Q4 2023 Prothena Corporation PLC Earnings Call

Operator: Thank you. Thank you. Good morning, ladies and gentlemen, and welcome to the Prothena Biosciences fourth quarter and full year 2023 financial results conference call. My name is Krista, and I will be your coordinator for today. At this time, all participants are in a listen-only mode.

Good day, ladies and gentlemen, and welcome to the protein up Biosciences fourth quarter and full year 2023 financial results Conference call. My name is Christa and I will be your coordinator for today at this time all participants are in a listen only mode. We will be facilitating a question and answer session.

Operator: We will be facilitating a question and answer session towards the end of today's call. If at any time during the call you require assistance, please press star, then zero, and a coordinator will be happy to assist. I would now like to turn the presentation over to Mark Johnson, Vice President of Investor Relations at Prothena. Please proceed. Thank you, Operator. Good afternoon, everyone, and welcome to today's call to review Prothena's business progress, fourth quarter and full year 2023 financial results, and 2024 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 8K filed today with the SEC. In addition, we are using supplemental slides, which are available on our investor website, events, and presentation section.

Towards the end of todays call if at any time during the call you require assistance. Please press Star then zero and a coordinator will be happy to assist you I would now like to turn the presentation over to Mark Johnson, Vice President of Investor Relations at Christina Please.

Proceeds.

Mark Johnson: Thank you operator, good afternoon, everyone and welcome to today's call to review proteins business progress fourth quarter and full year 2023 financial results and 2024 financial guidance.

Mark Johnson: Please review the press release, we issued earlier today, which is available on our website at Brooklyn at Dotcom and is also attached to a form 8-K filed today with the SEC. In addition, we're using supplemental slides, which are available on our investor website events and presentations section.

Speaker Change: On today's call Dr Gene Kinney, our pres.

Mark Johnson: On today's call, Dr. Gene Kinney, our President and Chief Executive Officer, will provide opening remarks, including an overview of Prothena's corporate and development strategy. Then, Brandon Smith, our Chief Operating Officer, will provide an update on our pre-commercial progress for our wholly-owned Britannia MAT program, which is in Phase 3 for the treatment of patients with Mayo Stage 4 ALM-Lidocaine. Dr. Hideki Garan, our Chief Medical Officer, will provide an update on our ongoing clinical program. John Nguyen, our Chief Financial Officer and Chief Strategy Officer, will then discuss our 2023 financial results and 2024 financial guidance before turning it back to Gene for closing remarks, at which point we will open up the call for a Q&A session. Before we begin, I would like to remind you that during today's presentation, we will be making forward-looking statements that are subject to certain risks, uncertainties, and other factors that could cause actual results to differ materially from those referred to in any forward-looking statement. For a discussion of the risks and uncertainties associated with our forward-looking statements, please see our press release issued today, as well as our most recent filings with the FBI. We disclaim any obligation to update our forward-looking statement.

Speaker Change: And Chief Executive Officer, who will provide opening remarks, including an overview of protein at corporate and development strategy and Brandon Smith, our Chief operating officer, who will provide an update on our pre commercial progress for our wholly owned for Panamax program, which is in phase III for the treatment of patients with Mayo stage for al Amyloidosis.

Doctor Hideki Guerin, our Chief Medical Officer will provide an update on our ongoing clinical programs Trung Nguyen, our Chief Financial Officer, and Chief Strategy Officer will then discuss our 2023 financial results and 2024 financial guidance before turning it back to Jim for closing remarks at which point, we will open up the call for a Q&A session.

Speaker Change: Before we begin I would like to remind you that during today's presentation, we will be making forward looking statements that are subject to certain risks uncertainties and other factors that could cause actual results to differ materially from those referred to in any forward looking statements.

Speaker Change: For a discussion of the risks and uncertainties associated with our forward looking statements.

Speaker Change: See our press release issued today as well as our most recent filings with the SEC, we disclaim any obligation to update our forward looking statements with that I'd like to turn the call over to Jim.

Mark Johnson: With that, I'd like to turn the call over to Mark. And thank you all for joining us today to review our 2023 financial results and business highlights. Let's begin with slide five.

Thank you Mark and thank you all for joining us today to review, our 2023 financial results and business highlights.

Jim: Let's begin on slide five.

Dr. Gene Kinney: Our mission at Prothena is to create transformational therapies addressing significant unmet medical needs for the millions of patients and their loved ones that are affected by devastating diseases caused by protein dysregulation. That mission is enabled by our deep scientific expertise, which serves as a unifying thread connecting our corporate strategy, our portfolio development, and the dedication that propels Prothenians every day. We continue to advance our mission, which has fueled our robust late-stage clinical pipeline, moving us closer to becoming a fully integrated commercial biotechnology. As a result of our commitment to our mission, we have created a robust portfolio of therapeutic drug candidates targeting both neurodegenerative and rare peripheral amyloid diseases, as shown on slide 6. Our portfolio includes four wholly owned programs and five partner programs.

Jim: Our mission at pristine is to create transformational therapies addressing significant unmet medical needs for the millions of patients and their loved ones that are affected by devastating diseases caused by protein dysregulation.

That mission is enabled by our deep scientific expertise, which serves as a unifying thread connecting our corporate strategy, our portfolio development and the dedication that propels Fresenius every day.

We continue to advance our mission, which has fueled our robust late stage clinical pipeline moving us closer to becoming a fully integrated commercial biotechnology company.

Jim: As a result of our commitment to our mission, we have created a robust portfolio of therapeutic drug candidates targeting both neuro degenerative and rare peripheral amyloid diseases as shown on slide six.

Jim: Our portfolio includes four wholly owned programs and five partner programs.

Dr. Gene Kinney: This intentional mix allows us to advance a fullsome portfolio by leveraging the benefits of working with key strategic partners on some programs while still maintaining the full upside potential for our wholly owned programs where we feel that we have unique insights and expertise. I'll discuss four of our ongoing clinical programs on the next slide, PRX12, Pertamumab, Presinezumab, and NNC6019. But first, I'd like to highlight the exciting progress across our earlier stage program. In July of 2023, we presented compelling preclinical results in a late-breaker poster presentation at AAIC for PRX123, our dual A-beta-tau vaccine program. And by year-end 2023, PRX123 received IND clearance and FastTrack designation from the FDA. Additionally, our ongoing neuroscience R&D collaboration with BMS made meaningful advancements in 2023 and into this year. BMS 986446, formerly PRX005, is a potential best-in-class antibody for the treatment of Alzheimer's disease that specifically targets a key epitope within the microtubule-binding region of tau.

Jim: This intentional mix allows us to advance a fulsome portfolio by leveraging the benefits of working with key strategic partners in some programs, while still maintaining the full upside potential for our wholly owned programs, where we feel that we have unique insight and expertise.

I'll discuss four of our ongoing clinical programs on the next slide <unk> 12 per gamma Mab person doesn't map and NMC $6 19.

Jim: But first I'd like to highlight the exciting progress across our earlier stage programs.

Jim: In July of 2023, we presented compelling preclinical results in a late breaker poster presentation at AIC for <unk> three our dual a beta Tau vaccine program.

Jim: And by year end, 2023, and <unk> three received IND clearance and fast track designation from the FDA.

Jim: Our ongoing neuroscience R&D collaboration with BNS made meaningful advancements in 2023 and into this year.

Jim: BMS 980, 6446, formerly <unk> five as a potential best in class antibody for the treatment of Alzheimer's disease that specifically targets the key epitope within the microtubule binding region of Tau.

Dr. Gene Kinney: In 2023, CMS opts into the global rights for this program with an additional milestone payment of $55 million and announced that the Phase I data supports advancing the program into a Phase II clinical trial in 2024. Additionally, for PRX-19, a potential best-in-class antibody for the treatment of neurodegenerative disease. We recently received FDA clearance for the IND application for this program as well. This is the second of three programs in our BMS collaboration. We remain well-funded to execute on our strategic objectives, taking us well beyond our upcoming clinical readout. As you will hear about in more detail later in this call, we ended 2023 with a strong cash position of $621 million. Moving now to slide seven.

In 2023 P. M S opted into the global rights for this program with an additional milestone payment of $55 million and announced that the phase one data supports advancing the program into a phase II clinical trial in 2024.

Jim: And prepare up 19, a potential best in class antibody for the treatment of Neurodegenerative diseases.

Jim: Recently received FDA clearance for the Iot application for this program as well.

Jim: This is the second of three programs in our BMS collaborations.

We remain well funded to execute on our strategic objectives, taking us well beyond our upcoming clinical readouts.

Jim: As you will hear about in more detail later in this call. We ended 2023 with a strong cash position of $621 million.

Jim: Moving now to slide seven.

Dr. Gene Kinney: Our clinical expertise and differentiated approach enables us to advance best-in-class and or first-in-class therapies that have the potential to transform the treatment landscape for protein dysregulation diseases. Today, I'd like to focus on four clinical programs that are nearing significant inflection points within the next 12 to 18 months. First, I'll discuss our wholly-owned programs, PRX-12 and Pertamumab, and then move on to our partner programs, Prasanesimab with Roche and NNC 6019 with Nova Nordisk. PRX-12 is our next generation investigational treatment for Alzheimer's disease, which targets a key epitope at the amino terminus of amyloid beta with high binding potency.

Jim: Our clinical expertise and differentiated approach enables us to advance best in class <unk> first in class therapies that have the potential to transform the treatment landscape for protein Dysregulation diseases.

Jim: Today I'd like to focus on the four clinical programs that are nearing significant inflection points within the next 12 to 18 months.

Jim: First I will discuss our wholly owned programs <unk> 12 and per cameraman.

Jim: And then move on to our partnered programs pressing doesn't map with Roche and NMC 16, 19 with Novo Nordisk.

Jim: <unk> 12 is our next generation investigational treatment for Alzheimer's disease, which targets the key epitope amino terminus of amyloid beta with high binding potency.

Dr. Gene Kinney: PIRX 12 was designed with the patient in mind, and we believe it has the potential to be best in class, transforming the treatment of Alzheimer's disease by meaningfully reducing the treatment burden associated with the currently available antibiotic therapy. Based on our market research, we understand that a treatment with similar efficacy and safety to currently approved anti-beta therapies but delivered as a once-monthly at-home subcutaneous treatment has the potential to be a dominant player in the market. In 2023, we presented compelling preclinical data at ADPD and AAIC, demonstrating that PRX12 binds to amyloid plaques with high avidity.

Parents 12 was designed with the patient in mind and we believe it has the potential to be best in class transforming the treatment of Alzheimer's disease by meaningfully reducing treatment burden associated with currently available anti a beta therapies.

Jim: Our market research, we understand that a treatment with similar efficacy and safety. The currently approved anti a beta therapy, but delivered as a once monthly at home subcutaneous treatment has the potential to be the dominant player in the market.

In 2023, we presented compelling preclinical data ADP D and the AIC.

Jim: <unk> 12 lines to amyloid plaques with high avidity.

Dr. Gene Kinney: PRX12 is currently being evaluated in a double-blind, placebo-controlled Phase 1 trial with the goal of identifying an optimal dose level or levels for a registration-enabling trial. The preclinical data, combined with the initial clinical data from our ongoing Phase 1 trial, are supportive of a once-monthly subcutaneous treatment with a potential best-in-class profile. Pertamomab seeks to address the high risk of early mortality that remains an urgent unmet medical need for patients with Mayo Stage 4 AL amyloidosis through its differentiated depleter mechanism, which is designed to clear accumulated amyloid and neutralize toxic light chain aggregates that are thought to cause organ dysfunction and failure. We are conducting the confirmatory phase 3 AFFIRM-AL clinical trial, evaluating Tamimab in We expect top-line results between the fourth quarter of 2024 and the second quarter of 2025.

Jim: Peter It's 12 is currently being evaluated in a double blind placebo controlled phase <unk> trial with the goal of identifying an optimal dose level or levels for a registration enabling trial.

Jim: The preclinical data combined with the initial clinical data from our ongoing phase one trial are supportive of a once monthly subcutaneous treatment with a potential best in class profile.

Jim: For Tim on that seeks to address the high risk of early mortality that remains an urgent unmet medical need for patients with Mayo stage for al amyloidosis through its differentiated depleter mechanism, which is designed to clear accumulated amyloid and neutralize toxic light chain aggregates that are thought to cause organ dysfunction and failure.

Jim: We are conducting the confirmatory phase III affirm <unk> clinical trial evaluating <unk> in patients with Mayo stage for Al Amyloidosis under a special protocol assessment or Spa agreement with the FDA with a primary endpoint of all cause mortality at an unprecedented significance level of zero.

Jim: One zero.

We expect topline results between the fourth quarter of 2024 in the second quarter of 2025.

Dr. Gene Kinney: Prasonezumab is an antibody for the potential treatment of Parkinson's disease designed to target a key epitope within the C-terminus of alpha-synuclein and is the focus of a worldwide collaboration with Roche. Roche is currently conducting the Phase 2b PDOVA clinical trial in patients with early Parkinson's. Roche completed enrollment in this trial in the first quarter of this year and expects to report top-line data later this year. And finally, NNC6019 is an amyloid depleter antibody for the potential treatment of ATTR cardiomyopathy. Novo Nordisk is currently conducting an ongoing phase 2 signal detection trial in patients with ATTR cardiomyopathy.

Jim: <unk> is an antibody for the potential treatment of Parkinson's disease designed to target a key epitope within the fee terminix about the nucleus and is the focus of a worldwide collaboration with Roche.

Jim: Roche is currently conducting the phase III <unk> clinical trial in patients with early Parkinson's disease.

Jim: Roche completed enrollment of this trial in the first quarter of 2023 and expects to report topline data later this year.

Jim: And finally I didn't see $6 19 is an amyloid depleter antibody for the potential treatment of <unk> cardiomyopathy.

Novo Nordisk is currently conducting an ongoing phase II signal detection trial in patients with HCR cardiomyopathy.

Dr. Gene Kinney: The trial has fully recruited its patients, with top-line results expected in the first half of next year. This is an exciting year of clinical trial execution for both Prothena and our strategic partners. As we look ahead, we are also thoughtfully building out our commercial leadership and market insights for Burkham. So to provide a little more context on our pre-commercial efforts, I will now turn the call over to Brandon.

Jim: The trial is fully recruited patients with topline results expected in the first half of next year.

Jim: This is an exciting year of clinical trial execution for both procedures and our strategic partners.

Jim: As we look ahead, we are also thoughtfully building out our commercial leadership and market insights for Canada. So to provide a little more context on our pre commercial efforts I will now turn the call over to Brandon Brandon.

Brandon Smith: Thanks, Gene. Moving on to slide 9. As we continue executing on our ongoing confirmatory phase 3 AFIRM-AL clinical trial, we are focused on building out our commercial capabilities to support Bertamomab as our first potential commercial product. Among patients with AL amyloidosis, a rare, progressive, and fatal disease, newly diagnosed individuals with significant cardiac involvement, such as Mayo Stage 4, are at the highest risk for early mortality. This remains a serious unmet need for patients and their families.

Brandon Smith: Thanks, Jan moving to slide nine.

Brandon Smith: As we continue executing on our ongoing confirmatory phase III affirm a clinical trial, we are focused on building out our commercial capabilities to support per Kevin that as our first potential commercial product.

Brandon Smith: Among patients with al amyloidosis, a rare progressive fatal disease newly diagnosed individuals with significant cardiac involvement touches Mayo stage four alright at the highest risk for early mortality. This remains a serious unmet need for patients and their families for Tim that is the only candidate to have shown a survival benefit.

Brandon Smith: Pertamumab is the only candidate to have shown a survival benefit in patients with Mayo Stage 4 AL amyloidosis in a randomized clinical trial, our previous Phase 3 vital trial. The ongoing confirmatory AFFIRM-AL trial was designed based on a spot agreement with the FDA to approve Pertamibab at a P-value of less than or equal to 0.1 for the primary endpoint of all-cause mortality Showing an early and sustained impact on mortality is a powerful differentiator, and if approved, we are confident that Pertamibab will be welcomed as a major advancement in the field and a key treatment option. Moving to slide 10.

Brandon Smith: With Mayo stage for Al Amyloidosis in a randomized clinical trial, our previous phase III <unk> trial.

Brandon Smith: The ongoing confirmatory affirm El trial was designed based on our Spa agreement with the FDA to approve preterm birth, and a P value of less than or equal to 0.1 for the primary endpoint of all cause mortality.

Brandon Smith: Showing an early and sustained impact on mortality is a powerful differentiator and if approved we are confident that will be welcomed as a major advancement in the field and a key treatment option.

Brandon Smith: Moving to slide 10.

Brandon Smith: The market dynamics for Bertamometh as our potential first commercial product are quite compelling. Our plan is to independently commercialize Bertamometh, and we believe that we will be able to efficiently reach prescribers for advanced patients with a focused commercial presence. This is a rare disease patient population with a targeted call point where hematologists with support from specialized cardiologists are the primary treating specialists.

Brandon Smith: The market dynamics for timber that is our potential first commercial product are quite compelling. Our plan is to independently commercialize for Kevin Matt and we believe that we will be able to efficiently reach prescribers for advanced patients with a focused commercial presence.

Brandon Smith: This is a rare disease patient population with a targeted call point or Hematologists, we support from specialized cardiologist at the primary treating specialists.

Brandon Smith: KOLs in the community at large recognize the urgent need for treatment that improves survival in patients with AL amyloidosis who are at high risk for early mortality. Based on epidemiological studies, we estimate there are over 20,000 patients with Mayo Stage 4 AL-amyloidosis across the major markets, including the United States, Europe, China, Brazil, and Japan. This is further supported by our claims data analysis to identify patients who are actively receiving treatment for AL amyloidosis in the United States. Based on this, we believe there are approximately 4,000 male stage 4 patients in the U.S. In addition, our U.S. and European market research indicates that approximately 75% of patients are treated in approximately 500 centers of excellence and amyloidosis specialty centers, usually within academic hospitals.

Brandon Smith: Kols and the community at large recognize the urgent need for treatments that improve survival in patients with al amyloidosis or at high risk for early mortality.

Brandon Smith: Based on Epidemiology studies, we estimate there are over 20000 patients with Mayo stage for al amyloidosis across the major markets, including the United States, Europe, China, Brazil, and Japan.

Brandon Smith: It is further supported by our claims data analysis to identify patients who are actively receiving treatment for al amyloidosis in the United States based on this we believe there are approximately 4000 Mayo stage four patients in the U S.

Brandon Smith: In addition, our U S and European market research indicates that approximately 75% of patients are treated at approximately 500 centers of excellence in amyloidosis specialty centers, usually within the academic hospitals.

Brandon Smith: Our team continues to build upon the existing relationships we've established with key opinion leaders (KOLs) and experts in the field through our extensive clinical programs for Birtamomab. We will continue to collaborate with these key opinion leaders and experts, along with organizations that publish treatment guidelines, such as NCCN and the International Society of Amyloidosis, to ensure they are fully aware of and informed about Birtamomab. This includes continuing to present our data at top medical congresses and publications in peer-reviewed journals. Today, we are building our commercial leadership team thoughtfully as we prepare for launch. I'll now turn it over to Zach to review our clinical program. Thank you, Brandon.

Brandon Smith: Our team continues to build upon the existing relationships, we've established with Kols and experts in the field through our extensive clinical programs for <unk>.

Brandon Smith: We need to collaborate with these kols and experts along with the organizations that published treatment guidelines, such as end CCN and the international Society of amyloidosis to ensure they are fully aware of and informed about prepayment about this.

Brandon Smith: This includes continuing to present, our data at medical Congresses and publications in peer reviewed journals today, we are building our commercial leadership team thoughtfully as we prepare for launch.

Speaker Change: I'll now turn it over to the executive to review our clinical programs.

Speaker Change: Yeah.

Dr. Hideki Garan: Let's continue with the TAMIM lab and review the results of our previous vital trial, which were published in the ASH peer-reviewed journal, Blood, last year. Importantly, we observed a survival benefit in the subset of approximately 30% of patients who are categorized as male phage 4-based. A Kappa Mai curve illustrating the separation is shown here on slide 12.

Speaker Change: Thank you Brandon, let's continue with <unk> and review the results for our previous vital trial, which we're publishing to Ash peer reviewed journal blood last year.

Speaker Change: Importantly, we observed a survival benefit in the subset of approximately 30% of patients who were categorized of Mayo stage for baseline a.

Speaker Change: Capital micro illustrating the separation is shown here on slide 12.

Dr. Hideki Garan: Demonstrating an early and sustained benefit, In this high-risk group, we observed a survival benefit, favoring Tamimab, reflecting approximately a 60% relative reduction of all-cause mortality, at a p-value of 0.021. This was further supported by meaningful and significant improvements in function, as measured by six-minute walk tests and quality of life, as measured by SS30. Turning to slide 13, expand on Brandon's earlier remarks. Based on our extensive analysis of the vital data, as well as further confirmation of the data with external statistical experts and leading positions in the field, we actively engage with the FDA to align on the path towards regulatory success with the Tandem Act. A spot was agreed to between Prothena and the FDA for the confirmatory phase three of the firm AL clinical trial, to be conducted in patients with AL amyloidos This is a time-to-event trial, and patients are randomized two-to-one to receive them for standard care or placebo for standard care at the end of 2023, based on a predetermined number of mortality.

Demonstrating an early and sustained benefit.

Speaker Change: In this high risk group.

Speaker Change: Serves a survival benefit savings <unk>, reflecting approximately 60% relative reduction of all cause mortality at.

Speaker Change: At a P value of 0.0 to one.

Speaker Change: This was further supported by a meaningful and significant improvements in function as measured by six minute walk test and quality of life as measured by SF 36.

Speaker Change: Okay.

Speaker Change: Turning to slide 13.

Speaker Change: Expand on Brandon's earlier remarks based on our extensive analysis of the final data as.

Speaker Change: As well as further confirmation of the data with external statistical experts and leading positions in the field.

Speaker Change: We actively engaged with the FDA to align on the path towards regulatory success for preterm birth.

Speaker Change: The start was agreed to between casino and the FCA for the confirmatory phase III clinical.

Speaker Change: Clinical trial.

Speaker Change: We conducted in patients with al amyloidosis.

Speaker Change: <unk> Mayo stage for baseline.

Speaker Change: With a pre agreed upon significance level of alpha less than or equal to 0.10.

Speaker Change: The primary endpoint of all cause mortality.

Speaker Change: This is a time to event trial and patients are randomized two to one on for Ken.

Speaker Change: Standard of care.

Speaker Change: Placebo plus standard of care.

At the end of 2023 based on a predetermined number of mortality events.

Dr. Hideki Garan: We were able to estimate that top-line results of the firm AL will be available between the fourth quarter of 2024 and the second quarter of 2025. We very much look forward to the results of this trial, moving us one step closer to getting this treatment to patients and families in need. Let's discuss PRX12, our potential best-in-class anti-amyloid beta treatment, starting on slide 14. We believe that PRX12 could be a treatment for early Alzheimer's.

Speaker Change: We've been able to estimate that top line results from <unk> will.

Speaker Change: It will be available between the fourth quarter of 2024 and second quarter of 2025.

Speaker Change: We very much look forward to the results of the trial moving us one step closer to getting this treatment to patients and families in need.

Speaker Change: Let's discuss <unk>, our potential best in class MTM going better treatment starting on slide 14.

Speaker Change: We believe that <unk> can be best in class anti amyloid beta treatment for early Alzheimer's disease.

Dr. Hideki Garan: In order to achieve this target product profile, we need to establish efficacy, convenience, and safety. TRX-12 was intentionally designed with the antibody attributes required to achieve a similar or better efficacy and safety profile to currently approved antivenom therapy, with clear differentiation as being administered, in a much more convenient and accessible once-monthly, at-home, self-contained trip. KRX-12 is a humanized IgG1 monoclonal antibody designed to provide a longer half-life than approved anti-invasive treatments with low immunogenicity. We've demonstrated highly potent binding hyphenate inversity and a slow off rate allowing for consistent target engagement, all of which are optimal for once monthly subcutaneous treatment.

Speaker Change: To achieve this target product profile, we need to establish efficacy convenience and safety.

Speaker Change: Sure. It's 12 was intentionally designed with the antibody attributes required to achieve a similar for.

Speaker Change: Or better efficacy and safety profile.

Speaker Change: Currently approved anti <unk> therapies.

With a clear differentiation.

Speaker Change: Administered in.

Speaker Change: In a much more convenient and accessible once monthly at home.

These treatments.

Speaker Change: Sure. It's 12, the humanized IGD, one monoclonal antibody designed to provide a longer half life and improved anti VEGF treatments with low immunogenicity.

We have demonstrated a highly potent binding hyatt <unk> and <unk> and a slow off rate, allowing for target engagement.

Speaker Change: All of which are optimal for once monthly subcutaneous treatment.

Dr. Hideki Garan: The ongoing PRF-12 Phase 1 trial, which we will discuss on slides 15 and 16, is designed to demonstrate a potential best-in-class profile in the clinic. Moving to slide 15, Assent 1 is our double-blind placebo-controlled single dose clinical trial evaluating PRx12 in healthy volunteers and participants with early Alzheimer's. The trial enrolled approximately eight participants per single steady-dose cohort, randomized three-to-one to receive a single subcutaneous dose of PRX12 or placebo and doses ranging from 70 to 400 milligrams. Moving on to the multiple setting dose cohorts on slide 16. Ascent 2 is our double-blind placebo-controlled, multiple ascending-dose clinical trial evaluating PRx12 in people with early Alzheimer's disease. Each NADD cohort is randomized 3-to-1 to receive PRX12 or placebo once monthly for six months at multiple dose levels. The objectives of the trial are twofold.

Speaker Change: The ongoing charge 12 phase one trial, which we will discuss on slide 15 and 16.

Speaker Change: It demonstrates the potential best in class profile into clinic.

Speaker Change: Moving to slide 15.

Speaker Change: One is our double blind placebo controlled single ascending dose clinical trial.

Calibrating PRC 12 in healthy volunteers and participants with early Alzheimer's disease.

Speaker Change: The trial enrolled approximately eight participants per single ascending dose cohort randomized three to one to receive a single subcutaneous dose of <unk> 12 or placebo.

Speaker Change: Doses ranging from 70 to 400 milligrams.

Speaker Change: Moving on to the multiple ascending dose cohorts on slide 16.

Speaker Change: Two is our double blind placebo controlled multiple ascending dose clinical trial evaluating <unk> in people with early Alzheimer's disease.

Speaker Change: Each match cohort is randomized three to one to receive <unk> or placebo once monthly for six months and multiple ascending dose level.

Speaker Change: The objectives of the trial are twofold.

Dr. Hideki Garan: One is to evaluate the safety, tolerability, immunogenicity, pharmacokinetics, and pharmacodynamics of PRX-12 in patients with early Alzheimer's, and two is to find the optimum dose level or levels for the registration-enabling clinical trial. There are a couple of key aspects to the MADD trial design that I'd like to highlight today. Participants are assigned to two groups of cohorts based on their APOE4 status, which we refer to as APOE4 A cohorts or B cohorts?

Speaker Change: One is to evaluate the safety Tolerability Immunogenicity pharmacokinetics and pharmacodynamics PRC 12 in patients with early Alzheimer's disease.

Speaker Change: And two is to find the optimal dose level four levels for a registration enabling clinical trial.

Speaker Change: There are a couple of key aspects to them that trumps line that I would like to highlight today.

Speaker Change: Participants are assigned to two groups of course based on April <unk> status, which referred to as.

Speaker Change: Cohorts four vehicles.

Dr. Hideki Garan: Participants in the A cohorts are either APOE4 non-carriers or heterozygous carriers. Each of these eight cohorts is evaluating approximately 32 participants with early Alzheimer's disease, in doses ranging from 45 to 400. In addition, we are evaluating A4-E4 homozygous carriers with separate D-cords for approximately 12 participants with early Alzheimer's, in doses ranging from 45 to 200 milligrams.

Speaker Change: Participants may eight cohorts are either April <unk>, non carriers or heterozygous carriers.

Speaker Change: Each of these cohorts is evaluating approximately 32 participants with early Alzheimer's disease.

Speaker Change: Ranging from 45 to 400 milligrams.

Speaker Change: In addition, we are evaluating April equal homozygous carriers with separate fee courts.

Speaker Change: Approximately 12 participants with early Alzheimer's disease and dose range from 45 to 200 milligrams.

Speaker Change: Following the first six months, which is placebo control.

Dr. Hideki Garan: Following the first six months, which is placebo-controlled, participants previously taking PRX-12 or placebo are eligible to receive an additional six-month dose of PRX-12 in an optimal legal extension. We have completed all stat cohorts and the double-blind portion of the initial 70 milligram MAD-A cohort. The Phase 1 clinical trial continues as planned, as the initial data supports once-monthly subcutaneous treatment and dose escalation in additional cohorts. We look forward to evaluating the full exposure-response relationship of PRX12 and expect to update you later this year. Turning now to President Zimab on slide 17.

Speaker Change: Frequency, taking <unk> 12 of CLO are eligible to receive an additional six monthly doses of <unk> and also nimble extension.

Speaker Change: We have completed all sad cohorts and the double blind portion of the initial 70 milligram, Matt a cohort the phase one clinical trial continues as planned as the initial data supports once monthly subcutaneous treatment and dose escalation and additional cohorts.

Speaker Change: We look forward to evaluating the full exposure response relationship of PX 12, and expect to update you later this year.

Speaker Change: Turning now to <unk> on slide 17.

Dr. Hideki Garan: President Inzamad, the first anti-alpha-synuclein antibody to demonstrate slowing the progression of Parkinson's disease in Phase 2 trials. Our partner, Roche, previously presented data from the Phase 2 PASADENA trial showing Prothenismab reduced one-year motor progression by 35%, as measured by the MDS-UPDRS Part 3, a scale of motor dysfunction in comparison to placebo. Roche continues to provide meaningful updates on the ongoing open-label extension from the trial, including recently at the Movement Disorders Society Congress in August. This brochure compares three-year progression of motor science in the Pasadena-Prasenetzma population with a propensity score balance cohort of real-world data from the Park Progression Markers Initiative, or PPMI. The Prozenizumab population shows 63% slowing progression, as measured by the MDS UPDRS Part 3 in the Early Start Progenizumab population as compared to the real-world data cohort. These data continue to support Prothena's potential effects on delaying motor progression in parking.

First anti Alpha <unk> antibody to demonstrate joined the progression on measures with Parkinson's disease in phase II trial.

Speaker Change: Our partner Roche previously presented data from the phase II Pasadena trial, showing pleasant has not reduced one year monitor progression by 31% as measured by the <unk> part III.

Speaker Change: The scale of motor function in comparison to placebo.

Speaker Change: Roche continues to provide meaningful updates on the ongoing open label extension from the trial.

Speaker Change: Including recently at the movement Disorder Society Congress in August.

Speaker Change: Roche compares three year progression of motor science, and the captivate presidents in that population.

Speaker Change: With a propensity score balanced cohort of real world data from the Parkinson's progression markers initiative for <unk>.

Speaker Change: The problem isn't that population of 62% slowing progression.

Speaker Change: As measured by the Mds <unk> part three.

Speaker Change: Early start president is in that population as compared to the real world data cohort.

Speaker Change: These data continue to support president <unk> potential effects on demand multi progression in Parkinson's disease.

Dr. Hideki Garan: Baroche has advanced President's Map into the Phase 2b Podoba trial, which is a double-blind placebo-controlled trial evaluating 586 patients with Early Parking. Participants are advised one-to-one to receive President's Map or placebo every four weeks for at least 18 months, and announced they have completed enrollment in the first quarter of 2023. The primary endpoint is time to clinically meaningful progression on motor signs of the disease, as assessed by a five-point or greater increase in the MDS UPDRS Part 3 from baseline. This disease progression may be correlated to meaningful worsening on the clinical global impression improvement scale. Roche expects to report top-line data from the Silver Trial later this year. Moving to NNC 6019 on slide 18.

Roche has advanced into.

Speaker Change: And to the phase III <unk> trial.

Speaker Change: It is a double blind placebo controlled trial evaluating <unk> 586 patients with.

Speaker Change: With early Parkinson's disease.

Speaker Change: Participants are randomized one to one to receive president's map or placebo every four weeks for at least 18 months.

Speaker Change: Roche announced they have completed enrollment in the first quarter of 2023.

Speaker Change: The primary endpoint is time to clinically meaningful progression on motor signs of the disease.

Speaker Change: As assessed by a five point or greater increase in the Mds <unk> part III from baseline.

This disease progression may be correlated with meaningful worsening on the clinical global impression of improvement scale.

Speaker Change: Roche expects to report topline data from the devote trial later this year.

Speaker Change: Moving to NMC six through nine months on slide 18.

Dr. Hideki Garan: MNC6019 is being developed by Novo Dornisk as a potential first-in-class amyloid depleter antibody for the treatment of ATTR cardiomyopathy. This is a rare, progressive, and fatal disease characterized by depositions of abnormal non-native forms of TTR protein and amyloid in vital organs, and NC6019 is thought to deplete both deposited amyloid and circulating non-native TTR to prevent further deposition and improve organ function. This mechanism in action has the potential to provide benefits for ATTR patients at high risk for early mortality due to amyloid deposition in vital organs. Nolan Nordisk is progressing this program in ongoing double-blind placebo-controlled signal detection phase 2 clinical trials. The trial has completed recruitment, and Noble estimates primary completion in the first half of 2025. Now I'd like to turn the call over to Tron for a discussion of our 2022 financial performance and our 2024 financial guidance. Ka

Speaker Change: And then C 69 is being developed by Novo Nordisk is the potential first in class Analogic leader antibody for the treatment of <unk> cardiomyopathy.

Speaker Change: This is a rare progressive fatal disease characterized by deposition of our normal non native forms of GTR protein and amyloid in vital organs.

Speaker Change: And then <unk> 600, <unk> hundred nine is thought to keep both deposited amyloid fluctuating nominated GTR.

Speaker Change: Further definition to improve organ function.

Speaker Change: This mechanism of action has the potential to provide medicine for <unk> patients at high risk for early mortality due to amyloid deposition in vital organs.

Speaker Change: Novo Nordisk can progressing this program and ongoing double blind placebo controlled.

Speaker Change: Detection phase II clinical trial.

Speaker Change: The trial has completed recruitment and noble estimated primary completion in the first half of 2025.

Speaker Change: Now I would like to turn the call over to Tran for a discussion of our 2022 financial performance and our 2024 financial guidance.

Tran: Uh huh.

John Nguyen: Thanks, Hideki. Today, we reported financial results that were favorable to our 2023 financial guidance. Please refer to our press release for a detailed breakdown of our financial results. As Gene mentioned during his opening remarks, our robust portfolio of wholly-owned and strategically partnered programs allows us to leverage partner payments while still maintaining the full upside potential of our wholly-owned programs. In 2023, BMS opted in to secure its global rights for BMS 986446, formerly known as PRX5, for $55 million. In terms of our 2023 financial performance relative to guidance, we had net cash used in operating and investing activity of $136.7 million, which was favorable to our guidance range of $148 to $161 million. The net loss was $147 million, which was favorable to our guidance range of $153 to $171 million.

Tran: Thanks for that.

Tran: Today, we reported financial results that were favorable to our 22023 financial guidance. Please refer to our press release for a detailed breakdown of our financial results as gene mentioned during his opening remarks, our robust portfolio of wholly owned and strategically partnered programs allows us to leverage partner payments while still.

Tran: Maintaining full upside potential of our wholly owned programs.

Tran: In 2023, BMS opted into the cure their global rights for BMS 980, 6446, formerly known as <unk> five.

Tran: $455 million.

Tran: In terms of our 2023 financial performance relative to guidance, we had net cash used in operating and investing activity of $136 7 million, which was favorable to our guidance range of $148 million to $161 million.

Net loss was $147 million.

Which was favorable to our guidance range of $153 million to $171 million.

Tran: As of December 31, 2023 casino had $621 million in cash cash equivalents and restricted cash which is favorable to our guidance of $600 million.

Tran: As of February nine 2024 for Athena had approximately $53 7 million ordinary shares outstanding.

John Nguyen: As of December 31st, 2023, Prothena had $621 million in cash, cash equivalents, and restricted cash, which is favorable to our guidance of $600 million. As of February 9, 2024, Prothena had approximately 53.7 million ordinary shares outstanding. Additionally, we continue to have a simple capital structure with zero debt. Turning to our 2024 financial guidance on slide 21, we expect our full year 2024 net cash used in operating and investing activities to be between 208 and $225 million. We expect to end the year with approximately $405 million in cash, cash equivalents, and restricted cash, which represents the midpoint of the range. The estimated full-year 2024 net cash used in operating and investing activities is primarily driven by an estimated net loss of $229 to $255 million, which includes an estimated $51 million of non-cash share-based compensation.

Tran: Additionally, we continue to have a simple capital structure with zero debt.

Turning to our 2024 financial guidance on Slide 21, we expect our full year 2024, net cash used in operating and investing activities to be between 208 and $225 million, we expect to end the year with approximately 405.

Tran: And cash cash equivalents and restricted cash which represents the midpoint of the range. The estimated full year 2024, net cash used in operating and investing activities is primarily driven by an estimated net loss of $229 million to $255 million, which includes.

Tran: An estimated $51 million of noncash share based compensation expense.

Tran: With that I'll turn the call back over to Jim to discuss our upcoming milestones.

Tran: <unk>.

Jim: Thanks, John moving to slide 23.

Jim: I'd like to acknowledge and thank the patients their families physicians and study site staff, who participate in all of our clinical trials without their support we could not elucidate the potential impact of the new medicines, we are developing.

John Nguyen: With that, I'll turn the call back over to Jeanne to discuss our upcoming milestones. Jeanne? Thanks, Tron. Moving on to slide 20. I'd like to acknowledge and thank the patients, their families, physicians, and study site staff who participate in all our clinical trials. Without their support, we could not elucidate the potential impact of the new medicines we're developing. I'd also like to thank our talented Prothenians for their ongoing commitment to advancing protein dysregulation science to make a real impact for the patients and families we serve. As we look ahead, we're excited to have meaningful catalysts across our programs with potential clinical readouts from four ongoing clinical trials within the next 12 to 18 months, which include top-line results from our confirmatory AFIRM-AL Phase 3 trial evaluating Camomab in Clinical data from our ongoing Phase 1 trial evaluating PRX12 as a potential best-in-class treatment for early Alzheimer's.

Jim: I'd also like to thank our talented provenience for their ongoing commitment to advancing protein Dysregulation science to make a real impact for patients and families. We serve.

Jim: As we look ahead, we're excited to have meaningful catalysts across our programs with potential clinical readouts from four ongoing clinical trials within the next 12 months to 18 months.

Jim: Which include topline results from our confirmatory affirm <unk> phase III trial evaluating <unk> in patients with Mayo stage for Al Amyloidosis.

Clinical data from our ongoing phase one trial evaluating <unk> as a potential best in class treatment in early Alzheimer's disease.

Jim: Topline results from the phase <unk> trial evaluating <unk> for Parkinsons disease being conducted by Roche.

Jim: And finally clinical data from the phase II signal detection trials evaluating <unk> hundred 60, <unk> 19 for the treatment of <unk> cardiomyopathy by Novo Nordisk.

I am proud of the progress that <unk> made in 2023 and continued into 2024.

Dr. Gene Kinney: Top-line results from the Phase 2b PDOVA trial evaluating presinesimab for Parkinson's disease being conducted by Roche. And finally, clinical data from a phase 2 signal detection trial evaluating NNC6019 for the treatment of ATTR cardiomyopathy by Novo Nordisk. I am proud of the progress that Prothena made in 2023 and continued into 2024.

Jim: We are well capitalized with a robust cash position and remain focused on advancing our clinical programs as we strive to become a fully integrated commercial biotechnology company.

Speaker Change: With that we'll now open the call to Q&A operator.

Speaker Change: Your question. Please press star followed by the number one on your Touchtone telephone. If your question has been answered or you wish to withdraw your question again press Star one please limit yourself to one question I repeat please limit yourself to one question.

Dr. Gene Kinney: We are well capitalized with a robust cash position and remain focused on advancing our clinical programs as we strive to become a fully integrated commercial biotechnology company. With that, we'll now open the call to Q&A. Operator, question? Please press star followed by the number one on your touchtone telephone. If your question has been answered or you wish to withdraw your question, again press star one. Please limit yourself to one question. I repeat, please limit yourself to one question. Press star 1 to begin.

Speaker Change: Our star one to begin please standby for your first question.

Speaker Change: Your first question comes from the line of Charles Duncan from Cantor Fitzgerald.

Charles Duncan: Please go ahead.

Charles Duncan: Yeah, Hi, good afternoon, Jean and team you've got a lot going on and limiting to one question and there will be a challenge, but I'll try to do that I'm wondered if you could provide a little bit more clarity.

Operator: Please stand by for your first question. Your first question comes from the line of Charles Duncan from Cantor Fitzgerald. Please go ahead. Yeah. Hi.

Charles Duncan: Patient enrollment in a sense.

Charles Duncan: Good afternoon, Gene and team. You've got a lot going on, and limiting it to one question will be a challenge, but I'll try to do that. I wondered if you could provide a little bit more clarity on the patient enrollment in Ascent 2, specifically what patients or what cohorts have been enrolled, both A and B in terms of which doses. And I'm wondering if you could provide a sense of what you meant with regard to giving an update later this year on data. Could you anticipate being possibly in a pivotal program in the latter part of 2005 or 2025? Yeah, thanks for the questions, Charles. I appreciate them.

Two.

Charles Duncan: Specifically, but what patient or what cohorts had been enrolled.

Charles Duncan: Both a b in terms of which doses and and I'm wondering if you could provide us.

Charles Duncan: Sense of what you meant with regard to giving you an update later on this year on data could you anticipate being possibly in a pivotal program in later part of 2005 or 2025.

Speaker Change: Yes. Thanks for the question is Charles I appreciate them. So I think first just with respect to timeline.

Dr. Gene Kinney: So, I think first, just with respect to timeline, you know, obviously, this is an ongoing trial, and we plan to share additional data as that data becomes substantive. I think, you know, in terms of when we plan to give an update on PRX 12, we do plan to provide an update this year. Whether that update is to update on timing or data is something that will still be determined. And I think in terms of your question around enrollment in the various cohorts, maybe I can ask Becky to address that question. Yeah, thanks, James.

Speaker Change: Obviously this is an ongoing trial and we plan to share additional data as that.

Charles Duncan: That data become substantive.

Charles Duncan: In terms of.

Speaker Change: When we plan to give an update on Parex 12, we do plan to provide an update this year whether that update is to update on timing for data is something that we will still determined.

Speaker Change: And I think in terms of your question around enrollment in the various cohorts, maybe I can ask to deci too.

To address that question.

Deci: Yeah. Thanks, James So yes, it's.

Dr. Hideki Garan: So yeah, enrollment's been very strong in our PRX 12 State 1 trial. There is a high level of interest once monthly, and we're proceeding with all coercives planned. And so this will allow us to fully explore those. Your next question comes from the line of Jay Olson from Oppenheimer. Please go ahead. Oh, hey.

Deci: Very strong.

Deci: Phase one trial.

Deci: Interesting.

Speaker Change: Thank you guys.

Speaker Change: It.

Speaker Change: Important to note that the data safety monitoring board.

Speaker Change: Loss of 45 four.

Speaker Change: And we're proceeding well of course as flat.

Speaker Change: It will allow us to fully explore those.

Speaker Change: Sure.

Speaker Change: Your next question comes from the line of Jay Olson from Oppenheimer. Please go ahead.

Jay Olson: Oh, Hey, thanks for the update and congrats on the progress we have another question about the PRC 12 Mad study can you talk about this six month open label extension and what do you hope to learn from that will patients on low doses switch to high doses and how will it impact your next steps for <unk>.

Jay Olson: Thanks for the update, and congratulations on the progress. We have another question about the PRxO12 MAD study. Can you talk about the six-month open-label extension, and what do you hope to learn from that? Will patients on low doses switch to high doses, and how will that impact your next steps for O12? Thank you. Thanks, Jay.

Thank you.

Speaker Change: Yes, Thanks, Jay Thanks for the question.

Dr. Gene Kinney: Thanks for the question. Well, maybe I can just start with the reminder that the study is double-blind and placebo-controlled for six months in duration, with patients receiving their specified dose level of placebo once a month by subcutaneous administration. Obviously, after that six-month period, we do provide the potential for an open-label extension for patients, and maybe, Hideki, you could just speak a little bit about that period. Yeah, so each patient within each cohort is allowed to enroll in Open Label Extension for six months, as you mentioned, and again, very strong enrollment, and people are very excited about the once-monthly sub-Q-Tel.

Speaker Change: Well, maybe I can just start with a reminder, that the study is double blind placebo controlled six months in duration with patients receiving their specified dose level of placebo.

Speaker Change: Once a month by subcutaneous administration.

Speaker Change: Obviously after that six month period, we do provide the potential for an open label extension for patients and maybe you can just speak a little bit about that period.

Speaker Change: Yes, so each patient within each cohort.

Speaker Change: The label extension for six months estimate and again very strong.

Speaker Change: Enrollment in.

Speaker Change: Very excited about the once monthly for Q.

Dr. Hideki Garan: And here, we won't have a, as he said today, it's not placebo-controlled, where placebo patients will now receive the drug. Of course, that will be the first time they receive it, but the other patients will continue to go on to have up to 12 months of protective treatment with PRX12, which we are capturing both safety, tolerability, and, of course, PK, sorry, pharmacodynamic. Your next question comes from the line of Michael DeFlore from Evercore ISI. Please go ahead.

Speaker Change: We won't have.

Speaker Change: Thanks, not placebo controlled placebo patients will now receive drug of course that will be the first time they receive it but the other patients will continue to go on to have up to 12 months.

Speaker Change: Treatment of Crs 12, which we are capturing a safety tolerability and of course PK.

Speaker Change: Good dynamic measurement.

Speaker Change: Your next question comes from the line of Michael D floor from Evercore ISI. Please go ahead.

Michael Yee: Thank you. Thank you. Thank you.

Michael Yee: Hi guys, thanks so much for taking my question. I just want to zero in on the comparable ARIA rates that we're seeing between the 70mg dose of 012 and placebo. So, when you consider how subcutaneous Bapinizumab had less ARIA rates compared to its IV version, and while Mechanimab SubQ had about equal ARIA rates versus the IV version, how do you reconcile this? And given that the engineering of 012 was optimized off of Vaponizumab, do you foresee similarly low ARIA rates for 012 at higher dosages? Thank you.

Speaker Change: Yes.

Speaker Change: Hi, guys. Thanks, so much for taking my question just wanted to zero in on.

Speaker Change: Comparable or your rates that we're seeing.

Michael Yee: Between the 70 milligram dosage 012 and placebo.

Michael Yee: When you consider how subcutaneous bapineuzumab had less or your rates compare to the IV version.

Michael Yee: And Wow Mccanna med sub Q had about equal or your rates versus the IV version, how do you reconcile this and given that the engineering of 012 was optimize off of Bapineuzumab do you foresee similarly, low Oreo rates.

Michael Yee: 4012 at higher dosage. Thank you.

Dr. Gene Kinney: Yeah, it's a great question, and you've got a lot built in there around the science, so I appreciate the question. I think what you're alluding to is really just how, you know, the biology of ARIA plays into dosing with these anti-amyloid agents. And as you say, I think, you know, there is evidence across the anti-A-beta field that there is an exposure-response relationship between, well, certainly it's almost on a linear basis with respect to amyloid reduction, but in the case of ARIA, a little different between antibodies, and I think that's what we're seeing. So you're making the point between Bapinuzumab and Leucanumab, and I think those are astute observations. As you say, with the Bapinuzumab work, I think as approximately equivalent exposures on an AUC basis were managed to be attained, what was observed, at least in the published literature, was less ARIA with that molecule; with Leucanumab's data, a little bit more comparable So what that indicates to us is really that it is molecule-dependent.

Speaker Change: Yes, it's a great question and you've got a lot built in there around the science. So I appreciate the question.

Speaker Change: I think what you're alluding to is really just how the biology of ARIA plays into dosing with these anti amyloid agents and as you say I think.

Speaker Change: There is evidenced across the anti a beta field.

Speaker Change: That there is a exposure response relationship between certainly it's almost on a linear basis with respect to amyloid reduction.

Speaker Change: But in the case of ARIA a little different between antibodies and I think thats what were seeing so you're making the point between bapineuzumab and locate them and I think those are astute observations as you say with the <unk> and that work I think as approximately equivalent exposures on an ASC basis were managed to be attained.

Speaker Change: What was observed at least in the published literature was with lesser ARIA with that molecule with locate them at the data a little bit more comparable so what that indicates to us is it really that it is a molecule dependent.

Dr. Hideki Garan: And, you know, what we need to understand as we see multiple dose-level cohorts with our molecule, PRX12, is that we need to understand that relationship. And we look forward to determining it as we explore the exposure-response relationship, as Adeki mentioned, from the 45-milligram monthly dose level through to the 400-milligram monthly dose level. With that said, I think you also kind of asked a little bit of a question there just in terms of what, you know, consistency means with placebo, and maybe I can just ask Adeki to comment on that piece. Yeah, thanks, Jay.

Speaker Change: And what we need to understand as we see multiple dose level cohorts with our molecule <unk> 12.

Speaker Change: That we need to understand that relationship and we look forward to determining that as we explore the exposure response relationship at the deck you mentioned from the 45 milligram monthly dose level through to the 400 milligram monthly dose level.

Speaker Change: With that said I think you also kind of asked a little bit of a question there just in terms of what.

Decade: Distancing meant with placebo and maybe I can just ask a decade to comment on that piece.

Decade: Yes, Thanks Keith.

Nina Rahimi: Just to remind you, we're running a double-blind placebo-controlled trial, and as reported at the 70-milligram dose, there was plaque burn as well as aria rates consistent with placebo. And the data that allows us to provide a therapeutic index for a full dose of smokable foot powder. And we, again, just to remind you, we have the ability to go up to 400 milligrams, and all these cohorts are... Your next question comes from the line Nina. Bit Retail Garg from Deutsche Bank, please go ahead.

Decade: Just to remind you we're running a double blind placebo controlled trial.

Decade: And as reported.

Decade: 70 milligram dose.

Speaker Change: After that we'll add audio risks consistent stable.

Speaker Change: That allows us.

Speaker Change: To provide a service index explorer.

Kurt.

Speaker Change: And again just to remind you we have the ability of the Florida program. This quarter are activated.

Speaker Change: Your next question comes from the line of Neenah.

Neenah: But retail garg from Deutsche Bank. Please go ahead.

Neenah: Hey, guys. Thanks for taking my question.

Dr. Gene Kinney: Hey, guys, thanks for taking my question, but just to kind of piggyback on the ARIA discussion here, I'm wondering if you can tell us a little bit about the comment on ARIA being consistent with placebo. Is that true for both the cohort A and the cohort B patients so far? So, both the A44 non-carriers and the heterozygous as well as the homozygous, and then I was just wondering if you could also talk a little bit about that.

Neenah: Just to kind of piggyback on the Rins discussion here.

Neenah: I'm just wondering if you can tell us a little bit about.

Neenah: Was the comment on R&D and consistent with placebo is that true for both the cohort a and the cohort b patients. So far simple eight four non carriers unless there was I guess as well as the homozygous.

Neenah: And then I was just wondering if you could also talk a little bit about some of the differences in activity that you are expecting between the 70 Mcdonough versus 200 400, and why you selected 204 hundred for both sad and Mad.

Dr. Hideki Garan: Some of the differences in activity that you're expecting between the 70 make dose versus 200 and 400 and why you selected 200 and 400 for both sad and mad. I know you talked a lot about the selection of 70 Meg as being based off of a C app, similar to the average to 10 mix per take adjucanumab, but just wondering how we should think about the higher doses. Yeah. Thanks, Nina, for the question. Maybe I can start, and then Hideki can again jump in here.

Neenah: And you had talked a lot about selection of 70, Meg as being based off of the <unk>. The average two <unk>, Panama, but just wondering how we should think about the higher doses.

Speaker Change: Yes, Thanks, Dana for the question, maybe I can start and then <unk> again jumped in here I think.

Speaker Change: First with respect to your question about the data that informs.

Dr. Gene Kinney: I think, first, with respect to your question about the data that informs what we've said about this molecule to date, which, you know, just again as a reminder, I think what we've indicated is that with the A cohort, which is the 70 milligram monthly cohort, we've seen evidence of what we would characterize as an encouraging reduction in amyloid. Obviously, that helps us to understand that we believe this is a once-monthly subcutaneous drug, and obviously, RA rates are, as you mentioned, consistent with placebo. What goes into informing that is obviously the data from the single-dose study as well as the cohort, the 70 milligram cohort I'm referring to in the multiple-dose study. The additional ongoing cohorts remain blinded, so this is a double-blind placebo-controlled study.

What we've said about this molecule to date, which just again as a reminder, I think what we've indicated is that with the a cohort which is the 70 milligram monthly cohort.

Speaker Change: We've seen evidence of what we would characterize as encouraging reduction in amyloid beta obviously that helps us.

Speaker Change: Just to understand that we believe this is a once monthly subcutaneous drug and and obviously <unk> rates as you had mentioned consistent with placebo.

Speaker Change: Goes into informing that is obviously the data from the single dose.

Speaker Change: <unk> as well as the cohorts the 70 milligram cohort I'm, referring to in the multiple dose study.

Speaker Change: The additional ongoing cohorts remain blinded. So those are it is a double blind placebo controlled study.

Dr. Gene Kinney: I think the other question was around the selection of the dose levels, and I think maybe I'll just ask Hideki to speak to that, other than to say that, you know, these dose levels that are being explored are the dose levels that were anticipated to be explored, and that we are continuing to conduct this study as we had anticipated, and it's moving forward at an encouraging pace, as Hideki indicated.

Speaker Change: I think the other question was really just around the selection of the dose levels.

Decade: And I think maybe I'll, just ask a decade to speak to that other than to say that.

Decade: These dose levels that are being explored or the dose levels that were anticipated to be explored and that we are continuing to conduct this study as we had anticipated.

Decade: And it's moving forward and an encouraging paces as the decade indicated a decade.

Decade: Yes, Thanks, Jim.

Dr. Hideki Garan: Yeah, thanks, Gene. So, as you mentioned, we're continuing to explore the doses in a phase 1 study, and that's the purpose of the phase 1 study, and just to remind you, in the 7th milligram, we did see an encouraging ammo reduction Next slide, please. 45 all the way up to 400.

Decade: As you mentioned, we're continuing to explore the dose.

Decade: Great.

Speaker Change: And just to remind you of the 70 <unk>, we do see that.

Speaker Change: Encouraging annual reduction consistent oratory, CLO and allowed us to really explore the full dose response curve 40 firewall the 400 milligram.

Yasmin Rahimi: And again, just to remind you of the hype. 612 has high buying potency, monthly sub-Q administration, and potentially could be best-in-class in FTA beta analysis. Your next question comes from the line of Yasmin Rahimi from Piper Sandler. Please go ahead. Hi, Dean. This is Jung-Goo Won for YAAD.

Speaker Change: And again just to remind you that.

Speaker Change: Extraordinary high volume.

Speaker Change: Once monthly.

Speaker Change: Once the sub Q administration and potentially be best in class.

Speaker Change: Hello.

Your next question comes from the line of Yasmin Rahimi from Piper Sandler. Please go ahead.

Speaker Change: Hi, Dan This is John <unk> on for Yaron, Thanks for taking our question.

Yasmin Rahimi: Thanks for taking our question. I'll just kind of dive more into the details of the ARIA rates. Given that you're enrolling both ApoE4 homozygotes and heterozygotes, we know that this sometimes leads to differences in ARIA rates. How does this factor into your expectations regarding both safety and efficacy across these populations? Yeah, no. Thanks for the question.

Yasmin Rahimi: Just kind of diving more into the details of the ARIA rates given that you're enrolling both <unk> for homozygous and heterozygous.

John: No that does sometimes differences in higher rates, how do those countries your expectations regarding both safety and efficacy across these populations.

Speaker Change: Yes, no. Thanks for the question I think there is kind of two questions built into that one in terms of how we're thinking about <unk> just across the entirety of the of the.

Dr. Gene Kinney: I think there's kind of two questions built into that, one in terms of how we're thinking about ARIA just across the entirety of the patient population, and I think the second is really just around how we think about this trial design. So let me start with ARIA, and obviously, you know, as we talk about ARIA rates, we're being specific to our patient-level cohorts. We are reporting data out as one would in a phase study relative to placebo, and I think that's what we indicated in our release in January, that ARIA rates in this 70 milligram cohort after six months of treatment were consistent with placebo. I think you're, you know, the point you're making about testing separately 8.4 homozygous carriers in these B cohorts is something that we're learning from the field.

Speaker Change: The patient population and I think the second is really just around.

How we think about this trial designed so let me start with <unk>.

Speaker Change: And obviously as.

Speaker Change: As we talk about ARIA rates were being specific to our patient level cohort.

Speaker Change: We're reporting data out as one would interface study relative to placebo and I think thats, what we indicated in our release in January that our rates in the.

Speaker Change: 70 milligram cohort after six months of treatment were consistent with placebo.

Speaker Change: I think you are.

Speaker Change: The point, you're making about testing separately for almost I get carriers.

Speaker Change: In the cohorts is something that we're learning from the field. So as we continue to iterate in this field across multiple companies. It does take a village to develop therapeutics in this space.

Dr. Gene Kinney: So, you know, as we continue to iterate in this field across multiple companies, it does take a village to develop therapeutics in this space. We are learning from each other, I think, on the clinical side, as well as the preclinical side, and one of the lessons I think that's becoming clear is that 8.4 homozygosity does tend to lead to a higher ARIA rate, and in the context of clinical trials, that can lead to, in some cases, misdosing or skipped dosing. Obviously, that's less than ideal as we start to think forward to efficacy-driven studies and registrational studies. We want doses that are optimized for the entirety of the population, not just parts of the population.

Speaker Change: We are learning from each other I think on the clinical side as well as the preclinical side.

Speaker Change: One of the lessons I think thats become clear that the API for homozygous city.

Speaker Change: Does tend to lead itself to a higher Oreo right and in the context of clinical trials.

Speaker Change: That can lead to in some cases.

Speaker Change: Dosing or skip dosing, obviously, that's less than ideal as we start to think forward to efficacy driven studies. The Registrational studies, we want doses that are optimized for the entirety of the population not just portions of the population. So we chose in the context of the phase one study to be a little bit more deliberate in evaluating these equally.

Dr. Gene Kinney: So, we chose, in the context of the phase one study, to be a little bit more deliberate in evaluating these 8.4 homozygous patients so that when we bring this entirety of the patient population back together in a clinical study, we're selecting dose levels and approaches that are optimized for the entirety of the population. So, that's kind of how we think about it from an ARIA perspective, and not just from an ARIA perspective but from a therapeutic index perspective. At the end of the day, as we think about the best-in-class for a molecule in this space, we think about three important variables: convenience, efficacy, and safety.

Speaker Change: For homozygous patients.

Speaker Change: So that when we bring this entirety of the patient population back together.

Speaker Change: In a clinical study that we're selecting dose levels and approaches that are optimized for the entirety of the population. So that's kind of how we think about it from an audio perspective and not just from an Ari perspective, but from a therapeutic index perspective at the end of the day as we think about best in class for a molecule in this space, we think about three important variables convenience.

Speaker Change: Efficacy and safety efficacy and safety of course, leading to the therapeutic index.

Dr. Gene Kinney: Efficacy and safety, of course, leading to the therapeutic index, but obviously, with the convenience factor, we think that's quite important with respect to patient burden. And as we've indicated in January, relative to the data that we have seen to date, we have given some directional guidance in terms of where we are in all of those encouraging levels of amyloid reduction. Once monthly sub-Q, we believe, is supported based on the data we've seen to date.

Speaker Change: But obviously with the convenience factor, we think thats quite important with respect to patient burden.

As we've indicated in January relative to the data that we have seen to date.

We've given some directional guidance in terms of where we are in all of those encouraging levels of amyloid reduction once monthly subcutaneous believe it's supported based on the data. We've seen to date is the approach we're continuing to take moving forward in our trial as planned and then of course, we've just talked about the ARIA being comparable to placebo.

Dr. Gene Kinney: It is the approach we're continuing to take moving forward in our trial as planned. And then, of course, we've just talked about ARIA being comparable with placebo. Your next question comes from the line of Rudy Lee from Lee Rink Partners. Please go ahead.

Speaker Change: Your next question comes from the line of Rudy Li from Leerink Partners. Please go ahead.

Rudy Li: Alright, Thanks for taking my question.

Rudy Lee: Thanks for taking my question. Just a quick follow-up on your dosing selection. Can you maybe talk about the rationale for including the 45 mg dose in assent 2 which was not tested in assent 1? I'm trying to get better safety, and any kind of information would be helpful.

Rudy Li: Quick follow up on your dosing selection.

Rudy Li: Can you maybe talk about the rationale, including the 45 milligram dose in the extent to which was not tested in a sense, what I'm trying to get a better safety.

Rudy Lee: Thanks. Thank you for the question. Maybe I can just take this one.

Rudy Li: Any color would be helpful. Thanks.

Speaker Change: Yes, maybe I. Thank you for the question and maybe I can.

Speaker Change: I can just take this one I think what we're looking for is to really have a full fulsome understanding of the exposure response relationship.

Dr. Gene Kinney: I think, you know, what we're looking for is to really have a full understanding of the exposure-response relationship. And we believe that evaluating dose levels from 45 milligrams to 400 milligrams provides us with a pretty comprehensive overview of that. And obviously, that exposure-response relationship is something that we're interested in, both in terms of amyloid reduction but also in terms of ARIA rates to understand that therapeutic index. So that's really what defined it.

Speaker Change: And we believe that evaluating dose level.

Speaker Change: From 45 milligrams to 400 milligrams provides us with a pretty comprehensive overview of that and obviously that.

Speaker Change: The response rate.

Speaker Change: <unk>, that's something that we're interested in both in terms of amyloid reduction, but also in terms of Oreo rates to understand is that therapeutic index.

Speaker Change: So that's really what what defined it I think is Hideki has already mentioned there has been very high level of interest in this study. So we'd been afforded also the opportunity to include a number of cohorts and we've been able to enroll those cohorts in a pretty favorable way. So I think that that really.

Dr. Gene Kinney: I think, as Hideki has already mentioned, there's been a very high level of interest in this study. So we've been afforded the opportunity to include a number of cohorts, and we've been able to enroll those cohorts in a pretty favorable way. So I think that really is the rationale for it.

Speaker Change: Is the rationale for it.

Michael Yee: Other than that, I would just say that these were the dose levels that we had pre-planned on testing. As we saw the first dose-level cohort, the 70-milligram dose-level cohort data, the decision was to continue to conduct this study in the way that had been previously intended. Your next question comes from the line of Michael Yee from Jefferies. Please go ahead. Hey guys.

Speaker Change: Other than that I would just say that these were the dose levels that we had pre.

Speaker Change: Preplanned on testing as we saw the first dose level cohorts, a 70 milligram dose level cohort data.

Speaker Change: The decision was to continue to conduct this study in the way that had been previously envisioned.

Speaker Change: Your next question comes from the line of Michael Yee from Jefferies. Please go ahead.

Hey, guys. Thanks for the question.

Michael Yee: Thanks for the question. I know there are a lot of questions around ARIA, and we just wanted to ask more specifically, when you say consistent with placebo, was there actually one case of ARIA in the placebo group and whether you would have expected that. And then if so, would you have expected ARIA in that type of range in the drug arm, given you have very little exposure, whereas the IV drugs, including Lekembi, have ARIA rates that are around 12%. So could you tie those two together and what would drive our confidence today for those listening that you can go to 200 milligrams and three times the dose and still thread the needle? Thanks for the question, Mike.

Michael Yee: I know theres been a lot of questions around ARIA and we just wanted to.

Michael Yee: Asked more specifically when you say consistent with placebo was there actually one case of <unk> in the placebo and whether you would have expected that and then if so would you have expected.

Michael Yee: Yes.

Michael Yee: That type of range in the drug arm, given you have very little exposure, whereas the IV drugs, including <unk> behalf already at rates that are around 12% to 20%.

Michael Yee: Could you tie those two together.

Michael Yee: Our confidence today for those listening that you can go to 200 milligrams and three times the dose and still thread the needle. Thank you.

Speaker Change: Yeah. Thanks for the question, Mike I mean, obviously this study is double blind placebo controlled.

Dr. Gene Kinney: I mean, obviously, this study is double-blind, placebo-controlled, and as we reported at the 70 milligram dose level, the ROE rates, as you say, were consistent with placebo. And I think that's the statement around where we are from a therapeutic index perspective, and what we think that therapeutic index then provides is the ability to move up in the dose range, as you've indicated. So I think Hideki's already mentioned that the 200 milligram dose level cohort is active, but actually, all dose level cohorts are active.

Speaker Change: And as we reported at the 70 milligram.

Speaker Change: Dose level.

Speaker Change: Rates as you say were consistent with placebo.

Speaker Change: That's.

Speaker Change: That's I think the statement around where we are from a therapeutic index perspective, and what we think that therapeutic index. Then provides us the ability to move up in dose range as you've indicated so I think a decade has already mentioned that the 200 milligram dose level cohort in fact, all dose level cohorts are active.

Dr. Gene Kinney: And so we're moving forward and exploring a full exposure-response relationship ranging all the way from 45 to 400. So I think, you know, what that should indicate is that we believe that the therapeutic index provides us with the sense that we have the potential for a best-in-class molecule. And again, for us, the best-in-class molecule is a function of the three variables, the convenience factor, which is really around patient burden, the efficacy, which in the case here, we're talking about really reducing amyloid, and then, of course, the safety, which I think everyone's very focused on ARIA, but we'll talk about safety in general and being permissive from a therapeutic index perspective to continue Hi, thanks for taking the questions. I guess I want to switch gears here and just ask a question about President Esmaeil.

Speaker Change: And so we're moving forward and exploring a whole.

Speaker Change: Exposure response relationship ranging all the way from 45 to 400 or.

Speaker Change: So I think what what that good indicators that we believe that the therapeutic index provides us with.

Speaker Change: The sense that we have the potential for a best in class molecule and again for us the best in class molecule.

Speaker Change: <unk> is a function of the three variables.

Speaker Change: Convenience factor, which is really around patient burden.

Speaker Change: Yes.

Speaker Change: The efficacy, which in the case here, we're talking about really a reduction of amyloid.

Speaker Change: And then of course, the safety, which I think everyone very focused on ARIA, but we'll talk about safety in general is being permitted from therapeutic index perspective to continue to continue to explore this fulsome exposure response relationship range.

Speaker Change: Your next question comes from the line of Jason Butler from citizens JMP. Please go ahead.

Hi, Thanks for taking my questions I guess wanted to switch gears here and just ask a question about.

Jason Butler: Can you just speak to us about how we should think about the magnitude of benefit or clinical meaningfulness around the primary endpoint and then how you envisage the product being incorporated into clinical practice? Thanks. Yeah, no, thanks for the question. Yeah, so, maybe just a quick refresher on what Roche has already shown with this molecule. So, starting with the Movement Disorder Society data last year, where they showed the three-year open-label extension data from the prior phase 2-pathodena study. And, you know, importantly, relative to the PPMI demographic matched group, they showed a 63% slowing of progression as measured by MDS-UPDRS Part 3. And more recently, we've seen the abstract published for the ADPD meeting, which will occur here in early March, where, you know, while that presentation hasn't happened yet, they have published the abstract. And there, they're talking now about four-year open-label data. I mean, at least on the MDS-UPDRS Part 3 scale, 117% less progression than that PPMI database group. And, in fact, even on the activity of daily living scale, the MDS-UPDRS Part 2, a 39% slowing of less progression than that PPMI data group. So we're very interested in this.

Jason Butler: President <unk>.

Jason Butler: Can you just speak to us about how you how we should think about magnitude of benefit or clinical meaningfulness around the primary endpoint and then how do you envisage the product being incorporated into clinical practice.

Speaker Change: Yeah no. Thanks for the question.

Speaker Change: So just maybe just a quick refresh of what Roche has already shown with this molecule so starting with the movement disorder Society.

Speaker Change: Data last year, where they showed the three year open label extension data from the prior phase II Pasadena study.

Speaker Change: And importantly relative to the PMI demographic matched group showed a 63% slowing of progression.

As measured by <unk> and more recently, we have seen the abstract published for the ADP the meeting which will occur here in early March where while that presentation. It hasnt happened yet they have published the abstract in there they're talking now about four year open label data and then at least on the you Peter SPD <unk>.

Speaker Change: <unk> three scale 117 less.

Speaker Change: Sent less progression then that PPA My database group and in fact, even on the activity of daily living scale. The Mds you Peter as part two.

Speaker Change: 39% slowing of preferred less progression in that <unk> data group. So so we're very interested in this obviously the Nova study.

Dr. Gene Kinney: Obviously, the Padova study is fully enrolled, as per Roche. This is, you know, a large study that is being run with high integrity. We've got 586 patients in this study randomized on a one-to-one basis. So, we're excited to see those results. I think it's based on, you know, strong science.

Speaker Change: Is fully enrolled as per Roche.

This is a.

Speaker Change: A large study that is being run with high integrity, you've got 586 patients in this study randomized on a one to one basis.

Speaker Change: We're excited to see those results I think it's based on strong science based on previous clinical data I think the way, they're thinking about the endpoints.

Dr. Gene Kinney: It's based on previous clinical data. I think the way they're thinking about the endpoint is informed by those prior studies. And then, ultimately, you know, the go-forward regulatory path. And I think, to your question, how this will ultimately be positioned will be determined by the data. And obviously, also, continued conversations between our partners at Roche and the regulators. And we have very high confidence that Roche will be as aggressive as is appropriate based on the data.

Speaker Change: Is informed by the prior studies.

Speaker Change: And then ultimately.

Speaker Change: The go forward regulatory path and I think to your question.

Speaker Change: How this will ultimately be positioned will be determined by the data and obviously also continued conversations between our partners at Roche and the regulators and we have.

Speaker Change: We have very high confidence that Roche will be as aggressive as it is appropriate based on the data set that they obtain.

Dr. Gene Kinney: I think one thing to add, too, in terms of the time-to-event endpoint is that it captures a five-point or greater increase, right, progression in the scale, which in and of itself is good enough for these to be clinically meaningful. They're also working on other clinical, you know, functional endpoints within the trial to correlate. And so we look forward to their continued discussion with regulators and, of course, the data. And we have time for one more question today, and it comes from Anana Ghosh from H.C. Rainwright. Please go ahead. Yeah, hi.

Speaker Change: But I think one thing to add to in terms of the time to event endpoints is that recaptured a five point or greater increase rate progression in the scale, which which sells roche for these to be clinically meaningful theyre also working on other political.

Speaker Change: Actual endpoints within the trial.

Speaker Change: So we look forward to their continued discussion with regulators and of course the data later this year.

And we have time for one more question today and it comes from and then it goes from H C. Wainwright. Please go ahead.

Speaker Change: Yeah, Hi.

Anana Ghosh: So, you know, just wanted to get your opinion on some of these concepts, which I don't think the street understands very well with respect to the PRX 412 program. So what has been, you know, how do we think that the AUC, the CMAX, and, you know, relative fractional occupancy when you are looking at data which comes from subcutaneous CTAD data and with respect to your idea of the PRX 412 development program? So any ideas with respect to those three factors will be very helpful to understand how to think about PRX 412 development going forward. Yeah, no; I appreciate the question. And yeah, it's an important question.

Speaker Change: Just wanted to get your opinion on some of these concepts, which I don't think the street understands very well with respect to Prs <unk> program.

Speaker Change: What has been how do we think.

Speaker Change: The EU fee the C. Max relative of traction in local currency. When you are looking at data, which comes from Laconia subcutaneous <unk>.

Speaker Change: <unk> and and with respect to your.

Speaker Change: Your idea on the pure external development program.

Speaker Change: Any ideas with respect to those two factors would be very helpful to understand how to think about <unk>.

Speaker Change: Development going forward. Thank you.

Yes, no I appreciate the question and.

It's an important question and <unk> you.

Dr. Gene Kinney: And, you know, you talked about mecanimab and aducanimab, and I think they're relevant as, you know, immunotermin is targeting anti-beta antibodies. And I think what we see with those antibodies as you look through the phase two data sets and into the phase three data sets is a relationship between removal of plaque and the dose response or exposure response relationship. So, in the case of mecanimab and aducanimab, that relationship is close to linear. But that's not true with every anti-beta antibody. Other antibodies show much more of an all or none effect. And I'd point to denanimab from that perspective around plaque clearance. I think with respect to ARIA, it's a little bit different. It is a little bit more molecule-dependent.

Speaker Change: You you.

Speaker Change: Talked about Makena Mab and as you can imagine I think theyre relevant as.

Speaker Change: Amino terminus targeting anti a beta antibodies and I think what we see with those antibodies as you look through the phase II dataset.

Speaker Change: Into the phase III dataset.

Speaker Change: Is a.

Speaker Change: Hey relationship between removal of plaque and.

Speaker Change: And the the dose response, so our exposure response relationship so and in the case of <unk> and as you can imagine that relationship is as close to linear that's not true with every anti a beta antibody other antibodies show a much more of an all or none effect and I pointed to nanometers from that perspective around plaque Clarence.

Speaker Change: I think with respect to <unk>, it's a little bit different it is a little bit more molecule dependent.

Dr. Gene Kinney: Although, you know, that being said, there clearly is a dose-effect relationship within molecules, but between molecules, there's a little bit of a difference. And we continue to believe that ARIA is a mechanistically driven event, meaning if you're removing plaque, you're going to increase the risk of observing ARIA. But as I said, the relationship between that and different antibodies may be a little bit different.

Speaker Change: Although that being said there clearly is a dose effect relationship within molecules, but between molecules, there's a little bit of a difference.

Speaker Change: We continue to believe that ARIA is a mechanism.

Speaker Change: Mystically driven event, meaning if you're removing plaque youre going to increase the risk of observing ARIA.

Speaker Change: But as I said the relationship between that.

Speaker Change: And different between antibodies may be a little bit different and so what we need to be informed by now is our data from multiple dose level cohorts from our ongoing phase one trial. So.

Dr. Gene Kinney: And so what we need to be informed by now is data from multiple dose level cohorts from our ongoing phase one trial so that we can better characterize the relationship between PRX12 exposure and RAE rates. And we think that, you know, as we collect additional dose level cohort data and as we think about, you know, future substantive data updates, we will be able to talk in more detail about what that means specifically for PRX12. Thank you, everyone. This is all the time we have today. I'll now turn it over to Jeanne Kinney, Chief Executive Officer, for closing remarks. Thank you very much, Operator, and I want to thank you all for joining us on the call today. We appreciate your interest in Prothena, and we look very much forward to sharing further updates on our product.

Speaker Change: So that we can better characterize the relationship between <unk> 12 exposure and our E rate and we think that as we collect additional dose level cohort data.

Speaker Change: And as we think about.

Speaker Change: Future substantive data update.

Speaker Change: We would be able to talk in more detail about what that means specifically for <unk> 12.

Thank you everyone. This is this is all the time, we have today I'll now turn it over to gene Kinney, Chief Executive Officer for closing remarks.

Gene Kinney: Thank you very much operator, and I want to thank you all for joining us on the call today. We appreciate your interest in Pristina and we look very much forward to sharing further updates on our programs.

Gene Kinney: Have a good afternoon.

Speaker Change: Thank you for participating in today's conference call. This concludes the presentation and you may now disconnect good day.

Speaker Change: Okay.

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Dr. Gene Kinney: Good afternoon. Thank you for participating in today's conference call. This concludes the presentation, and you may now disconnect. Good day.

Speaker Change: Thanks.

Speaker Change: Yeah.

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Speaker Change: Yeah.