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spk09: Good day, and thank you for standing by, and welcome to Q3 2022 Adios Pharmaceuticals, Inc. Earnings Conference Call. At this time, all participants are on a listen-only mode. After the speaker's presentation, there'll be a question-and-answer session. To ask a question during the session, you'll need to press star 1-1 on your telephone. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Holly Manning. Please go ahead.
spk03: Thank you, Operator. Good morning, everyone, and welcome to Agios' third quarter 2022 conference call. You can access slides for today's call by going to the investor section of our website, Agios.com. With me on the call today with prepared remarks are Brian Goff, our Chief Executive Officer, Dr. Sarah Guins, our Chief Medical Officer and Head of Research and Development, Richa Poddar, our Chief Commercial Officer, and Cecilia Jones, our Chief Financial Officer. 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 forth in our most recent filings with the FCC and any other future filings that we may make with the FCC. With that, I will turn the call over to Brian.
spk10: Thanks, Holly, and good morning, everyone. It's a privilege to join you today on my first AGIOS financial results call as Chief Executive Officer nearly three months after assuming the role in August. AGIOS has a longstanding legacy of scientific excellence in clinical execution and is on the cusp of broadening its ability to change the treatment landscape of rare and genetically defined diseases. With the recent launch of PyroKine and its extensive clinical and preclinical pipeline, the opportunity that lies ahead for Agios and the patients it serves is exciting. Since joining in August, as I've dug into the business and met so many of our talented team, my optimism and excitement for the future of Agios has grown for several reasons. The strength of the culture and patient orientation is even better than I perceived during my diligence process. The emphasis on our shared mission of improving lives is palpable across all functions within the organization and part of the fabric of the decisions we make, the people we hire, and the reason we come to work every day. Second, for a company of our size, the depth and breadth of activity across all areas of the business is remarkable. 2022 has been a year of execution with five pivotal studies and two early-stage trials underway, an ongoing commercial launch in the U.S., an active filing in the EU and Great Britain, an advancing preclinical pipeline, and broad business development efforts to continue to build out our pipeline. And finally, while the PyroKine launch was always attractive based on my experience and passion for rare diseases, I've come to further appreciate the unique combination of a first-in-class, first-in-disease launch with a pipeline of significant near-term indication expansion opportunities. In addition to the importance of this launch as the first ever treatment available for patients with PK deficiency, it also serves as a foundation for us to build commercial capabilities as we prepare for future potential expansion into similar but meaningfully larger rare diseases like thalassemia. IGOS has all the ingredients to make a difference in the lives of patients with rare and genetically defined diseases, and I'm honored to lead this team to drive long-term growth and value together. Turning to the third quarter and recent progress as outlined on slide five, we accomplished several key priorities and advanced others as we head into the end of the year. First, I'm pleased to welcome Cecilia Jones to Agios in her first quarterly call as our Chief Financial Officer. Cecilia, who started at the end of September, has extensive experience working for rare disease-focused companies and a strong track record of financial leadership, shaping strategy, and talent development. She has already proved to be an excellent thought partner for myself and the leadership team. In addition, we strengthened our Board of Directors with the additions of Dr. Raul Bilal and Cynthia Smith. Raul and Cynthia are seasoned biopharmaceutical executives with critical expertise that will help us maximize our potential. Within R&D, the clinical and medical teams have been busy securing a positive CHMP opinion for pyrokine in the EU, initiating the AG946-MDS Phase 2A trial, publishing data from our thalassemia and PK deficiency clinical programs in top-tier medical journals, securing an expansive set of data for presentation at ASH in December, and making progress on enrollment for our thalassemia and sickle cell disease trials, which Sarah will cover in more detail. On the commercial front, with just two full quarters under our belt since the approval of PyroKind earlier this year, We continue to make important progress and are very much in the dynamic learning phase of launch. We've identified several important lessons this quarter that allow us to further tailor our tactical approach and evolve our marketing mix to more efficiently target HCPs, drive disease education and urgency to treat, and facilitate initiation of pyrokine therapy. Richa will discuss some of these learnings and tactics shortly. And finally, last week, we completed the monetization of the TIPSOVO royalty that we obtained from the survey transaction, providing us with more than $130 million in capital to invest in high-value opportunities for the business. As I look to the last few weeks of the year, our priorities, as shown on slide six, are very clear. Continue to drive enrollment across our thalassemia and sickle cell disease pivotal trials, secure approval of pyrokine for PK deficiency in the EU and Great Britain, and drive towards continued commercial success for our U.S. launch. I'd like to thank each and every Agios employee for the fantastic work accomplished this quarter and for their support in my own learning and onboarding during these first few months. With that, I'll turn it over to Sarah.
spk13: Thanks, Brian. 2022 has been a year of significant execution for the research and development organization. We have continued to pioneer the field of PK activation and broaden the potential applicability of this mechanism to a range of diseases with significant unmet needs while also advancing our earlier pipeline. As highlighted on slide 9, our clinical focus for PK acquisition is to transform the course of hemolytic and acquired anemia by increasing red blood cell energy, health, and longevity. By improving the overall health of the red blood cell, our aim is to impact the downstream consequences of hemolysis and ultimately improve how patients feel and function. To date, we have demonstrated remarkable consistency in the largest clinical data set for PK activator across our three most advanced therapeutic areas, sickle cell disease, thalassemia, and PK deficiency, and become the first company to do so. Moving to slide 10, at the ASH annual meeting taking place in December in New Orleans, More than 20 abstracts from Agios and our collaborators were accepted for presentation, which further underscored the clinical consistency across diseases, as well as the commonalities of the underlying pathophysiology of these diseases. Specifically, we look forward to sharing new data demonstrating the long-term impact of treatment with pyrokines in PK deficiency and thalassemia, as well as the SAD and MADS data for our novel PK activator, AG946. More to come on our ASH abstracts when they go online today at 9 a.m. Eastern Time. Turning to our most advanced PK activator, Mitopivac, known commercially as Pyrokine, became the first FDA-approved therapy for PK deficiency in February, and we continue our efforts to expand utility of this medicine to all patients with PK deficiency. This summer, we initiated two randomized placebo-controlled trials of pyrokines in pediatric patients with PK deficiency ages 1 up to 18, shown here on slide 11. Activate Kits will enroll pediatric patients who are not regularly transfused, and Activate Kits C will enroll pediatric patients who are regularly transfused. In addition, we have been busy advancing our marketing authorization application for fire kind in adults with PTA deficiency through the EMA process this year, and we're pleased to receive a positive CHMP opinion in September. Last month, we submitted a marketing authorization application in Great Britain under the European Commission Decision Reliance Procedure. We expect to receive a decision from both the EU and Great Britain regulatory authorities by year end. If approved, we are committed to providing patient access through our global managed access program. This program provides a pathway for eligible adults receiving care in the EU and Great Britain who are diagnosed with CK deficiency to have access to pyrokines. We will provide drugs free of charge regardless of the patient's insurance coverage. Pyrokine will not be available under the Global Managed Access Program for indications under investigation or outside of the label, including thalassemia, sickle cell disease, and pediatric PK deficiency. Moving to thalassemia on slide 12, we are very excited to have the potential to establish pyrokine as the first oral therapy to improve hemolytic anemia and ineffective erythropoiesis across the spectrum of beta and alpha thalassemia. including transfusion-dependent and transfusion-independent thalassemia. The impressive data generated in the core period of our Phase II study of non-transfusion-dependent beta and alpha thalassemia, shown on slide 13, were published in the journal Lancet in August and we'll be sharing updated data from the extension portion of the trial at ASH. Given that approximately 60% of thalassemia patients currently have no available treatment options, advancing our pivotal program as quickly as possible is a high priority for our team. Specifically, we are working toward enrolling a meaningful portion of patients across two global pivotal trials of pyrokines, Energize and Energize C, which are described on slide 14. As a reminder, NRGISE is a randomized placebo-controlled trial in both alpha and beta thalassemia patients who are not regularly transfused with a primary endpoint of hemoglobin response. NRGISE-T is a randomized placebo-controlled trial in both alpha and beta thalassemia patients who are regularly transfused, defined as a 6 to 20 red blood cell units transfused during the 24 weeks prior to randomization with a primary endpoint of transfusion reduction response. In sickle cell disease, we are exploring pyrokines in an operationally seamless phase 2-3 study known as a rise-up, with the goal of being the first potential oral agent to improve anemia, reduce COCs, and improve quality of life by increasing native hemoglobin, resulting in reduced pain and fatigue. Moving to slide 16, we are actively enrolling patients in the phase 2 portion, which will randomize 69 patients one-to-one-to-one to 50 mg pyrokine twice daily, 100 mg pyrokine twice daily, or matched placebo. The primary endpoints are hemoglobin response, defined as equal or more 1 g per deciliter increase in average hemoglobin concentration from week 10 through week 12 compared to baseline and safety. Our goal is to complete enrollment in the Phase 2 portion by the end of this year. Upon completion of the double-blind portion of the Phase 2, we will evaluate the totality of the data before triggering the start of Phase 3. The outcome of the primary endpoints is the first step, then we will take into account secondary endpoints from the study, including changes in markers of hemolysis, rate of sickle cell pain crisis, and patient-reported fatigue. Our collaborators at the NIH and University of Utrecht continue to treat sickle cell patients with pyrotines in extension studies, which will also provide longer-term treatment data to support our decision. With Phase II success, these data will also allow us to make a determination on the dosing paradigm for the Phase III portion as pre-specified in the protocol. As an operationally seamless study, meaning we are able to use same clinical trial sites to enroll two distinct sets of patients in the phase two and in the phase three, we have the ability to increase the speed at which we can transition from one phase to the next. In addition, we can assess the need for modifications to the phase three based on the outcome of phase two without impact on statistical and regulatory aspects of the trial. We will share the outcome of the phase two portion of the study and our go-no-go decision next year. I'll now turn to slide 17 and AG946, our novel PK activator, which provides the opportunity to further build our PK activator franchise and pursue multiple potential therapeutic paths. We have completed the phase one single ascending and multiple ascending dose cohorts in healthy volunteers. And initial results supporting AG946 profile as a potent PK activator will be presented at the ASH meeting in December. We recently initiated the sickle cell disease part of the study in order to obtain data for this molecule in a hemolytic anemia. In September, we initiated our AG946 lower risk MDS clinical program. As outlined on slide 18, MDS are a heterogeneous group of rare hematological malignancies characterized by ineffective erythropoiesis, abnormal cell maturation, dysplasia, and progressive cytopenias. Anemia, the most common feature of low-risk MDS, occurs in approximately 90% of patients, and about half will develop red blood cell transfusion dependence. Primary therapeutic strategies are limited for patients with low-risk MDS anemia and include erythropoiesis-stimulating agents or transfusions. Additional treatments are indicated only in specific MDS subtypes and generally with limited responses achieved. We believe AG946 has the potential to enhance red blood cell functionality and survival by increasing glycolysis and ATP production and improved differentiation of erythroid cells in bone marrow, potentially improving anemia caused by ineffective erythropoiesis in lower-risk MDS, similar to thalassemia. The first step in our clinical program is the Phase IIa component of the Phase IIa-IIb study shown on slide 19, which is an open-label proof-of-concept study of one dose level of HE946 in patients with lower-risk MDS. In summary, we are very pleased with the progress made against our 2022 key milestones this quarter across all programs and are continuing to drive toward our remaining priorities for the year. With that, I will now turn the call over to Richa.
spk12: Thanks, Sarah. As Brian highlighted, this quarter has been one of continued learning, deep strategic assessment, and refinement of our priorities and tactics in order to drive success in these early days of launch. Success, as we define it, is creating an important commercial foundation for our PK Activator franchise. We believe this foundation is key to our long-term success as shown on slide 21. As the first real-world proof point for Pyokind, we are establishing a strong base of real-world evidence and uncovering the opportunities for the first PK activator on the market, in addition to being the first ever therapy available for patients with PK deficiency. While this initial launch will be a modest revenue generator, it establishes a commercial capabilities platform in rare and genetically defined diseases and serves as an important introduction for us to the broader hematology community, where there's significant overlap with future potential indications. These learnings, capabilities, and relationships will be invaluable as we prepare for multiple potential launches in the next four to five years. In the first quarter, which represented the second full quarter of the PyroKine launch, we generated net US sales of $3.5 million which is indicative of increased patient demand offset by modest inventory build in the prior quarters of launch. In assessing the results from this quarter, I will start with the key metrics we have observed so far, which are shown on slide 22. As of September 30th, we now have a total of 84 unique patients with completed pyrokine prescription enrollment forms, a 64% increase over total PEFs at the end of Q2. Of these PEFs, there were a net of 56 patients on pyrokine therapy, which includes those patients with new prescriptions and those continuing treatment, a 51% increase since quarter two. It continues to take approximately four to six weeks to convert a PEF to a filled prescription, a trend that is unlikely to shorten in the near term. Discontinuations to date have been low. But in the fourth quarter, many early patients will be reaching the six-month time point for efficacy assessment as recommended in our label. As we observe non-responding patients come off therapy, we will be able to make better assessments of adherence and persistence for those who stay on therapy. As we saw last quarter, these patients are coming from a broad, unique prescriber base of 80 physicians diversified across the country. Patients coming on therapy represent a range of demographics and disease characteristics that is consistent with the adult PK deficiency population. In terms of peer dynamics, our national account directors continue to have positive interactions with peers. The peer mix to date aligns with our prelaunch expectations as outlined on slide 23. The payer policy is being developed aligned to the indication statement or the clinical trial eligibility criteria as anticipated. In addition, prior authorization criteria align to rare specialty medicine and typically include the need for genetic testing, consultation with a specialist, and baseline hemoglobin and transfusion history. Moving to slide 24, we are pleased with the continued interest in our anemia ID kit, which is a free genetic testing program designed to help patients with a general diagnosis of hemolytic anemia of unknown etiology to receive an accurate diagnosis. As of September 30th, more than 5,300 kits have been ordered, a 26% increase since Q2. Consistent with last quarter, approximately 25% of kits have been completed, and the PK deficiency positivity rate for those completed tests remains in the mid-single-digit percentages. Of the positive tests, Approximately 60% were adults and 40% pediatrics. In taking a thoughtful view of launch progress to date, there are key aspects that have been consistent with our expectations and others that are driving learnings and tactical pivots to drive continued growth. PK deficiency is an ultra-rare disease with no centers of excellence, which means the majority of physicians only have a handful of patients with diagnosed or suspected PK deficiency. As such, this is a disease that is poorly understood and often gets lost in the diagnostic triage as shown on slide 25. Despite approval of pyokine, this has not led to a rapid movement to diagnose and treat at the rate we anticipated. This is in part because we are working against the established behavior of inaction. Therefore, continuing to educate on the critical nature of differential diagnosis through genetic testing continues to be of utmost importance. we are also recognizing that beyond the physician, it is equally, if not more important and effective to empower and activate patients to self-advocate for diagnosis and treatment. Looking ahead to the fourth quarter, we have been focused on evaluating tactical shifts and localized experiments to increase initiatives that are working and fill gaps in our launch strategy based on these new learnings. Importantly, the impact pyokine has on the lives of patients is evident. And we are encouraged with these early launch successes and the positive experiences we are creating with the broader PK deficiency community. However, we have much more work ahead of us on behalf of these patients. As I laid out at the beginning, these learnings, our knowledge base, and the connections we are making are setting us up for success as we continue to expand the applicability of pyrokine to all eligible patients with PK deficiency, as well as longer term for other genetically defined diseases. With that, I'll now turn it over to Cecilia to review third quarter financials.
spk02: Thanks, Richa. Our third quarter 2022 financial results can be found in the press release we issued this morning, which I will summarize. More details will be included in our 10-Q filing later today. Turning to slide 27, as Richa shared, PyroKine's net revenue for the second quarter was $3.5 million. on a weeks-on-hand basis remained slightly lower throughout the quarter from where we ended Q2. As a reminder, we anticipate low levels of inventory given our limited distribution network, which consists of one specialty pharmacy and one specialty distributor. Growth to net continues to be in the 10 to 20 percent range as expected based on other rare disease launches. Cost of sales for the quarter was $517,000. Turning to operating expense, research and development for the third quarter was $65 million, an increase of $1 million compared to the third quarter of 2021. Selling general administrative expenses were $29.1 million for the third quarter, representing a $1.9 million increase over third quarter 2021. The increase in SG&A expense was primarily due to an increase in workforce-related expenses. TPSOVA royalty revenue, which is recorded under royalty income from gain on sale of oncology business on our income statement, was $4.4 million. TPSOVA royalty income will cease in 2022 due to the sale of these royalty rights to SAGAR's healthcare partners. We ended the quarter with cash, cash equivalents, and marketable securities of approximately $1 billion, which excludes the $131.8 million of cash received from SAGAR for the sale of our royalty rights to give service. With this cash balance, we expect to be able to execute our current operating plan through major catalysts and to cash flow positivity without the need to raise additional equity. In the current environment, we are grateful for a strong balance sheet, but also mindful to maintain this advantage and ensure the capital necessary to execute on our promising clinical programs and retain flexibility for BD. We continue to be laser-focused on capital allocation to only our highest priorities, proactively managing our expense base and evaluating opportunities to add to our pipeline. I'll now turn the call back to Brian to close us out.
spk10: Thanks, Cecilia. To summarize, we're pleased with the continued progress across the organization, and our priorities for Key 4 are clear. We're focused on driving demand for our launch in PK deficiency while applying learnings along the way to strengthen our commercial capabilities platform for future expansion. Our R&D organization is dedicated to enrolling our pivotal trials in thalassemia and sickle cell disease, while continuing to advance our pediatric PK deficiency and MDS studies. And we aim to be responsible stewards of our balance sheet and continue to evaluate meaningful opportunities for value creation. As always, thank you for your continued support of Agios. With that, operator, please open the line for questions.
spk09: And thank you. As a reminder to ask a question, you'll need to press star one on your telephone. We ask that you limit yourself to one question and one follow-up. Again, we ask that you limit yourself to one question and one follow-up. And one moment while we queue up for questions. And one moment for our first question. And our first question comes from Gregory Renza from RBC Capital Markets. Your line is now open.
spk04: Hi, this is Yilong for Greg. Congrats on the quarter and thank you for taking our questions. Maybe first on pyrokines, wondering if you could help us think about how the prescription enrollment forms convert to patients on pyrokines and what are the push and pulls to think about in this process? And then maybe another one for Cecilia, you know, as we've had two full quarters since the pyrokine launch, how are you thinking about forecasting and potentially providing revenue guidance? Thank you.
spk10: Great, thanks for the question. Maybe we'll have Richa start with the first one.
spk12: So, thanks again for the question. As far as PEM conversions to FILS is concerned, BioKind enrollment form, the prescription enrollment form, serves as an enrollment into our patient support services. So that's how the flow goes. They get enrolled into MyRGOs, get connected to a patient support manager who helps them navigate through the benefits investigation process as well as get them access to therapy. And then we navigate through the prior authorization criteria that have been established by the peers to help them figure out what is needed in order to get them to fulfill. So when we reported the 84 and the 56, The 56 are the patients that have received at least one bill. It takes about four to six weeks to get from a PEF to a bill, and that's really driven by the PEA criteria that have been established by the peers. And I'll turn it over to Cecilia to address the second bit.
spk02: Thank you, Richa. I think it's a little early in our launch, and we're learning a lot, but we are considering when to provide guidance, and we've provided one of the peers.
spk04: Great, thank you. Thank you.
spk09: And thank you. And one moment for our next question. And our next question comes from Mark Fram from Cowan. Your line is now open.
spk01: Thanks for taking my questions. Rich, I realize it's kind of early in this process, but can you kind of characterize the typical reauthorization criteria you're expecting to be applied and You know, I guess how much broader do you think that could be on average versus, you know, the primary endpoint in the trial?
spk12: Yeah, Mark, thanks for the question. So the way to think about it is, again, as you said and preempted it, it is a little bit early to comment on the specifics because we're still working through that. And as you know, most of the patients will get to that six-month response evaluation time point in Q4. So we know more about what the reauthorization criteria are going to be. Our goal is to really help payers appreciate and understand how our label is set up. So that's what our goal is with them, which is to say, don't just look at hemoglobin or transfusion burden, but also look at chronic hemolytic parameters, which influence how patients feel and function. So that is part of the dialogue that's happening right now. So still too early to comment on specifics around that.
spk10: Mark, I'll just add that so far, We've not had real hurdles of any kind from the payer perspective. It still is early in the launch, but we don't expect this to be a managed category because it's on the ultra-rare side. And the team, I must say, is making really good progress with the payers as well.
spk01: Okay, that's helpful. And then maybe just on the patients that are getting added kind of in the last quarter or more recently, can you characterize these more recent ads in terms of Is it when success is on kind of what you spoke to in the prepared remarks reach of, you know, getting these patients who maybe haven't been in under active care but have been diagnosed previously into therapy? Or is it more being driven by, you know, things like anemia ID and stuff, actually making the new differential diagnosis?
spk12: So I... The specifics around that mark would be a little bit hard to characterize. And as we noted before, anemia ID is designed to test for hemolytic anemia of unknown etiology. So it's not specific to PKD. And therefore, we can't directly tie that back to which patients have been identified through anemia ID. Our goal and our focus has been on driving education from the physician standpoint to help them appreciate the need and urgency to diagnose PKD and raise that in the sort of diagnostic triage process, which currently is lower in the diagnostic triage process, right? So that disease education from a physician standpoint needs to continue and continues to remain a focus for us. And then, inversely, on the other end, we also want to make sure that patients are educated about their disease and know how to have those conversations with their physicians so that they can be empowered to take a more active role in their diagnosis and treatment. So that push-pull component of our strategy is what's driving demand and will continue to remain a focus for now and forever more in this disease space.
spk01: Okay, thank you.
spk09: Thank you. And one moment for our next question. And our next question comes from Mark Bredenbach from Oppenheimer. Your line is now open.
spk06: Hey, good morning. Just a couple of quick ones for me. First of all, I'm wondering how we should be thinking about pricing of pyrotide in Europe. What are you guys seeing as maybe the most appropriate comps for this drug in Europe in terms of pricing? And also, in light of the recent top-line Phase III data from Bruce Patterstaff, in low and intermediate risk MDS. Is that impacting or influencing your plans for developing AG-946 in MDS in any way? And maybe you can just take an opportunity to highlight the main differentiators between 946 and Luce-Patterson. Thank you. Sure.
spk10: Good morning, Mark. It's Brian. I'm going to start with the first one, and then Sarah can certainly comment on MDS and our thoughts there. For XUS, and I won't get into specifics about pricing at this stage, what I would like to emphasize is that while we are awaiting and expecting the final approval of PirateKind in Europe and Great Britain, as we noted on the call, That'll be an important win for PKD patients. Near-term, what we've decided to do is focus on ensuring access for the PKD patients that we know would very much like to have access to pyrokine. And so, as Sarah mentioned on the call, we're very proud of the fact that we have a global managed access program in place. That's not commercial, obviously. That's to make sure that adult PKD patients can have access. So stepping back, though, which I think is behind your question about the revenue opportunity, the majority of that we see as occurring in the U.S. When we think about ex-U.S., Europe specifically, we're continuing to assess the commercial access plans, but we're doing that in concert with a bigger picture, and that is the pathway that we could see towards potential larger prevalent launches namely thalassemia and sickle cell disease. I'll just add that we're not at this stage when we think about commercialization. We're not looking to build out on our own a sales force or commercial team ex-US. We're looking at partnering opportunities, but we're going to be very selective in how we do that. And all of that is what will guide us on how to commercialize, and to your question, what the appropriate pricing would be.
spk13: And for the second question around the LUSPATRCEP data, so we don't believe the recent outcome of the LUSPATRCEP trial has any impact on our clinical development plans. We are continuing, as is, are very excited about them. I think the biggest differences are, of course, there is a very different route of administration. We have an oral convenience that is very important, especially also in an elderly population. But then, most importantly, there is a very different mechanism of action, and we believe that PK activation in the context of enhancing red blood cell functionality and survival is very important in the context of this disease. And our clinical development program is really set up to encompass ESA-naive patients and ESA-refractory patients, so basically all comers with lower-risk MDS, which we believe is an advantage of how we've designed our program to date.
spk06: Okay, thanks so much for taking the questions, and congrats on the quarter.
spk09: And thank you. And one moment for our next question. And our next question comes from Greg Harrison from Bank of America. Your line is now open.
spk07: Good morning. This is Jason on for Greg. Thanks so much for taking our questions, and congrats on the progress. I was hoping you could provide a little bit more color on the initial launch dynamics of PyroKine. Is the initial demand matching your expectation? Is there growing awareness starting to track into new patient starts? Just trying to think about an inflection in the more medium term. And then in terms of the initial inventory build, any concern that this could impact treatment starts this quarter? Thank you.
spk12: Sure. So I'll kick us off here, Jason, and then have Cecilia comment on the inventory component. So from an initial demand standpoint, the way to think about it is we are going to continue to remain laser-focused on demand generation because that is going to be really important in this disease phase. A couple of points to highlight about the disease itself. I think we are encouraged with what we saw this quarter in the growth we saw in the new prescription enrollment forms because that's really the leading predictor for how the launch is going. It's a story of breadth, breadth in terms of the kinds of physicians prescribing the drug as well as breadth as the kind of patients that are being prescribed drugs. So in the second full quarter of launch, we are continuing to see that dynamic playing out. That being said, the two things that we have to get right and will take time is one is diagnostic efficiency. There is a... sort of triage process that happens from a diagnostic standpoint where PKD gets lost in that funnel. And our goal is with the availability of treatment to raise that urgency from a physician standpoint so that they are testing for and diagnosing PKD more early in that diagnostic funnel than they are today. So that's one. And the second component is given the rarity of the disease and the fact that this is a chronic condition that does not have centers of excellence and it's a diffuse patient population, having the patient play a very active role in their diagnosis and treatment. So empowering them with the tools and educating them to ensure that they know how to have those conversations with the healthcare providers becomes very, very important. And that's part of our tactical pivot that we've made as well. So the focus on demand generation will continue. As we also indicated in the past, this is going to be a slow and steady launch. This is not going to be some magical like hockey stick inflection point that we anticipate. So it's going to be slow and steady, but it's really the foundation for our commercial capability building, as Brian alluded to in his opening remarks, for what's to come in the future with thalassemia and sickle cell.
spk02: And in terms of inventory, we did see some inventory. There is nothing we would expect in the first couple of quarters, but we anticipate low levels of inventory going forward. As a reminder, we have a limited network distribution, which is one specialty for us. Sorry, one specialty pharmacy and one specialty distributor.
spk07: Great. And so that inventory is sufficient, you think, to handle that new patient builds as we go forward the next quarter or so?
spk03: Yes.
spk07: Perfect. Thanks so much for taking our questions.
spk09: Thank you. And one moment for our next question. And our next question comes from Andy Behrens from SCB. Your line is now open.
spk08: Thanks. I'm sorry if I missed this because I was bouncing between a couple of calls. I'm wondering if you can give us any color on the genotypes of the patients that are using the drug. maybe those that are not actually using the drug. And it's early, but any comment on the persistence rate would be appreciated. And then just one on the MDS opportunity. A fair number of patients do get EPO off-label, so just wondering how we should think about a PKR drug entering that treatment paradigm.
spk12: So hi, Andy. Thanks for the question. So in terms of the patient characteristics, we've had use across the board in terms of the kinds of patients that have been prescribed drugs. So we have seen patients irrespective of age, splenectomy status, and symptomology, regularly transfused, not regularly transfused, get drug. To your specific question around genotypes, we haven't provided specifics, but the way to think about it is from a payer prior auth criteria, if the payer policy does not include the double non-missense mutated patients, then those patients would not be able to get therapy unless they met our financial eligibility criteria and could get on our free drug program. So that's the one caveat. I would say it's dependent on the payer policy, but in general, we are not seeing physicians limiting use of the drug based on a specific disease or patient characteristic.
spk10: And maybe I'll just add, Andy, that for persistency, we're in the period right now where we're starting to get initial data. I would say we're on track with what we expected, but it's too early to make too many projections from the standpoint where we are at this stage in launch. You may recall from the clinical trial, the response rate was about 40% to 45% with pyrokine. And moving forward in the real world, what we'll be looking at is how do payers respond at the six-month mark of treatment to the, you know, the criteria that they put in place, as well as is the synchronization of patient visits with their doctor to do the appropriate monitoring. Is it exactly in six months? And we'll just have to monitor that over time, but we feel good with how we're progressing on that front so far.
spk08: Okay.
spk10: Yeah, you bet. And Sarah can cover MDS.
spk13: Yes, sure. So the question around EPO and off-label use for EPO. So the way we have designed our program right now is to really study patients who may be naive to any erythrocephalic agent or who have been refractory. We currently are not planning in this proof-of-concept study to enroll patients who are on EPO actively because we're truly looking for efficacy at this point. specifically to our drug.
spk08: Okay. Thank you.
spk09: Thank you. And if you have a question, that is star 11. Again, if you have a question, that is star 11. And one moment for our next question. And our next question comes from Salveen Richter from Goldman Sachs. Your line is now open.
spk11: Good morning. This is Andrea on for Salveen. Thanks for taking our questions. For the first one, recognizing that it's early, but maybe another question on pricing for purikine, how are you thinking about this for indications such as thalassemia and sickle cell? Do you expect that to be in line with how you've priced it for PKD?
spk10: Yeah, Andrea, thanks for the question. I'll take that one. Again, I think that with pricing, we're not going to go into specifics at this stage, but I'll just say that directionally, what will await, of course, is the data, which is so critically important. And we're very excited about the progress we're making on enrollments with the thalassemia energized and energized T trials, as well as the phase two portion of sickle cell disease with rise up. And we've been very clear about our ambitions to get to that data point following the successful enrollment. Once we have that, then we'll take a thoughtful look at pricing. In general, thalassemia is a step up in terms of patient prevalence from where we are with PKD. And then sickle cell, as you know, is another step up from even thalassemia. We're talking about In thalassemia, 18,000 to 23,000 patients. In the U.S., in EU5, in sickle cell disease, in the U.S. alone, you know, we're in the neighborhood of 100,000 patients. So that plus the data will guide us on the appropriate pricing decision. I know that's a nonspecific answer, but as far as I think we should take it for now.
spk11: No problem. Thanks so much. And then maybe just a broader question, just wondering if you could provide some updated thoughts here on how you're thinking about potential business development activities for the future and how this would interface with your existing pipeline. Thanks so much.
spk10: Yeah, you bet. And I'm going to combine that as well with at least acknowledgement of what we had in our comments earlier that we're really pleased to have completed the TIPSOVO royalty monetization deal with SIGGARD. And what that does is obviously further strengthen our balance sheet, which is already, as we described it, in an enviable position, particularly in this market. So that will add to our optionality as to what we do with our capital deployment. For BD, we have an ambition to further strengthen our pipeline as well as diversify. particularly diversification from PKR activation. And internally, because we believe BD is so important for us over the long term, we've also enhanced the size of our BD team internally, and that should give us more quality, more quantity, capacity from a search and evaluation and diligence standpoint. The way I think about it is our sweet spot for business development would be potentially synergy with rare non-bullied hematology disease areas where we're currently focused. That could be one part in or leverage of the building rare disease capabilities that we're working on on the foundation of our PKD launches Rich has talked about. And then lastly, of course, for us in rare diseases, whatever we do, we'll have to have line of sight to transformational benefit for patients. That's mission critical from our perspective. So we're not time bounding you know, when we will do a deal or how many deals we do, but we do feel really good about our capital position and our focus will be on value creation in a very disciplined approach.
spk11: Okay. Thank you so much for the caller.
spk09: Thank you. And one moment for our next question. And our next question comes from Danielle Brill from Raymond James. Your line is now open.
spk05: Hi, guys. Good morning. Thanks for the question. I'm curious what percent of patients that have been diagnosed with your anemia IV kits are actually opting to go on treatment. Thank you.
spk12: Hi, Daniel. This is Richa. So thanks again for the question. So as noted before, anemia IV is designed for hemolytic anemia of unknown etiology, so it's not specific for the diagnosis of PKD. So there's really no way for us to know compliantly what patients diagnosed through anemia IV have been put on therapy. The way we think about this is our focus continues to remain around demand generation and that involves both a top-down approach, ensuring that the healthcare providers are appropriately elevating PKD in the diagnostic triage process, while also empowering and activating patients so that they know to have those conversations with their healthcare providers to ensure that they can get diagnosed and treated. So that continues to be our focus, but specifics around translation of anemia ID into patients is not possible.
spk05: I see. I guess, are the docs that are ordering the ID kits the same as the docs prescribing the drug?
spk09: They certainly can be, yeah.
spk10: And as we have noted, you know, we believe anemia ID as one of the, few select tools that are really important for our continued progress and launch. We believe that we have that with anemia ID. But I would not categorize it as it's exclusive for those who prescribe.
spk05: Understood. Thank you for the question. Sure.
spk09: Thank you. And I am showing no further questions. I would now like to turn the call back over to Brian Goff, CEO, for closing remarks.
spk10: All right, thanks a lot, Justin, and thanks, everyone, for your questions and your continued interest in our progress. As always, I want to thank my AGIOS colleagues for their dedication, for their passion to make a difference for patients. I also want to thank all of the patients, caregivers, and physicians who partner with us in so many ways, and especially those who participate in our clinical trials across indications. Our connections across stakeholders and our collective efforts fuel our ongoing innovation impact for people to find diseases. So thanks a lot for joining us today, and you may now disconnect.
spk09: This concludes today's conference call. Thank you for participating. You may now disconnect.
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