Q1 2025 Arrowhead Pharmaceuticals Inc Earnings Call
Ladies and gentlemen, welcome to the Arrowhead Pharmaceuticals conference call.
Speaker Change: Throughout today's recorded presentation, all participants will be in a listen-only mode. After the presentation, there will be an opportunity to ask questions. I will now hand the conference over to Vince Anzalone, Vice President of Investor Relations of Arrowhead. Please go ahead, Vince.
Speaker Change: Good afternoon, thank you for joining us today to discuss Arrowhead's results for its fiscal 2025 first quarter, ended December 31st, 2024.
us today from management our president and
Speaker Change: CEO, Dr. Chris Anzalone, who will provide an overview of the quarter, Dr. Bruce Given, Interim Chief Medical Scientist.
who will provide an update on our Cardiovinabolic Pipeline.
Senior Vice President and Head of Global Cardio-Medibolic Franchise.
Dr. James Hamilton, Chief of Discovery and Translational Medicine.
Speaker Change: who will discuss our earlier stage development programs and Ken Myszkowski, our Chief Financial Officer, who will give a review of the financials. We'll then open up the call to questions. Before we begin, I would like to remind you that comments made during today's call contain certain forward-looking statements.
Speaker Change: Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act.
Speaker Change: Law statements, other than statements of historical fact, are forward-looking statements and are subject to numerous risks and uncertainties that could cause actual results to differ materially from those expressed in any forward-looking statement.
Speaker Change: For further details concerning these risks and uncertainties, please refer to our S&P filings, including our most recent annual report on Form 10-K and our quarterly reports on Form 10-Q.
Speaker Change: I'd now like to turn the call over to Chris Anzalone, President and CEO.
Thank you all. Thank you.
Chris Anzalone: Thanks, Vince. Good afternoon, everyone, and thank you for joining us today.
Speaker Change: Earlier today, we announced that the Licensing Collaboration Agreement with Sarepta Therapeutics is closed.
Speaker Change: Arrowhead expects to receive a $500 million upfront payment in the next 10 days and has already received $325 million through the purchase by Sarepta of Arrowhead common stock priced at $27.25 per share.
Speaker Change: Arrowhead will also receive $250 million dollars to be paid in annual installments.
Speaker Change: of $50 million over five years and has the potential to receive an additional $300 million in near-term payments associated with the continued enrollment of a Phase I-II study of AeroDM1, which we are on track to achieve during the next 12 months.
Speaker Change: Taken together, this adds up to $1.375 billion in cash payments.
Speaker Change: We are also eligible to receive development milestone payments of between $110 million and $410 million per program, and sales milestone payments between $500 million and $700 million per program.
Speaker Change: The total potential value of this deal including upfront payments, equity investments, and potential milestone payments exceeds 11 billion dollars. On top of that we are also eligible to receive tiered royalties on commercial sales.
Speaker Change: This was clearly a big deal and a critical step for Arrowhead to bring balance back to our business model, which in part relies on partnering non-core assets to provide capital for us to develop and commercialize our own wholly owned assets.
Speaker Change: In addition to the substantial immediate capital infusion, the deal also accomplishes a few equally important goals. One brings in a partner with extensive development, regulatory, and commercial expertise for development of drugs they have in-licensed.
2. Increases Arrowhead's focus in the cardiometabolic space
Speaker Change: 3. Reduces the forward growth in our R&D expenses as Sarepta assumes clinical development responsibilities for multiple programs and 4. Provides the potential for substantial downstream non-dilutive capital as milestones and ultimately royalties are earned.
Speaker Change: We are now funded into 2028 and potentially through multiple commercial launches by Arrowhead and our partners.
Speaker Change: We believe we are now well-positioned for growth in 2025 and beyond. We see three primary value drivers fueling this growth from our internal development activities in the near term. These are plazazurin, obesity, and CNS.
Speaker Change: Let's begin with Plozacaran. We expect our first commercial launch of Plozacaran to drive substantial growth. Pending positive FDA review and approval, launch could take place late this year.
Speaker Change: We see the value proposition of Blivastoran in FCS as quite clear and a substantial differentiation from any other available therapy.
Speaker Change: We think the magnitude and consistency of triglyceride lowering, the potential ability to get patients to triglyceride goal, convenient quarterly dosing schedule, and well-tolerated safety profile simply make pozaciran a very difficult drug candidate to compete against.
But this is just the first step.
Speaker Change: We are also confident that our current Phase 3 studies, Shasta 3, 4, and 5, have the potential to show similar differentiation and value in the much larger severe hypertriglyceridemia, or SHTG, population, and we believe this represents an attractive and underappreciated commercial opportunity.
Speaker Change: We are now on pace to complete enrollment for the Registrational SHASTA-3, SHASTA-4, and MIRA-III studies this year, which would enable study completion in 2026 and a subsequent SNDA filing.
Speaker Change: That would substantially broaden the reach of Plozacaran and provide a large opportunity for growth. As we have said in the past, we believe Plozacaran has the potential to be a $2-3 billion per year drug in the SHTG market alone.
Speaker Change: Turning to obesity, we believe our two early-stage programs, AERO-INHBE and AERO-ALK7, represent high-value opportunities with near- and mid-term data readouts that can provide more clarity on where they may fit in the obesity and metabolic treatment paradigm.
Speaker Change: James will talk about the status of the programs in a moment, but we see the targets and pathways as very promising.
Speaker Change: Both programs are supported by published human genetic studies and the preclinical data have demonstrated dramatic results with the potential to fill gaps in the current standard of care.
Speaker Change: It appears that Arrowhead is the first company to start clinical studies against the INHB target and may currently be the only company able to address the ALK7 target, which utilizes a new version of our TRMM platform capable of delivering to adipocytes.
Speaker Change: The third area that we see driving near-term growth is our emerging CNS pipeline, including the new TRMM platform, which in animal models appears capable of delivering siRNA across the blood-brain barrier, including deep brain distribution, using subcutaneous injection.
Speaker Change: Near-term clinical proof of concept would truly be disruptive and we think would open the door to treating many millions of patients without adequate options.
Speaker Change: Our initial efforts with this platform addressed Huntington's, Alzheimer's, and Parkinson's disease, all devastating conditions that lack good treatment options.
Speaker Change: We believe that HTT, MAPT, and alpha-synuclein are the most validated targets in Huntington's, Alzheimer's, and Parkinson's, respectively. And these are the targets we are addressing with AeroHTT, AeroMAPT, and AeroSNCA, respectively.
Speaker Change: Our preclinical data in non-human primates have been very compelling, and we are now focused on completing IND slash CTA enabling studies and GMP manufacturing to support early clinical trials.
Speaker Change: We anticipate having CTAs for Aero HTT and Aero MAPT toward the end of this year and for Aero SNCA in early 2026.
Speaker Change: SREPTA has the right to take HTT forward and we are currently focused on keeping MAP-T wholly owned. We have not made a decision yet on partnering versus retaining Aero SNCA.
Speaker Change: As I mentioned, we believe the triumvirate of plazasterin, obesity, and CNS will be our primary near-term value drivers. It is also the way investors should think about our focus. We are building a growing cardiometabolic pipeline, which includes obesity, and we will see where the new CNS platform takes us as clinical data come in.
Speaker Change: In addition to Pitupal Dasaran, Arrow ALK7, and Arrow INHPE, our cardiometabolic franchise includes Zodasaran, our Ang PTL3-targeting drug candidate.
Speaker Change: We expect to begin a Phase III study in HOFH next quarter with sodaceran.
Speaker Change: We have a large amount of clinical data with this candidate and feel confident that it could be an effective medicine with an attractive dosing schedule in this population.
Speaker Change: This would be a relatively simple addition to our FCS and SHTG sales representatives bags So the incremental commercial costs associated with this additional potential product are expected to be minimal
Speaker Change: The phase 3 study will be small, and this is a good use of fairly modest resources for us.
Speaker Change: Where else can we go in Cardiometabolic? As I mentioned, Arowalc-7 is important not only because of the compelling target to treat obesity, but also as a proof of concept that we can address adipocytes.
Speaker Change: Adipose is the largest endocrine organ in the body and, as such, is expected to be a rich environment for cardiometabolic and obesity targets. We expect to build this out.
Speaker Change: Similarly, we believe the initial candidates built on our new CNS platform are important because of the neurological targets they address, representing some of the most challenging, poorly treated public health crises remaining, and also because they offer the possibility of disruptive clinical proof of concept.
Speaker Change: We also see important opportunities to develop additional obesity candidates based on new CNS targets. Remember that RNAi is a rifle shot, and as our understanding of obesity increases, we see a role for highly specific intervention that could only be practical with systemic delivery.
Speaker Change: We believe that this has the possibility to treat difficult diseases with reduced risk of safety and tolerability challenges that have led to so much disappointment in the CNS drug development space.
Speaker Change: This year we also plan to expand our cardiometabolic presence with a CTA for our first dimer. It is designed to silence expression of both APOC3 and PCSK9 and we hope it will combine the triglyceride lowering qualities of plosaceran with the LDL-C lowering properties of other PCSK9 inhibitors.
Speaker Change: With this focus on cardiometabolic and a wait-and-see with CNS, we have a number of programs that are non-core. These are potential partnering opportunities and could bring additional immediate and long-term capital.
Speaker Change: Janssen generated compelling clinical data with aero PMPLA-3 and addressing a genetically defined mash population that could number in the 10 million persons range in the major pharmaceutical markets could be attractive to the right company. This is a program for which we will seek a partner.
Speaker Change: We have learned much about our pulmonary platform through the various clinical programs. It appears to be well tolerated and quite effective at delivering to the deep lung. It is our intention to find a good partner to help identify new deep lung targets and develop a suite of candidates.
Speaker Change: Similarly, we have been very impressed with knockdown data coming out of the AeroRage clinical studies, but given the complexity and expense associated with developing this as an asthma and or COPD drug, we will seek a partner for Phase 2 and beyond.
Speaker Change: Clinical data from both AeroC3 and AeroCFB have been quite good and both candidates appear to do what they are designed to do. There are clear markets one or both could address including C3 glomerulopathy, IgA nephropathy, and certain lupus populations.
Speaker Change: We would like to find the right partners to develop these candidates.
Speaker Change: This is where we are now and what we see as key growth drivers for the future.
Speaker Change: Let's review how we got here and a few key accomplishments from the quarter and since our last earnings call.
Speaker Change: First, and more importantly, the U.S. FDA accepted the new drug application for investigational plazaceran for the treatment of familial cholomyconemia syndrome.
Speaker Change: This is our first NDA filing which is a key milestone for Arrowhead and we are pleased that it was accepted for filing. The FDA provided a PDUFA action date of November 18, 2025 and indicated it is not currently planning to hold an advisory committee meeting.
Speaker Change: We now know the potential launch date pending FDA review and approval, so we continue our work to be ready for an efficient launch on day one. Andy will talk about the work in a moment.
Speaker Change: Sticking with Dasaran, in November we announced new results from the Phase 3 Palisade study and the open label extension from our Phase 2 Muir and Shasta 2 studies.
Speaker Change: These data were presented in two oral presentations at the American Heart Association Scientific Sessions 2024, and Palisade data were simultaneously published in the AHA Journal of Circulation.
Speaker Change: The data continue to be promising across studies, across the spectrum of triglyceride disorders, and after short and long-term follow-up. In addition, pledacerin has been overall generally well-tolerated to date.
Speaker Change: During the quarter we also initiated a Phase 1-2 clinical trial of our first obesity candidate, Aero INHBE, and recently received regulatory clearance in New Zealand to initiate the clinical study of our second obesity candidate, Aero ALK7.
Speaker Change: As I mentioned, these programs represent potential drivers for growth for Arrowhead, so we are excited to get both moving into and through early clinical studies.
Speaker Change: Lastly, we presented interim healthy volunteer results from a Phase 1-2 clinical study of AeroCFB for the treatment of complement-mediated diseases.
Speaker Change: Data have been compelling so far and we anticipate additional data readouts later this year.
Speaker Change: With that overview, I'd now like to turn the call over to Dr. Bruce Given. Bruce?
Thank you, Chris. Good afternoon, everyone.
Bruce Given: As Chris mentioned, the big highlight for the clinical and regulatory teams was the submission and subsequent acceptance of our first new drug application, or NDA, by the US FDA for investigational plesiastra for the treatment of familial chylomicronemia syndrome, or FCS.
Bruce Given: The FDA provided a PDUFA action date of November 18, 2025, and indicated it is not currently planning to hold an Advisory Committee meeting.
Bruce Given: We also expect to submit approval applications to additional global regulatory authorities in coming months for Plesiastra for the treatment of patients with FCS.
Bruce Given: FCS is a severe and rare disease that often is caused by various biogenic mutations that lead to extremely high triglyceride levels.
The normal level is triglycerides below 150 milligrams per deciliter.
but patients with FCS typically have triglycerides in the thousands.
Bruce Given: Such severe elevations can lead to various serious signs and symptoms, including acute and potentially fatal pancreatitis, chronic abdominal pain, which can be as frequently as daily, diabetes, and cognitive issues.
Bruce Given: The clinical basis of the NDA submission is comprised of the findings in the Phase III Palisade study, which were positive, with supportive confirmatory evidence from the Phase II clinical studies of the SUMMIT program.
Bruce Given: Palisades successfully met its primary endpoint in all multiplicity controlled secondary endpoints.
Bruce Given: including statistically significant reductions in triglycerides, ApoC3, and the incidence of acute pancreatitis.
Bruce Given: In Palisade, Plozacaran achieved deep and durable reductions in triglycerides with median changes from baseline of approximately 80% in the Plozacaran 25 mg group.
Bruce Given: and a statistically significant 83% reduction in the risk of developing acute pancreatitis compared to placebo in the pooled plazastran 25mg and 50mg group.
Overall, Plos Astra has been generally well tolerated to date.
Bruce Given: In the Palisade study, the most frequently reported treatment-emergent adverse events for the 25 milligram dose that is proposed for marketing approval were abdominal pain, COVID-19, nasopharyngitis, and nausea.
Bruce Given: In addition to FCS, we are making good progress on the other phase three studies in the summit program.
Bruce Given: These are SHASTA-3, SHASTA-4 in patients with severe hypertriglyceridemia, or SHTG, and MIR-3 in patients with mixed hyperlipidemia.
Bruce Given: The SHASA studies are designed to assess safety and efficacy, and the MIRR study is to provide additional safety data needed for the expected SHTG supplement to our plazacerin NDA.
Bruce Given: The Shasta studies are global, randomized, double-blind, placebo-controlled phase 3 studies to evaluate the efficacy and safety of plazasirab in adult patients.
Bruce Given: with SHTG and prior documented evidence of fasting triglyceride levels greater than 500 milligrams per deciliter.
Bruce Given: Eligible subjects will be randomized to receive either Plozasiran at 25 milligrams or placebo.
Bruce Given: The double-blind treatment period duration will be one year, where subjects receive a total of four quarterly doses.
Bruce Given: After month 12 eligible subjects will be offered an opportunity to continue in an optional open label extension.
Bruce Given: Shasta three and four and Mira three are all enrolling well and we are on schedule to reach full planned enrollment this year which would enable study completion in 2026 and subsequent SNDA filing.
We are also working towards initiating SHASTA V.
Bruce Given: The Phase III study in patients with SHTG, they're at high risk of acute pacular titus.
We intend to initiate that study this year.
in patients with homozygous familial hypercholesterolemia or HOFH.
following a successful phase 2 study called GATEWAY.
Bruce Given: We will provide more details on that study when it is initiated later this year. This is another program that makes sense as it is potentially complementary to the medical affairs and commercial organizations we are building to support a plazazurin launch.
Bruce Given: and there is significant overlap in types of physicians who treat FCS and HOFH, both rare and lipid disorders.
I'll now turn the call over to Andy Davis.
Thank you.
Speaker Change: Thank you, Bruce. The recent acceptance of our first NDA by the U.S. FDA for investigational plisacerin is incredibly energizing for the FCS community.
Speaker Change: The frequent feedback we receive from both physicians and patient societies who have read about plisastrin in last year's publications continues to be very encouraging. They cite several potential differentiating attributes of plisastrin that I will discuss briefly.
First, the reduction in triglycerides is both deep and durable.
Speaker Change: As Bruce mentioned in his remarks, in Palisade, plazastrin reduced triglycerides from baseline by an unprecedented approximately minus 80% as early as month one, and maintained this reduction with minimal variation throughout the full 12-month treatment period.
Speaker Change: Second, people living with FCS for the first time have real hope of achieving triglyceride levels below guideline-directed risk thresholds associated with acute pancreatitis, such as 880 and even 500 milligrams per deciliter.
Speaker Change: At least half of the patients at the 25 mg dose in Palisade saw TGs below 500 mg per deciliter, with approximately 75% achieving levels below 880 mg per deciliter.
Speaker Change: To support physician education on guideline-directed risk thresholds, we previously announced the launch of our disease awareness campaign.
Speaker Change: A key focus of our messaging is to educate the community about expert guidelines, which recommend maintaining triglyceride levels below 500 mg per deciliter to reduce the risk of acute pancreatitis.
Speaker Change: Third, the triglyceride reductions from baseline were consistent in patients with genetically confirmed and clinically diagnosed FCS.
Speaker Change: Results from Palisade, published in the journal Circulation, showed that plazastrin at the 25 milligram dose induced rapid, deep, and sustained reductions from baseline in ApoC3 of greater than minus 90 percent
Speaker Change: and in triglycerides of approximately minus 80 percent, independent of gene variants causing SCS.
Speaker Change: We believe this supports the potential value of plisastrin in patients with clinically diagnosed disease, regardless of genetic status.
Speaker Change: Fourth, plazasterin is the first and only investigational medicine to achieve a statistically significant reduction in the risk of developing acute pancreatitis in patients with genetically confirmed and clinically diagnosed FCS. This is truly the outcome of most importance for physicians, patients, and payers.
Speaker Change: And lastly, Plazastrin demonstrated generally favorable safety and tolerability with low rates of discontinuation for adverse events, and is conveniently dosed every three months, potentially reducing the treatment burden on both physicians and patients.
Speaker Change: As we prepare for the potential launch of Plazastron at the end of this year, we have built highly experienced market access and marketing organizations, and our clinical development colleagues have established a fully operational medical affairs function.
Speaker Change: Medical science liaisons from medical affairs are in the field conducting scientific exchange. Our market access colleagues are presently engaging with payers to communicate clinical and economic evidence and our national sales director will be executing our final field force hiring plans in the coming months.
Speaker Change: We are on track, and we're incredibly excited about the possibility of bringing investigational plazastron to FCS patients and their families. I'll now turn the call over to Dr. James Hamilton.
James Hamilton: Thank you, Andy. First, I want to give a quick review and update on two of the programs that are part of the Sarepta collaboration, AeroDUX4 and AeroDM1.
James Hamilton: These are both muscle-targeted programs in Phase I-II studies, which Arrowhead will continue to run until study completion, at which time Sarepta will assume responsibility for clinical development and ultimately commercialization.
James Hamilton: We are currently conducting a Phase I-IIa double-blinded placebo-controlled dose-escalating study to evaluate single and multiple ascending doses of Arrow DM1 in up to 48 subjects with myotonic dystrophy.
Thank you.
James Hamilton: We're in the dose escalation stage of the study, and we are enrolling patients at a good pace.
James Hamilton: We expect to reach the enrollment targets in the SREPTA agreement, which would trigger an additional $300 million in payments and potentially have first data to report this year, pending discussions with SREPTA and agreement on disclosure timing.
James Hamilton: Moving on to the second Sarepta-partnered muscle-targeted program, AeroDUX4. This is also in a phase 1, 2-way dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AeroDUX4 in adult patients with FSHD type 1.
The study is designed to enroll up to 52 subjects.
James Hamilton: Like AeroDM1, we are in the dose escalation stage and should have first data available to report this year, also pending discussion and agreement with Sarepta.
James Hamilton: These are both very interesting programs for muscle diseases with no adequate treatments available.
James Hamilton: Our preclinical data have been very compelling and we believe the programs have the potential to be best in class.
James Hamilton: Our colleagues at SIRESA have extensive neuromuscular development, regulatory and commercial expertise, so their input at this time is helpful and their strategic direction and involvement in the future clinical development and commercialization will be critical.
James Hamilton: We have a high degree of confidence that the SIRREPTA team can help accelerate the programs and maximize the chances for clinical commercial success.
James Hamilton: I also wanted to give a quick update on our obesity programs, Arrow Inhibin E and Arrow Out 7.
James Hamilton: These programs are both designed to intervene in a biological pathway regulating fat storage, which in an environment of nutrient excess, can become dysfunctional and overactive.
James Hamilton: Aeroinhibin E is designed to reduce expression of activin E, which is a ligand for adipose ALK7, while aeroALK7 is designed to reduce expression of the ALK7 receptor itself.
James Hamilton: In preclinical models, both programs demonstrated substantial reductions in fat mass versus control while simultaneously preserving lean mass.
James Hamilton: In addition, both targets are supported by human genetics, where loss-of-function carriers have favorable body composition and metabolic characteristics compared to non-carriers.
James Hamilton: We always prefer genetically validated targets because we think they reduce biology risk and give important insight into predicted safety and tolerability.
James Hamilton: For Arrow Inhibin E, in December, we began dosing in a Phase I-IIa dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of Arrow Inhibin E in up to 78 adult volunteers with obesity.
James Hamilton: In part one of the study is designed to assess single and multiple doses of aryl inhibin E monotherapy, and part two of the study is designed to assess aryl inhibin E in combination with terzepatide, a subcutaneously administered GLP-1-GIP receptor coagulant.
James Hamilton: We see the potential to have initial data from Part 1 of the study later this year.
James Hamilton: For AeroALK7, we recently received regulatory clearance in New Zealand to initiate a Phase 1-2a first-in-human dose escalating study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of AeroALK7 and up to 90 adult volunteers with obesity.
James Hamilton: We are completing manufacturing of drug supply as we speak and anticipate dosing to initiate in the middle of the year.
James Hamilton: During the last quarter, we also presented interim clinical data from a phase 1, 2A clinical study of AeroCFB, which targets complement factor B and is being developed as a potential treatment for various complement-mediated diseases.
James Hamilton: The data were presented at the 8th Complement-Based Drug Development Summit.
James Hamilton: Complement factor B plays an important regulatory role in amplifying complement alternative pathway activation and has been identified as a promising therapeutic target for complement-mediated kidney disease such as IgA nephropathy.
James Hamilton: which is the most common glomerular disease worldwide and carries a high lifetime risk of progression to end-stage renal disease.
James Hamilton: In the Phase I two-way study, circulating levels of CFB protein were reduced by a mean of up to 90% to date with a duration of response greater than three months.
James Hamilton: Additional data from the higher dose levels and multi-dose cohorts are pending and will be presented at an appropriate medical conference.
James Hamilton: AeroCFB also demonstrated reductions in measures of alternative complement pathway activation with mean reductions at or approaching 100% in AH50 and Weisslab AP at multiple dose levels.
James Hamilton: AeroCFB has been generally well tolerated to date with safety data supportive of further clinical development.
James Hamilton: Treatment emergent adverse events have been mostly mild and severity with none leading to steady drug discontinuation.
James Hamilton: We look forward to completing Part 1 of the study over the coming months and subsequently look ahead to Part 2 of the study in patients with IgA nephropathy.
I will now turn the call over to Ken Myszkowski.
Thank you, James, and good afternoon, everyone.
James Hamilton: As we reported today, our net loss for the quarter ended December 31st, 2024, was $173.1 million, or $1.39 per share, based on 124.8 million fully diluted weighted average shares outstanding.
James Hamilton: This compares with a net loss of $132.9 million, or $1.24 per share, based on 107.4 million fully diluted weighted average shares outstanding for the quarter ended December 31, 2023.
James Hamilton: Revenue for the quarter ended December 31st, 2024 was $2.5 million, compared to $3.6 million for the quarter ended December 31st, 2023.
James Hamilton: Revenue in the current period relates to our collaboration agreements with GSK.
James Hamilton: Revenue in the prior period primarily related to the recognition of revenue from our license and collaboration agreements with Chiquita and GSK.
James Hamilton: Revenue recognition related to the SREPTA License and Collaboration Agreement will begin during the quarter ending March 31, 2025. Revenue will be recognized over a period during which we are providing key performance obligations.
James Hamilton: This is primarily related to our responsibilities to manage certain clinical trials for the clinical candidates to which we granted SREPTA an exclusive license agreement.
James Hamilton: Total operating expenses for the quarter ended December 31st, 2024 were $163.9 million compared to $140.1 million for the quarter ended December 31st, 2023.
James Hamilton: The key drivers of this change were increased candidate costs and salaries as the company's pipeline of clinical candidates has both increased and advanced into later stages of development.
James Hamilton: Net cash used by operating activities during the quarter ended December 31st, 2024 was $146.3 million compared to $117.8 million for the quarter ended December 31st, 2023.
James Hamilton: The increase in cash used by operating activities is driven primarily by higher research and development expenses.
James Hamilton: Turning to our balance sheet, our cash and investments totaled $552.9 million at December 31, 2024.
James Hamilton: Including the $825 million in upfront payments from the SREPTA agreements, our pro forma cash and investments would be $1.4 billion at December 31st, 2024.
Based on our expected cash inflows from the Sarepta Agreement.
James Hamilton: Debt repayments, as well as other cash burn, we expect our cash and investments balance to be approximately $1 billion at the end of calendar 2025, and we expect to have cash runway into 2028.
James Hamilton: Our common shares outstanding at December 31st, 2024 were $125.6 billion.
Chris Anzalone: With that brief overview, I will now turn the call back to Chris.
Thanks, Ken.
Chris Anzalone: Not only do we see several growth drivers over the coming years, we have a robust potential catalyst calendar in 2025.
Chris Anzalone: Throughout the year, we expect multiple events that we believe are important.
For Bledaceran, we expect the following key events.
Chris Anzalone: Initiate SHAFTA V in patients at high risk of acute pancreatitis.
Fully enrolled Shasta 3, Shasta 4, and Muir 3.
Make additional global regulatory submissions.
Chris Anzalone: commercial launch in FCS in the U.S. and potentially the EU pending review and approval.
Professor Dasaran, initiate phase 3 HOFH study.
Chris Anzalone: For the obesity programs, we expect to initiate dosing in the Phase 1-2 study of Arrow ALK7 and potentially have the first data for Part 1 of the Phase 1-2 study of Arrow INHPE.
Chris Anzalone: For FasciSaran, our investigational RNAi candidate partnered with Takeda and being developed to treat the liver disease associated with alpha-1 atropine deficiency.
Chris Anzalone: we have the potential to reach full enrollment of the Phase 3 Redwood study.
Chris Anzalone: For AeroDUX4, AeroDM1, and AeroMMP7, we have the potential for initial data in the Phase 1-2 studies and the potential to achieve $300 million milestones payments from SREPTA.
Chris Anzalone: For both complement programs, Aero CFV and Aero C3, we have potential data readouts. And lastly, for the emerging CNS pipeline, we anticipate filing CTAs for our first systemically delivered and subcutaneously administered programs.
Chris Anzalone: As always, there is a lot going on at Arrowhead to be excited about. Thank you for joining us today, and I would now like to open the call to your questions.
Speaker Change: Thank you. If you would like to ask a question, please press star 1-1 on your telephone. You will then hear an automated message advising your hand is raised.
Chris Anzalone: If you would like to remove yourself from the queue, please press star 11 again.
Chris Anzalone: We also ask that you limit yourself to one question, and please wait for your name and company to be announced before you proceed with your question. One moment, please.
Speaker Change: Our first question will come from the line of Luca Ese.
of RBC Capital, your line is open.
Luca Ese: All great, thanks so much for taking my question, and obviously congrats on closing the deal with Sarepta. Maybe, James, on obesity, can you just talk a little bit more about inhibi? I know you're testing both, but is this fundamentally a monotherapy play in your head?
Luca Ese: or this is more like an add-on therapy to GLIP-1 or whatever's next for this category. It may be related. You just talk about what will be a downside case for the data later this year, and maybe an upside case for
Luca Ese: the data later this year, what's the bogey here? So any call there, much appreciated. And then maybe Bruce, super quickly, we've obviously seen Novartis is pushing out their data to next year for LPLA. Just wondering what was your reaction to that news and what does this mean for the broader category, including all paths around? Again, any call there, much appreciated. Thanks so much.
Speaker Change: Sure, thanks Luca. I can take a shot at the first question. Like you said, we are studying aero-inhibiny in monotherapy as well as in combination with terzepatide. We'll have to wait and see how the data look. We haven't really made a call on what the future path, development path, will look like for that molecule.
Speaker Change: And similarly, I think we'll just have to wait and see. We don't have really a specific bogey to hit, I think. We'll see how the data evolve on both the monotherapy side and in the combination arms.
Speaker Change: And just to be clear, obesity is not a one-size-fits-all condition, and I don't think people who are in it are thinking of it that way. This is a huge number of patients.
Speaker Change: with a variety of different needs. And so, you know, we're we're developing.
over time a suite of
Speaker Change: of drug candidates against it that could be used in combination with each other in combination with others in combination with
Speaker Change: with existing therapies in combination with new therapies. We are really excited about these two pathways and we think they're a great step forward and it's just not clear how the world is going to use these or frankly any other obesity drugs that are coming online.
Speaker Change: And finally your question about LP little a I don't have a lot of insight here Yeah, we're not on the inside of certainly the Novartis program. We're not on the inside of the Amgen program. So Yeah, we really don't know. I mean, I think you know in general I would say that I'm more excited you know about El Paso and just because I think it's
Speaker Change: It's a more effective agent with respect to knocking down LP little a.
Speaker Change: It's certainly more convenient than an anti-sense approach and probably better tolerated as well. I'm generally more excited about Opacaran from a cardiovascular disease perspective. But, you know, what's going on?
Speaker Change: with Novartis's compound and frankly even what's going on with Amgen's compound. I don't have an inside track on that information.
Thanks so much, guys.
Thank you. One moment for the next question, please.
Speaker Change: And our next question will be coming from the line of David Leboeuf of City. Your line is open.
David Leboeuf: Thank you very much for taking my question. I'm curious in the early days from what you've seen talking to your doctors regarding ApoC3 and current commercial launches, is there any feedback you're getting from doctors on what they're seeing?
David Leboeuf: Yeah, I'm just happy to comment on the feedback that we continue to receive with respect to plazastron, which as I mentioned they view as highly differentiating.
Thanks for taking my question.
Thank you and one moment please for the next question.
Speaker Change: Our next question will come from the line of Ellie Murrow of UBS. Your line is open.
Speaker Change: Hi, this is Jasmine on for Ellie. Thanks for taking our question and congratulations on the announcements today. I just wanted to follow up on an earlier
Speaker Change: So for Inhibin-E and ALK7, will we see weight loss data or anything on body composition from the Phase I, IIa trials? And if at this early time point we won't see that yet, what are you looking for to see from the PKPD results to give you confidence to move forward? Thanks.
Yeah, I think from the...
Speaker Change: In part one of the study, the monotherapy arms, we will be looking at
Speaker Change: at Body Composition based on full-body MRI, as well as, of course, weight loss.
and we'll look at them, the usual.
Speaker Change: phase 1 metrics, of course, safety and plasma PK, which will likely look like the other GalMAC sRNAs, and then we can measure the biomarker active in E in the blood. So that's the direct biomarker of gene target knockdown.
Great, thank you.
Thank you and one moment for the next question.
Speaker Change: Our next question will come from the line of Marie Rakoff of Jeffries. Your line is open.
Marie Rakoff: Hi, congrats on the progress and thanks for taking my question.
Speaker Change: I was going to ask about the Shasta 5 study. I know you plan to start this study in second quarter, and you've mentioned it could include 140 patients, and the purpose is mostly for payers.
Speaker Change: For this study, do you have estimates on what the timeline to data could look like? And can you talk more about the strategy here? I guess, could the totality of acute pancreatitis data de-risk an outcomes study or potentially even replace the need to run a CBOT study?
So Mario.
Mario: It's hard to predict, no one's ever attempted a trial like this before, that it'll be the first ever outcome study focused on pancreatitis as the primary endpoint.
Mario: It will be enrolling patients that are at clear risk for pacreatitis. So, you know, the enrollment timeline is, um...
Mario: You know a sort of to be determined you might say and in addition to that, you know as as with a c-bot for instance it is
Mario: an outcome study, so we will go until we get the required number of events. So it's not a fixed duration after enrollment is complete, but in fact it will keep going until the required number of events are seen.
Mario: So, you know, a couple levels of uncertainty there. We feel good about it. You know, we think it will be We think it'll be well received by you know by clinicians But but in reality, it's hard to really predict exactly when it'll happen
Mario: We think it will be a very important study though, and we think it will especially be a very important study to payers and to health assessment organizations.
Mario: especially outside the U.S. where places like the U.K., Germany, these health assessment organizations are very, very important. Health technology assessment organizations are very important. They really determine whether or not, you know, patients are going to have access to a new drug.
Mario: So, you know, we think this is going to be a revolutionary study, first of its kind, you know, practice changing.
And it will impact the U.S. as well.
we anticipate less so than it will in Europe.
Mario: The second part of your question, I didn't quite understand if you were asking whether it would
limit the need for, you know, for a CVOD.
Mario: I don't really think so, you know, just because I think that the question of...
Mario: Episclerotic risk related to triglycerides is really separate from the question of pancreatitis risk.
So I think there are two very important risks.
Mario: but they're really independent questions and especially for patients with milder forms of hypertriglyceridemia where the pancreatitis risk is quite low but the atherosclerosis risk is still very important.
Mario: And we think, you know, based on genetic data, represents an area of really unmet medical need and, you know, persistent residual risk of atherosclerotic cardiovascular disease.
Mario: We think we're the first, you know, the first drug that's really in a position to truly assess that risk and assess the opportunity, you know, for a drug that, you know, quite, you know,
quite effectively reduces triglycerides to impact that cardiovascular risk.
Speaker Change: Got it. It's all helpful perspective. Thanks for taking my question.
Thank you. One moment for the next question.
Speaker Change: And our next question will be coming from the line of Edward Tintoff of Piper Sandler. Your line is open.
Speaker Change: Great. Thanks, guys. Thanks for all the updates and for everybody as well out there.
Speaker Change: Question with respect to Europe and overseas with Clos d'Azur. Now that we've gotten, you know, the U.S.
Speaker Change: situation sort of laid out. What are plans for Europe and would you be partnering overseas? Are there certain thresholds?
Speaker Change: We're waiting for, you know, would there have to be additional studies? Just maybe you can update us on sort of what thinking is overseas, both for FCS, but also longer term for severe hypertriglyceridia and new things.
Speaker Change: Thanks for the call. This is Andy. So we're currently planning
We're currently planning for commercialization in European markets.
Speaker Change: along with a commercial partner. And so there will be more details on that in the future. We're incredibly excited about the large European markets and bringing plazastrine, investigational plazastrine, to those patients there as well.
Thank you.
Thank you. One moment for the next question, please.
Speaker Change: And our next question will be coming from the line of Patrick Tuchio.
of H.G. Reynolds. Please go ahead.
Patrick Tuchio: Thanks. Good afternoon and congrats on all the progress here. I've got a couple of follow-ups. The first is just...
Speaker Change: Can you review how you envision plazastron's competitive positioning relative to olizaracin in both FCS, but also in the broader severe high triglyceride populations?
Speaker Change: and how these product profiles could compare in the real-world setting, particularly as we look towards the potential launch upcoming for Plazastron FCS.
Speaker Change: And then just separately, just mention the adipose tissue targeting platform. I'm just curious, you know, what targets or disease areas do you view as being attractive as you look to build out this program from this part of the pipeline? And when may you have an update for us on this build out?
Speaker Change: Thank you for the question. This is Andy. I'll address the first part of your question related to differentiation. I'll speak primarily to the plisacerin data, but I would encourage you to
Speaker Change: to do your own comparison between the Balance and Palisade studies to the extent you want to understand the key differences yourself.
Speaker Change: differentiators that we see is around the reduction in triglycerides. As we've talked
Speaker Change: a triglyceride reduction from baseline, which is largely unprecedented, approximately minus 80% from baseline. And we see that as early as month one and then continued throughout that full 12-month treatment period. So I think that's the first point of differentiation one would focus on.
Speaker Change: I think the second point of differentiation is what that means for FCS patients as far as achieving guideline directed risk thresholds
Speaker Change: So, many of these society guidelines point to less than 500 mg per deciliter as the goal to which they want to get FCS patients below in order to reduce the risk of acute pancreatitis.
Speaker Change: So, obviously, the larger the TG reduction from baseline, the greater the proportion of FCS patients who are likely to achieve that guideline-directed goal. So, we think that's a key area of differentiation as well.
Speaker Change: And third, in comparison those studies you'd have an appreciation for the fact that Palisade studied both genetically confirmed and clinically diagnosed patients and what we saw was that
Speaker Change: Plazastrin was the first and only investigational medicine to achieve a statistically significant reduction in the risk of acute pancreatitis in that population. So again, an important point of differentiation. We spoke to acute pancreatitis as an important outcome for payers and patients.
Speaker Change: and physicians, and so seeing a statistically significant difference in palisade is an important differentiator. And then lastly,
Speaker Change: The safety profile has been generally very tolerable with low rates of discontinuation for adverse events. And importantly, we see in every three-month dosing with plazaster, and that's different from the alternative. That's only four injections a year.
Speaker Change: patients tell us is they prefer fewer injections and what physicians tell us is that helps with compliance and adherence and so they're quite excited about in every three month dosing regimen.
Speaker Change: So that would be, I think, the final point of differentiation I might point you towards. So those are just a handful of differentiating attributes of plisastrin that...
We recognize as a team.
Bruce Given: So let me chime in too. This is Bruce Given again.
Bruce Given: You know, I think it's a little easier to kind of, you know, put balance and palisade side by side than it is to necessarily put
Bruce Given: you know, what they're going to look like, what Olazarsan is going to look like in SHTG. I think we have a pretty good idea of what we would predict is going to be seen with Plozasuram because I think it's very likely that
Bruce Given: that Shasta 2 gives us a pretty good idea of what we're going to see there.
Bruce Given: I do want to just say, generally speaking, I think both for FCS and for SHTG, this is one of these markets where, you know, the industry, both us and
Bruce Given: Ionis. It's going to be an education market. We're going to be opening up this market. This has been, these essentially have been almost untreatable diseases, very poorly treated diseases with available, you know, currently available agents that have been around for decades.
Bruce Given: mostly generic, mostly not promoted. So, you know, I'm not sure, you know, while the street tends to think about head to head, you know, I think this is more going to be expansion. And in fact, having a couple of players in the market is going to help us expand.
I mean, we obviously like, you know, that side-to-side comparison.
Bruce Given: that Andy talked about. But I actually think the thing that's gonna benefit the patients most here is that there's gonna be two sets of voices out there trying to be sure that physicians get well-educated about these markets, understand that there are treatments now, that these treatments make a difference.
Bruce Given: and I think, you know, it's probably more a question of how much the two of us can expand the pie, you know, than necessarily competing for a fixed pie, because at this point I don't think there's, I don't think that's the case.
So I would just add that from a medical perspective.
Bruce Given: And on the obesity question, the adipose question, Patrick, this is James. So, you know, the indications that we're looking at, of course, include things like obesity, type 2 diabetes,
Lipodystrophy is also on the list.
Bruce Given: And we have a lot of targets that are of interest in the Adipa site. Of course, we're not going to share these targets.
Bruce Given: publicly at this time. I think, you know, we're evaluating those targets pre-clinically and you'll learn about the individual targets as they reach the clinic.
Great, thank you so much.
Thank you. One moment for the next question.
Speaker Change: And our next question will be coming from the line of Mainac, Montaigne.
of B Riley Securities, your line is open.
Speaker Change: Yes, good afternoon. Thanks for taking our questions and congrats on the Serapta deal close. So on that Serapta partnership, maybe a couple of quick questions. On AODM-1, you have cohorts four and five.
exploring 12-meg per kg quarterly and semi-annual dosing.
Speaker Change: Just to clarify, when you have day 180 biopsy data from both cohorts 4 and 5, is that part of disclosure within this year, or is that sort of a follow-up to a...
Speaker Change: initial sort of SAD, early MAD update you have this year. And then similarly for Aeroducts IV, which is understandably a larger study, how further would you be along in the MAD when you and your partners at Apta may look to put out an initial update this year?
Speaker Change: Hey Mike, our job here is to continue these programs moving forward as quickly as we can. We think these are important drugs. We look forward to handing them over to Sarepta once we finish the current studies.
Speaker Change: We really can't give you any guidance on data readouts because that's entirely up to Sarepta. We will be generating data all year when they decide to present data, when data are...
Speaker Change: interpretable and such you know we'll be we'll be really up to them so
Speaker Change: Okay, okay, understood. And just a quick one on Zodacirin and HSH, maybe if you could contrast the phase 3 target patient population with that of IFKISA and could patients theoretically get both antibody and sRNA?
to have optimal outcomes. Thanks again for taking the question.
Speaker Change: Yeah, I don't think that they'll be used together, and I think the target population is basically
you know, very much the aphkisia target population.
You know, Akisa, of course, is.
Speaker Change: An intravenous infusion, it has the same liability as all the monoclonal antibodies have for...
patients that occasionally develop severe allergic reactions.
Speaker Change: It's a monthly dosing, but I think the patient population itself, which is essentially...
Speaker Change: you know, patients that, you know, are still, you know, still have, you know, high LDL cholesterols despite, you know, high dose statins and PCSK9 inhibitors.
and that's basically the patient population.
Speaker Change: You know, there's a nuance there. You also pick up some patients that are intolerant to statins, but essentially, you know, the biggest part of the population are patients that, despite high-dose statins, you know,
Speaker Change: and PCSK9s are still not at goal, which is basically the DFQs of population as well.
Bye, thank you.
Thank you. Thank you. Thank you.
Thank you.
Thank you. One moment for the next question.
Speaker Change: And our next question will be coming from the line of Andrea Newkirk of Goldman Sachs. Your line is open.
Andrea Newkirk: Good afternoon. Thanks so much for taking our question. Maybe a follow-up to the prior one. Could you just speak a little bit more on this decision to restart efforts with Sodastrin and maybe quantify for us the magnitude of the commercial opportunity that you do see in HOFH to justify the incremental investment that you expect to see on both the R&D as well as the commercial side? Thanks so much.
Andrea Newkirk: Sure, so the Threft Deal of course gave us capital that we could reconsider that opportunity. That to us felt like as close to a no-brainer as exists in this industry.
Andrea Newkirk: The data, so far, has been good in the clinical programs, and it was just, it was sitting
Andrea Newkirk: It's not a gigantic market, of course, but the incremental commercial costs there are quite low because we are going to be addressing this market with Pulsasaran anyway, and so as I mentioned in the prepared remarks, you know, we're almost just there.
Andrea Newkirk: adding this to the bag of existing sales representatives. And so it doesn't cost very much more to do the phase three. It costs almost nothing more to do the added commercial. So we just saw that as a market that
We could take share, and so we plan to.
Thank you. One moment for the next question.
Speaker Change: And the next question is coming from the line of Manny Ferraro of Lee Rink. Your line is open.
Speaker Change: Hey guys, thanks for taking the question. A couple quick ones to clarify. When you talked about your pro forma cash balance, etc, a billion dollars,
Speaker Change: You said that was one of the things that came to account was debt service, and you described it as debt repayment.
Speaker Change: Are we to assume that you're going to be putting capital to paying down the 15% debt that you took out or should we just assume that that is debt service in the form of interest? And then I have a follow-up.
Speaker Change: when we bring capital in from milestone payments and such. So that is included in the cash balance that I referred to earlier. And to the extent there are further milestones down the road, certain percentage of those would be considered debt repayments. But we wouldn't be making anything beyond that.
Speaker Change: Okay, that's helpful. And then apropos of your answer to the last question regarding having a little more capital in hand and feeling sort of, you know, we,
Speaker Change: reinvigorate the ZASRAN program for the Outchasting Opportunities OFH. I want to hop back to PloZASRAN, how you should think about the CVOT, how you've got potential gating to restart that, timing to pursue a CVOT, and how to think about your own view on
Speaker Change: what are getting events to begin such a study and the capital that you put into place and how that might affect
Speaker Change: your willingness to partner other assets to continue to keep the balance sheet running, given that that adds meaningful opex.
Speaker Change: It's a great question. I don't have a firm answer for you, other than the fact that we, you know, we would like to do that CBOT, you know, the
The rationale for that is clear, and I'll let
Speaker Change: I'll let Bruce expand upon that in a second. We'd like to do that. What we're waiting on is additional capital. And so we're just not prepared to start that until we've got a better line of sight on additional capital to fund that.
We do have a lot of capital now, that's good.
Speaker Change: But we're going to need an influx of additional capital, substantial additional capital, before we would consider starting that.
Speaker Change: I sort of listed some of the current programs that we are interested in partnering at some point at least.
Speaker Change: Arrow Rage is one. We'd like to do a discovery partnership in pulmonary. We'd like to do a partnership with C3, with with Factor B, with PMPLA 3.
Speaker Change: We've got a number of these that are not core to our business.
We're happy to let go of.
Speaker Change: We are we and and we'll see what kind of capital can come in with those
You know, what's...
Speaker Change: Importantly, you know, there are some programs that are just off-limits, at least for right now. ALT-7 and NHIBany, we think, have too much value in them, at least in the near to mid-term, to think about partnering, so we're just not going to do that.
Speaker Change: MAP-T is another one. You know, we're going to hold on to that, at least for right now, and see where that goes. We would certainly consider doing a discovery partnership in CNS in, you know, with some limited number of targets, you know,
Speaker Change: Let's see if some capital comes in with that type of partnership. We could consider an Alpha-Nucleon partnership. It's not something that we're really focused on right now, but it's something that we would consider. It's not off-limits like MAP-T, I guess is what I'm saying.
Speaker Change: For those of you who may not be up to date on the case we're doing at CVOT, there's just an increasing body of information from Mendelian randomization studies, especially, you know, indicating that, you know,
you know, to very, very low levels.
Speaker Change: looks like from these Mendelian randomization studies in GWASes that a significant amount of that residual risk is explainable by elevations in triglyceride-rich lipoproteins.
and, you know, and again, Puzasrans.
Speaker Change: And if you use the Mendelian randomization data to sort of model what you expect, there's a pretty good expectation that this could be very effective in patients with
Speaker Change: mixed hyperlipidemia, and patients whose severe hypertriglyceridemia kind of stays out of the chylomicronemia range, so sort of from that 500 to 800 or so milligrams per deciliter, that range.
Speaker Change: We think that a CBOT would have a very good chance of demonstrating substantial reduction in residual risk despite LDL being well controlled. We would like very much to do this.
Speaker Change: This is the drug to finally answer that question in our minds.
So, scientifically, this would be an extremely interesting study.
Speaker Change: to cardiologists, probably not that different from how they feel about LP little a at this point from the standpoint of just a very, very important question to answer scientifically.
Speaker Change: that the FHTG market alone, which of course would not require the CVOT, you know, we have ongoing pay freeze now. We said we're going to be fully enrolled this year, we believe, and we think those studies will be finished in 2026.
You know, those enable...
addressing a market that we think
Speaker Change: It makes Plozacaran a $2-3 billion per year drug alone. So, yes, we do like the idea of continuing to expand the reach of Plozacaran, but even with what we're doing right now, we think that makes Plozacaran a larger drug.
of sort of contractually agreed upon payments for debt service.
Speaker Change: but not including additional voluntary pay down of principal beyond that. You expect to have cash pro forma near the end of this year about a billion dollars.
Speaker Change: Despite that, given your existing OpEx and CapEx you expect for your platform, you still need more capital to be able to feel comfortable moving forward into the CBOT.
Is that a correct interpretation of what you just said?
Speaker Change: That's a correct interpretation of what I said, because again, remember that we've got other stuff going on that we think are going to drive value as well, and obesity.
Speaker Change: and the CNS and the existing SHDG studies alone. So yes, those will absorb capital as well. That's why we would need additional capital to come in in order to start a CBOT.
Okay. Thank you for clarifying that. That was really helpful.
Thank you very much.
Thank you.
Thank you. One moment for the next question.
Speaker Change: And our next question will come from the line of Brendan Smith of TD Cal, and your line is open.
Brendan Smith: Hi, great, thanks guys for taking the questions. Actually, just a really quick one on Zodaciran. I know you referenced the phase 3 in HOFH that's going to start next quarter, but given the development cost synergies that you mentioned with Plozaciran and, you know, kind of the, you know, taking a look at the whole balance sheet and everything within the cardiometabolic pipeline,
Brendan Smith: I'm just wondering if you have any plans to potentially pursue heterozygous FH with Zodacirin, like maybe if it works in HOFH or potentially simultaneously, I'm guessing not that though.
Brendan Smith: or have you kind of just decided to put the idea to bed at HOSH and just kind of pursue any other indications with other drugs? Thanks.
Brendan Smith: Yeah so you know the I mean we've looked at that very carefully and and we actually think that if you take the patients that you know that receive
Thank you. Thank you.
Brendan Smith: appropriate doses of statins and you add on to that PCSK9 inhibition.
Brendan Smith: There is a persistent unmet medical need in patients that cannot get to goal inside of that.
at HEFH Market.
Brendan Smith: frankly, probably to include a commitment for a CVOT, and we simply don't think in that case the juice is worth the squeeze.
Brendan Smith: If there were a way to do a tailored program that focused on where the unmet medical need still is after PCSK9 addition to statins.
Brendan Smith: That would be worth going after, but we've explored that and there does not appear to be a regulatory path to do that. So the answer is no, we're not looking at HEFH for that reason.
Gotcha. Okay. Thanks very much, guys.
Thank you. One moment for the next question.
Speaker Change: And our next question is coming from the line of Jason Gilbury of Bank of America. Your line is open.
Hey guys, thanks for squeezing me in.
Speaker Change: For me, I'm just kind of curious how you guys are thinking about this two- to three-year window where you launch Plazasteran for SES, and if you think that's enough time.
Speaker Change: for revenues to be meaningful and, you know, as you think about the challenge really of
Speaker Change: taking this largely undiagnosed patient group and getting them into what sounds like, if you talk to a clinician.
Speaker Change: who are already prescribing Tringle's a small number of specialist centers to prescribe the Scriptor. Or if you look at it more as sort of an educational launch, and it's really all about it's HTG, just kind of curious to get your perspective there.
Yeah, thanks, Jason. This is Andy.
Speaker Change: have not had great options for them with respect to pharmacotherapy. And so plazastrine being available...
Speaker Change: We think we'll truly be a game changer for many of these FCS patients, that's what they've told us. And so we do believe in the return on investment over the next two to three years for plazastron and FCS specifically.
Speaker Change: and we're heavily focused on bringing those patients a treatment option that didn't exist previously.
Speaker Change: I would just say as it relates to any future markets, there is a high degree of overlap, as you would know, between those physicians that will be interested in treating for SHTG.
Speaker Change: medical and commercial related activities conducted over the next two to three years focused on FCS. No doubt there'll be an overlap of those physicians that will be interested in understanding that therapy for patients who have SHTG as well.
Got it, thanks.
Chris Anzalone: Thank you and that does conclude today's Q&A session. I would like to go ahead and turn the call back over to Chris for closing remarks. Please go ahead.
Chris Anzalone: Thanks everyone for joining us today. We look forward to seeing you next quarter.
Chris Anzalone: This does conclude today's conference call. Thank you for joining. You may now disconnect.