Prothena Corporation PLC (PRTA) 2016 Q4 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Prothena fourth-quarter 2016 financial results conference call.

(Operator Instructions)

As a reminder, this conference call is being recorded. I would now like to introduce your host for today's conference, Mr. Randy Fawcett, Vice President of Finance, you may begin.

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 a 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 our 2016 highlights, as well as corporate and pipeline accomplishments. 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 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 provision 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 would like to turn call over to Gene.

Thank you, Randy, and thank you all for joining us this afternoon. It's a pleasure to be here today to discuss our 2016 and recent accomplishments, and the milestones we're looking forward to in 2017. On today's call, I'll highlight the progress we've made on each of our clinical programs, talk briefly about our key corporate accomplishments, and then turn it over to Tran for 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'd like to first comment on one event in 2016 that we were distinctly sad 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. We will miss Dale, and we'll forever be indebted to the scientific legacy that remains.

Following this profound loss, with credit to our Board of Directors and leadership team for quickly instituting our succession and strategic plan, we have 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 charities designated by his family. To us, it served 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'll 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 and cell adhesion. In 2016, we reported positive data for each of our clinical programs in these areas and continued to raise awareness of our novel antibodies through the publication and presentation of scientific results. We ended 2016 with a 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 will 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, a 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 US 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 soluable aggregates and deposited amyloid can cause dysfunction, and ultimately organ failure, and approximate 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 treatment approaches target the soluble aggregates and deposited amyloid that drives organ dysfunction and failure. The goal of these treatments is to control hematologic burden by targeting clonal plasma cells to decrease the production of new light chain. These 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 principal in amyloid disease, that simply focusing on decreasing new protein production may be insufficient to provide patient benefit in most cases. In the context of AL amyloidosis, for example, it is clear that hematologic control, in the absence of organ benefit is of 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 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 an 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 in organs. NEOD001 is the first immunotherapy directly targeting AL amyloidosis to receive Fast Track Designation from the US Food and Drug Administration. In 2016, we continued to advance our two pivotally designed studies of NEOD001 in patients with AL amyloidosis and 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 1/2 study of NEOD001 in patients with AL amyloidosis and 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 of 2016, and also presented 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.

As a reminder, this Phase 1/2 study enrolled a total of 69 patients with AL amyloidosis and persistent organ dysfunction, including 27 patients in the dose-escalation portion of the study, and an additional 42 patients in the expansion phase. All of the patients in this study had been previously treated with plasma cell-directed therapy and continued to experience organ dysfunction.

In the expansion phase of this study, patients were enrolled 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 NEOD001, with a mean treatment duration of 12.8 months. 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. Improvement in patient NIS-LL scores resulted in a response rate of 82%, or 9 of the 11 patients in the peripheral neuropathy expansion cohort, where 2 of 9 responders showed complete resolution of peripheral neuropathy, as measured by NIS-LL.

As Dr. Gertz pointed out in his presentation, this was the first time that improvement in peripheral neuropathy was seen in patients with AL amyloidosis. These response rates, achieved across three organ systems in our study, compared favorably to published historical response rates in patients previously treated with plasma cell-directed therapy. Additionally, a post-hoc subset analysis of the NEOD001 Phase 1/2 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 1/2 study, we remain confident in the design and powering 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 2b 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 the 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're 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. As 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 best response, as defined by a change in NT-proBNP. NT-proBNP is a widely clinically validated functional biomarker that predicts survival in patients with AL amyloidosis following intervention and has been demonstrated by numerous retrospective and prospective studies. Demonstrating a significant effect on cardiac response as measured by NT-proBNP, 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-proBNP as a surrogate endpoint for clinical outcome and survival.

Turning to the VITAL Amyloidosis Study, we're also continuing to enroll this study, which is a Phase 3 global registrational, randomized double-blind placebo-controlled study enrolling newly diagnosed treatment-naive patients with AL amyloidosis and 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 NEOD001. The primary composite endpoint in this study is event based and consists of all-cause mortality or cardiac hospitalizations. This study is designed to support full global regulatory registration.

Keeping with the theme now of peripheral amyloid disease, I'd like to next highlight our preclinical program for ATTR amyloidosis, PRX004. PRX004 is an investigational monoclonal antibody designed to specifically target and clear the misfolded forms of the TTR amyloid protein, found in a disease known as transthyretin-mediated 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 ATTR with cardiomyopathy; wild-type ATTR, which occurs sporadically and also involves 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 fibral formation, which most commonly affect the heart and nervous system.

Prothena has generated a monoclonal antibody that selectively bind to amyloid or 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 of ATTR in patients with either wild-type or hereditary TTR-mediated amyloidosis. From the antibodies we generated, we selected PRX004 as a 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 will turn to PRX002, a monoclonal antibody for the potential treatment of Parkinson's disease and other synucleinopathies. PRX002, also known as RG7935, is the primary focus of our world-wide collaboration with Roche. Parkinson's is a neurodegenerative disease that affects 7 million to 10 million people worldwide, making it the second-most-common neurodegenerative disease after Alzheimer's.

The disease is characterized by the neuronal accumulation of aggregated alpha-synuclien in the central and peripheral nervous systems that result in a wide spectrum of worsening, progressive motor and non-motor symptoms, and are 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 motility 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 L-DOPA or dopamine agonists, but these only address a subset of systems typically related to motor impairment. Symptomatic therapies do not target the underlying cause of the disease and, as the disease progresses and dopaminergic neurons continue to be lost, these drugs lose effectiveness, often leading to debilitating side effects.

PRX002 is being developed as a potentially disease-modifying approach, to slow the progressive neurodegenerative consequences of this disease. PRX002 targets alpha-synuclein, a protein that is widely understood to be intricately involved in the onset and progression of Parkinson's disease. Targeting alpha-synuclein has the potential to slow or reduce the neurodegeneration associated with alpha-synuclein misfolding, and/or its cell-to-cell transmission.

As you may recall, in 2015, we reported positive results from a Phase 1 single ascending-dose study in healthy volunteers, demonstrating target engagement, as well as the positive safety, immunogenicity, and pharmacokinetic profile for PRX002. In November of last year, we reported results from the Phase 1b double-blind placebo-controlled multiple ascending-dose study in 80 patients with Parkinson's disease. This study was designed to assess the safety, tolerability, pharmacokinetics, and immunogenicity of PRX002. This study demonstrated acceptable safety and tolerability across all dose levels, up to and 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- and 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 robust penetration of PRX002 in the central nervous system, which exceeded our expectations based on our preclinical experiences. We observed a dose-dependent increase in PRX002 in the cerebral spinal 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 2 study that will further explore the potential of PRX002 as a disease-modifying treatment for Parkinson's disease. Together with our partner at Roche, we plan to initiate a Phase 2 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's biological expertise in cell adhesion extends 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 have made 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 a cell-adhesion molecule that is a specific marker for TH17 cells, which are known to play an integral role in the initiation and propagation of inflammation in autoimmune 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 their 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 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 blood vessel walls. 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, these cells appear to be disproportionately involved in propagation of inflammation -- inflammatory diseases under pathogenic conditions. Targeting the T cell, rather than any individual cytokine, they 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 1 double-blind placebo-controlled single ascending-dose study in 40 healthy volunteers. The data showed that PRX003 was safe and well tolerated at all 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 expression, 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 these successful results, we're currently conducting a randomized double-blind placebo-controlled Phase 1b 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 the PASI, and also look to the pharmacodynamic profile in order to determine a dosing strategy for our Phase 2 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 in psoriasis, but our assumption is that we will pursue an alternate indication with greater medical need for our Phase 2 program. Therefore, in September of last year, we announced that, based on meeting certain pre-specified criteria in the ongoing Phase 1b study, we intend to pursue development of PRX003 for the potential treatment of psoriatic arthritis.

Psoriatic arthritis is a disease where TH17-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 cell, 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've 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 a planned Phase 2 study, assuming, of course, that the Phase 1 data is permissive. We will therefore forgo an interim analysis, and now expect full top-line data from the Phase 1b 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 toward 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?

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 a net loss of $48.9 million and $160.1 million for the fourth quarter and full year of 2016, as compared to a 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 a 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 periods 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 revenue of $0.3 million and $1.6 million for the fourth quarter and full year of 2015. As expected, the decrease 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 trials, 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 of 2015.

As of December 31, 2016, Prothena had $391 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 of 2016. As of February 10, 2017, we have approximately 35 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 million to $170 million, which includes an expected milestone payment from Roche upon initiation of the Phase 2 study of PRX002.

We expect to end the year with approximately $224 million in cash, which represents the midpoint 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 million 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?

Thanks, Tran. 2016 was a 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 NEOD001 to regulatory authorities. For NEOD001, we expect to fully enroll 100 patients in PRONTO by the end of this month and to report results from this study in the second quarter of 2018. For the Phase 3 VITAL Amyloidosis Study, we expect to complete enrollment in the second quarter of this year.

For PRX002, we expect to initiate a Phase 2 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 1b 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. At this time, we will open the call for questions. Sandra?

(Operator Instructions)

Michael Yee, RBC Capital Markets.

Hey, guys. Thanks, good afternoon. Congrats on all the progress. Two questions: First is, can you clarify for us again why the psoriasis data would be in Q3, and why you're 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 think that's worth investing in, and whether you think that's something you could go ahead with? Thanks so much.

Mike, maybe I'll jump in here, and then Tran may want to add some color to it as well. So let's start with the neuropathy study. Agreed, I mean, I think the data that we heard at ASH from that prospectively defined cohort out of the Phase 1/2 was very, very encouraging.

Looking at a stand-alone neuropathy study, that's something certainly that we'll 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 both the PRONTO and VITAL studies, we'll be looking at neuropathy for those patients that have both cardiac involvement, as well as neuropathy.

I think if you go look at the literature there, the older literature suggests that number is 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, at least the light's been shining a little bit brighter on this part of the disease, we're starting to see numbers closer to 30% to 40%. So we think there could be a significant number of 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 this space as well, and then also sponsored studies. 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.

Okay.

Anything to add on that Tran before I turn it --?

I think the one thing maybe to add, too, to that is that whatever path that we take in terms of whether we rely on the subset analysis from the PRONTO and VITAL trials to support a neuropathy discussion with regulators, or a separate trial, I think what we want to have confidence in is that whatever route that we do take, that we have a high confidence that the regulators will also see it the same way, with that pathway.

So if it's a separate trial, then hence we want to make sure we're speaking to regulators about that trial design, and have a high confidence that it's something they will accept. Or if we don't do that, then again, in our current trials that we're running from a subset analysis perspective.

Okay. And on psoriasis?

Yes, on the psoriasis question, so, Mike, I think taking a hard look at that, and just -- 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 and ability to differentiate in that space, particularly in a Phase 1b underpowered study, I think is low. And so, really the goal of that interim analysis for us initially was to accelerate the initiation of the Phase 2 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 aspects, we've ended in a place where we believe we can pull that whole study forward. And in fact, as you know, the initial idea was an interim mid-year-ish, 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 and the initiation of a Phase 2 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's out there today, this was the most expeditious path, and that's why we made that decision.

Okay. Thank you.

Okay. Thanks, Mike.

Andrew Peters, Deutsche Bank.

Hey, guys. Thanks for taking my questions, and congrats on all the progress as well. Couple of questions for me. I guess first, regarding D001 in VITAL, you talked about guidance to completing enrollment in 2Q. I just want to understand a bit, how has the enrollment rate, and importantly 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 changing outcomes in amyloidosis. I just wanted to check in and see if any updates from that study had any impact on your thinking about VITAL? Has it been consistent with what you're seeing on a blinded basis from the study so far?

Yes. Thanks, Andrew, for that question. A couple pieces on that. So first, as you accurately said, the expectation around enrollment is that we will complete that in the second quarter. And we've been very consistent in saying our expectation, based on survival curves, is somewhere between 12 to 18 months behind the last patient in, which puts us to the latter part of 2018 for VITAL, last patient, last visit. So I think, we haven't change 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, we'll let folks know. So the absence of that information would suggest that we don't have any confidence that we're -- off of our expectations, right? So I think today we maintain those expectations, and don't have any evidence to suggest that we are 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 curves -- I want to say it was Figure 3C in that paper -- really from 2005 to present, there's been no change in survival rates. And that's significant, since that time frame really represented a shift from the old alkylating agents like melphalan, to the more commonly used proteasome inhibitors like bortezomib. And those survival curves are very similar to what we've seen in other publications, like the Kumar publication, and even what was reported by University of Pennsylvania at the ASH meeting in December.

And so at least from an external perspective, we think that with the exception of some single center studies with relatively low ends, where maybe survival is starting to look better across the board, what that paper seemed 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 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.

If you look at the Kumar et al 2014, and 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 was between 45% and I think 60%. And if you look at the two-year survival that was quoted in those graphs without autologous stem cell therapy was around 55% mortality at 24 months.

So again, they all seem to corroborate with each other, and I think that still hasn't changed our view or 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, and able to narrow in the timeline, we clearly will do so at that time.

Okay, perfect. And then, just a quick follow-up on 003, just want to understand a bit more your longer-term goals for the program, encouraging to see 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 a pretty wide range of indications, how do you think about the longer picture goals? Is this a program you want to keep in house, like D001, or view it as something more similar to 002, just given the potential size of the opportunity, but also size of the clinical costs associated with those studies? Thanks.

Yes, good question, Andrew. So again let me start, and Tran will 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 and anticipating moving forward into that Phase 2 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 a great example, most of those started in rheumatoid arthritis, found that they could significantly differentiate in the psoriasis space, kind of established that beachhead in that space, became their lead indication. And then, as they went, developed 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 those cytokines in the joint, we expect that we may be able to show a differentiated efficacy profile. And so that's what we will be testing in that Phase 2 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 2's 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 are in a broad-based indication space, we anticipate that we would need to start thinking at some point about partnering the -- particularly on the commercial side, as we noted, there are very well-established commercial field forces out there that we would likely need some help from.

Yes, I think just to add on to that, I think we continue to educate those strategic folks about X003, regarding its biology and mechanism of action and likely areas of advantage. And so, I think it behooves us in terms of our current financing to bring it to a point where either we run the next trial for that Phase 2 proof-of-concept on PSA. Or if someone was to come in and give us outsized economics now for it, I think, and try to build the indications sooner, I think those are all things that we'll need to balance. But as of right now, I would say from a base case perspective, expect us to -- if the data from the Phase 1b psoriasis trial is permissive, that we'll run that Phase 2 in psoriatic arthritis.

Great. Thank you.

Thanks, Andrew.

Geoff Meacham, Barclays.

Hi, guys. This is Evan on for Geoff. Thanks for taking the questions, and congrats on the progress. First one on D001: So with the PRONTO data expected by the second quarter of 2018, do you expect with a potential change in the regulatory environment, we saw the passing of the 21st Century Cures Act, more flexibility in using that type of endpoint to get D001 approved?

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 -- I think we'll know a little bit more at that point.

I think what we can sink our teeth 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. We're encouraged at 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 an 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-proBNP, as a surrogate efficacy outcome measure for interventional studies in AL amyloidosis with cardiac involvement. And then thirdly, and I mentioned this in the call today, they submitted draft guidance document to the FDA at the end of last year, which as at least part of that document again reiterated their view that use of NT-proBNP and the cardiac response biomarker should be utilized in interventional studies, in as much as it is very predictive of survival in this patient population.

I'd point, too, to some work at ASH. A lot of the previous work that the Amyloidosis Research Consortium was relying on were retrospective data, was very robust data, 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 a prospective manner NT-proBNP 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. I think, 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.

All right.

I think from a -- sorry, go ahead.

No, I'll let you finish, Tran.

I was just going to say, from a base case though perspective, we're still advocating that the PRONTO trial will mainly serve as discussions with European regulators around potential for conditional approval, if the data is permissive. And that clearly what Gene is sharing is we're going to work like hard in the background to continue to work with US regulators. But as of right now, that's not what we want to grow as an expectation.

Yes, let me -- 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 have received to date, and what we feel relatively comfortable with. And that would be that as a base case, a positive PRONTO 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.

In FDA we feel like we'll need VITAL for 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 advantage that case within the US, and I think that's a very important point.

Okay, great. And then, can you remind us what the expected milestone is for the Phase 2 of X002? Did you disclose that?

So, no, absolutely, that's actually a really great question. We've clearly built it in to our guidance and our cash burn, so to speak, from a net-net perspective. We can't disclose the exact amount, but what we can say is that the Phase 1 milestone that we received for the initiation, right, for the first healthy volunteer dose was $15 million. And so, in a Phase 2, you would think it would be some magnitude bigger than that, than the $15 million.

But clearly, as that trial gets initiated and the first patient gets dosed, we'll make that announcement along with the Phase 2 trial design and timing of all that. And so, we'll do all that at hopefully sometime this year, we're hoping in the first half, but for now we're guiding to 2017.

Okay. So that's potentially a first-half event, but not guaranteed at this point.

That's what we're hoping for, yes. We'll try and execute to that, but at the end of the day we're at Roche's timeline.

Just one more on a high level, how do you think about the development plan for X004, with clinical development expected in early 2018? What are your thoughts on moving that forward in to -- actual in to patients?

So it's a little premature to give you a development plan or outline, but I will suggest a few points, which is what we -- one of the things we really like about our antibodies is, first and foremost, they don't appear to interfere or interact with the normal form of transthyretin. And so, it's normal form, where it carries out its normal function, is known to be tetrameric, and we've shown some data in the amyloid publication from last year that, in fact, our antibodies really don't interact or bind to that tetrameric form at all. But as that tetrameric form breaks down into misfolded forms -- and also in the amyloid state where you're looking at the deposition on 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 sequence, but also in most of the common familial forms, both the polyneuropathy and ultimately cardiomyopathy indications. And really what it will come down to from a strategy perspective is just how we stage those indications. But what we like about the antibodies is it opens up that field for us into almost the entirety of the transthyretin related disease populations.

But we do see the therapies as highly complementary, right, in terms of the other RNAi or anti-sense strategies that are out there, in terms of moderating or decreasing production of transthyretin. Very similar in AL amyloidosis, where you're decreasing the production of light chain with plasma cell dyscrasia therapies -- again, very complementary. So I think in the way we are developing AL amyloidosis -- 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 trial, in a similar fashion as I think you can see with our D001 program.

Thank you so much.

Thanks, Evan.

Tazeen Ahmad, Bank of America.

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 catalyst?

Sure. Absolutely. Around X002, again, that's the next milestone that we expect to receive is from the initiation of that Phase 2 trial that we're guiding to sometime basically this year in 2017, and that we're hopefully pushing for in the first half.

That being 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 1 initiation milestone was $15 million. And so, clearly the Phase 2 should be some magnitude larger, given it's a Phase 2, larger than $15 million. But what we'll be able to do is when we actually earn that milestone, we'll announce it, and we can talk much more in detail about it.

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

I think what we would do is obviously top-line release as quickly as we can, and then we would follow that up with a more detailed scientific presentation, as has been our custom. I think you're exactly right though, Tazeen. What we've been able to do is now having pretty good understanding of exactly when we're done enrolling that study, and given that it's a 12-month observation period, clearly last patient last visit is 12 months after last patient in. So add a little bit of time for database lock and analysis, and that puts us right there in the second quarter. But again, I think our typical style, we'd do a top-line press release, then we'd follow that with a more detailed scientific discussion at a scientific meeting.

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

Well, let's see. So in that year, there's the International Society -- or International Amyloidosis Society meeting will be that year, and obviously, ASCO, and then later in the year ASH, but --.

Okay, so ASH would be the last possible one.

Yes, I think that'd be -- that's all the way back in December. So we'd probably look to share the data before then, but it's a little hard to say, until we have the full data set, exactly what medium we'd go through.

Okay.

But those are the likely suspects.

Thanks.

Yes.

Kennen MacKay, Credit Suisse.

Hey, thanks for taking the questions. So just on PRONTO, you mentioned this could be over-enrolled. Wanted to get a perspective of how overenrolled we're talking here? Is this going to be like 1 to 2 patients, single digits, or could this maybe be like 12 or more patients?

So obviously I can't say for sure, because what we're doing is we're saying we're randomizing our 100th patient here this month. And whoever is still in screening and active in screening at that time, we'll allow to finish that screening process.

And so, obviously whoever is eligible through that screening process will be 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.

Wow, okay, so that's actually pretty significantly over (multiple speakers).

Part of the reason we're actually allowing for the overenrollment, 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.

Got you. Okay, thanks for the color on that, Gene. And then again, just one more follow-up on the X003 announcement. So I just wanted to get your perspective, if there was anything additional that we would see in the final data here versus the interim data that would help in Phase 2 powering or decision making on study design in psoriatic arthritis?

Yes, absolutely -- well, it helps on a couple different fronts, right. So first and foremost, I think understanding how to dose the Phase 2 is the key thing for us. As we shared in the Phase 1 single dose healthy volunteer study, we have a pretty good handle on the different pharmacodynamic measurements of the different potential mechanisms of action, right. We describe the process of demargination, down regulation, 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 2. Just by way of example, and I will say this is a double-blind placebo-controlled study. So 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.

The other front where this helps quite a bit, clearly, is from a regulatory interaction perspective. Clearly, being able to go to the regulators with a unblinded data set, even just from a safety tolerability perspective, is a significant advantage in those conversations, over showing up with a blinded safety database. And so, I think that helps us on that front as well.

Got you. Okay, thanks, Gene. 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, the 11-1F4. This targets the amyloid fibril form of the light chain, but maybe you can just speak a little bit to the differentiation between D001 and this agent?

Yes, this is an antibody that originally came from UT Knoxville; it's Alan Solomon's lab. We know this antibody well. 11-1F4 ultimately went from Knoxville, up to Columbia, and Suzanne Lentzsch did a great job with it up there, working with the National Cancer Institute.

So 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 form. So they're going to continue, I would assume, to work on that antibody, and further develop it into a humanized form. I would assume; I don't know that to be true.

The kind of head nod to that was in the Phase 1b study that Suzanne ran at Columbia. She was providing the drug on a weekly basis versus monthly. I haven't seen all the tolerability data, but I think -- we're at a monthly dosing. We have, I think, a pretty good construct, low ADAs at this point. So I think we feel pretty good about where we are, relative to that antibody.

I did see it was recently picked up by a company, but at least in their first press release they indicated that they're planning on Phase 2 study sometime in 2018. So I think we feel pretty comfortable where we are with our antibody.

Got you. Thanks so much for the color, and thanks for taking the questions, and happy Valentine's Day to everyone on the team (laughter).

Thanks. You, too.

Yun Zhong, SunTrust.

Thank you for taking the questions. And first, a very specific one about the NEOD program, if I may. About the VITAL study, why does the study require the first line chemotherapy to be a proteasome inhibitor-containing regimen?

Yes, a good question. So frankly, I would say -- I'm going to make this number up a little bit -- well, I'll just say the vast majority of what's used right now in these patients are proteasome inhibitors. I don't know if it's 75%, or somewhere in that range. But what I would say is, given that, and given that that's a widely used regimen, we wanted to make sure that we didn't have an imbalance in safety signals that was due to the first line chemotherapy.

And so we needed to harmonize that in our protocol, but we needed to harmonize it with a regimen that's commonly used. And so, we elected to use a bortezomib-containing regimen. That allows us to make sure that there's a balance in any safety events which occur due to those cytotoxic chemotherapeutic agents, and that we don't have an imbalance there that could be misattributed to NEOD001.

I see. And then about the Phase 2 study for PRX002, are you able to share a reasonable size, and maybe the duration of treatment to maybe see a meaningful clinical efficacy?

Well, yes, I mean, I think we can talk about it generally. I think as Tran said earlier, we can't give specific details around the Phase 2 study design. But 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 transporter SPECT scans. We know that the disease progresses over, call it, 9 to 18 months by about 8% to 15% on those types of scales.

And so, clearly this approach is not a symptomatic approach. It's meant to be a disease-modifying approach. And so, what you would be looking for is deviation from that pathological progression of the disease over a time frame in that range.

And what you need to see is enough progression of disease so that within some variance that gives you confidence 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 has been done. And so, that's actually quite good. And we have a couple of tools like the UPDRS and the DaTscan that seem to track progression at about the same rate.

I think the only -- the challenge that you have to really think about quite a bit in Parkinson's is that a concomitant L-DOPA or symptomatic drug usage is something that will impact the UPDRS. And so, you just need to make sure you 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.

I see. And a last question about the PRX003, you talked about this, a potential criteria for you to move the Phase 2 study forward. Are you able to elaborate a little on the criteria? And is it possible that anything might come out from the Phase 1b study that can potentially change your plan for the Phase 2 study?

No, I think that's always possible. We're data-driven, and so anything that happens in the Phase 1b should inform us on the Phase 2, which is another advantage, I think, of starting, actually running the Phase 2 off a completed study, as opposed to starting that process off an interim.

So what are the criteria? We haven't given the exact criteria, so I will defer from doing that. I'll say generally what we are 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 2 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 1b, and we really want to pull that data out to be able to design correctly how we're going to dose in our Phase 2 study. So I think that's probably the most important.

Are there results that could impact what we do next? Always. If we were seeing remarkable activity, you'd consider a parallel psoriasis study. But that's not our base case assumption.

I see. Thank you for the questions again.

Thank you.

Jay Olson, Oppenheimer.

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 2 trial, 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. But 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?

Yes, Jay, I really don't have the 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, so 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 and we receive a milestone. And at that point, I think we'll be able to share more information. So apologies for that.

No, totally understood. And then, I guess just on PRX003, you 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?

Yes, well, 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 the dose levels being tested to really give us the best information with which to select the right dosing approach for the Phase 2 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 unblinded conversations with regulatory agencies, which I think is a more productive conversation, and I anticipate will give us more confidence moving into the Phase 2 study that the design of that study is appropriate with respect to regulatory feedback.

I think the one thing I would add to what Gene just said also, in the interim analysis we weren't sure whether we could get to the highest dose in time, in terms of the 30 milligrams per kilogram. But we were certain that we could deliver 1, 3, and 10, which is the first three dose cohort level.

And so, in this way, by forgoing the interim, and bringing back up the full analysis or full trial, we're now able to include the 30 milligrams per kilogram in the time period that we discussed, which is I believe the third quarter. So that's maybe just a little bit more color, in terms of why we were able to forgo the interim, get more data on the full data set, and bring it forward still at the same time.

Yes. That's helpful, thank you. I just had one follow-up question on NEO001. 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?

Yes, I mean, 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, 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.

Okay.

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 the space, independent of a company that's 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.

Okay, thank you.

And this does conclude today's Q&A session. I'd now like to turn the call back over to Dr. Gene Kinney for any further remarks.

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 our advancements that we expect to propel our programs toward potential commercial availability for patients. And thank you all very much. And as Andrew said, Happy Valentine's Day.

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.