Prothena Corporation plc
Q4 2016 Earnings Call Transcript

Published: 15 Feb 2017

[Operator:]

Good day, ladies and gentlemen and welcome to the Prothena Fourth Quarter 2016 Financial Results Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will follow at that time. [Operator Instructions] As a reminder, this conference call is being recorded. I would now like to introduce your host for today's conference Ms. Sandy Fawcett, Vice President of Finance. You may begin.

[Sandy Fawcett:]

Thank you, Sandra. Good afternoon, everyone and welcome to Prothena's investor conference call to review our fourth quarter and full-year 2016 financial results and business progress, as well as our 2017 financial guidance. Please review the press release we issued earlier today, which is available on our website at prothena.com, and is also attached to Form 8-K filed today with the SEC. Speaking on today’s call we have Dr. Gene Kinney, our President and Chief Executive Officer who will discuss or 2016 highlight as well as corporate and pipeline accomplishment; and Tran Nguyen, our Chief Financial Officer, who will review our financial results for the fourth quarter and full-year of 2016 and 2017 financial guidance. Gene will then provide an overview of the upcoming milestones and open the call for Q&A. Before we begin, I'd like to remind you that during the course of today's presentation, we will be making statements regarding Prothena's future expectations, plans and prospects that constitute forward-looking statements under the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements are based on estimates, projections and assumptions that may prove not to be accurate and actual results may differ materially from those anticipated due to known and unknown risks, uncertainties and other factors. For a discussion of the risks associated with our forward-looking statements, please see our press release issued today, as well as our most recent Form 10-Q filed with the SEC and also the Form 10-K we will soon be filing with the SEC. We disclaim any obligation to update our forward-looking statements. With that, I'd like to turn the call over to Gene.

[Gene Kinney:]

Thank you, Sandy. And thank you all for joining this afternoon. The pleasure to be here today to discuss our 2016 and recent accomplishment and the milestones we're looking forward to in 2017. On today's call, I will highlight the progress we've made on each of our clinical programs. Talk briefly about our key corporate accomplishment. And then turn it over to Tran for a review of our year-end financial results and 2017 financial guidance. Before we begin talking about the terrific progress we've made across our pipeline. I would like to first comment on one event in 2016 that we were distinctly said about and of course I'm referring to the loss of Dr. Dale Schenk, our Former CEO and Co-Founder. With Dale’s passing, we lost first and foremost a friend and the broader scientific community lost a true innovator who will missed Dale and will forever be indebted to the scientific legacy that remain. Following this profound loss, with credit to our Board of Directors and leadership team for quickly instituting our succession and strategic plan. We've been able to seamlessly advance the business. This progress is also thanks to the efforts of our talented and dedicated employees whose relentless pursuit of new therapies for patients drives our ability to steadily advance our programs. I'd also like to thank those of you on the call today and our entire biotech community for the outpouring of support during the time of Dale's passing. In addition to your very kind words many of you made generous donations to the charity designated by his family. To us, it serves to underscore how fortunate we are to work in biotech. It's an incredible community that puts people first. So thank you on behalf of the entire Prothena team and also on behalf of Dale’s family who appreciated the messages of condolence during a very sad time. Now I will turn to an overview of our 2016 key milestones and highlight what lies ahead in 2017 and beyond. As you know we focus on two areas of science where we have deep domain expertise protein misfolding or cell adhesion. In 2016, we reported positive data for each of our clinical programs in these areas. And continue to raise awareness of our novel antibodies through the publication and presentation of scientific results. We ended 2016 with the balance sheet that should enable continued development of both our clinical and preclinical programs as we seek to deliver differentiated protein immunotherapies to patients. I’ll next discuss our scientific programs in more detail and I'd like to begin with a high level review of our programs in the area of protein misfolding. And start with our most advanced program NEOD001 monoclonal antibody for the potential treatment of patients with AL Amyloidosis. There are two broad categories of amyloid disease, those in the periphery and those in the central nervous system. AL Amyloidosis is a peripheral amyloid disease, which is systemic, progressive and often fatal due to organ dysfunction. While there are other types of systemic amyloidosis, including the AA and ATTR amyloidosis, patients with AL Amyloidosis represent the majority of the systemic amyloidosis. AL Amyloidosis is a rare disease that affects between 30,000 to 45,000 patients with an annual incidence rate of 10,000 to 15,000 patients in the U.S. and Europe. In AL Amyloidosis, light chain proteins produced by clonal plasma cells misfold, aggregate, circulate through the body and deposited amyloid in VITAL organs, most commonly in the heart and kidney, but also in peripheral nerves and other organs. These circulating soluble aggregates and deposited amyloid can cause this function and ultimately organ failure and approximately two-thirds of all patients with AL Amyloidosis have two or more organs that are impacted by the disease. There are no approved treatments for AL Amyloidosis and for the majority of patients current treatment is limited to the use of cytotoxic chemotherapeutic agents. However, none of these treatments approaches target the soluble aggregate in deposited amyloid that drives organ dysfunction and failure. The goal of these treatments is to control the hematologic burden, and targeting clonal plasma cells to decrease the production of new light chain. The cytotoxic agents are often poorly tolerated and patients may become refractory to their effect and/or relapse. In addition, for patients who undergo these plasma cell-directed chemotherapeutic treatments approximately 75% of patients do not achieve adequate organ benefit, even if they achieve hematologic control. This is important because it exemplifies the principle in amyloid disease that simply focusing on decreasing new protein production maybe insufficient to provide patient benefit in most cases in the context of AL Amyloidosis for example, it is clearly hematologic control in the absence of organ benefit is have limited value to this patient population. The nature of the disease means that patients do not get better without intervention and will experience progressive organ dysfunction that often leads to death. For example when AL Amyloid builds up in the heart, it leads to a progressive restrictive cardiomyopathy with associated cardiac dysfunction. As such there remains a significant unmet need for a well tolerated therapy that can improve organ function and survival by directly neutralizing circulating soluble aggregates and clearing deposited amyloid from organs. NEOD001 is an antibody being developed as a disease modifying therapy for AL Amyloidosis that specifically targets the amyloid that drives organ dysfunction and failure. As immunotherapy, NEOD001’s proposed mechanism of action is the neutralization of misfolded light chain in circulation and clearance of deposited amyloid through immunotherapy mediated clearance or phagocytosis of the amyloid deposited on organs. NEOD001 is the first immunotherapy directly targeting AL Amyloidosis to receive fast track designation from the U.S. Food and Drug Administration. In 2016, we continue to advance our two pivotally designed studies of NEOD001 in patients with AL Amyloidosis in cardiac dysfunction and I will provide more detail on each of those studies in a moment. Also in 2016, Dr. Morie Gertz of the Mayo Clinic presented results from our Phase I/II study of NEOD001 in patients with AL Amyloidosis persistent organ dysfunction at two medical conferences. He presented interim data from this study in an oral session at the International Symposium on Amyloidosis in July, 2016, and also presenting data from the completed study in an oral session at the American Society of Hematology Conference in December of 2016. It's worth mentioning that this was presented as part of the first oral session at ASH entirely dedicated to AL Amyloidosis, which was great to see from the perspective of the growing awareness of this grievous disease. Has remainder, this Phase I/II study enrollment the total of 69 patients with AL Amyloisdosis in persistent organ dysfunction, including 27 patients in the dose escalation portion of the study and an additional 42 patients in the expansion phase. All over the patients in this study had been previously treated with plasma cell direct therapy and continue to experience organ dysfunction. In the expansion phase of the study, patients were rolled into three prospectively defined cohorts consisting of 15 patients with predominantly cardiac dysfunction, 16 patients with renal dysfunction and 11 patients with peripheral neuropathy. Over the course of this study, patients received more than 990 separate infusions of nearly one with mean treatment duration of 12.8-month. As demonstrated in the results NEOD001 continued to be safe and well tolerated with no dose limiting toxicities or anti-drug antibodies and no treatment related discontinuations or treatment related serious adverse events. Data from the study also demonstrated improvement in three organ systems, cardiac, renal, and peripheral nerve. Specifically the results of the best response analysis showed that 53% or 19 of 36 of the cardiac evaluable patients demonstrated a cardiac response and 64% or 23 of the 36 renal evaluable patients demonstrated a renal response. In addition, an improvement in peripheral neuropathy in patients from the prospectively defined peripheral neuropathy expansion cohort was demonstrated by a mean 35% decrease in the Neuropathy Impairment Score-Lower Limb or NIS-LL measured at month 10. Improvements in patient NIS-LL scores resulted in a response rate of 82% or nine of the 11 patients in the peripheral neuropathy expansion cohort where two of nine responders showed complete resolution of peripheral neuropathy as measured by NIS-LL. As Dr. Gertz pointed out in his presentations, this was the first time that improvement in peripheral neuropathy was seen in patients with AL Amyloidosis. These response rate achieved across three organ systems in our study compared favorably to published historical response rate in patients previously treated with plasma cell-directed therapy. Additionally, a post-hoc subset analysis of the NEOD001 Phase I/II study results demonstrated that organ responses were not related to the time or depth of hematologic response achieved from previous plasma cell-directed therapy nor were they related to the time or type of prior therapy. This analysis was also presented during the same AL Amyloidosis oral session at the ASH Conference in December by Dr. Michaela Liedtke from the Stanford University School of Medicine. Based on these positive data from the Phase I/II study, we remain confident in the design empowering of our two ongoing clinical studies, the PRONTO and VITAL Amyloidosis studies. Moving now to the PRONTO and VITAL studies, our enrollment efforts in 2016 allow us to remain on track with our previous guided timelines for both of these studies. The PRONTO study is a Phase IIb global registration directed randomized, double-blind, placebo-controlled trial enrolling previously treated patients with a primary diagnosis of AL Amyloidosis and cardiac dysfunction. Patients in PRONTO are being randomized on a one-to-one basis to receive either NEOD001 or placebo. Based on current enrollment status, we expect to be fully enrolled with 100 patients in PRONTO by the end of this month. As a patient focused Company and because of the grievous nature of this disease and a high level of interest in this study, patients already in screening will be allowed to complete the process and will be subsequently randomized provided that they meet eligibility requirements. Because of this we are likely to be over enrolled. Our maximum screening period by protocol is 28 days with an average screening time to date of approximately 19 days. Accordingly, we expect all patients in screening to complete that process sometime in March. This is a 12-month study and accounting for time for database lock and data analysis, we expect to announce results in the second quarter of 2018. The primary endpoint of the PRONTO study is cardiac test response is defined by a change in NT-proBMP. NT-proBMP is a widely clinically validated functional biomarker that predicts survival in patients with AL Amyloidosis following intervention it has been demonstrated by numerous retrospective and prospective studies. Demonstrating a significant effect on cardiac response as measured by NT-proBMP along with supporting secondary outcomes has the potential to expedite our development timeline and provide an additional opportunity to engage with European regulators. We also continue to closely follow the important work of the Amyloidosis Research Consortium or ARC as they continue their dialogue with regulators on this topic. Most recently in December of 2016, ARC reported the submission of draft guidance to the FDA on developing new therapies in AL Amyloidosis. Amongst other topics this guidance reiterated the AL Amyloidosis research community's assessment of the evidence for NT-proBMP as a segregate end point for clinical outcome and survival. Turning to the VITAL Amyloidosis study, we are also continuing to enroll this study which is a Phase III global registration randomized, double-blind, placebo-controlled study enrolling newly-diagnosed, treatment-naïve patients with AL Amyloidosis in cardiac dysfunction. We expect to fully enroll this study with approximately 230 patients in the second quarter of this year. These patients are being randomized on a one-to-one basis to receive standard of care therapy with or without nearly one. The primary composite endpoint in this study is event based and consists of all cause mortality or cardiac hospitalizations. The study is designed for support full global regulatory registration. Keeping with the theme now of peripheral amyloid disease. I'd like to next highlight our pre-clinical program for ATTR amyloidosis PRX004. PRX004 is an investigational monoclonal antibody designed to specifically targeting alpha-synuclein the misfolded form of the TTR amyloid protein found in a disease noted transthyretin immediate amyloidosis or ATTR amyloidosis. Similar to AL Amyloidosis, ATTR amyloidosis is a rare progressive and sometimes fatal disease, characterized by deposition of aggregates of misfolded protein or amyloid in organs. In ATTR amyloidosis the precursor protein, transthyretin or TTR is produced primarily in the liver in its normal tetrameric form, TTR serves as a transporter for thyroxine and vitamin A. There are three types of ATTR amyloidosis, hereditary TTR with cardiomyopathy, wild-type ATTR which occurs for radically and also involve cardiomyopathy and hereditary ATTR with polyneuropathy. In the Hereditary forms of this disease the body makes a mutant form of the TTR protein. To date more than 100 reported types of TTR mutations have been reported that promote amyloid fiber formation which most commonly affect the heart and nervous system. Prothena has generated monoclonal antibodies that selectively bind to amyloid were diseased forms of the transthyretin protein. Preclinical data published in March of 2016 in the journal amyloid suggest that Prothena’s antibodies have unique biological activity that may lead to the prevention of deposition and enhancement of clearance from ATTR in patients with either wild type or hereditary TTR mediated amyloidosis. From the antibodies we generated we selected PRX004 as lead candidate and in 2016 we began producing clinical supply. We plan to initiate a clinical study in patients with ATTR amyloidosis in early 2018. Moving from amyloid diseases of the periphery, and into amyloid diseases in the CNS I'll turn to PRX002 monoclonal antibody for the potential treatment of Parkinson's disease and others synucleinopathies. PRX002 also known as RG7935 is the primary focus of our worldwide collaboration with Roche. Parkinson's is a neurodegenerative diseases that affects 7 to 10 million people worldwide making it the second most common neurodegenerative diseases after Alzheimer's. The disease is characterized by the neuronal accumulation of aggregated alpha-synuclien in the central and peripheral nervous system that result in a wide spectrum of worsening progressive motor and non-motor symptoms and a persistent throughout the disease. While the disease is most commonly known for the motor symptoms classically associated with Parkinson's disease non-motor symptoms such as loss of sense of smell, sleep disturbances or gastrointestinal matelote issues may present many years earlier. Current treatments for Parkinson's disease are primarily directed at managing the early motor symptoms of the disease, mainly through the use of levodopa and dopamine agonists. For these only addresses subset of symptoms typically related to motor impairment. Symptomatic therapies do not target the underlying cause of the diseases and as the disease progresses and dopaminergic neurons continue to be lost, these drugs lose effectiveness after leading to debilitating side effects. PRX002 has been developed as a potentially disease modifying approach to slow the progress of neurodegenerative consequences of this disease. PRX002 targeting alpha-synuclein of protein that is widely understood to be interplay involved in the onset and progression of Parkinson's diseases. Targeting alpha-synuclein has the potential to slower reduce to neurodegenerative associated with alpha-synuclein misfolding and or is cell to cell transmission. As you may recall in 2015 we reported positive results from a Phase I single ascending dose study in healthy volunteers demonstrating targeting engagement as well as the positive, safety, immunogenicity and pharmacokinetic profile for PRX002. In November of last year we reported results from the Phase IB double blind placebo controlled multiple ascending dose study in 80 patients with Parkinson's diseases. The study was designed to assess the safety tolerability, pharmacokinetics and immunogenicity of PRX002. This study demonstrated acceptable safety and tolerability across all those levels up to including 60 milligrams per kilogram the highest dose level tested with no serious or severe treatment emergent adverse events in patients treated with PRX002. In addition to achieving acceptable safety and tolerability, the study demonstrated target engagement and robust antibody penetration in the CNS. Specifically, the data demonstrated a rapid dose in time dependent reduction of free serum alpha-synuclein of up to 97%, a statistically significant result that was maintained following two additional monthly doses. In addition, we saw a robust penetration of PRX002 in the central nervous system, which exceeded our expectations based on our preclinical experience. With dose-dependent increase in PRX002 in cerebrospinal fluid and a mean concentration of 0.3% of PRX002 relative to serum across all dose levels. These data further support our belief that we can choose doses that target and saturate the aggregated pathogenic forms of alpha-synuclein in the brain for a Phase II study that will further explore the potential of PRX002 as a disease modifying treatment for Parkinson's disease, together with our partner Roche, who plan to initiate a Phase II clinical study this year. Turning now to the second area of science, where we focus. Diseases mediated by cell adhesion or cell trafficking. I'd like to highlight PRX003 for the potential treatment of inflammatory diseases, including psoriasis and psoriatic arthritis. This is our third program in clinical development. Our team is biological expertise and cell adhesion extents back to the development of Tysabri for relapsing-remitting multiple sclerosis and PRX003 builds on our expertise in this area. Our scientists working in this space and make key discoveries about the cell adhesion molecule CD146, also known as melanoma cell adhesion molecule or MCAM that is the basis of our strategy for PRX003. CD146 is cell adhesion molecule that is a specific marker for Th17 cells, which are known to play an integral role in the initiation of propagation of inflammation in auto immune conditions. Th17 cells contribute to pathogenesis via the release of multiple inflammatory cytokines and while they are best known for the secretion of interleukin-17, it has become increasingly understood that the role in pathogenesis is the result of the release of multiple cytokines including TNF alpha, interleukin-6, interferon gamma, interleukin-22 and CCL20, all of which have a well documented role in the pathogenesis of various other autoimmune diseases including psoriatic arthritis, psoriasis, rheumatoid arthritis, ankylosing spondylitis and secondary progressive multiple sclerosis. Th17 cells are defined by their expression of the cell adhesion molecule CD146. CD146 enables the mechanism whereby Th17 cells adhere to, and migrate across a blood vessel wall. PRX003 is designed to block the ability of these pathogenic Th17 cells to move out of the bloodstream and into tissue by blocking the interaction of CD146 and laminin Alpha-4, which our scientists discovered, is the binding partner on the vascular endothelium for CD146. Although Th17 cells represent fewer than 5% of T-cells, T-cells appear to be disproportionately involved in propagation of inflammation under – inflammatory diseases under pathogenic condition. Targeting the T-cell rather than any individual cytokine may provide a highly specific way to impact the pathogenic pro-inflammatory Th17 cells while leaving the vast majority of immune cells unaffected to carry out their normal function. In June of last year, we reported results from our Phase I double-blind, placebo-controlled single ascending dose study in 40 healthy volunteers. The data showed that PRX003 was safe and well tolerated to all of dose levels meeting the primary objective of the study. There were no serious adverse events, dose limiting toxicities, anti-drug antibodies or hypersensitivity reactions. In this study, we saw a dose-dependent reduction in CD146 expressions with a dose-dependent duration of response. At the highest dose, results demonstrated more than 95% neutralization of CD146 meaning nearly all binding sites were blocked by PRX003, suggesting that a single infusion of PRX003 may safely sequester Th17 cells in the blood and block CD146 mediated infiltration of Th17 cells across blood vessels into tissue. Building on the successful results, we are currently conducting a randomized double-blind placebo-controlled Phase Ib multiple ascending dose proof-of-biology study of PRX003 in patients with psoriasis. This trial is designed to further assess the safety, tolerability, pharmacokinetics and immunogenicity of PRX003 in patients with psoriasis. In this study, we will evaluate the Psoriasis Area and Severity Index known as PASI and also look to the pharmacodynamic profile in order to determine a dosing strategy for our Phase II program. As you know there are effective therapies available for psoriasis today and we realize that there is a very high bar for any future treatment in this disease to differentiate from existing therapies. If we were to observe a clearly differentiated profile in this study, we would not preclude further clinical development of psoriasis, but our assumption is that we will pursue an alternate indication with greater medical needs for our Phase II program. Therefore, in September of last year, we announced that based on meeting certain pre-specified criteria in the ongoing Phase Ib study; we intend to pursue development of PRX003 for the potential treatment of psoriatic arthritis. Psoriatic arthritis is a disease where T17 mediated biology is known to contribute to the pathology and there is a clear unmet medical need for more effective therapy. Many current treatments target a single cytokine such as TNF or IL-17 and while targeting individual cytokines is moderately effective for some patients. According to the National Psoriasis Foundation approximately 45% of patients with psoriatic arthritis are dissatisfied with their current treatment. By targeting the Th17 cells and thereby both TNF and IL-17 and also many other cytokines that play a role in the pathogenesis of this disease. We believe that PRX003 may provide a new and potentially more effective treatment for patients with psoriatic arthritis. We have recently refined our clinical development plan for PRX003 and have decided to accelerate the overall program in order to minimize the timeline to the initiation of the planned Phase II study assuming of course, that the Phase I data is permissive. We will therefore forgo an interim analysis and now expect full topline data from the Phase Ib study in patients with psoriasis sooner in the third quarter of this year. We are looking forward to sharing data from this study and believe PRX003 has a great deal of potential as a new immune cell targeting approach for psoriatic arthritis as well as a wide range of other inflammatory diseases. Finally, I'd like to highlight that this past year our management team was further strengthened with the appointment of Carol Karp as Chief Regulatory Officer. Carol who leads our regulatory quality and safety functions joins us with significant global experience across several therapeutic categories and will be invaluable to our ability to advance our clinical program towards the registration and planned commercialization of NEOD001. At this time, I'd like to turn the call over to Tran for a discussion of our financial results. Tran?

[Tran Nguyen:]

Thanks, Gene. First, our cash burn from operating and investing activities in 2016 was approximately $134 million, which was favorable and at the low end of our guidance of $132 million to $142 million. In 2016, we reported net loss of $48.9 million and $160.1 million for the fourth quarter and full-year of 2016 as compared to net loss of $24.2 million and $80.6 million for the fourth quarter and full-year of 2015. Net loss per share were $1.41 and $4.66 for the fourth quarter and full-year of 2016 as compared to net loss per share of $0.76 and $2.66 for the fourth quarter and full-year of 2015. Included in the net loss for the fourth quarter and full-year of 2016 was share-based compensation expense of $5.2 million and $24.9 million compared to $3.3 million and $10.4 million for the respective prior year period in 2015. We reported total revenue of $0.2 million and $1.1 million for the fourth quarter and full-year of 2016, as compared to total revenues of $0.3 million and $1.6 million for the fourth quarter and full-year of 2015. As expected the difference in revenue for the fourth quarter and full-year of 2016 was primarily due to lower revenue from our collaboration agreement with Roche. R&D expenses totaled $39.8 million and $119.5 million for the fourth quarter and full-year of 2016 as compared to $17.9 million and $58.4 million for the fourth quarter and full-year of 2015. The increase in R&D expenses in the fourth quarter and full-year of 2016 was primarily due to product manufacturing, clinical trial and personnel cost. R&D expenses included non-cash share-based compensation expense of $1.9 million and $7.1 million for the fourth quarter and full-year of 2016 as compared to $1.3 million and $4.3 million for the fourth quarter and full-year of 2015. G&A expenses totaled $9.6 million and $41.1 million for the fourth quarter and full-year of 2016, as compared to $6.6 million and $23.1 million for the fourth quarter and full-year of 2015. The increase in G&A expenses was primarily due to personnel costs. G&A expenses also included non-cash share-based compensation expense of $3.3 million and $17.8 million in the fourth quarter and full-year of 2016, as compared to $1.9 million and $6.1 million for the fourth quarter and full-year 2015. As of December 31, 2016, Prothena had $391.0 million in cash, cash equivalents and restricted cash and no debt. Our strong year-end cash position was supported in part by the $128.6 million in net proceeds we received through our equity offering in January 2016. As of February 10, 2017, we have approximately 35.0 million ordinary shares outstanding. Now turning to our 2017 financial guidance, we expect full-year 2017 net cash burn from operating and investing activities to be $160 to $170 million, which includes an expected milestone payment from Roche upon initiation of the Phase II study of PRX002. We expect end the year with approximately $224 million in cash which represents the mid-point of the range. The estimated full-year 2017 net cash burn from operating and investing activities is primarily driven by an estimated net loss of $177 to $191 million, which includes an estimated $26 million of non-cash share-based compensation expense. With that, I’ll turn the call back over to Gene to summarize our upcoming milestones for 2017 and into 2018. Gene?

[Gene Kinney:]

Thanks Tran. 2016 was the year with positive data milestones across our entire pipeline. As we move forward in 2017 and look forward into 2018 we expect continued momentum across our pipeline and to progress our planning activities in preparation for the submission of nearly one to regulatory authorities. For nearly one we expect to fully enroll 100 patients in PRONTO by the end of this month and to report results from the study in the second quarter of 2018. For the Phase III VITAL Amyloidosis Study we expect to complete enrollment in the second quarter of this year. For PRX002 we expect to initiate a Phase II clinical study together with our partner Roche in patients with Parkinson's disease this year. For PRX003 we expect to report results from the Phase Ib multiple ascending dose study in patients with psoriasis in the third quarter of this year. And for PRX004 we expect to initiate clinical development in early 2018. So thank you for joining the call and this time we will open the call for question. Sandra?

[Operator:]

And our first question will come from the line of Michael Yee with RBC Capital Markets. Your line is now open.

[Michael Yee:]

Hey, guys. Thanks, good afternoon. Congrats on all the progress, two questions. First is , can you clarify for us again, why the psoriasis data, I guess would be in Q3, and why you are forgoing the interim? How should we interpret and read into that? And then secondly, on D001, you mentioned about your cohorts and the neuropathy data, just wondering if you could run a study in neuropathy, whether that would be another upside indication, whether you'd think that's worth investing in, and whether you think that something you could go ahead with? Thanks so much.

[Gene Kinney:]

Mike maybe I’ll jump in here and then Tran me want to want to add some color to this well. So let's start with the neuropathy study agreed I mean I think the data that we heard ash from that prospectively defined cohort of the Phase I/II was very, very encouraging. Looking at a standalone neuropathy study that something certainly that will consider the right way to get that information out I think we have a couple of opportunities to be able to think about doing that. Clearly as a subset analysis in those PRONTO and VITAL studies will be looking at neuropathy for those patients that have both cardiac involved as well neuropathy. I think if you go look at the literature there. The older literature suggests that number somewhere around 15% but in some newer survey work that's been done where the attention has I think kind of been exemplified a little bit more of the lights been shining look at brighter on this part of the diseases. We're starting to see number is closer to 30% to 40%. So we think there could be a significant number patients even in the VITAL and PRONTO studies where we can look at that. We can always obviously go and think about investigator sponsored studies in the space as well and then also sponsored studies and we haven't committed to how we want to pursue that, but I think it's fair to say that we see a strong signal there and it's something that we do want to follow-up on and so how we do that I think is under consideration.

[Michael Yee:]

Okay.

[Gene Kinney:]

Anything to add on that, Tran before…?

[Tran Nguyen:]

I think the one thing maybe to add to that is that whatever path that we take in terms of whether we will lie on the subset analysis from the PRONTO and VITAL trials to support our neuropathy discussion with regulators for a separate trial. I think what we want to have confidence then is that whatever route that we do take that we have a high confidence that the regulators will also see at the same way with that pathway. So if it's a separate trial then we want to make sure, we're speaking the regulators about that trial design and have a high confidence that something to that will accept or if we don't do that then again in our current trial that we're running from a subset analysis perspective.

[Michael Yee:]

Okay, and on psoriasis?

[Gene Kinney:]

And then on the psoriasis, yes on the psoriasis question, so Mike I think taking a hard look at that and just I mean I kind of mentioned it in the discussion, which is that the treatments that are currently out there for psoriasis do quite well. The potential inability to differentiate in the space particularly in a Phase Ib under-powered study, I think is low. And so really the goal that interim analysis for us initially was to accelerate the initiation of the Phase II study in psoriatic arthritis, where we feel like the biology has a better opportunity to differentiate and so looking through some kind of innovative clinical design aspect, we've ended in a place where we believe we can pull that whole study forward and in fact as the initial idea was an interim kind of mid-year and then full data set toward the end of the year. We've been able to accelerate that full data set now into the third quarter, which decreases the white space between that psoriasis study in the initiation of Phase II psoriatic arthritis study. So thinking more to the most rapid path to a clinical proof of concept in a disease space, where we think this mechanism has a strong opportunity to differentiate from what out there today. This was the most expedition path and that's why we made that decision.

[Michael Yee:]

Okay. Okay, thank you.

[Gene Kinney:]

Okay. Thanks Mike.

[Operator:]

And our next question comes from the line of Andrew Peters with Deutsche Bank. Your line is now open.

[Andrew Peters:]

Hey, guys. Thanks for taking my questions and congrats on all the progress as well. A couple of questions for me, I guess first regarding NEOD001 and VITAL. You talked about guidance to completing enrollment in 2Q, I just want to understand a bit, how has the enrollment rate and importantly kind of the event rate, has that been consistent with your initial modeling? And then I noticed the recent paper published in blood from the Mayo Group I believe talking about the changing outcomes in amyloidosis. I just wanted to check in and see if any kind of updates from that study had any impact on kind of your thinking about VITAL as event consistent with what you're seeing I guess on a blinded basis from the study so far?

[Gene Kinney:]

Yes, thanks Andrew for that question. So a couple pieces on that, the first as you accurately said that the expectation around enrollment is that we will complete that in the second quarter and we've been very consistent and saying our expectation based on survival curves is somewhere between 12 to 18 months following last patient in which puts us to the latter part of 2018 for a VITAL, last patient, last visit. So I think we haven't changed that guidance. Obviously, we are tracking our internal event rates and if and when we ever get to a point where we have a level of confidence that that timeline needs to shift let folks know to the absence of that information would suggest that we don't have any confidence that were off of our expectations right. So I think today we maintain those expectations and don't have any evidence to suggest that we're off base there. I think the blood paper was a very interesting paper. The one thing that was quite interesting from our perspective is that if you look at the overall survival curve, I want to say it was a figure three seeing in that paper, really from 2005 to present, there's been no change in survival rates and that's significant since that timeframe really represented a ship from the old alkylating agents like Melphalan to more commonly used proteasome inhibitors like ixazomib and the survival curves are very similar to what we've seen in other publications like [indiscernible] publication and even what was reported by the University of Pennsylvania dash meeting in December. And so at least from an external perspective, we think with the exception of some single center studies with relatively low ends where maybe survival starting to look better across the border. What that paper seem to indicate to us is that the majority of benefit you're seeing is not coming from chemotherapy, but rather from more widespread use of stem cell therapy or at least a better selection of patients for stem cell therapy. So actually that didn't change our expectations or our guidance at all, in fact, if anything it continues to look very consistent.

[Tran Nguyen:]

So if you look at the [Kumar at all] 2014 in the blood paper you're talking about in terms of the graph that actually excludes autologous stem cell therapy as Gene just referenced. On the [Kumar] what we saw was 12 to 24 months mortality between 45% and I think 60%. And if you look at the two years survival that was quoted in those graphs with autologous stem cell therapy was around 55% mortality at 24 months. So again all seem to cooperate with each other and I think that still haven't changed our view, our projections in terms of our estimates of event rates that we need for our trial. And so again, as Gene said, as we collect more blinded events enable to narrowing the timeline, we clearly will do so at that time.

[Andrew Peters:]

Okay, perfect. And then just a quick follow-up on PRX003, I just want to understand a bit more kind of your longer term goals for the program encouraging to see kind of this acceleration of data on the psoriasis side and going into psoriatic arthritis. But just want to understand as of now how you're thinking about say beyond psoriatic arthritis given the mechanism could be applicable to kind of a pretty wide range of indications. How do you think about kind of the longer picture goals? Is this a program that you want to keep in-house like D001 or view it as something more similar to PRX002 just given the potential size of the opportunity, but also size of the clinical costs associated with those studies? Thanks.

[Gene Kinney:]

Yes. Great question, Andrew. So again let me and Tran jump in, but I think in terms of the strategy around PRX003, one I think important key differentiation relative to PRX002 is obviously we are fully prepared in anticipating moving forward into that Phase II proof-of-concept. The overall strategic approach that we're taking with this molecule for precisely the reason that you point out, its potential utility in multiple Th17 related inflammatory conditions is to really find that beachhead. And what I mean by that is if you look to other programs in the biotech world, I think the anti-IL-17s are great example. Most of those started towards arthritis sounds that they could significantly differentiate in the psoriasis space kind of establish that beachhead in that space became the lead indication and then as they went develop those other indications along the way to round out the indication statement. We see a very similar approach here which is that for a disease like psoriatic arthritis where we know multiple Th17 related cytokine pathways are relevant. I’d point to the TNF pathway, I’d point to the IL-17 pathway even the IL-6 pathway. These are Th17 related cytokines and so by targeting the cell which is the presumed source of the cytokines in the joint, we expect that we maybe able to show a differentiated efficacy profile. And so that’s what we’ll be testing in that Phase II study. Having established that beachhead I think it gives us a lot of opportunity and flexibility around the program, clearly at that point we can make a decision as to how much we want to do with respect to multiple Phase II to explore other indications versus moving forward full steam in that psoriatic arthritis space and coming back and picking up those indications later. And frankly, some of that will be determined by our capital spend and how we actually deploy our capital resources that we have at the time. Ultimately, I think if we're in a broad-based indication space, we anticipate that we would need to start thinking at some point about partnering particularly on the commercial side. As we noted there are very well established commercial field forces out there that we would like beneath them help from.

[Tran Nguyen:]

Yes, I mean I think just to add on to that I mean I think we continue to educate those strategic folks about PRX003 regarding it biology and mechanism of action and likely areas of advantage. And so I think in terms of our current financing to bring it to a point where either we run the next trial or that Phase II people concept of PSA or someone to come in and give us outside economics now or I think and try to build the indication sooner. I think those are all things that will need to balance. But as of right now I would say for a base case perspective expect if the data from the Phase Ib psoriasis trial is primitive that will run that Phase II in psoriatic arthritis.

[Andrew Peters:]

Great. Thank you.

[Gene Kinney:]

Thanks Andrew.

[Operator:]

And our next question comes from the line as Geoff Meacham with Barclays. Your line is now open.

[Unidentified Analyst:]

Hi guys. This is [Evan] on for Geoff. Thanks for taking the questions and congrats on the progress. First one on NEOD001, so with the PRONTO data expected by the second quarter of 2018, do you expect with potential change in the regulatory environment we saw the passing of the 21st Century Cures Act more flexibility in using that time end point to get do you want to approved.

[Gene Kinney:]

Yes, it’s a great question, Evan unless it happened during our call. I don't think we've heard who the new FDA commissioner is yet. So I think a lot you know I think a little bit more at that point. I think what we can think deep into as opposed to talking about a phenotypic shift within FDA a little bit more is really the work that the amyloidosis research consortium is doing and we are encouraged that their activities. They've approached the FDA really on three fronts right they've certainly been very active on the patient voice initiative which as you correctly indicate is a important part of the 21st Century Cures Act. They've also been pursuing for some time now the qualification procedures within the FDA and here I think they've been pretty clear that they're looking to qualify cardiac response as defined by change in NT-proBMP has a very good efficacy outcome measure for interventional studies and AL Amyloidosis with cardiac involvement. And then thirdly and I mentioned this in the call today they submitted draft guidance documents to the FDA at the end of last year which has at least part of that document again reiterated their view that use of NT-proBMP and the cardiac response biomarker should be utilized in interventional studies and as much as it is very predictive of survival in this patient population. I’d point two to some work at ASH a lot of the previous work that the amyloidosis research consortium was relying on the retrospective data was very robust data but don't get me wrong but it was retrospective nonetheless. At ASH in 2016 there were actually two groups the UK group and the Italian group which published independent studies which independently showed that in the prospective manner NT-proBMP was predictive of survival again in this disease and so I think it's a very robust biomarker. It clearly both from retrospective and prospective data without any exception is predictive of survival uniquely in this patient population. And I think you know with strong data I think it will be a good dialogue with the agency where the agency is at least with respect to FDA at that point in their thinking about this biomarker. I can't really comment on today, but we are encouraged that they continue to be educated by an independent third party like the amyloidosis research consortium.

[Tran Nguyen:]

I’ll just going to take from a base case so perspective we're still advocating the positive trial will mainly serve as discussions with European regulators around your potential for conditional approval if the data permits of them that clearly what Gene sharing is we are going to look like card of the background to you know to continue to work with U.S. regulators, but at it that that's not what we want to growth expectations.

[Gene Kinney:]

I mean I mean I think that's a very important point. Right which is that our base case. And what we communicate is based on feedback that we received to date and what we feel relatively comfortable with and that would be that as a base case a positive process study with the right data sets could serve as discussion points for conditional approval in Europe but we don't hold that as a base case for FDA. I mean the FDA we feel like will need VITAL for a full approval and then also VITAL for full approval in Europe. That does not mean that we won't work hard in the background to manage that case within the U.S. and I think that's a very important point.

[Unidentified Analyst:]

Okay. Great. And then I don't know can you remind us what the expected milestone is for on the Phase II of X2?

[Tran Nguyen:]

So that's actually a really great question. I mean we clearly built it into our guidance that our cash burn so to speak from a net interest perspective. We can't disclose the exact amount, but we can say is that the Phase I milestone that we received for the initiation right for the first healthy volunteer dose was $15 million. So in a Phase II, you would think would be some magnitude bigger than that in the $15 million. But clearly as that trial gets initiated in the first patient get dosed will make that announcement along with the Phase II trial design and in timing of all that and so we'll do all that hopefully sometime this year. We're hoping in the first half, but for now we're guide into 2017.

[Unidentified Analyst:]

Okay, so that is potentially a first half of them, but not guaranteed at this point, correct?

[Tran Nguyen:]

That's what sort for yes.

[Unidentified Analyst:]

Okay.

[Tran Nguyen:]

We plan to execute to that, but at the end of the day, we’re adverse this time line.

[Unidentified Analyst:]

And just one more on a high level, how do you think about the development plan for X4 with clinical development expected in early 2018? What are your thoughts on moving that forward into actual integration?

[Gene Kinney:]

Yes, so it's a little premature to give you a kind of development plan or outline, but I will just a few points, which is what we – one of the things we really like about our antibody is first and foremost, they don't appear to interfere or interact with the normal form of transthyretin. And so it’s normal form of area that is normal function is known to be tough America and we've chosen data in the amyloid publication from last year that in fact our antibody really don't interactive or buying touch America from at all. But as that touch America form breakdown into misfolded forms and also in the amyloid state where you are looking at the deposition of tissue, we see very good interaction of our antibody with the TTR under those conditions. Moreover, we've been able to look at all of the most common familial mutations within TTR and find that where our antibody interacts with the protein. Those really aren't at the same places, the most common mutations and so our expectation is that we should be able to pursue a plan that allows us to test both in wild-type patients meaning native amino acid sequences. But also in most of the common familial forms, both the polyneuropathy and ultimately cardiomyopathy indications, and really what it will come down from a strategy perspective is just how we stage those indications. But what we like about antibody is opens up that field for us into almost the entirety of the transfer written related to the population.

[Tran Nguyen:]

So that we do see the therapies as highly complimentary right in terms of the other RNAi or [NXM] strategies that are out there in terms of moderating or decreasing production of transthyretin, very similar in AL Amyloidosis where you are decreasing the production of like chain with plasma cell dyscrasia therapy, again very complementary. So I think in the way we're developing our NEOD001 for AL Amyloidosis. If there are therapies that come online and approved for peripheral neuropathy or for cardiomyopathy, we will clearly account for them in our clinical trials in a similar fashion as you can see with our D001 program.

[Unidentified Analyst:]

Thank you so much.

[Tran Nguyen:]

Thanks [Evan].

[Operator:]

And our next question comes from the line of Tazeen Ahmad with Bank of America. Your line is now open.

[Tazeen Ahmad:]

Hi, thanks for taking my questions, most of which have already been asked. But I’m sorry Tran, if I missed this earlier. Can you just remind us of what kind of payment you would expect from Roche on the next catalysts?

[Tran Nguyen:]

Sure, absolutely on around X2, again that’s the next milestone that we expect to receive is from the initiation of that Phase II trial that we're guiding to do sometime basically this year in 2017 and that we're hopefully pushing for the first half. That being that said, I can't tell you the exact number because we're not allowed to disclose that. But what we can talk about is the Phase I initiation milestone was $15 million and so clearly Phase II should be some magnitude larger - Phase II larger than $15 million. So what will be able to do is we actually earn that milestone, we’ll announce it and we can talk much more in detail about it.

[Tazeen Ahmad:]

Okay. And then maybe just one quick question on PRONTO. I think your last guidance was that PRONTO would read out in some time in 2018 and now you're confident that you'd be able to read it out in the second quarter. Would it be a topline press release or what kind of data should we expect in that initial data release?

[Tran Nguyen:]

Yes. I think what we would do is, obviously topline release as quickly as we can and then we follow that up with the more detailed scientific presentations has been our custom. I think you're exactly right. What we've been able to do is now having a pretty good understanding of exactly when we're done enrolling that study and given that a 12 months observation period. Clearly, last patient last visited 12 months after last patient in, so a little bit for time database lock and analysis and that puts us right there in the second quarter. But again, I think our typical style, we do a topline press release and we follow that with a more detailed scientific discussion at a scientific meeting.

[Tazeen Ahmad:]

I see. And just can you remind us what types of meetings would be appropriate for that type of data?

[Gene Kinney:]

Let see, so in that year there is International Amyloidosis Society meeting will be that year and obviously ASCO and then later in ASH.

[Tazeen Ahmad:]

Okay. So ASH should be the last possible one.

[Gene Kinney:]

Yes. I think that's always back in December, so probably look to share the data before then, but it's a little hard to say until we have the full dataset on exactly what meeting we get to, but those are the likely suspect.

[Tazeen Ahmad:]

Thanks.

[Operator:]

And our next question comes from the line of Kennen MacKay with Credit Suisse. Your line is now open.

[Kennen MacKay:]

Hey, thanks for taking the questions. So just on PRONTO, you mentioned this could be over enrolled, wanted to get a perspective of how over enrolled we're talking here, is this going to be like one to two patients sort of single digits or could this maybe be like a dozen or more patients?

[Gene Kinney:]

So obviously I can't say for sure because what we're doing is we're saying, we're randomizing one 100 patients here this month. And whoever is still in screening and active in screening at that time will allow to finish that screening process. And so obviously whoever is eligible for that screening process were able to be enrolled. Given where we are and how many patients we have in screening today. I think it's probably more than single digits, but probably less than 25, right, somewhere in that range.

[Kennen MacKay:]

Okay. So that's actually pretty significantly overwhelming.

[Gene Kinney:]

Well, I mean part of the reason we're actually allowing for the over enrollment to be frank is the level of interest that we received in this study has really been pretty heartening and remarkable. And so clearly as a patient first company, we're not going to turn those patients away if they've given of their time to come to the centers and start the screening process and that's exactly why we're doing that. So a little bit will depend on how many patients are actually still in active screening once we get to 100, but whoever is there we’ll let finish the process.

[Kennen MacKay:]

Gotcha. Okay, thanks for the color on that Gene. And then, again, just one more sort of follow-up on the PRX003 announcement. So I just wanted to get your perspective if there was anything additional that we'd see and sort of a final data here versus the interim data that would help in powering or decision making on study design in psoriatic arthritis?

[Gene Kinney:]

Yes. Absolutely. It helps on a couple different fronts right, so first and foremost I think understanding how to dose to Phase II is the key thing for us. As we shared in the Phase I single dose healthy volunteers study, we have a pretty good handle on the different pharmacodynamic measurements of the different potential mechanisms of action, right. We described the process of the demargination, downregulation and occupancy and obviously we can follow that over time. So the question becomes which of these is critical or which combination of these is critical for clinical outcome. And understanding that tells us a lot about how to dose in a Phase II just by way of example and I'll say this is a double-blind, placebo-controlled study if I don't know anything here, but by way of example if we learned that demargination was a critical component of providing perhaps earlier efficacy, we may choose to go into a loading dose followed by a maintenance dose strategy. If we find that that's really not contributing to the biology and it's much more about maximum neutralization of the Th17 cell then we may use a straightforward dosing paradigm. So that's what we're trying to get out of the study and clearly the sooner we get that answer, the sooner we can actually design the right dosing strategy for the psoriatic arthritis study. So I think that's important on the other front where this helps quite a bit clearly is from a regulatory interactions perspective. Clearly being able to go to the regulators with a unblinded dataset even just from a safety tolerability perspective it is a significant advantage in those conversations over showing up with a blinded safety database. And so I think you know that helps us on that front as well.

[Kennen MacKay:]

Gotcha. Okay thanks. And then maybe just one follow-up from some additional data we saw at ASH and this is coming from this other anti AL Amyloid monoclonal antibody from Columbia 11-1F4 and this sort of targets amyloid fibril form of chamber, maybe could you speak a little bit to the differentiation between the NEOD001 and this agent.

[Tran Nguyen:]

Yes, I know this is from - and this is an antibody that originally came from UT Knoxville to Alan Solomon lab, we know this antibody well. 11-1F4 ultimately went from Knoxville up to Columbia and [Suzanne Lynch] did a great job with it up there working with the National Cancer Institute. So you know it's an antibody that targets a form of AL so it is directly AL targeting as best we know the antibody at this point in time. It remains in a chimeric from, so you know they're going to continue I assume to work on that antibody and you know further develop into humanize form I would assume I don't know that be true. There's a kind of head not to that was in the Phase Ib study that Suzanne ran at Columbia and she was providing the drug on a weekly basis versus monthly I haven't seen all the tolerability data but you know I think we're at a monthly dose thing we have I think a pretty good contract below 88 at this point so I think we feel pretty good about where we are relative to that antibody I didn't see it was recently picked by a company. But at least in their first press release they indicated that they were planning on Phase II study some time in 2018. So I think we feel pretty comfortable where we are with our antibody.

[Kennen MacKay:]

Gotcha. Thanks so much for the color and thanks for taking the questions and Happy Valentine Day to everyone on the team.

[Gene Kinney:]

Thank you.

[Operator:]

And our next question comes from the line of Yun Zhong with SunTrust. Your line is now open.

[Yun Zhong:]

Thank you for taking my question Sandra. First, we are specific want about the NEOD program if I may. About the VITAL study why the study requires our first line chemotherapy to be [indiscernible].

[Gene Kinney:]

Yes, good question. So frankly the I would say we make this number up a little bit, but well I just say the vast majority of what use right now in these patients are pretty some inhibitor I don’t 75% is somewhere in that range, but what I would say is you know given that and given that the widely used regimen. We wanted to make sure that we didn't have an imbalance the safety signal that was due to the first line chemotherapy and so we needed to harmonize that in our protocol, but we need to harmonize it with a regimen commonly used and so we elected to use the [indiscernible] containing regimen that allows us to make sure that there's a balance in the any safety events which occurred due to those cytotoxic chemotherapeutic agents and that we don't have an imbalance there that could be miss attributed to nearly one.

[Yun Zhong:]

I see. And then about the Phase II study for PRX002, are you able to share reasonable size and maybe the duration of treatment for you to maybe see meaningful clinical efficacy?

[Gene Kinney:]

Well, yes I mean I think we can talk about generally I think as Tran said earlier we can’t get specific details on the Phase II study design. When I think what we can say is that there has been good work done by the Michael J. Fox Foundation and others and I think using clinical outcome measures like the MDS, UPDRS using imaging approaches like the dopamine transporters, SPECT scan. We know that the disease progresses over call it nine to 18 months by about 8% to 15% on those types of scale. And so clearly this approach is not a symptomatic approach. It's meant to be a disease modifying approach and so what you'd be looking for a deviation from that pathological progression of the disease. Over a timeframe in that range and what you need to see is enough progression of the diseases that within some variants that gives you confident that you're deviating from that progression. And so I think that's how you would do it. The advantage that we have I think a little bit in Parkinson's disease is that we kind of know what those variants are. We know what that progression should be. Some of this work's been done and so that's actually quite good and we have a couple of tools like the UPDRS and that scan seem to track progression at about the same rate. I think the only challenge that you have to really think about quite a bit in Parkinson's is that concomitant for symptomatic drug usage is something that will impact the UPDRS and so you just need to make sure he control for that over any given study and really pull out that disease modifying effect and obviously we've been thinking a lot about that with Roche and I think the design will reflect that when we're able to talk about it.

[Yun Zhong:]

I see, and last question about the PRX003. You talked about this some potential criteria to you to move the Phase II study forward and are able to elaborate a little of the criteria and is it possible that anything might come out from the Phase Ib study that can potentially change your plan for the Phase II study?

[Gene Kinney:]

Yes. No, I think that's always possible. We're data driven and so anything that happens in this Phase Ib should inform us on the Phase II which is another advantage I think starting actually running the Phase II off a completed study as opposed to starting that process of the an interim. So what are the criteria, we haven't given it the exact criteria, so I will defer from doing that. I would say generally what we're looking for is clearly we want to see that there's some biological activity that would be as expected. But most importantly it goes back to what I was talking about earlier, which is we need to be able to select the right dosing paradigm, the right dosing approach for our Phase II study. And so we really need to appreciate and understand how the mechanism of actions of PRX003, which we can measure through our pharmacodynamic measures, is related to clinical outcome and we'll be looking at that in this Phase Ib and we really want to pull that data out to be able to design correctly how we're going to dose in our Phase II study and study. So I think that's probably the most important – are there a result that could impact what we do next, always if we were seeing remarkable activity you would consider a parallel psoriasis study. But that's not our base case assumption.

[Yun Zhong:]

I see. Thank you for that question again.

[Gene Kinney:]

Thank you.

[Operator:]

And our next question comes from the line of Jay Olson with Oppenheimer. Your line is now open.

[Jay Olson:]

Hi, I'll add my congrats on the progress and thank you for taking the questions. I just wanted to follow-up on PRX002 as we look ahead to initiating the Phase II trail and recognizing you can't give a lot of details, but and it sounds like this study might start more towards the first half of the year. So can you give us some idea of when we could expect data from this study and specifically whether or not there might be an interim analysis?

[Gene Kinney:]

Yes. I really don't have these details to share today. To be honest we're hopeful that it starts in the first half of the year that’s not entirely under our control, that's not something we're guiding to definitively. But beyond that we're not going to be able to speak in detail about the study design and the different elements of the study really until that study begins we receive a milestone at that point I think we'll be able to share more information, so apologies for that.

[Jay Olson:]

Okay. Totally understood. And then I guess just on PRX003 you've touched on this a little bit, but could you please walk us through the decision to skip the interim and maybe the mechanics behind how that would have slowed down the program?

[Gene Kinney:]

Yes. I think as I described before, I think it's on a couple of fronts right, I mean first and foremost by accelerating the overall program. I think what we can do is get a more fulsome look across all of the dose levels being tested to really give us the best information with which to select the right dosing approach for the Phase II study and it gets us that information sooner by about a quarter actually. The second thing it does for us is on the regulatory front. It allows us to have unblended conversations with regulatory agencies which I think is a more productive conversation and I anticipate will give us more confidence moving into the Phase II study that’s the design of that study is appropriate with respect to regulatory feedback.

[Tran Nguyen:]

I think the one thing I would add to what Gene just said also in the interim analysis, we weren't sure we could get to the highest dose in time in terms of the 30 mg/kg, but we were certain that we could deliver one, three and 10 which is the first three dose cohort level. And so in this way by foregoing the interim and bringing back up the full trial, we're now able to include the 30 mg/kg in the time period that we discussed which is I believe the third quarter. So that maybe just a little bit more color in terms of why we're able to forego the interim, get more data on the full dataset and bring it forward still at the same time.

[Jay Olson:]

Yes, that’s helpful. Thank you. I just had one follow-up question on NEOD001, you had mentioned the draft guidance that was submitted by the Amyloidosis Research Consortium and recognizing that this is separate work independent from Prothena. Could you comment on how and when the FDA might respond to that draft guidance?

[Gene Kinney:]

Yes. So obviously these aren't under any given timelines, so the FDA doesn't have a distinct timeline with which they need to follow-up. But that said, it's our understanding that draft guidance was submitted at the invitation of the agency and if that's true, I would anticipate that the agency will do something with that document in a not too distant future. I think what they do with that document is really the bigger question. How much teeth once that gets put out into the public domain as draft guidance from the FDA and how much teeth will it have, how loose will it be around the wording and I think that's something we can't predict at this point in time. But I’ll say this Jay, I think from our perspective from our seat, if we're able to have a conversation with the FDA following the receipt of PRONTO data being able to talk to a group that's been informed and educated by really some of the world's best scientists in this space, independent of a company that sponsoring a trial I think is a great advantage for both the agency and for us in part because obviously on their side they're well educated as to the data that surrounds this. And on our side, we can focus on the study results in any discussion as opposed to the primary outcome measure, and I think that's very important.

[Jay Olson:]

Okay. Thank you. End of Q&A

[Operator:]

And this does conclude today’s Q&A session. Now, I would like to turn the call back over to Dr. Gene Kinney for any further remarks.

[Gene Kinney:]

Thank you, Sandra. And thank you all for joining us this afternoon. We appreciate your interest in Prothena and our programs. Over the coming months, we look forward to sharing your advancements that we expect to propel our programs towards potential commercial availability for patients. Thank you all very much, and as Andrew said, happy Valentine's Day.

[Operator:]

Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program and you may all disconnect. Everyone have a great day.