Prothena Corporation plc (PRTA) Q4 2019 Earnings Report, Transcript and Summary

Good afternoon, ladies and gentlemen, and welcome to the Prothena Fourth Quarter and Full Year 2019 Financial Results Conference Call. [Operator Instructions]. I would now like to turn the conference over to your host, Mr. Randy Fawcett, Senior Vice President of Finance and Operations. Please go ahead.

Thank you, Joanna. Good afternoon, everyone, and welcome to Prothena's investor conference call to review our fourth quarter and full year 2019 financial results and business progress as well as our 2020 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. On today's call, Dr. Gene Kinney, our President and Chief Executive Officer, will discuss our pipeline programs and corporate progress. Following Gene's comments, Tran Nguyen, our Chief Operating Officer and Chief Financial Officer, will review our financial results for the fourth quarter and full year of 2019 and this year's financial guidance. Gene will then provide an overview of 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.

Thanks, Randy, and thank you all for being on our call today for a discussion of our pipeline and the upcoming milestones we're looking forward to in 2020 and beyond. During the past year, we have continued to advance our pipeline focused on neuroscience and diseases caused by misfolded proteins. These are areas where our deep domain expertise intersects with an unmet and often increasing medical need, and we are applying our capabilities against novel targets with the potential to change the course of many of these devastating conditions. Our diverse pipeline is based on our expertise in neuroscience and the ability to integrate insights around brain function as well as the biology of protein misfolding and how to optimally target toxic confirmations. We leverage these areas of expertise to identify and design novel approaches that aim to impact the underlying pathogenesis across several disease states. We are also leveraging our neuroscience expertise and relationships through our business development efforts, where we continue to evaluate external opportunities to potentially expand our neuroscience pipeline. We ended 2019 with a balance sheet that enables continued development of our clinical, preclinical and discovery programs through key milestones, and we're excited about the breadth and progress of our pipeline. I want to start by providing an update on the clinical programs: prasinezumab and PRX004. Prasinezumab, currently in a Phase II clinical trial, is an investigational monoclonal antibody for the treatment of Parkinson's disease and other synucleinopathies. In 2013, we entered into a worldwide development and commercialization collaboration with Roche for prasinezumab. Parkinson's disease is the second most common neurodegenerative disease affecting an estimated 7 million to 10 million people worldwide, and its incidence continues to increase based on an aging population. Parkinson's disease is characterized by the neuronal accumulation of aggregated alpha-synuclein in both the central and peripheral nervous systems, which results in neurodegeneration and a wide spectrum of progressive motor and nonmotor symptoms that are persistent throughout the course of disease. While the disease is most commonly known for motor symptoms such as bradykinesia, stiffness and tremor, nonmotor symptoms such as cognitive deficits, fatigue, sleep disturbances or constipation are also common and disabling. Current treatments for Parkinson's disease only address a subset of the symptoms. Levodopa and dopamine agonists are primarily directed at managing the early motor symptoms, but these agents become less effective over time and do not address the underlying cause of the disease. Prasinezumab is being developed as a first-in-class approach with the goal of reducing clinical decline in Parkinson's disease. Our antibody targets alpha-synuclein, a protein that is widely understood to be integrally involved in the onset and progression of Parkinson's disease. Alpha-synuclein is the major constituent of Lewy bodies, a pathogenic hallmark of Parkinson's disease and other synucleinopathies, and there's genetic evidence for a causal role of alpha-synuclein in Parkinson's disease. Genetic abnormalities in the alpha-synuclein gene such as duplications, triplications or point mutations that cause autosomal dominant forms of Parkinson's are thought to lead to the overproduction or modifications of alpha-synuclein protein that facilitate aggregation and formation of intracellular pathology. The scientific community has also increased its understanding of how cell-to-cell transmission of alpha-synuclein potentially initiates the spread of pathogenic forms of this protein through different regions of the brain. Research has shown that pathology originating in one region of the brain or even in the periphery may spread to other regions as the disease advances. And in fact, the progression of Parkinson's disease symptoms is reflected in the areas of the brain where alpha-synuclein pathology has developed. Prasinezumab aims to impact the underlying disease progression by preferentially targeting the pathogenic forms of alpha-synuclein and blocking this cell-to-cell transmission. Our research in this space dates back many years. The effects of immunotherapy with the murine form of prasinezumab demonstrated that it crossed the blood-brain barrier, decreased intraneuronal alpha-synuclein pathology and protected synapses from degenerating, resulting in improvements in both motor and cognitive behavior in multiple preclinical models. In 2018, JAMA Neurology published results from our Phase Ib double-blind, placebo-controlled, multiple ascending dose study, which assessed the safety, tolerability, pharmacokinetics and immunogenicity of prasinezumab in 80 patients with Parkinson's disease. As described in the publication, in addition to acceptable safety and tolerability across all dose levels, prasinezumab demonstrated target engagement in serum and dose-dependent CNS penetration that supported advancing to the ongoing Phase II PASADENA study with the 2 dose levels being evaluated. We believe these dose levels are sufficient to target and saturate the aggregated pathogenic forms of alpha-synuclein in the brain. The Phase II PASADENA study of prasinezumab in patients with early Parkinson's disease is a 2-part clinical study that enrolled 316 patients and is being conducted by our colleagues at Roche. The last patient visit in Part 1 of the study took place toward the end of 2019. As such, we expect to report top line results from Part 1 of the study this year. As a reminder of the study design, Part 1 is a randomized, double-blind, placebo-controlled, 3-arm study that is designed to evaluate the efficacy and safety of prasinezumab in patients at 52 weeks. In Part 1, patients are randomized on a 1:1:1 basis to receive 1 of 2 active doses of prasinezumab or placebo via intravenous infusion every 28 days. The dose levels being assessed are 1,500 milligrams in the first prasinezumab arm and depending on body weight, either 3,500 or 4,500 milligrams in the second prasinezumab arm. Eligible patients were not expected to require dopaminergic-based therapy or need to change their stable MAO-B inhibitor regimen for at least 52 weeks. Part 2 of the study is a 52-week blinded extension phase, in which patients from the placebo arm of the study were rerandomized onto 1 of 2 active doses of prasinezumab on a 1:1 basis, so that all participants are on active treatment. Patients who were originally randomized to an active dose will continue at that dose level for the additional 52 weeks. In Part 2, patients are allowed to use concomitant dopaminergic therapy. Any patient who medically requires initiation of dopaminergic therapy or change in regimen of a MAO-B inhibitor during Part 1 of the study have their subsequent data censored for the primary endpoint analysis. You can view additional details on the study at clinicaltrials.gov. The primary endpoint of this study is the change from baseline in the Movement Disorder Society Unified Parkinson's disease rating scale, or MDS-UPDRS, total score of sections 1, 2 and 3 at the completion of Part 1 at week 52. For the primary endpoint, the study was designed with 80% power at a one-sided alpha of 0.1 to detect a 37.5% benefit in each treatment group versus placebo at week 52. Key secondary endpoints, in addition to safety and tolerability, include DAT-SPECT imaging. This imaging approach detects presynaptic dopamine transporter protein in the brain and is considered a biomarker of functional dopaminergic neuron terminals. DAT-SPECT is used as a diagnostic tool for Parkinson's and also has been used in clinical study to monitor neurodegeneration of dopaminergic nerve terminals, which is thought to underlie disease progression. In addition to DAT-SPECT, there are multiple exploratory endpoints, including those derived from a digital biomarker smartphone application. The digital biomarker smartphone application was piloted in our Phase Ib study and demonstrated that daily testing with the app generates reliable, clinically valid data in patients with Parkinson's disease. In PASADENA, these initial learnings were built upon to develop a smartphone app that comprehensively measures core signs of Parkinson's disease remotely and continuously, meaning throughout the day and not only in the clinical setting or at certain time points, and objectively, via smartphone sensors. The digital testing encompasses measures designed to assess phonation, postural and rest tremor, manual dexterity, bradykinesia and balance. We expect to assess the Phase II study results by evaluating multiple endpoints, including the primary endpoint and select secondary and exploratory endpoints. Now I'd like to highlight a second clinical stage program, PRX004, for the potential treatment of ATTR amyloidosis. PRX004 is an investigational antibody designed to specifically target misTTR without affecting the native or normal tetrameric form of the protein. misTTR is the term we use to describe nonnative forms of the transthyretin, or TTR, protein that likely underlie both hereditary and wild-type ATTR amyloidosis. ATTR amyloidosis is a peripheral amyloid disease characterized by deposition of TTR amyloid in vital organs. It is rare, progressive and often fatal. ATTR amyloidosis can be hereditary when caused by a mutation in the TTR gene or wild-type when it occurs sporadically. In both forms of the disease, patients can experience a spectrum of clinical manifestations affecting multiple organs, most commonly the heart and/or the nervous system. The TTR protein is produced primarily in the liver, and in its normal tetrameric form serves as a transport carrier for thyroxin and retinal binding protein, which is a transporter for vitamin A and it's also implicated in neuroprotective functions. It is generally accepted that at the time of diagnosis, affected organs in both hereditary and wild-type ATTR patients contain extracellular amyloid deposits. These deposits together with soluble nonnative confirmations of TTR are believed to cause organ dysfunction. Newly available therapeutics for ATTR amyloidosis have demonstrated clinical benefit by impacting the biological pathway leading to the formation of amyloid deposits. These approaches are designed to reduce production of native forms of the TTR protein or bind to tetrameric TTR and slowed dissociation. However, neither of these approaches target misTTR or tissue-deposited amyloid directly. While these new therapies represent great advances for patients with ATTR amyloidosis, we believe, based on the available clinical data to date, that a large unmet medical need remains for 2 groups of patients. The larger group are patients diagnosed with wild-type or hereditary ATTR and cardiac dysfunction, particularly in New York Heart Association class III or IV. For these patients, a more rapid and/or greater survival benefit remains to be demonstrated. The other unmet need is for hereditary ATTR patients whose peripheral neuropathy is not responsive to treatment with therapies that are silencer mechanisms of action. PRX004 was designed to target misTTR directly by binding to an epitope on the TTR protein that is exposed when the native form of the tetramer disassociates. This epitope continues to be exposed during this folding of the protein. The biological goal following treatment with PRX004 is to deplete the deposited amyloid and circulating misTTR to improve organ function. PRX004 has been shown in preclinical studies to promote clearance of amyloid fibrils through antibody-mediated phagocytosis to inhibit amyloid fibril formation and to target soluble aggregate forms of misTTR. We believe this differentiated depleter mechanism of action could be developed as a monotherapy for the treatment of ATTR amyloidosis and might also complement existing therapeutic approaches, which either stabilize or reduce production of the native TTR tetramer. Our ongoing Phase I study of PRX004 is designed as an open-label, multicenter, 3 plus 3 dose escalation study to determine the safety, tolerability, pharmacokinetic and pharmacodynamic properties of PRX004 in patients with hereditary ATTR amyloidosis with peripheral neuropathy, who may also have cardiomyopathy. The study includes the use of our proprietary misTTR biomarker assay that measures target engagement through changes in the level of unbound misTTR in plasma. In the escalation phase of the study, patients received PRX004 intravenously once every 28 days for up to 3 infusions. Six dose levels are being evaluated: 0.1, 0.3, 1, 3, 10 and 30 milligrams per kilogram. Eligible patients, who complete the escalation phase, can enroll in a long-term extension phase of the study and receive up to 15 additional infusions of PRX004 every 28 days. At the end of 2019, we reported interim data from the escalation portion of the Phase I study of PRX004 in patients with hereditary ATTR amyloidosis. In the interim analysis, 15 patients in the dose escalation phase of the study had each received 3 infusions in dose level cohorts 1 through 5, representing 0.1, 0.3, 1, 3 and 10 milligrams per kilogram. PRX004 was found to be generally safe and well tolerated and demonstrated pharmacokinetic profiles consistent with that of an IgG1 monoclonal antibody. Target engagement was demonstrated by a dose-dependent decrease in plasma levels of unbound misTTR, which is the misTTR not captured by PRX004, as measured by our misTTR assay. For the three patients in the 10 milligram per kilogram dose level, which was the highest dose level reported in the interim analysis, the maximum observed reductions in misTTR levels, which occurred within 24 hours of the first infusion, were 54%, 66% and 76%. And as expected, because PRX004 is designed to recognize an epitope exposed only on the misTTR species, there was no apparent impact on levels of normal tetrameric TTR. Of the 15 patients from cohorts 1 through 5, 12 patients were eligible for the long-term extension and were enrolled as of December 2019. Of the 3 patients not enrolled in the long-term extension, 2 patients were from cohort 1 were ineligible due to early termination during the escalation phase and 1 patient from cohort 2 was ineligible based on the long-term extension screening criteria. As reported in the interim analysis, no dose-limiting toxicities were observed in the escalation phase. In cohorts 1 through 5 of the escalation phase, 1 severe treatment-emergent adverse event was reported, which was a worsening of a preexisting condition deemed unrelated to PRX004 by the investigator and subsequently resolved. These interim data support continuation of the Phase I study as planned, and we expect to report additional data from our dose-escalation and long-term extension portions of the study later this year. Now I'd like to briefly discuss our early stage pipeline. We have an active discovery and preclinical pipeline that is advancing new programs to potentially address a broad spectrum of devastating diseases. Our global neuroscience collaboration with Bristol-Myers Squibb is focused on 3 discovery-stage programs, tau, TDP-43 and a third undisclosed target. All 3 of these targets are implicated in a range of neurodegenerative diseases that currently have no disease-modifying therapies, including Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis or ALS, chronic traumatic encephalopathy and progressive supranuclear palsy among them. There's a strong consensus that the type of sequential transmission that I described earlier for Parkinson's disease may also underlie the progression of several other neurodegenerative diseases. For example, transmission of pathology between different brain regions has also been proposed in Alzheimer's disease with beta amyloid and tau. More recently, cell-to-cell transmission of TDP-43 pathology has been described in ALS and frontotemporal dementia. Antibodies may be effective as disease-modifying therapies through several potential mechanisms, but we believe that preventing the uptake and seeding into healthy cells is an important step in slowing or halting disease progression. Our extensive research in this space as well as recent clinical developments in the field suggests that the efficacy of a therapeutic is likely to be dependent on the binding characteristics to selected epitopes. Once complexed with pathogenic proteins, antibodies may also promote clearance of pathogenic species via, for example, phagocytosis and perivascular clearance. The knowledge about common mechanisms of disease propagation at the molecular level and our increasing understanding of how to effectively intervene in this process enables our efforts to develop highly targeted and potent antibodies that aim to intercept the transmission process and prevent further neurodegeneration. Our preclinical tau program exemplifies our unique approach and methodology. We have tested a large number of antibodies to epitopes along the tau protein, including posttranslational modifications and found that only a few have resulted in a superior profile compared to those that have been described by other groups for their ability to block the binding of tau to neurons and prevent the downstream neurotoxic effects. We believe that understanding this biology and what may drive the efficacy of these antibodies is important to increase our confidence in selecting and optimally evaluating a clinical candidate. Last year, we initiated cell line development of a lead candidate for our tau program, and our IND-enabling studies are ongoing. We are applying a similar approach to generate clinical candidates against TDP-43 and the third undisclosed target that is part of our collaboration with Bristol-Myers Squibb. The collaboration with our colleagues at Bristol-Myers Squibb continues to be productive. As you may recall, Prothena is responsible for the execution of these programs through the preclinical and early clinical stages of development dependent upon various clinical option exercise periods by Bristol-Myers Squibb. Finally, I want to provide an update on one aspect of our early stage pipeline that we have accelerated on a number of fronts, and that is our proprietary Alzheimer's disease programs. Building on our foundational science in the discovery and development of anti-abeta antibodies and vaccines for Alzheimer's disease, we continue to be highly active in this space. As you are aware, several of our scientists were responsible for elucidating the potential causal role of misfolded proteins in Alzheimer's disease and worked on developing the first anti-abeta antibodies clinically tested. Last year on this call, we discussed our abeta discovery effort, including our proprietary novel anti-abeta antibodies that we believe may offer significant improvements for patients and their families over what can be envisioned by those currently undergoing clinical testing. We have initiated cell line development of lead candidates in this program and expect to initiate IND-enabling studies this year. Separately, we have also initiated new discovery activities on a number of our other programs in our Alzheimer's portfolio. We are very interested in the new analysis of the larger aducanumab dataset presented at CTAD in December from the EMERGE and ENGAGE studies. Those data are consistent with our belief that antibodies that target abeta protein at an optimal epitope, and in particular, antibodies with high binding streams that broadly interact with both soluble and insoluble pathological forms of the abeta protein will ultimately be a successful first step towards slowing the relentless progression of neurodegeneration in Alzheimer's disease. I've spoken about our work in tau and abeta, and I want to also emphasize how closely linked we believe these 2 proteins are in driving the pathophysiology of Alzheimer's disease and their important role in disease onset and progression. Evidence suggests Alzheimer's pathology results from a complex interplay among pathogenic tau and abeta proteins. Phosphorylated tau in the brain is a well-understood hallmark of Alzheimer's pathology associated with cognitive decline. In fact, research closely links abeta to the rapid spread of tau phosphorylation. Because of this intricate relationship between pathogenic forms of these proteins, we continue to believe that both abeta and tau play important roles in the potential treatment and prevention of Alzheimer's disease. Ultimately, we believe that interventions that target each and/or both of these proteins have the potential to reduce the clinical decline in or prevent the onset of Alzheimer's disease. As such, we are forwarding discovery activities for both antibodies and vaccines. We believe our team with its scientific expertise in diseases caused by neurological dysfunction and protein misfolding has the capabilities needed to drive transformational innovation. We look forward to providing updates on these programs as they progress. So with that said, at this time, I'll turn the call over to Tran for a discussion of our financial results. Tran?

Thanks, Gene. Today, we reported favorable 2019 cash burn from operating and investing activities of approximately $53.5 million, which was below our updated 2019 guidance of $57 million to $65 million. As of December 31, 2019, Prothena had approximately $378 million in cash, cash equivalents and restricted cash and no debt. Please refer to the press release issued today for further details regarding our fourth quarter and year-end 2019 financial results. Turning to our 2020 financial guidance, we expect the full year 2020 net cash burn from operating and investing activities to be $60 million to $76 million and to end the year with approximately $310 million in cash, which represents the midpoint of the range. The estimated full year 2020 net cash burn from operating and investing activities is primarily driven by an estimated net loss of $84 million to $106 million, which includes an estimated $23 million of noncash share-based compensation expense. With that, I'll turn the call back over to Gene to summarize our upcoming milestones. Gene?

Thanks, Tran. So as we move forward in 2020 and beyond, we expect continued progress in our pipeline and look forward to coming back to you as we have data to report. Before we talk about our upcoming milestones, I'd like to first recognize 2 groups of people who make a measurable contribution towards our ability to execute our highly ambitious goals. I want to first thank the patients and clinicians who participate in our studies. Because without their support, we could not elucidate the potential value of the new medicines we're developing. I'd like to also acknowledge and thank our very talented employees for their ongoing commitment to helping patients by advancing our science. Now turning to a summary of our R&D milestones. For prasinezumab, the last patient last visit in Part 1 of the Phase II PASADENA study took place toward the end of 2019, and we continue to expect to report results from Part 1 of the study this year. For PRX004, the Phase I study is ongoing and we expect to report additional detailed data, including data from the 30 milligram per kilogram cohort and data from the long-term extension portion of the study later this year. We are also making important advances in our discovery pipeline. We are progressing our collaboration with Bristol-Myers Squibb and expect to advance our IND-enabling activities for tau this year. We also expect to initiate IND-enabling activities for our abeta program this year. So that said, at this time, we'll open the call for questions. Joanna?

[Operator Instructions]. Your first question comes from the line of Christopher Marai from Nomura.

Congratulations on the year and a great update, appreciate that. Firstly, I was just going to hit up on perhaps PRX004 and the next data that you might release and sort of plan. I'm assuming it's too late to present it at ISA later this quarter. And then secondarily, with respect to your clinical trial plans that it seems you laid out, did I hear correctly, in polyneuropathy, you look at patients who have progressed following knockdown agents or the RNAi or tafamidis?

Thanks, Chris, for the question. So I think there's two questions there. The first was timing for more data with PRX004. And I think there, we'll be consistent with what we've done in the past. We want to make sure that we disclose additional data, notably the higher level cohort, the 30 mg per kg cohort, from the escalation phase of the study as well as some of the early long-term extension data, and we would likely do that at a scientific conference this year. As would be typical for us, we wouldn't commit to what that scientific conference would be until we've got that abstract done and accepted, and we'd let the street know at that point in time. So we don't have much more to add on that piece. I think in terms of the clinical trial plans for PRX004, what -- the way we're thinking about it at this point and I think what we tried to communicate is where we feel the residual unmet medical need is for patients with ATTR amyloidosis. And we see 2 groups of patients broadly, right? In one group, you're talking about both wild-type and hereditary ATTR patients with cardiomyopathy. And there, I think there's a significant medical need to prolong survival and have a survival benefit, particularly in patients that are in a more severe cardiomyopathy state. So these would be your New York Heart Association class III and IV patients and ultimately, potentially being able to see more rapid improvement, say, something that occurred in the first 18 months, even amongst the more milder patients. I think on the other side, when you think about polyneuropathy, what we look at here in terms of unmet need, there're a number of studies that plus or minus show that about 1/3 plus or minus, depending on the publication, of patients on silencer treatment are characterized as nonresponders and there are different ways that nonresponders are characterized. There's no standard definition of that across the field, just to be very clear. But we see, obviously, there being potential need to improve treatment for those patients as well. So that's where we see the potential need and space. And broadly, when we think about further development of PRX004, we think the depleter mechanism of action that PRX004 possesses is something that kind of lends itself well to think about both stand-alone kind of trials, where we can think about PRX004 by itself, but we can also think about it as a potential additive approach to the existing therapeutic approaches in as much as the biology is complementary and not competitive.

Okay. Great. And then just to sort of follow-up, with respect to that polyneuropathy population, is there any indication that some of those patients may have irreversible damage and that you wouldn't be able to sort of reverse it or help now even with your differentiated approach? And then lastly, when we think about you guys kicking off some of these trials, presumably sort of these 2, 3, if you will, given the [indiscernible], you started on Phase I? And what sort of timing should we think about with respect to those trials kicking off? Or would you wait for a partnership or something to that effect to get those settled?

Well, I think we will continue to look at the dose escalation data from the higher doses, and we'll look at the long-term extension data. But that being said, we'll let the data guide us in terms of ultimate timing. And clearly, some of these conversations need to be done with regulators in terms of the next steps. In terms of reaching the broadest patient population, clearly, cardiomyopathy would be a major first step, given the size of that opportunity, and hereditary neuropathy is clearly a little bit smaller or a lot smaller. But in terms of our belief in terms of reversal of damage in maybe sicker patients, I think what we -- we don't have exact data in ATTR patients to understand that and even the clinical data that's being shown hasn't really borne that out in terms of -- where we get our confidence from is we go back to our NEOD001 data in terms of our Mayo Stage IV patients, who are the sickest patients in the AL population, where, in the wild, I think there are -- the median OS is about 6 months. And then, of course, in our trial, the control arm was about 8 months. And so, of course, on our treatment side, it was not reached, I think, at a 9-month period. I think we had a hazard ratio below just 0.5.

On all-cause mortality.

That's right. On all-cause mortality. So that gives us a belief that at least in -- from a cardiomyopathy perspective, in a patient population, although different, that dies a lot sooner that you -- that we were able to intervene there with an antibody with a similar mechanism, clearly. But we'll have to continue to look for data here in the Phase I to give us that signal. We clearly like where -- what we showed at the end of the year last year, where we've showed proof of mechanism, where we've shown we can interact with the misTTR, which we believe is the pathogenic species in a very short period of time.

Your next question comes from the line of Charles Duncan from Cantor.

Thanks for that detailed update on the platform and the pipeline. I need to take another approach to trying to understand kind of news flow. I doubt you'll really be able to give us much granularity, but I'll give it a shot any way. And that is if you think about the PASADENA data, you said you anticipate data this year. And yet for PRX004, you qualified it by saying later in the year. And so I guess, I'm wondering if you anticipate updates out of PASADENA before PRX004? Or did I misread that?

No. Thanks for the question, Chaz. Yes, I mean, so right now, with PASADENA, we're saying 2020. And I think what we can do is kind of reiterate some of the timing on that. Clearly, that study was fully enrolled with 316 patients in late 2018. As I mentioned on the call, the last patient visit for Part 1 was towards the end of 2019. All that said, Roche is operationally in charge of that study. So ultimately, those time lines are theirs. And at this point, in terms of granularity, I think all we're comfortable saying is 2020. But PASADENA is -- again, just to remind everyone, PASADENA is a study that is 80% powered with -- at a one-sided alpha of 0.1 to detect a 37.5% benefit at week 52 for each of the dose levels against placebo. So it is very much a signal-detection study. It's meant to be directional and informative and really to guide us in terms of what it would take to design an appropriate Phase III, if, in fact, the data indicates that we should be moving forward. So that's where we are. And again, we can't provide any more detail than that at this point in time, but we'll be excited to see the data when it comes.

Chaz, in regards to your relative question between PRX004 and PRX002, I think you're reading too much into that. I think both datasets will land at the appropriate scientific or medical conference this year.

Okay. Okay. That's fair. And that makes sense to me. And then one additional question on prasinezumab and Part 1. Not that you need the cash, but can you remind us whether or not there could be a milestone payment with the completion of Part 1? Or would it be perhaps later in the program?

Actually, the -- we haven't disclosed the size of the milestone, but I'll give a little bit of a recap. We received a milestone for Phase 1 start, which was $15 million. And we received another milestone for initiation of Phase II, which was $30 million. We will -- if there is a Phase III and it initiates, we'll receive the third clinical milestone upon the initiation of Phase III.

Your next question comes from the line of Michael Yee from Jefferies.

Two questions. One is following up on the Parkinson's study. Could you just provide some color and thoughts around what you think is a great scenario? And what you think is -- or what do you think the key data you'd like to see and these endpoints are to support an active drug? Maybe just talk about that, and how you're thinking about it with your partner? And then the second question is a little more off the radar -- I guess, off the rails, which is, as you mentioned in your press release, you added 2 new Board members, one of which is a known biotech investor. I think there's questions around would you be thinking about monetizing assets, thinking about various forms of monetization of things? Maybe just talk to that addition to the Board. And how you guys are thinking about where that could create value and monetization of some of the assets?

Well, let's start with the first part of your question and then -- oh, you might have to remind us on the second part, but I think I know where you're going there. But in regards to PRX002 and what we would be looking for, I think it's good here to take a step back and think about the totality of data that will be produced by PASADENA. I mean, the way you can think about that, too, is Biogen, who is about 6-plus months behind us, they have a safety, tolerability, primary where they look at secondary and exploratory endpoints such as DAT-SPECT and other endpoints. It's the same thing here. I mean, although we have a primary endpoint of MDS-UPDRS, we'll be looking at the primary, select secondaries like DAT-SPECT, and of course, the digital biomarkers that are in the exploratory bucket. So we'll be looking at all of that comprehensive data to understand how to move forward to a Phase III. So I think that would be -- for us, home run data is -- we have data that we can move forward with.

I agree completely. And just -- I just want to make sure I remind everyone as well. This is not a study that was powered in a traditional way that you would power an efficacy study. This study is powered at 80%, again, with a one-sided alpha 0.1 to detect relatively large effects at 37.5%. We really are asking -- what we really are asking from this study is can we derisk the approach to a Phase III by designing an appropriate Phase III trial. And across the multiple endpoints, many of which we think could be informative, that's what we need out of the trial in order to be able to continue to move the program forward. So I think that's what we're looking for, and I think that's what anyone was thinking about how you would move this through the Phase II to Phase III setting would be thinking about.

And I think in terms of your second question regarding EcoR1 Oleg Nodelman's appointment to the Board, clearly, the Board -- it was a very welcomed addition to the Board and his decades-long expertise around financial and strategic investing is clearly very additive. And it's a perspective that the Board welcomes. In terms -- you said something about monetization. I mean, I think at the end of the day, not just Oleg, but other Board members and also the senior management team, we're going to do what's in the best interest of both patients and, of course, our shareholders as a derivative of all that. So the point is, I think he continues to be very productive for us. I think our BD efforts have actually been turned on a little bit higher to continue to add to our neuroscience pipeline, although, clearly, the major thing we'll always stick to is our expertise in neuroscience and also protein misfolding from an understanding of the biology. So that's -- we're really excited by having him on the Board, and he's been clearly very helpful. Including, we also had another addition of Paula Cobb, who has also operational expertise, ex-Biogen, and she's been very helpful and instrumental from an operational perspective, too.

Your next question comes from the line of Kennen MacKay from RBC.

This is Bikram on for Kennen. Just on the early pipeline, maybe you can elaborate on what is guiding your confidence in amyloid beta program, that would be really helpful?

Yes. Well, I mean, I think we are clearly encouraged by the October announcement from Biogen around aducanumab and further by the data that they shared at CTAD in December, particularly around the EMERGE and ENGAGE trials. I think what the data appear to indicate is that an antibody like aducanumab that would be expected to interact with both the soluble and insoluble forms of abeta that at appropriate concentrations for appropriate length of time that there may be some impact on clinical endpoints. And obviously, we'll see what happens as Biogen continues to move that program through now the regulatory process. There's a lot of unknown there, a lot to occur even this year, and we'll certainly see what happens there. Nonetheless, I think there's consistency of data now across several programs, and it encourages us that at some point, a molecule in this space will be a first entrant in the treatment of neurodegeneration in Alzheimer's disease. When we look at the slate of candidates currently undergoing clinical trial, we think, for a number of reasons, that there are opportunities to continue to push that science forward in the interest of patients and their families. One angle on that is, obviously, patient access. We think that will be a significant issue. There are some estimates that up to 35 million individuals across the world suffer from Alzheimer's disease. And with those kinds of numbers, making sure that you maximize patient access to potential useful treatments will be critical. And so we, obviously, think about that quite a bit as we think through our programs targeting abeta, including our abeta monoclonal antibodies that I discussed in the call. And as I said on the call as well, we think that tau continues to be another very important pathological driver of the cognitive decline that you see in Alzheimer's disease. I think there's a lot of literature around that, that supports that statement. And from our perspective then, understanding how intricately those 2 proteins interact with each other in the context of the disease, i.e, abeta and tau are not separate entities per se. It's known, for example, that abeta can actually lead to the phosphorylation of tau. There's a number of studies out there that look at that. And those kinds of pathways lead us to believe that approaches that target both abeta and tau are maybe a potential opportunity to continue to push treatments forward. So we see a lot of opportunity in that space. We see that opportunity around both monoclonal antibodies as well as potential vaccines, and we see the opportunity both in the treatment as well as the potential prevention of the disease.

Your next question comes from the line of Jay Olson from Oppenheimer.

Since prasinezumab is in the lead and you'll be reading out the first clinical efficacy endpoints for an alpha-synuclein antibody in Parkinson's diseases here, could you maybe comment on the potential registrational path forward? And do you expect to conduct two pivotal Phase III studies? Or do you think that you'll only be required to conduct one and maybe PASADENA could count as one of your pivotal studies?

Yes. So those are great questions and obviously, will be subject of much discussion not only with Roche, but obviously, regulators as well. I think it's premature at this point to really speculate on what a Phase III clinical program would or could look like. Clearly, we would want to do that fully informed by the Phase II data in as much as we expect it to be directionally informational in terms of how we think about those things. So I think the questions you're asking are great questions. I think it's just a little bit premature on this call to really speculate as to what regulators might require or what a fulsome Phase III program would look like.

But clearly, all of those alternatives are on the table. And Jay, they'll be data dependent. So that's a great question, but we need to have more data in order to answer that.

Your next question comes from the line of Bert Hazlett from BTIG.

Just with regard to the BMY-Celgene collaboration, could you remind us of the structure of that collaboration and the decision-making process that you'll need to go through to advance tau and TDP-43 to IND studies? And then are the same people at the table now that, that collaboration is closed? Just interested to find out a little bit more about the dynamic now that Celgene is part of BMS?

Yes. Maybe, I'll answer the last part of that question a little bit first and then get to the first part last, which is the team that's on the ground in terms of the joint steering committees are the same, and they moved on over to Bristol, which has been welcomed -- a welcomed effect. And so we're still working on a collaborative basis every day. And so we continue to move all the programs forward. From an economic and decision-making perspective, as you can recall -- well, as you do recall, we had an upfront of $100 million across 3 different targets and, of course, an equity investment of $50 million, which allowed us to take control over decision-making of how to move those 3 programs forward. In terms of how BMS -- Celgene/now BMS, we participated at IND of each of the programs, they would have the ability to opt in -- or exercise their option right for U.S. rights at IND, and then for ex U.S. rights after Phase I.. And then from there, they can choose one way or the other, but they can choose to basically operate the program from there in terms of execute the Phase IIs and the Phase IIIS, depending on the clinical plan going forward. And then, of course, there's downstream clinical, regulatory, first commercial sale, and then we have royalties after that. So that's kind of how it all is both governance and economically spread between the three programs.

I'm showing no further questions at this time. I would now like to turn the conference back to you, Mr. Gene Kinney, CEO.

Thanks, Joanna. Appreciate it. And thank you all for joining us this afternoon. We appreciate your interest in Prothena, and we look forward to sharing future updates on our programs. Thank you.

Ladies and gentlemen, this concludes today's conference. Thank you for participation, and have a wonderful day. You may all disconnect.