – Chief Medical Officer

Gene G. Kinney – Chief Scientific Officer and Head-Research

Analysts

Michael J. Yee – RBC Capital Markets LLC

Steve Byrne –Bank of America Merrill Lynch

Jason D. Kantor – Credit Suisse Securities LLC

Christopher Marai – Wedbush Securities

Jonathan Eckard – Citigroup

Operator

Good day, ladies and gentlemen and welcome to the Prothena presentation of NEOD001 Interim Phase I Data Conference Call. At this time all participants are in a listen-only mode. Later we will have a question-and-answer session and instructions will be given at that time. (Operation Instructions) As a reminder this conference is being recorded.

I’d now like to turn the call over to Dr. Dale Schenk, President and Chief Executive Officer. Sir the floor is yours.

Dale B. Schenk

Thank you very much operator, and welcome to all of you joining us this afternoon. So joining me on today’s call to discuss the interim NEOD001 Phase I data that was presented earlier this week, during the poster section at the international symposium on Amyloidosis are Dr. Marty Koller, our Chief Medical Officer and Dr. Gene Kinney, our Chief Scientific Officer, and Head of R&D. We will be going through few slides this afternoon and then we will open the call for questions.

I would like to begin by very much thanking the patients and the clinical investigators involved in the ongoing NEOD001 Phase I trial. Their effort is very much appreciated and supported. Please note that we will be making forward-looking statements based upon current information and expectations. Please review the slide presentation available for download in the Investors section under events and presentations on our website at www.prothena.com. I encourage you to read slide two entitled forward-looking statements for certain factors that could cause actual results to differ materially from our forward-looking statements.

We’ve recognized AL Amyloidosis is a complicated disease. The disease is progressive, fatal and AL patients have few treatment options. While there are number of agents that are important for controlling plasma cells. The majority of patients continue to suffer from organ dysfunction even if light chain production by plasma cells can be stabilized. Currently, there are no therapies directly targeting Amyloid and based on our studies today, we believe NEOD001 may ultimately be a potentially safe treatment option for these patients.

Now turning everyone’s attention to the slide presentation, slide three lays out an overview of AL Amyloidosis. So if you look and turn to slide three. Let’s go through some of the data on the slide as we know or it’s has been documented, its an orphan disease with approximately 15,000 patients in the U.S. and Europe combined, it’s a misfolded Light Chain that deposits primarily in the heart and the kidneys and in other organs. The median survival overall for all patients suffering from the disease is approximately, three years though varies a great deal depending on the organs involved.

And currently as I said previously there is no currently approved treatment, what is important to note is that the treatments that are currently is the existing AL chemotherapy approach is reduce the protection of AL, but as we have mentioned, it doesn’t address the existing toxic amyloid, either the deposited amyloid or the misfold of aggregates of AL.

Now if you will turn to Slide 4, I would like to point out a couple of things on this slide. The first point is that of the various peripheral Amyloidosis, AL comprises the majority of the cases and TTR or transthyretin make most of the rest of the Amyloidosis. There are currently as I mentioned a number of treatments in clinical trials that all targets the plasma cells to reduce the production of Light Chain and as you will see in the upper right of the slide, what NEOD001 does is very different it actually targets specifically the misfolded Light Chain either in the aggregates or in the fibrils. What is important here is that specificity is critical; it doesn’t react with the Light Chain that is normally and correctly folded in a normal immunoglobulin. And so we enhanced specificity is ultimately important to its overall action, okay.

Finally moving to Slide 5, I know what you mention the aggregates in the fibrils, but lets talk about them just a bit more, there is the base among scientists, which aspect of amyloid is most detrimental. The fibrils certainly do form material dislocation of tissue in the tissues they embed whether in this case kidneys or cardiac tissue, which can of course cause disruption and potential damage, but the soluble aggregates can also, because of their nature of being misfolded can interact very non-specifically with cell surface proteins including ion channels.

As is already been said NEOD001 will find to both in the case of the soluble aggregates, it will neutralize them by physically bind into them and in the case of the fibrils to interaction with Monocyte and directly and disrupt the fibrils and ultimately result in clearance. As we go through the rest of the presentation, keep in mind that both actions can be operated and this is important to know.

And so with that introduction, I would now like to turn over the session – the webcast to the clinical aspects of the presentation and specifically I would like to turn the call over to Marty Koller to discuss the Phase 1 study.

Martin Koller

Thank you, Dale. I am on Slide 6 study 001 is an on going Phase 1 trial in patients with AL Amyloidosis the primary objectives are safety, tolerability which are being a maximum tolerated dose or Phase 2 recommended dose. The secondary objectives are pharmacokinetics and immunogenicity. Exploratory objectives are hematologic response and organ response which are determined by NT-proBNP, proteinuria and alkaline phosphatase. This is a reminder NEOD001 doesn’t treat the underlying plasma cell dyscrasia. So there is no expectation of altering the hematologic response.

Slide 7, the study is an on going study and the design is listed in the upper part of the slide it’s a multiple ascending dose (3+3) design. The doses are listed on the slide ranging from 0.5 mg/kg to 30 mg/kg. In the dose escalation portion of the study up to 30 patients can be treated. And the protocol allows for an expansion for additional patients with organ involvement. The bottom part of slide constitutes in key enrollment the criteria for inclusion and exclusion.

The only one that I want to point out is the one that each patient have at least one prior systemic therapy with at least a partial hematologic response. But they all needed to have on going organ involvement to be considered for this type.

With that I would like to turn the call over to Gene, who will talk to the data.

Gene G. Kinney

Thank you, Marty. Marty introduced nicely I think that part of this study will be and as just looking at biomarkers of organ response and organ function. I’d like to start actually with a bit of review of some of the biomarker responses and NT-proBNP responses which we’re using as a primary biomarker to evaluate cardiac response. So NT-proBNP as you may know reflects cardiac stress this is a hormone that’s produced by cardiomyocyte and certainly has a long history in the field of heart failure. And has been used for this purpose for many, many years, we know that its also relevant in AL amyloidosis there are number of papers now published suggesting that levels of NT-proBNP at baseline are prognostic with respect to clinical outcome. Then in fact changes in NT-proBNP following intervention are also prognostic with respect to clinical outcome.

For this study we used what we feel is a very stringent criteria, which was developed by Consensus Panel of AL experts we adopted that Consensus approach into the trial in order to characterize patients as either responders, progressors or stable patients. And of course this response criteria takes into account normal assay and patient variability.

As shown on Slide 8, I can describe that progression and response criteria for you, what it requires for a patient to be evaluated to have baseline NT-proBNP level of ≥650 pg/mL. In the case of response what’s required is starting from that baseline to demonstrate a 30% reduction and an overall decrease of NT-proBNP of >300 pg/mL. So its an end statement both of those are required in order to be a per-protocol responder. Progression is the inverse of this a progressor would be a patient that again has base line level of NT-proBNP greater than or equal to 650 pg/ml and shows an increase in NT-proBNP of greater than 30% and greater than an absolute increase of 300 pg/ml. For patients that meet neither of those criteria, they are considered stable on this measure.

If we go to Slide 9, this talks a little bit about the patient demographics that we recruited into the study. The data that was presented at the ISA meeting was an interim analysis of 18 patients that were evaluated as of March 11 data current study. There is 18 patients again across 6 dose levels, the current plan at the dose escalation portion of this study is to fully enroll at 7 dose cohort levels. As you can see, the patients that were recruited into the study, they received to reflect a general population, the majority of these patients had renal or cardiac involvement, the medium number of organs involved was two which is consistent for this general population, and you can see the mean base line NT-proBNP for all patients regardless of whether they had head cardiac involvement or not was 936 pg/ml.

I’ll talk a little bit more about the 9 valuable patients in a moment here but just to mention at this point that of the 9 valuable patients these are patients with NT-proBNP responses of greater than or equal to 650 pg/ml. The mean value of those patients was above 1,700 pg/ml.

If we go to Slide 10, this really shows where we are in terms of the dosing as of the interim evaluation, the data cut again at March 11. As you can see across this slide, we have 18 patients currently enrolled in 6 dose level cohorts out of the 7 plans. They received to date 106 cycles of NEOD001 and we are very encouraged by this high number of cycles that we’re seeing at this point.

So I feel that this reflects a relatively benign safety profile of this molecule or a priority expectation actually going into the study based on an assessment of other clinical trails in both this population as well as generally in oncology suggested that we could plan, forward, expect about four cycles in terms of the amount of time the patients would stay on this molecule. That said, we far exceeded the efforts to be at the lower doses where the opportunity was there to do so.

As you can see in this slide, there are four discontinuations as of the date of the cut off, one each for logic progression, one for cardiac complication, in one case there was a withdrawal of consent and in the last case a withdrawal of NT-proBNP progression. It’s important to note that none of these discontinuations were considered to study drug related. And I’ll talk a little bit more about the discontinuation as I show you individual patient data around the NT-proBNP activity.

Slide 11 shows really the disposition of how we think about these patients with respect to cardiac involvement. Diagnosis based on patient history and physical advent patients came into the study of course with the diagnosis of AL Amyloidosis to support the compensate of cardiac biomarkers also with and without cardiac involvement and you can see how that breaks down the top of that slide. So again based on this clinical diagnosis, 12 patients were considered to have cardiac involvement while six were not. So that includes total of 18 patients. If we go down to the bottom part of this slide you can how using the NT-proBNP cardiac biomarker criteria of greater than or equal to 650 pg/ml further devised its population.

Using this criteria for base line assessment while we find that 10 of the 18 patients actually meet the criteria of having a greater than or equal to 650 level at baseline and eight do not, of the patient that do enter the criteria that has the greater than or equal to 650 pg/mL level. You can see further on the right how those patients breakdown. In one case, out of the 10 patients that met that criteria, we had no case post baseline data as of the data cover point, so four of that patients was not included in the analysis.

Of the remaining nine patients the so called evaluable patient, we found that eight patients were either classified as responders or were stable. One patient was classified as progressor. If we further [difect] (ph) settlement category of responders or stable, you find that five of those eight patients were considered responder, one or in three of those eight patients were considered stable. Now you will know I think if you compare the top of the slide versus the bottom of the slide, that there were some patients that were originally diagnosed clinically with cardiac involvement that actually were not included in the assessment of NT-proBNP chain primarily because their levels of baseline NT-proBNP were bellow 650 pg/mL cut-off point.

In those patients that its fair to say that the lowering of NT-proBNP was generally consistent with the overall general biological affect that we are observing in patients that need to cut off, but of course its important to note that their integrals for specific analysis due to the fact that their baseline levels do not meet the requirement.

As we move to Slide 12 then, this really starts to breakdown into much more detail some of the response profile that we are seeing. I think in a macro level, we can say that we are very encouraged with the both rapidity and the depth of the affect of the response is slight below numbers of patients completely enrolled in this study.

It should be noted that somewhere between 15% to 30% of patients are known to be able to show a response on this type of cardiac bio marker following plasma cell directed therapy, but when that happens its generally thought that it tends to be very slow and gradual in progression. Thus the current data where we see a relatively rapid affect of onset as well as a relatively high magnitude of affect would be somewhat inconsistent with an affect that was due entirely to a prior plasma cell directed therapies.

More over as I showed you earlier the patients in this group tended to be generally reflective of the overall ALWAYS Amyloidosis population with a reasonable level of cardiac involvement at a baseline level above 1700. I think it’s interesting to know that a bit more of a micro level that of the five patients that were considered responders, four of those five achieved response at Predose Cycle 2, so very early in the process.

But as we kind of move done the list here and you look at the second and third patient down, you could see that that response continue to deepen if you will, but the best response in those patients particularly those two patients was ultimately seen at Postdose Cycle 8. We did have four discontinuation as I mentioned earlier, the first patient on this list the very top actually discontinued following Cycle 7, this was due to hematologic progression and we actually think this is interesting so I think Martin made the point that this drug NEOD001 is not targeting the plasma cell and therefore is not expected to have an impact on the hematology measures. And so to continue to see a encouraging effects on this cardiac biomarker despite the hematological progression is notable.

If we go down the lost and look at the fourth patient down and this was a patient that was showing a response and withdrew from the study due to simply a withdraw of consent, voluntary withdrawal from the study.

And of course as we go down to the sixth patient down in the list you can see a withdraw and in this case. This is the case that I mentioned earlier where the patient was due to progression of NT-proBNP response. Now the one additional patient at this point to adjust add a little bit of additional information is the second patient down in the list.

This patient is quite interesting and as much as this patient has surgical procedure during the course of the study (indiscernible) that actually exist before the study started. So now this is of course the non-related condition during the trial. Once that surgical procedure took place this patient has fluid retention followed by cardiovascular related events. These are genes not to be studied related. Interestingly if you look at this patient who actually had quite a good response, so as a responder level at predose cycle two as well as a best response of predose cycle eight. Following the retention of that’s fluid in the subsequent event this patient progressed rapidly in terms of NT-proBNP levels that can be treated with predose cycle 10 and 11 circle.

This patient ultimately did not receive a dose at cycle 11 and ultimately discontinued due to cardiac complication, what we find encouraging about these data or that NT-proBNP does indeed seem to be a very dynamic and sensitive markers cardiac state and function and seems to be acting appropriately in this set of patients.

So as we move to Slide 13, as Marty said the primary and secondary objectives of this study were to look at safety and tolerability as well as to look at pharmacokinetics this is a pharmacokinetic slide just showing with concentrations of NEOD001 in patients following various doses, what you have here is those single dose and repeat dose pharmacokinetic data up to 8.0 mg/kg and a single dose kinetics curve based on a 16 mg/kg dose.

We’re very encouraged by these pharmacokinetic datas we feel it’s our typical and inline with our expectations for monoclonal antibody and we also note that even as the very last point sample of the 28 day point we see residual exposure following dosing with NEOD001 and this suggest in general that the 28 day dosing cycle that we employed in the Phase 1 is appropriate.

Slide 14, really just shows the treated emergent adverse event table in general this is a very clean safety and tolerability profile for this molecule with no dose limiting toxicities observed to date. We had no drug related series adverse events, and importantly when we looked at immunogenicity or anti-drug antibodies no more detected in any patient to date as of the cut off.

So finally then on Slide 15, just to summarize as Dale mentioned to you residual organ dysfunction following plasmic cell treatment or plasmic cell directed treatment remain the significant unmet medical need in patients with AL Amyloidosis, NEOD001 in this study based on the interim data appears to be safe and well-tolerated, with a PK or pharmacokinetic profile that’s consistent with dosing every 28 days and importantly, we didn’t see any hypersensitivity reactions or development of anti-drug antibodies.

And I showed you 18 patients in six dose level cohorts have received 106 cycles of NEOD001 in the ongoing Phase 1 study to date, of these 18 patients, 9 patients redeemed a valuable for biomarker response as a set by NT-proBNP that is to say that they had NT-proBNP value of greater than rate of 650 pg/mL and at least one post-baseline NT-proBNP determination. Based on that response in analysis 8 of these 9 patients had a cardiac biomarker response where were considered stable.

So when we look at these data in total, we are very encouraged, we think this molecule to date has shown that in Phase 1 well-tolerated that is UK access antibody should. And we see very encouraging cardiac biomarker responses. And so based on the profile so that randomized placebo control Phase 2/3 study are launched in patients with AL amyloidosis particularly dose with cardiac involvement.

And so with that said, I'll turn the call back over to Dale to summarize our upcoming new deal on milestones in 2014. Dale?

Dale B. Schenk

Yes, thank you, Gene. Thanks very much Gene. In summary, this year we plan to initiate a Phase 2/3 clinical study of NEOD001 in the fourth quarter, and communicated additional data from the ongoing Phase 1 study later this year.

We encourage by the safety profile on the preliminary cardiac biomarker responses absorbed in the ongoing NEOD001, Phase 1 study in patients with AL amyloidosis with persisted organ dysfunction. These nM results suggested a double-blind placebo-controlled Phase 2/3 study is wanted to further evaluate safety and efficacy of NEOD001.

At this time, we are ready to open the call for questions. Operator?

Question-and-Answer Session

Operator

(Operator Instructions) Our first question comes from the line of Michael Yee with RBC Capital Markets. Your line is now open. Please proceed with your question.

Michael J. Yee – RBC Capital Markets LLC

Yes, hi thanks guys. Two questions, there is some discussion about Tran interrupt with the data based on patients invest hematological response in the past. And I wanted to understand, how you interrupt that data given the VGPR and CR, I think you made a point that you said, you would not expect to see such short crops on Cycle 2. Do we have any information on these patients BNP going back before that, whether stable and then assumes got the drug it flap, particularly patients two, three, four. How we interrupt with that based on these prior responses add with the piece of drugs?

Dale B. Schenk

Yes, Gene, would you like to answer that?

Gene G. Kinney

Yes, thanks Mike, it’s a great question. So prior to the study because all site don’t necessarily measured NT-proBNP there other forms of BNP like can also be measured in various site might measured various forms of that. One of which is just straight BNP. One of the things you need to do the source of study is actually bring everybody to the same measurement.

And so in the short answer to your question, there we don’t have available to surrogate expensive histories of proBNP history that we can take a look at. That’s I can tell you that we’ve certainly looked at baseline levels, some of the sites is a normal quarters you know not with prior that protocol will actually do a second assessment in advance of any near the one drug dosing. And leased on those occasions we didn’t see any great variability in the – in those assessments between measurements. That’s does not done in every case so it’s a small and it’s too much a out of that kind of assessment.

Michael J. Yee – RBC Capital Markets LLC

But the key here is that you think the short crops on Cycle 2 and sustained for many of those earlier patient...

Dale B. Schenk

Yes.

Michael J. Yee – RBC Capital Markets LLC

As what as you think oligomer staying for many of those earlier patient is what you think a science of promising activity.

Gene G. Kinney

Well, I think there is two points to that, right. The first is that, I think in a general population, the number that most people talk about are somewhere between 15% to 30% of any patients with cardiac involvement might show a response following plasma cell directed therapy. When that does occur, it tends to be a relatively low and slow process. In other words, very gradual over long period of time and this is what we are being told by our key opinion leaders.

If you think about that, first, just from a general population perspective, there is nothing to suggest that we recruited in our patient population relative to the general population. If you look at our demographics, it seem to be in line with the general population. What’s more, it appears that these patients – that we’ve specifically recruited in and evaluated for this cardiac biomarker response as a reasonable level of ongoing cardiac involvement based on NT-proBNP levels.

So all of that said, I mean I think you its – first from a percentage basis, the percent responders is higher than you would expect based on the overall population. And then I think in terms of the low/slow approach, the idea that you are seeing that responses in the 60% to 70% decreased range that you are seeing responder, responses if you will as early cycle too both argue against a very low gradual type of effect, right. It appears to be a reasonable size effect that is occurring relatively quickly following the start of the NEOD001 demonstration.

Michael J. Yee – RBC Capital Markets LLC

Okay. And the second question then is, if you feel that those are responders and there is signs of activity that drop, how you interpret that with the higher doses we are sort of seeing either progression or sort of some jumping around and mix data there. It seems a lot of more consistent at the low dose, any thoughts there?

Unidentified Company Representative

Yes, go ahead sorry.

Unidentified Company Representative

So, yes, I think it’s a very important point Mike and it becomes an important point when we start to think about dose election for the future study. I think there are a couple of key points to be made around dose response. And the first is we shouldn’t think of dose response in this type of study like we would say with an antagonist (indiscernible). This is a large molecule antibody that’s interacting with Amyloid.

When I stuck here, the second Dale I think give you some color on his experience in this field. He is of course been in the field for long, long time. And I think overall its a little less dose sensitive then you might expect traditional pharmacology D for reasons for protein genetics. If I think that’s point one and we knew this coming into this interim analysis that the higher dose level for example we were going to have simply less data because patients would have an opportunity beyond the drug for fewer cycle.

I mentioned at the outset that there was one patient for example that actually meet the 650 baseline criteria but for which we did not yet have a proof based on assessment. That is patient in fact 16 milligrams per kilograms but again you can imagine that as of the data cut off, we just didn’t have enough time to quite a lot of post based line assessment. And so I think as this data fills in, we’ll have a better sense of dose effect.

The final point that I’d just make is that there is also a piece of biology here that needs to be taken into account. Particularly at the level of cardiac tissue, there is a lot work in this field than in other field prices quite frankly that suggest sign will aggregated forms of the protein so the so called the maybe very important in driving ongoing toxicity, at the same time its’ well established as that they are in soluble forms that actually sit on the tissue that cause structural disruption of the tissue, what we know from a lot of the Amyloid work we’ve done and a lot of kinetic workout there. Is that the ability of these antibodies to get in a neutralized soluble toxic forms it may happen at faster time points and potentially with lower relative concentrations that might be needed to be clear the in soluble forms.

And so, it may also be I don’t want to discount this profitability that we are learning something important about the biology here. Of course, we need more data to really speak to that. But I think, it’s certainly interesting, and Dale maybe you have few comments on this topic as well.

Dale Schenk

Yes, now I think that was that I’ll only reiterate one or two things you said. One is that, of course if something to look at it as we go further, we have very limited data in terms of dosing obviously of the higher doses at this point and has changed that. We’d actually, if you look at the Amyloid related therapies to date we’ve never really seen a dose response. Whether it’s pre-clinical or even clinical areas, you tend not, we didn’t walk into it excepting to see dose response and no effect dose is forming – in our animal models was completely maximally effective in the various animal models. We felt that was a time pass interest in terms of a dose, it’s entirely possible but it has been - which was our lowest sales for the soluble (indiscernible) is completely sufficient.

And that’s our general view on it, I think if you are thinking about fibrils than absolute dose and time matters much more than if you are thinking about the soluble aggregates, thanks.

Michael J. Yee – RBC Capital Markets LLC

Thanks guys.

Operator

Thank you. Our next question comes from the line of Steve Byrne with Bank of America. Your line is now open. Please proceed with your question.

Steve Byrne –Bank of America Merrill Lynch

So, if you enroll the three patients in the 30 mg/kg cohort and might you consider making sure that they have base volume levels of proBNP above that 650 pg/mL level just to make sure that they are valuable?

Dale Schenk

Yes, either Gene or Marty, you could answer that. I don’t know that’s certainly in the protocol I wouldn’t know.

Martin Koller

I’ll answer that. Steve, the way protocols written it doesn’t allows to that in the escalation portion of the study, but in the expansion portion of the study we could do that.

Steve Byrne –Bank of America Merrill Lynch

All right. One other one for you Marty, might you consider in that expansion phase another cohort where you are. Baseline proBNP levels are relatively high say in that 6,000, 8,000 levels were some of the perspective studies have indicated you really have maximal separation of the capital micro curves if you use levels that high might you consider cohort of these sicker patients just to evaluate that before you go into phase 2?

Martin Koller

That’s an excellent question, and certainly we something that we could considered in conjunction we are talking and over with the investigators. However, it’s not always possible to get that type of patient into these types of studies, that are that severally ill. When you are talking about 6,000, 7,000 that maybe too well for enrollment of studies. But we’ll certainly consider and discuss it with investigators as well.

Steve Byrne –Bank of America Merrill Lynch

Okay thank you.

Operator

Thank you. Our next question comes from the line of Jason Kantor with Credit Suisse. Your line is now open. Please proceed with your question.

Jason D. Kantor – Credit Suisse Securities LLC

Great. Thanks for taking for my questions. I have a question on the baseline as well as the design and then future question. On the design, you said that they have to have our response to biotherapy of CR better. Is that – that’s response biotherapy or the response to the most recent therapy. That question number one. Question number two, are you able to give the mean or median number of fire regiment, that was missing from the post through I think it will be helpful for everyone. And then, finally, could you discuss what’s your current thinking is around possible endpoints for Phase 2/3 trial for this patient population. Thanks.

Dale Schenk

Martin, you want to answer that.

Martin Koller

Sure. I will say that last part first. We are in discussions and with investigated and certainly with regulators about the design for the Q3 study. And we will make that popular get later day one since determines. As far as the number of treatments are concerned that the treatments ranged anywhere from the one to four regiment sorry, and so its quiet a diverse group patients.

Although it’s a small number represents a general idea what these patients go through. As far as partial response, the partial response at these day partial response was required as a best hematologic response for anyone of their regiment that they underway – not the last regiment that they underway. Is that answer your question?

Jason D. Kantor – Credit Suisse Securities LLC

Yes. But its bring them other so, you are saying that the most recent therapeutic may have not responded to at all, the device out there was the required at this patient needed not be in required in classes out there. We saw and I mean that they need to perhaps some part of at in a level of the depression there.

And then, just in terms of natural history of proBNP any patients would you expect somebody do its on their first therapy getting a CR they have a different type of proBNP profile most streaming then somebody is on their 2013 and not responding it all. How should we think about that in terms of thinking about the data and that’s my all questions. Thanks.

Martin Koller

As Gene said, with regards to the type of response that they would have on or off chemotherapy would be a low slow responses, not a perceptives drop like we see in our guidance that. So, I don’t think if matter that they had a complete response or partial response to their most recent therapy. The type of NT-proBNP profile reached in discussions with key opinion leaders could be very different and observe very differently. And Gene went through to that in his discussion. As far as the last response to the chemotherapy one patient actually came into the study with affects response as a very good partial response. This is last response with a non-response and it just causes the way oncologists look at this then actually report this out.

Tran Nguyen

If I could treatment with Gene, but that’s not in consistent with what you saying about not requiring plasma directed therapy at the time of entry, right because of your best response and the very good partial response then you had non-response one or more times, it maybe deems that’s the best response you are going to have right, that maybe where are you no longer our eligible work interesting further plasma cell directed therapy, you could come in to this study providing that you had ongoing for an involvement as Martin laid out an inclusion, exclusion criteria.

Jason D. Kantor – Credit Suisse Securities LLC

Got it. Thanks.

Operator

Thank you. Our next question comes from the line of Chris Marai with Wedbush Securities. Your line is now open. Please proceed with your question.

Christopher Marai – Wedbush Securities

Hi good afternoon guys, thanks for taking my question. I’m wondering with respect the mechanisms of action that you proposed with NeoD001 and had you know really a pre-clinical data that you have gained today. Is there anything in the clinical data that today really support some of your thesis that this product is in fact showing the activity in patient with Amyloidosis? Thanks.

Unidentified Company Representative

Well let me start that then I’ll give it to Gene. I think as we said almost on this call the largest statements we made about AL on our data today pre-clinically are neared in many other misfolding protein disease and so when we were talking – when you look at say the Cardiac Biomarker that we’ve been speaking about and you see fairly rapid changes, when we say that that might be consistent and you know being careful with science is to say might be consistent with the antibody interacting with soluble aggregate, that plus the fact the fact that these misfolded aggregate whether they are AL or actually any misfolded protein can really disrupt ion channels. It’s at least consistent with what we are seeing, but it’s a scientific hypothesis like most medicine. Gene you want to add?

Gene Kinney

No, I just agree and underscore what you are saying. I mean I think the data are interesting, clearly I think they weren’t moving forward to a double-blind placebo controlled study where we can have questions about placebo group and interrogate that, but certainly the rapidity to launch that in the depths of that believe onset is intriguing from a mechanism of action perspective, but until accurately pointed out it allows us to generate hypothesis, but we cant fill any conclusion certainly based on these data sets.

Christopher Marai – Wedbush Securities

Okay great and then another question maybe just to elaborate maybe a little bit more on the text of patients enrolled, it has career protocol and I guess that came to physician. How likely is it that they enroll patients to that had ongoing reasonable organ of response from a prior therapy is it extreme strange with a Phase I -- for investigator to put patient at risk, if they’re already responding? Could you maybe elaborate on how the protocol may have dictated the type of patient to enroll or how traditional (indiscernible) enroll a trial that could help us understand on how these patients were selected? Thanks.

Dale Schenk

I’ll hand that over to Gene or Martin in a moment. I’ll just say the way we – I think you are probably aware most of these patients once they get a chemotherapy or whatever treatment they are going to get, there is not much that can be done for them if they have organ evolvement, other than the typical treatment. So it’s not like there are a lot of tools available to the – go ahead Marty or Gene.

Gene Kinney

Maybe I can start Marty can jump in I mean I (indiscernible) saying, I mean I think it’s probably a couple of thing. One, certainly I think the physicians in this space know the data and they know that even under the best circumstances the percentages are against you right. So even if you have a good hematologic response the likelihood of having a good organ response still remains low. I think in terms of exactly how this trial went, it’s certainly we selected patients that has some hematologic control and the as the biggest question, Jason mentioned the overall idea here was that because our drug doesn’t interact particularly with the plasma cell that we wanted to make sure that the patients were coming into this study that we’re going to require plasma cell directed therapy at the onset?

And so at least having some level of hematologic control, but very importantly still having some level of organ involvement and as I mentioned before and gave you that number the level of baseline involvement in these nine evaluable patients being over 1700 is certainly not an insignificant level, so clearly these patients were cardiac involved, Marty I don’t know if you want to add that.

Martin Koller

That really sums up the way the patients were outlined in inclusion and exclusion criteria very nicely.

Dale Schenk

And I would just add I think actually the situation is almost the opposite its not why with, its what else do they have to turn to. Okay thanks.

Christopher Marai – Wedbush Securities

Okay thanks for taking my question.

Operator

Thank you (Operator Instructions) our next question comes from the line of Jonathan Eckard with Citi. Your line is now open. Please proceed with your question.

Jonathan Eckard – Citigroup

Thank you for taking my question. (indiscernible) most of my questions have been answered, but maybe if you could help us understand what the normal proBNP trend you see at AL patients that’s not getting hematological response, but kind of those patients at trial maybe have some hematological control, but not getting a organ response. I guess the question stems from (technical difficulty).

Dale Schenk

Yes, John I think, I heard you what you are asking is would a normal trend be in this patient population that had say cardiac involvement over time?

Jonathan Eckard – Citigroup

Correct.

Dale Schenk

In the absence of intervention, I’ll hand again that over to Marty and Gene, I’ll just if their cardiac situation gets worse which it will inhabitable get it would go up, the time course of that will be quite variable. With that go ahead Marty or Gene.

Martin Koller

Yes. These patients have restricted cardiomyopathy, if they are having continuous heart failure signs and symptoms. One would anticipate some of the clinical point of view a gradual deterioration over time. And with that one would expect a sustained or ever increasing NT-proBNP profile that’s what one would anticipate with – of course that kind of vary from patient-to-patient.

Jonathan Eckard – Citigroup

Okay thank you very much. I will ask my question later.

Dale Schenk

Okay, Sorry we couldn’t hear you better. We could hear the last part of it.

Jonathan Eckard – Citigroup

I’m off that. Thanks.

Operator

I’m not showing any further question in the queue at this, I would like to turn the call back over to Dr. Dale Schenk for any closing remarks.

Dale Schenk

Okay we’ll thank you. In conclusion we thank you all for joining us today and we appreciate your continued interest in Prothena. Thank you operator as well. Thanks everyone.

Operator

Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program. And you may now disconnect. Have a good day everyone.

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