Q4 2024 Agios Pharmaceuticals Inc Earnings Call
Thank you operator, good morning, everyone and welcome to <unk> conference call and webcast to discuss our fourth quarter and full year 2024 financial results and recent business highlights you can access the slides for today's call by going to the investors section of our website at <unk> Dot com.
On today's call I'm joined by our Chief Executive Officer, Brian Goff Dr.
Speaker Change: Doctor, Sarah Hughes, Chief Medical Officer, and head of research and development. So I didn't even know about chief commercial officer, and Cecilia Jones, Chief Financial Officer.
Speaker Change: Before we get started I would like to remind everyone that some of the statements. We make on this call will include forward looking statements actual events and results could differ materially from those expressed or implied by any forward looking statements as a result of various risks uncertainties and other factors, including those set.
Speaker Change: Fourth in our most recent filings with the SEC and any other future filings that we may make with the SEC.
Brian: And with that I'm pleased to turn the call over to Brian.
Brian: Thanks, Chris Good morning, everyone and thank you for joining us our mission at <unk> is to develop and deliver transformative medicines that elevate and extend the lives of patients living with rare diseases.
Brian: We are especially focused on rare diseases that result in the dysfunction and destruction of red blood cells.
Brian: Coding pyruvate kinase deficiency, thalassemia, sickle cell disease, and lower risk myelodysplastic syndromes or Mds.
Brian: Our lead product pirate kind of pyruvate kinase activator has a novel mechanism of action that improves red blood cell metabolism and increases the amount of energy or ATP available to support Red blood cell health.
Brian: Today, we are pleased to share with you our results from the fourth quarter as well as reflect on accomplishments throughout 2024, and our expectations for the exciting new year ahead.
Brian: A rare blueprint for success uniquely positions us to drive significant growth and shareholder value creation over both the near and the long term.
Brian: First we have the exciting prospect of two additional commercial launches to support what we consider to be a multibillion dollar growth opportunity for our lead product pirate kind.
Brian: We are planning for a potential approval and launch in balance EMEA in September of this year, followed by sickle cell disease in 2026.
Brian: Second our early and mid stage pipeline is robust and poised for clinical advancement offering a strong foundation for innovation and growth.
Brian: And finally supporting it all is our highly experienced team with a proven track record of execution excellence and our strong balance sheet, which puts us in the enviable position of being able to independently grow the company and execute on these exciting opportunities.
Brian: 2024 was an exceptional year of execution and scientific excellence at our Geos as shown on this slide with check marks for each of the key milestones, we projected one year ago.
Brian: We meaningfully advanced each of our key programs, including filing for regulatory approval in <unk> across four markets.
Brian: And completing enrollment in our phase III rise up study for sickle cell disease and.
Brian: And we continue to progress our early pipeline building the foundation for sustainable long term growth.
Brian: After a transformative 2024, we believe 2025 is a breakout year for our Geos.
Brian: Over the next 12 months, we will focus on three key priorities number one maximizing the potential of the <unk> franchise number two advancing and diversifying our key pipeline programs and number three strategically focusing our capital deployment to sustained and draw.
Brian: <unk> of our growth.
Brian: And building on all of that was accomplished in 2024, we have another year ahead with compelling commercial regulatory and clinical milestones.
Brian: We announced topline results from the activate kids phase III trial of <unk> in pediatric patients with PK deficiency, who are not regularly transfused.
Brian: <unk> first pediatric clinical program for <unk> in a rare hemolytic anemia, and we are excited for Sarah to share with you. The positive topline data from this study in just a moment.
Brian: We also anticipate some exciting developments for our mid and early stage pipeline programs for.
Brian: For Teva payback, our novel PK activator, formerly known as AG 946, we expect to complete enrollment in the ongoing phase <unk> study in lower risk Mds by year end.
Brian: And initiate a phase II study in sickle cell disease by mid 2025.
Brian: Additionally, we expect to file an investigational new drug application for <unk>, three six rsi RNA targeting tempur six inhibition intended for the treatment of polycythemia Vera in mid 2025.
Brian: And the most significant expected events for 2025 include the September 7th to do for goal date for our <unk> filing of pirate kind in thalassemia and the phase three readout of the rise up study of <unk> in sickle cell disease by year end.
Brian: As you can see this year promises to be exciting with multiple catalysts across our pipeline that hold significant value for shareholders and have transformative potential for patients.
Brian: With those introductory comments, let me now hand, it off to Sara to review our exciting progress in R&D.
Sara: Thanks, Brian.
Sara: Our pipeline includes a well rounded mix of late stage programs nearing the market entry and promising mid and early stage opportunities that showcase our therapeutic depth and breadth.
Sara: We prioritize opportunities, where our expertise and resources can make a measurable impact and create significant value.
Sara: As you May have seen this morning, we announced topline results from our second phase III pediatric study activate kits, which evaluated <unk> in pediatric patients with PK deficiency, who are not regularly transfused.
Sara: This complements the phase III activate Steve study of missed that is that the children with PK deficiency, who are regularly transfused, which read out top line data in August of last year.
Sara: Turning to the results of the activate T study.
Sara: A total of 30 patients aged one to less than 18 years old were enrolled with 19 randomized to me talking about twice daily and 11 randomized matched placebo.
Sara: All patients in both arms completed 20 week double blind period.
Sara: The primary endpoint of the study with hemoglobin response defined as a greater than or equal to one five grams per deciliter increase in hemoglobin concentration from baseline that is sustained at two or more scheduled assessments at weeks 12 16 in 'twenty during the double blind period.
The primary endpoint of the study was next there were 31, 6% or six of 19 patients in the <unk> arm, achieving a hemoglobin response compared to zero percent or zero 11 patients in the placebo arm.
Sara: In addition improvements and changes from baseline for markers of hemolysis were observed in the midst of arm compared to the placebo arm.
Sara: In the 20 week double blind period, a similar proportion of patients have been first events and to meet that developed in placebo arms and there were no discontinuation of study treatment due to adverse events for any reason.
Sara: The safety results were consistent with the safety profile for Mr. Vivek previously observed for adult patients with PK deficiency, who are not regularly transfused.
Sara: With data now available from the randomized placebo controlled double blind period of both phase III pediatric PK deficiency study, we look forward to sharing more detailed findings with the community and interacting with regulators.
Sara: The activate and activate T phase III studies, Mark <unk> first pediatric clinical program for our rare hemolytic anemia, providing valuable insights that will help shape the company's future clinical programs evaluating the topic back in pediatric patients with thalassemia and sickle cell disease.
Sara: Now turning to thalassemia. This is a rare lifelong inherited blood disorder that causes chronic anemia in patients with thalassemia, often experience a range of debilitating complications such as organ damage stroke and better serious health issues.
Sara: Robin management strategy for thalassemia, such as blood transfusions, and Iron Chelation therapy can also lead to significant secondary effects compounding the health challenges patient space.
Sara: To date patients have limited or no effective treatment options with 67% of diagnosed patients in the U S have no approved therapies.
Sara: In 2024, we announced positive results from the Energizer and energize the phase III trial evaluating with Dr. <unk> versus placebo in adults with non transfusion dependent and transfusion dependent alpha or beta thalassemia, respectively.
Sara: A top line summary of the results across these two studies is shown on the left hand side of this slide.
Sara: Based on the favorable benefit risk profile observed in both the inner Jonathan Eric is the phase III studies, we believe <unk> has the potential to become a foundational and convenient oral medication for thalassemia patients regardless of genotype or transfusion needs.
Sara: In December we announced the simultaneous filing for regulatory approval of Pirate guide for this indication in the U S. The European Union Kingdom of Saudi Arabia, and the United Arab Emirates.
Sara: Last month, we announced that the FDA accepted our supplemental new drug application with the <unk> goal date of September seven 2025.
Sara: Moving onto sickle cell disease.
Sara: Inherited lifelong blood disorder is estimated to affect approximately 120000 to 135000 individuals across the U S and EU five with a global prevalence exceeding $3 million.
Sara: Clinical features of sickle cell disease, or chronic hemolytic anemia, and Faisal occlusion, which can lead to poor quality of life organ damage and early mortality.
Sara: There is an urgent need for novel therapeutic options to elevate the standard of care for patients suffering from this debilitating and life threatening disease.
Sara: Based on the positive results from our phase II <unk> study along with encouraging data from other hemolytic anemias with shared pathophysiology, we see significant potential with Mr. <unk> in sickle cell disease as well.
Sara: The phase III <unk> study completed enrollment in October 2024, with over 200 patients enrolled globally, achieving this milestone just over a year after recruitment again.
Sara: In this study we have two independent primary endpoints hemoglobin response, an annualized rate of sickle cell pain crises and Danny either primary endpoint allows us to apply all started the trial secondary end points with our secondary endpoints. We are using a variety of measures to assess with tap if thats a potential in improving how patients feel.
Sara: <unk> function.
Sara: We expect to report top line results from this phase III study in late 2025, with a regulatory filing and potential U S approval in 2026.
Sara: We believe with topic will have the potential to emerge as a best in class therapy aimed at addressing the high unmet need in this disease by improving anemia, reducing sickle cell pain crisis, and making patients feel better.
Sara: Next I'd like to give a brief update on <unk>, which is currently being explored as a potential treatment option for low risk Mds and sickle cell disease.
Sara: With lower risk Mds, we aim to deliver the first oral therapy that addresses anemia due to ineffective erythropoiesis in the disease.
Sara: This disease affects approximately 75 to 80000 patients in the U S and EU five with lower risk Mds accounting for approximately 70% of all Mds cases.
Sara: Last year, we initiated a phase II study of <unk> in Mds, featuring three cohorts at doses of 10, 15, and 20 milligrams all of which are higher than the five milligram dose in the phase Iia study.
Sara: Enrollment is proceeding well and we are on track to complete enrollment later this year.
Sara: Additionally, last September the FDA granted orphan drug designation to <unk> in this indication underscoring the importance of bringing an oral treatment option to patients suffering from this rare disease.
Sara: Sickle cell disease, given the significant medical need in the heterogeneous disease treating physicians emphasize the importance of having multiple treatment options available in 2024, we presented phase one results of the buffet bought in sickle cell disease at the Ash annual meeting based on these findings we will advance this clinical program to face.
Sara: Two developments with patient enrollment expected to begin in mid 2025.
Scott: With that I will now turn the call over to Scott.
Scott: Thanks Sarah.
Speaker Change: 'twenty one do you think we have the potential to expand <unk> indication to include the leukemia and sickle cell disease addressing the needs of these very underserved.
Scott: Based on population.
Scott: With our anticipated launching pellets EMEA later this year, we are aiming to deliver thus far as therapy indicated to treat all subtypes of the disease and with sickle cell disease. Our goal is to deliver a novel oral therapies that improve anemia, we do see today as a closing.
Scott: Prices for Vlccs and improves what peak.
Scott: By expanding <unk> into this larger patient populations, we aim to transform the treatment landscape for patients living with these diseases, thereby creating a multibillion dollar opportunity for our company and our shareholders.
Scott: Our team is working diligently to prepare for a potential near term launch entellus EMEA with three key areas of focus.
Scott: First we are using our robust disease state education campaign that highlights the disease pathophysiology. The long term complications of the disease and current standards of care and the importance of frequent monitoring and management.
Scott: Second we are right sizing our cross functional team to ensure a successful launch in this larger yet still ahead of market.
Scott: For example, four became efficiency our sales team was about 18 to 20 professional.
Scott: Portola EMEA, we have strategically growing the sales organization to approximately twice that size.
Scott: And third well.
Scott: As deeply engaging and educating payers on the leukemia to facilitated disease understanding and support patient access.
Scott: There are approximately 6000 adults diagnosed with <unk> in the U S.
Scott: With most patients diagnosed before birth.
Scott: With the availability of claims data, we can identify where these patients are managed within the healthcare system offering via local R&D for our launch preparations.
Scott: Within that population, we estimate that biogas and Michelle Lone Star, we will address approximately 65% of the adult <unk> patient population.
Scott: We expect thanks, Sean with more frequent contact with our health care system due to their disease symptoms to become see therefore therapy sorry.
Scott: These patients include Dulles corner transfusion dependent as well as those that are not transfusion dependent already experiencing complication or debilitating fatigue.
Scott: Our team is actively engaged in the field.
Seniors with deepening our understanding of these diverse based on segment and the multi cultural day management of the disease.
Scott: As we move forward increasingly.
Scott: Increasingly a larger launch in Brazil.
Scott: We are anchoring on the transformative profile of bioscience into leukemia characterized by a number of alright.
Scott: This is potentially the first therapy for both alpha and beta thalassemia patients.
Scott: The first oral therapy for the disease.
Scott: Treatment to demonstrate quality of life improvements for non transfusion dependent patients.
Scott: And the first treatment to demonstrate therapy six week durability of effect in reducing transfusion burden.
Scott: This is what motivates us to do.
Scott: All of our borrowing lines to people suffering from leukemia as quickly as possible.
Scott: Finally, let me provide a brief update on the current launch of Paragon and begin the <unk>.
Scott: <unk>.
Scott: In the fourth quarter of blended one before we generated 10.
Scott: Million in net <unk> revenue compared to $9 million in the third quarter of 2024.
Scott: In the U S. A total of 223 patients have completed a prescription enrollment forum, including 12 in the fourth quarter of plans it once before.
Scott: 6% increase versus the prior quarter.
Scott: This has translated into a 530 net thank you Anthony.
Scott: Therapy or ultra rare disease.
Scott: We believe the capabilities, we continue to strengthen towards the current launch will provide a firm foundation from which to maximize the potential.
Scott: U S launches of Biocrime into leukemia in 2025.
Scott: And in sickle cell disease in 2026.
Scott: Looking at the months ahead, our team will continue to sharpen its focus on the preparations for launch with the leukemia as our main priority.
Scott: We are excited about the commercial potential of the leukemia.
Scott: This is driven by the following three factors.
Hans: Thanks Hans are diagnosed.
Scott: And now include a health care system.
Scott: <unk> disease is well characterized and theyre, well established well and based on advocacy groups.
Scott: We are confident that all of these elements.
Scott: With our robust proliferation will pave the way for a successful launch.
In closing, we are inspired and energized by the potential to bring a new therapy to this underserved patient population.
Cecilia: With that I will turn the call over to Cecilia.
Cecilia: Thanks Peter.
Cecilia: Our fourth quarter 2024 financial results can be found in the press release, we issued this morning and more detail will be included in our 10-K, which will be filed later today.
Cecilia: Let me now take a moment to provide some context and highlight a few key points.
Cecilia: Fourth quarter 2024, net <unk> revenue was $10 $7 million.
Cecilia: Increase of 51% compared to $7 $1 million in the fourth quarter of 2023.
Cecilia: We note that revenue in Q4 of 2024 were higher primarily driven by year end stocking and adjustments to certain revenue reserves.
Cecilia: These accounted for approximately $1 $6 million in Q4, and we do not expect these items to repeat in the first quarter of 2025.
Cecilia: While lower in the fourth quarter of 2020 for gross to net has generally been and is expected to be in the 10% to 20% range on an annual basis consistent with other rare disease launches and will experience quarter to quarter variability.
Cecilia: Cost of sales for the quarter was one $3 million.
Cecilia: R&D expenses were $82 $8 million for the fourth quarter, an increase of $5 $3 million compared to the fourth quarter of 2023.
Cecilia: This was primarily driven by workforce related expenses.
SG&A expenses were $51 $7 million for the fourth quarter, an increase of $16 $4 million compared to the prior year quarter.
Cecilia: This was primarily driven by an increase in commercial related activities as we prepare for the potential approval of <unk> in 2025.
Cecilia: It is worth noting that we received a total of $1 $1 billion in milestone payments. Following the FDA approval of <unk>, which were recorded in the third quarter.
Cecilia: These payments included a $905 million payment from royalty pharma in connection with the Aurora sorry, the nib royalty purchase agreement announced in late 2024, as well as a $200 million payment from Servier in connection with agile divestiture of its oncology business in 2020.
Cecilia: One.
Cecilia: As a reminder, we retain a 3% royalty on annual U S. Net sales of <unk>, sorry, the nib greater than $1 billion.
Cecilia: Taking all this into account we ended the fourth quarter with cash cash equivalents and marketable securities of approximately $1 $5 billion.
Cecilia: We expect that this balance together with anticipated product revenue and net interest income will provide the financial independence to prepare for potential viracon launches into less EMEA in sickle cell disease advanced existing progress.
Cecilia: Genetically expand our pipeline through both internally and externally discovered assets.
Cecilia: Going forward and with our Purdue for data insight, we are shifting our focus to preparing for the potential launch entellus EMEA and we expect 2025 revenues for PK deficiency to be relatively flat compared to 2024.
Cecilia: Regarding pellets EMEA. It is worth reminding everyone that it can be several weeks, particularly at launch between prescription enrollment for them and their patients initiating therapy.
Cecilia: Combined with the expected time to set up their access we're looking at a more of a partial quarter.
Cecilia: Q4, which should be factored into modeling revenue expectations for 2025.
Cecilia: Obviously, we are eager for the September 7th we do for data to arrive and the team is well prepared for it.
Cecilia: Looking into 2026 and beyond we are optimistic about the team's ability to translate the favorable market dynamics, whether described earlier into a significant revenue trajectory for thalassemia.
In closing, we remain focused on creating shareholder value, including by proactively managing our cost base and deploying a disciplined cash relocation approach as we prepare to support potential future launches of private bank.
Cecilia: As we move towards additional potential value, creating milestones in the near term I am confident that our balance sheet will continue to enable us to execute from a position of strength.
Brian: I would now turn the call back over to Brian.
Brian: Thanks, Cecilia before we conclude I would like to highlight one more piece of news from our press release this morning.
Brian: Dr. David <unk> has informed us that he will step down from our board of directors effective February 28, 2025 to devote more time to his other commitments. He will continue to serve as a strategic advisor to our Geos as leadership team concentrating on advancing the company's clinical development programs.
Brian: <unk>.
Brian: David has been with <unk> for 15 years, serving as the company's CEO for 10 years and throughout as a member of the board of directors.
Speaker Change: On a personal level I'd like to thank David for his friendship Mentorship and guidance throughout my years, leading our Geos. He has played an instrumental role in shaping our company into what it is today on behalf of the entire organization.
Speaker Change: Also want to express our deep appreciation for his invaluable contributions we are truly grateful and look forward to continuing our collaboration with him in his new advisory role.
Speaker Change: 2024 was marked by exceptional progress at <unk> as soon as you have heard we have exciting regulatory and clinical milestones ahead in 2025.
Speaker Change: We believe 2025 will be a breakout year for the company based on anticipated approval and launch of <unk> in thalassemia.
Speaker Change: Critical phase III readout in sickle cell disease, and important anticipated progress across our mid and early stage pipeline.
Speaker Change: In closing I'd like to briefly reinforce the sealy. His comments, we have a very strong balance sheet, which provides us with the ability to independently execute across our key priorities, which include maximizing the potential pirate kind launches in thalassemia and sickle cell disease advancing our existing.
Speaker Change: Early and mid stage clinical programs and expanding our pipeline with both internal and external opportunities we remain.
Speaker Change: Committed to disciplined cash allocation, ensuring our strong balance sheet supports the achievement of key milestones and positions us for continued value creation.
Speaker Change: We look forward to the future as we strive to change the trajectory of these rare diseases with that I'd like to open the call for questions. Operator, Please open the line.
Speaker Change: Thank you if you'd like to ask a question. Please press star one one.
Speaker Change: If your question has been answered and you'd like to remove yourself from the queue. Please press star one again, we ask that you. Please limit yourself to one question and a follow up.
Speaker Change: Our first question comes from Eric Schmidt with Cantor Your line is open.
Eric Schmidt: Well, thanks for taking my question or question and follow up and congrats on all the progress looking forward to another remarkable year in 2025.
Eric Schmidt: Maybe first for Sir what's the company's plan or strategy for updating the investment community on the safety profile of <unk> that should there be any further pieces of the powder cellular injury or any signals whatsoever. There.
Speaker Change: And then for Brian.
Speaker Change: Now for probably the past year or so I think you've been talking about the multibillion dollar potential metope that.
Speaker Change: These additional indications how do you think about peak sales potential in either thalassemia or sickle cell disease as you construct that multibillion dollar estimate thank you.
Speaker Change: Sure. Thanks, Eric.
Speaker Change: <unk> you want to start on the first question sure. So thanks for the question so.
Speaker Change: As we have done when we were aware of this new safety information for thalassemia, we have update at the Investor community at the time that we were able to make that call that there was a change in the safety profile of the drug. So if anything would change to the safety profile of the drug as we currently understand it.
Speaker Change: And we make that call then we would update you guys.
Speaker Change: As well.
Eric Schmidt: And on the second question Eric on.
Eric Schmidt: On the multibillion dollar potential that we see for pirate time.
Eric Schmidt: I will say that we're very excited for the position that we have right now with all the momentum the backdrop of the clinical data as well as now that the <unk> date for thalassemia that we talked about and just to characterize why we have such conviction in the long term potential.
Eric Schmidt: That was <unk>.
Eric Schmidt: We as we said on multiple calls two thirds of the patient population in the U S have no approved therapy option, which presents a profound opportunity in terms of unmet need for those patients and we look at the combined opportunity of both the energizing the <unk> T data and it is.
Eric Schmidt: A really compelling profile so that'll be obviously, the first step on that multibillion dollars pathway the second.
Eric Schmidt: With sickle cell disease, I think it's been really obvious to the whole community that the unmet need in sickle cell disease has always been very high and it has actually increased in the past few months, given some of the challenges and limitations and available therapeutic options.
Eric Schmidt: So thats an important step for us too and of course, we'll be in a position to give more guidance as we move through these approval pathways. The launch phases and in the case of sickle cell disease, it's getting to the point of the data readout at the end of this year for the rise up phase III study, so a lot of conviction.
Eric Schmidt: Thats, all with pirate China and of course, we're building out a PK activation franchise beyond that with the benefit of Teva peer that as we've noted we are pursuing a phase II study in sickle cell disease as well as.
Eric Schmidt: We're already enrolling in our phase <unk> for low risk Mds, So a lot of opportunity ahead.
Speaker Change: Thank you. Our next question comes from David <unk> with TD Cowen Your line is open.
Speaker Change: Hi, Jim This is David on for Mark Congrats on all the progress and thanks for taking my question.
Speaker Change: Two one on sickle cell, so I'll take the liver tox disclosure and I'll share.
Speaker Change: Can you provide any details on changes to the sickle cell trial protocol is it mostly in the OE portion or.
Speaker Change: Or are there any changes to the core portion of the trial and then I have a follow up.
Speaker Change: Thanks for the question. So we in the core period. So after we had made that call. We took a look at the monitoring across all of the trials and.
Speaker Change: We were already monitoring in our core period for our liver test and so on.
Speaker Change: Along the way in each of our trials into blinded period, which is very in line with how people.
Speaker Change: <unk> therapies in the real World and monitor monitor drugs in the beginning when they start Ah patients on drug in the open label, we have to make a tweak to aligned.
Speaker Change: Monitoring frequency so once a month to what we were doing into the core periods of the sickle cell disease trial. So now everybody is being monitored across all of our programs.
Speaker Change: Once a month for the first six months of exposure.
Speaker Change: That's helpful and then.
Speaker Change: Cabo is being explored in sickle cell how should we think about the development part. There is this more of like a proof of concept before moving into other diseases or if the trial is successful do you actually plan to move forward.
Speaker Change: Into pivotal development in sickle cell with this program yes.
Speaker Change: I think thanks, Steve, Yes, I think I'm going to have set a comment on that from a longer term commercial perspective, because again, it's a real benefit to have not one but two.
Speaker Change: Opportunities in this very complex very high unmet need disease.
Speaker Change: Absolutely.
Speaker Change: When we think about sickle cell disease, Brian mentioned it there is such a high unmet need in the patient community and we hear it loud and clear from clinicians that there is a need for more than one treatment options with the need for one more Walmart and lumpy FD base. So as we currently stand with Veeva.
Speaker Change: We are looking for an opportunity to build a sickle cell disease franchise across both viral guides and type of feedback in terms of specific co positioning of the two products and how are we going to develop that with veeva, while we will be guided by the data as always we'll need to see the rise update we'll need to see the debit favor.
Speaker Change: Phase II data, we will be looking at the competitive environment at that point in time and so alright.
Speaker Change: Closely together to develop a clinical development plan, which will not only meet the needs of regulators, but will be commercially viable for us as well.
Speaker Change: And as we get closer to the mid year start we'll of course give more clarity on the trial design and exactly what that looks like.
Speaker Change: That's helpful. Thank you.
Speaker Change: Sure.
Speaker Change: Thank you. Our next question comes from Gregory <unk> with RBC capital markets. Your line is open.
Speaker Change: Great Good morning, Brian and team congrats on the progress in the year and thanks for taking my question.
Speaker Change: Brian maybe just dipping into into the pipeline and as you get your handle on the PK activation portfolio I just wanted to ask about your enthusiasm or how you're characterizing.
Speaker Change: Your level of enthusiasm with respect to AG one a one that the PIH stabilizer, maybe just remind us of that specific mechanism, how it stabilizes ph and perhaps why it should work well with patients who don't respond to the cofactor treatment. Thank you.
Speaker Change: Sure. The first thing I will just say Greg is I am not I do not pick favorites among children within our pipeline we are really proud of.
Speaker Change: All of the.
Speaker Change: Across the pipeline.
Speaker Change: As my first comment the second is we're in a really good position of strength from a diversification within the pipeline in both type of asset disease as well as stage of development with respect to AG 101, which is a phenylalanine hydroxylase stabilizer.
Speaker Change: In a way it's similar to part of a kinase activation stabilizes the enzyme that's needed for the conversion of phenylalanine to tyrosine. We're in phase one now and of course, we look forward to giving continued updates as we make progress on the development opportunity.
Speaker Change: But this is a very high unmet need population, we're talking about 35000 to 40000 patients.
Speaker Change: A very small subset of those who are actually actively treated and they have frankly very limited treatment options. So.
Speaker Change: It's another mark of excellence that this came out of the Geos developments.
Speaker Change: Covered in development.
Speaker Change: And again, it's right in the sweet spot of what we do best at our Geos, which is address high unmet need in rare diseases, and we definitely look forward to giving you more updates.
Speaker Change: Okay. That's helpful and maybe just a broader question taking a step back.
Speaker Change: You look at your potential cash deployment internally and of course externally how are you seeing the market for external asset, especially in light of what is the rather active market not just domestically, but also globally.
Speaker Change: Yes, Great question first of all to reinforce what you just said, we're clearly is one of our key ingredients.
Speaker Change: Yes.
Speaker Change: Compelling rare disease company with a very bright future ahead, and we're pleased with the I'll call. It enviable strength of our balance sheet.
Speaker Change: And that enables us to as a first priority as I noted in my comments to make sure that we maximize these launch opportunities we have thalassemia.
Speaker Change: With a <unk> date. This year, we have sickle cell disease potentially next year following the rise up readout, so thats job one.
Speaker Change: Job two is as you just asked me we have other mid and early stage products in our pipeline, we want to make sure that we continue to deliver on those value creating inflection points.
Speaker Change: And then to your question.
Speaker Change: Actually scaled up our business development capabilities, particularly from a search and evaluation standpoint.
Speaker Change: I think it's important.
Speaker Change: Is any healthy company, we will do is to be very disciplined in that approach, but we're very clear on what would match well with the <unk> rare disease capabilities, which continue to increase particularly on the commercial side.
Speaker Change: And we look in domestically and we also have global line of sight as well, but we'll be very thoughtful and disciplined.
Speaker Change: Where we believe we can add significant value creation.
Speaker Change: Great. Thanks, Brian.
Speaker Change: You bet. Thanks, Greg.
Speaker Change: Thank you. Our next question comes from Greg Harrison with Scott Scotiabank. Your line is open.
Speaker Change: Hey, good morning, Congrats on the progress and thanks for taking the question.
Speaker Change: Thinking about how how.
Speaker Change: How do you think investors should be.
Speaker Change: Modeling the launch trajectory.
Speaker Change: <unk> in thalassemia, and maybe in 2026 understanding there'll be some time to get access and lag time.
Speaker Change: Before initiating therapy and <unk>.
But would you expect there to be pent up demand or an initial bolus in some of these patient groups that you discussed is the initial launch focus.
Brian: Yes, Thanks, Brian.
Brian: To start by just saying I'm really proud of setup and her entire commercial organization that has been so dedicated to particularly disease state education for thalassemia, which is very much needed in this arena.
Brian: And so we're really well positioned and prepared for now that <unk> date in September and study you want to comment on what those dynamics look like towards the end of the year.
Brian: Absolutely. So thanks for the question.
Brian: The team is working very diligently to prepare for launch.
Brian: And we are super excited by the opportunity to provide this treatment options to patients in the U S.
Brian: You mentioned, we've given guidance on our initial launch focus which cover about 65% of all of that the lithemia adults lithemia patients in the U S, which is 4000.
Brian: 6000.
Brian: In total for us.
Brian: On a long term perspective, we are definitely educating till increase the urgency to act the monitor and treat these patients having said that we don't expect to have an initial bolus in patients.
Brian: Got it.
Brian: Today, our Doctor is frequently these days, depending on their transfusion dependent and non transfusion dependent status and complications. So we will expect to capture these patients as they come and of course, we will continue with the disease education to ensure that the right conversations that are happening for them to make that property at Jive for the best treatment for patients moving.
Brian: Forward.
Brian: Yes.
Brian: This is smart triaging too when we say, 65% targeting it doesn't of course mean, we don't eventually target the other 35%, but we're making thoughtful choices to make sure that we get off to a solid start in terms of the launch ramp.
Brian: The team has said I had noted earlier has already been so called right sized for this opportunity.
Brian: And now the intensive focus between now and the launches disease education, and then once we get clarity on the label and we have that launch opportunity, we're going to be in a great position.
Speaker Change: Thanks, that's helpful. I also wanted to ask about.
Speaker Change: The Gulf region, and the launch there are you getting a better handle on the commercial potential.
Speaker Change: In the region and how should investors be thinking about that opportunity.
Speaker Change: Yes, we are seeing the Gulf region, obviously, the U S is our number one commercial priority as an organization and then when we look ex U S. The golf is the second commercial opportunities for us within the golf.
Speaker Change: Saudi Arabia is the biggest market.
Speaker Change: As we've noted we have breakthrough designation in that region and we're working very closely with the new but its team.
I'll go through the regulatory process.
Speaker Change: In Saudi Arabia, when we think about launch ramp in that region.
Speaker Change: The way I would think about it is more closely related and stimulus to the European market dynamics, It's a national healthcare system. When there is a national decision on approval enterprise. However, we deem the different segments within Saudi Arabia, and the health care system. For example, the private sector the Ministry of Health.
Speaker Change: As well as academic institutions will needs to work with those segments into health care system to ensure that there is a formulary access which can take time to ramp up over time, but there is a big commercial opportunity from patient numbers, and we will navigate that with Newbridge accordingly.
Speaker Change: Great. Thanks, so much.
Speaker Change: Thank you.
Thank you. Our next question comes from Chris Raymond with Piper Sandler Your line is open.
Chris Raymond: Yes, thanks for taking the question.
Speaker Change: Two questions.
Chris Raymond: First I guess.
Speaker Change: On the PD studies in <unk>, I think you've characterized activate and activate kids T.
Chris Raymond: I was giving insights.
Speaker Change: Into future.
Chris Raymond: <unk>.
Speaker Change: Work and Sal and sickle cell can you maybe elaborate a little bit on this benefit would you expect.
Speaker Change: Some perhaps short circuiting I guess.
Speaker Change: Our pediatric program, there or would there potentially be labeling benefit sort of out of the gate.
Speaker Change: Just from this work and then and then the second question I know <unk> had this question.
Speaker Change: A number of times, but just on the <unk> and a potential panel just with all this focus on liver injury.
Are you.
Speaker Change: Companies rarely hope for a panel but.
Speaker Change: It would seem that with all of this.
Speaker Change: Attention. That's on this this actually might be beneficial just to sort of put it.
Speaker Change: Some light on this.
Speaker Change: Thoughts there.
Speaker Change: On your desire there a panel or not thank you. Thanks, Chris sorry, you want to start on on thank you start with pediatric yeah, I'll start with the pediatrics. So.
Speaker Change: Well why are they are saying that this is really helpful is pediatric development is very heart rates and solid transfusion trials are also very hard to run. So we have worked through a lot of logistical things that we needed to consider for those pediatric trials and they have not experience implementing these PDF.
Speaker Change: Quick trials and bringing them to a successful completion all of those lessons learned along the way we will apply to any other future pediatric trial. We run. So there is a huge benefit from actually having that hands on experience and that.
Speaker Change: That will in fact.
Speaker Change: Things like feasibility startup and clinical trial logistics on any of those programs. So.
Speaker Change: So we are we're very happy with that and then of course, because we're following a very similar path across the hemolytic anemia adult development.
Speaker Change: We went from <unk> to <unk> for sickle cell disease have benefit risk.
Speaker Change: And the PK the adults and now in the Dol adults. There is a lot of lessons that can be applied from adults to pizza as well. So we are we're just in general very excited about.
Expanding the patient population, there and then Zach or any label negotiation you go through helps with the next label negotiation Thats also multiple benefits along the way in regards to the <unk>.
Speaker Change: <unk> date and the potential for a panel. So we are very very happy that the Purdue date has been announced so far September 7th.
Speaker Change: We have not heard that we would be having a panel at this point in time. So indeed panels are a lot of work both for us and for the FDA. So.
Speaker Change: I'm not sure if I.
Speaker Change: Carefully.
Speaker Change: The assessment.
Speaker Change: That we might be hoping for a panel I would I would.
Speaker Change: I don't know I think either way, we will be ready if it would happen.
That being said I do think you already have a light on what actually happened because we have the PK deep label update with the warning precaution, which truly highlights what we have observed in the thalassemia patient population.
Speaker Change: And that assessment has been.
Speaker Change: No agreed upon with the FDA for the label update in PK data. So I think we're good with that with the current data.
Speaker Change: Thank you.
Chris Raymond: Thanks, Chris.
Speaker Change: Thank you. Our next question comes from Alex Stranahan with Bank of America. Your line is open.
Speaker Change: Hey, guys. Thanks for taking our questions and congrats on the update.
Speaker Change: From us as well and look forward to a busy 2025 ahead.
Speaker Change: Just two from us.
Speaker Change: Thinking about the process of scaling your sales force for Bell.
Speaker Change: Given the entered I'd say it's.
Speaker Change: Both been presented at major medical meetings.
Speaker Change: What is your sense of the level of awareness amongst physicians as well as <unk>.
Speaker Change: And advocacy groups that this kind of tracking with what your hopes are is there may be more work to do there.
Speaker Change: Has this fed into the number of reps you hired for commercialization or not really.
Speaker Change: Yes study do you want to get started yeah, absolutely. So first of all.
Speaker Change: In a very disciplined way once we had the data from the <unk>.
Speaker Change: Savi, we made that decision until actually pressed the button.
Speaker Change: And started right sizing the customer facing organization for launch the way we have approached the launch any rare disease launch is a very comprehensive way focusing on the patients physicians and payers and ensuring we have the rights.
Speaker Change: Organizationally, we have already right sized.
Speaker Change: We have already right sized.
Speaker Change: The sales force in particular as we've said we had about 18 to 20.
Speaker Change: Accumulated anemia specialists covering became efficiency for the Lithemia given the fact that we have very well established ICD 10 codes. It allowed us actually rightsize the organization of property, but appropriately so.
Speaker Change: Valid data about double that size.
Speaker Change: On awareness perspective, the team has been in the field in the U S.
Speaker Change: The next thing both with the Joe Welcome Unity, but also with the the prescriber base majority of which is community hematology and I can tell you all are aligned with expectations. There is a high awareness not only of the disease, but the potential for new therapeutic options for these patients and <unk> profile.
Speaker Change: We're continuing our efforts on disease state education, with both patients and physicians.
Speaker Change: As well as we are very welcome that states as an organization with the patient community and the patient advocacy groups, Sarah and I actually had the opportunity to meet with team recently.
Speaker Change: And I can tell you that the excitement that come from from those groups is very very high for the potential of <unk>. So we are working hard to prepare I can tell you. We are ready for launch and the team now is actually going deeper and deeper to make sure that we execute very successfully from the beginning on the opportunity ahead of us.
And the of course before we got the <unk> date, we didn't we didn't know when.
Speaker Change: Dave will be set and so the team has any great prelaunch team does we've been prepared for a range of scenarios.
Speaker Change: The fact that we now know what September set and the team are maximizing this opportunity in terms of disease state awareness between now and then every month, we see continued progress with the KOL community as well as the in the community treating physicians, they're doing a great job.
Speaker Change: Thanks for that and then just a quick one on the pediatric PK.
Speaker Change: I'm curious if you just to put a finer point if you intend to seek approval in both transfusion populations that regularly and nuts are regularly transfused.
Speaker Change: And whether you think approval across the patient groups could could be warranted.
Speaker Change:
Speaker Change: Given the totality of the data across the two studies. Thank you.
Speaker Change: Yes, that's an emphatic, yes, Sachin got it yes, when you ask the question I actually know that yes.
Speaker Change: So the data across the two trials is really supportive of benefits.
Speaker Change: Total positive benefit risk profile across the patient population we regularly.
Speaker Change: Regularly transfused trial, we have patients still have patients who are completely transfusion free so that is an.
Speaker Change: Enormous clinically meaningful benefit and then here on this trial, we clearly have positive results across the board.
Speaker Change: Statistically significant across.
Speaker Change: Using both methodologies basically methodology and a frequent just approach. So we're very pleased with that as well and we're looking forward to.
Speaker Change: And hopefully obtain that broader label for patients with <unk>.
Speaker Change: I know this is an investor call, but from what fuels us as an organization is the.
Speaker Change: The stories that we hear from patients and these are.
Speaker Change: And PK PD in general of course power kind of the only approved therapy for adult patients and these parents have had kids to summit bins will not demised and others are.
Speaker Change: Waiting it might have that as a potential and to have this promising data.
Speaker Change: Clinically relevant in the activate <unk> T trial with transfusion dependent pediatric patients and now with today's data. This is really compelling and we will certainly do our best to move that along with the regulators at the right time to make this available for patients.
Speaker Change: Thank you.
Speaker Change: Thank you.
Speaker Change: Thank you. Our next question comes from <unk> Richter with Goldman Sachs. Your line is open.
Speaker Change: Hi, Good morning. This is lidia on for solving thanks, so much for taking my question and congrats on all the progress maybe just a follow up to the previous question on pediatric PK D. Could you just discuss how expanding into the pediatric population could potentially impact the total opportunity in TKD. Thanks, so much.
Speaker Change: Yeah, absolutely. So the pediatrics is about 20% of the <unk> opportunity as we navigate these ultra rare disease. When we look at the pediatrics trial as Sarah mentioned for US. It's a good opportunity to provide treatment options for patients in need that currently have.
Speaker Change: No treatment options, but very importantly is the is a starting point for us to continue with the pediatric development across all of the other indications.
Speaker Change: The learning is that the lithemia potentially sickle cell disease in the future.
Speaker Change: Yes, I think maybe just to reinforce the point that facility are made earlier too.
Speaker Change: PK PD revenue.
Speaker Change: This is about 20% of the population, but this is an ultra rare population and so again the way we look at PK D. This year, particularly in light of the preparation and focus we have for thalassemia is where.
Speaker Change: We're expecting flat revenues over 2024, but again for pediatrics.
Speaker Change: It's an important addition, when we get to that point for treatment Optionality for these patients.
Speaker Change: Excellent.
Speaker Change: Thank you.
Speaker Change: Thank you. Our next question comes from Tess Romero with J P. Morgan Your line is open.
Speaker Change: Okay.
Tess Romero: Hey, guys. Thanks, so much for taking our questions.
Tess Romero: Sure My brief financial question from Us to start to see area in terms of your Opex. What is the right way to think about the evolution of your SG&A expenses in the cadence of a ramp up there over 2025 and enter 2020 sacks and on the R&D side any additional color you can give us there.
Tess Romero: I have one follow up.
Tess Romero: Sure. Thanks for the question. So as we mentioned we continue to proactively manage our cost base is not as part of our disciplined capital allocation approach that being said as Brian described earlier, we have three buckets or three priorities on that the first one is preparing to maximize the power of <unk>.
Tess Romero: Community with their potential.
Tess Romero: To have back to back lunches and also advancing the pipeline for both SG&A and R&D, we expect to see growth year over year in the coming couple of years USD seven point over a point of variability not everything obviously straight line, but we do anticipate to see growth.
Tess Romero: Both items.
Speaker Change: Okay and can you quantify what growth means.
Speaker Change: We haven't given specific guidance on growth, but like I said, we're being very disciplined on how we approach. This makes that I've mentioned, we waited to see that's alethia data to kickoff the bigger ramp on center Femia, we're doing a similar approach on Cisco said.
Speaker Change: We wanted to try to be prepared and we don't want to find.
Speaker Change: Find ourselves in a positive scenario, what we did and therefore that like regulation that very disciplined approach.
Speaker Change: And then within that from a timeline perspective can you lay out for our regions beyond the U S. How youre thinking about timing of approval now on <unk>.
Speaker Change: About.
Speaker Change: The EU, Saudi Arabia, and the UAE.
Speaker Change: Yes, I think Sarah you want to comment there instead of can touch on commercialization approach the timing of approval.
Speaker Change: The <unk> date for the FDA that's September.
Speaker Change: September 700 that is announced and everything the others. It's less they don't give proactively a date by which they will approve so it depends on how the process go into round.
Speaker Change: The amount of questions you get along the way, but we're very excited about the progress that is currently being made and.
Speaker Change: Are on track to deliver.
Speaker Change: Yeah and from a commercialization perspective as I commented earlier in the Gulf region, where the biggest opportunity Saudi Arabia. After you have an approval we will need to go through the access and formulary discussions with the different breadth of the country. So the actual ramp is going to take some time.
Speaker Change: Uh huh.
Speaker Change: Very similar to how the European Health care systems work for.
Speaker Change: Europe from a commercialization perspective, we're looking for a potential partnership there as well.
Speaker Change: Soon as we have PMA approval.
Speaker Change: You'll be able to actually navigate the European health care systems as well as you know very well in Europe is a country by country pricing and reimbursement decisions. So again there'll be a time lag between approval and actually an actual commercialization in Europe.
Speaker Change: Okay. Thanks, so much.
Doug: Thanks, Doug.
Speaker Change: Thank you I'm showing no further questions I'd like to turn the call back over to Brian for closing remarks.
Speaker Change: Alright, Thanks, a lot Michelle Thank you very much everybody for participating in today's call. We are a month and a half into the start of what promises to be a very busy and exciting year, it's an exciting time at <unk>.
Speaker Change: We really believe that we're poised to deliver transformative new therapies for patients and create significant long term value to shareholders. So thanks again, and we look forward to speaking with you again soon.
Speaker Change: Thank you for your participation. This does conclude the program and you may now disconnect everyone have a great day.
Speaker Change: Okay.
Speaker Change: [music].
Speaker Change: Okay.
Speaker Change: Yes.
Speaker Change: Okay.
Speaker Change: Okay.
Speaker Change: [music].
Speaker Change: Yes.
Speaker Change: Okay.
Speaker Change: [music].
Speaker Change: Yes.
Speaker Change: [music].
Speaker Change: Uh huh.
Speaker Change: Yes.
Yes.
Speaker Change: Okay.
Speaker Change: [music].
Speaker Change: Okay.