Q2 2022 Agios Pharmaceuticals Inc Earnings Call

Speaker: Good morning and welcome to Agios' second quarter 2022 conference call.

Operator: At this time, all participants are in a listen-only mode. There will be a question and answer session at the end of the call.

The countries.

Operator: Please be advised that this call is being recorded at Agios' request.

Good morning, and welcome to <unk> second quarter 2022 conference call. At this time all participants are in a listen only mode. There will be a question and answer at CIT.

A question and answer session at the end of the call.

Please be advised that this call is being recorded at arch else's request I would now like to turn the cough so over.

Operator: I would now like to turn the conference over to Holly Manning, Senior Director of Investor Relations.

Jacqueline: Thank you so much, and congrats again on the quarter.

Operator: Thank you for participating.

Sure Holly Manning senior director of Investor Relations. Please go ahead.

Holly Manning: Please go ahead.

Jacqueline: Thank you.

Operator: You may now disconnect.

Okay.

Thank you operator, good morning, everyone and welcome to the second quarter of 2022 Conference call you can access slides for today's call by going to the investors section of our website at <unk> Dot Com with me on the call today with prepared remarks are Dr. Jackie Fouse, our chief executive.

Officer, Dr say, arguing our chief Medical Officer, and head of research and development, Richard <unk>, Our Chief commercial officer, and Jonathan Biller, Our Chief Financial Officer, and head of corporate Affairs 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 SEC and any other future filings that we may make with the SEC with that I'll turn the call over to Jeff.

Holly Manning: Thank you, Operator.

Operator: We have a question from Salveen Richter with Goldman Sachs.

Thanks, Holly good morning, everyone and thanks for joining our second quarter 2022 results call.

The first half of 2022 has been remarkably productive across all facets of our business.

Continued to be impressed by the focused execution of the <unk> team and their connection to each other and our vision of making an impact on the lives of patients.

Holly Manning: Good morning, everyone, and welcome to Agios' second quarter 2022 conference call.

Operator: Your line is open.

In February our World Class commercial organization launched our first genetically defined disease medicine, <unk>, which is the first FDA approved therapy to treat pyruvate kinase deficiency and the first ever approved PK activator.

Today, We report impressive commercial performance for our first full quarter of launch, which Richard will cover in more detail.

Tom Young: Hi.

Our exceptional clinical team initiated two pediatric PK deficiency pivotal studies as well as in sickle cell disease cohort of the AG 946 phase one trial.

I'll now operate operationalize ing the aging non Forsakes Mds study and continuing to advance site activation and patient enrollment across three pivotal studies of Paragon and Dallas, EMEA and sickle cell disease.

Tom Young: This is Tom Young for Salveen.

In May we made the tough decision to evolve our research organization, which has led to the ongoing integration of our R&D teams and enhanced our research focus and business development activities.

Tom Young: Thank you for taking our question.

And in June we had a robust presence at the European Hematological Association meeting in Vienna, with broad preclinical translational and clinical updates across the programs.

Sarah will review, our preclinical and clinical programs momentarily.

Tom Young: Could you expand on the launch trajectory of pyrokine and PKD?

A highlight for me occurred a few weeks ago when Rjr's employees came together for our first company off site since the start of the pandemic two and a half years ago. It was an incredible reminder of the expansive talent. We have at all just in the interconnected culture that continues to thrive through the dynamic evolution of our business turn.

Tom Young: Are you planning to continue the same efforts to identify patients, or are you utilizing new efforts to expand patient identification?

Holly Manning: You can access slides for today's call by going to the Investor section of our website, agios.com.

Tom Young: And how many patients that are positive with the anemia ID test actually moved to pyrokine treatment?

Now to slide five a few weeks ago, we announced that as of Monday August eight I will transition to the role of chair of the board of directors and Brian Goff will become the new Chief Executive Officer of Rgs.

Speaker: Thanks, Holly.

Tom Young: And lastly, on PKD and sickle cell, how are you thinking about the market opportunity, specifically which group of patients do you think are most suitable for pyrokine?

Brian has vast experience in hematology rare diseases, and commercial and operational leadership cultivated over the course of 30 years of global biopharmaceutical companies I strongly believe that he is the right leader to guide <unk> through its next chapter.

Tom Young: Thank you.

As I reflect on my time as CEO I am proud of the bold strategic decisions that we made as a team our resiliency in the face of a global pandemic and the individual lives that we've touched through the medicines. We've created my confidence in the odd Joe's team and its ability to make a positive impact on the world remains steadfast.

Speaker: Good morning, everyone, and thanks for joining our second quarter 2022 results call.

Richa: Yeah, so I'll start with maybe anemia ID and then work backwards.

Richa: So, first of all, I think it's just really important to remember that from a compliance standpoint, there is no way for us to know which patient that has been identified as a PKD patient, which physician that patient belongs to.

Speaker: The first half of 2022 has been remarkably productive across all facets of our business. I've continued to be impressed by the focused execution of the Agios team and their connection to each other and our vision of making an impact on the lives of patients. In February, our world-class commercial organization launched our first genetically-defined disease medicine, PyroKind, which is the first FDA-approved therapy to treat pyruvate kinase deficiency and the first ever approved PK activator.

Richa: It's just really important that we continue to drive disease awareness as well as get improved diagnosis over time.

Richa: Anemia ID, again, is not specific to pyrokine deficiency, but has been designed within the needs of the community, which is to help do a differential diagnosis on the hemolytic anemia of unknown etiology.

Speaker: Today, we report impressive commercial performance for our first full quarter of launch, which Richa will cover in more detail.

Richa: And that's where the value for the test comes in and is being utilized.

Richa: We're seeing continued growth in the test because there is value seen from the community in the utilization of the test and doing that differential diagnosis so they can tailor the treatment to their patient, depending on the kind of hemolytic anemia the patient has.

And it's for that reason that I'm. So excited to continue to play a role and that mission is chair of our board.

Starting Monday I'll be focused on helping Brian orchestrated a smooth transition into his role as CEO , serving as a sounding board and point of reference while also giving him space to learn and make decisions. I also look forward to working with my colleagues on our board to fully leverage and evolve our collective board skill set so that we can continue.

<unk> to be a great resource for <unk> and the management team as we move into a bright future as a rare and genetically defined diseases focused company.

Speaker: Our exceptional clinical team initiated two pediatric PK deficiency pivotal studies, as well as a sickle cell disease cohort of the AG946 Phase I trial, all while operationalizing the AG946 MDS study and continuing to advance site activation and patient enrollment across three pivotal studies of PyroKind in thalassemia and sickle cell disease.

Richa: And now, for at least one of those hemolytic anemias, the pyrokine deficiency, we have a treatment.

Standing here today <unk> is operating from a position of strength with a first in class commercial launch five pivotal trials underway multiple early stage clinical studies planned or underway, a promising preclinical pipeline and an enviable balance sheet that provides significant optionality.

For the future growth of the business I look forward to continuing to be part of this amazing team and I. Thank each of you for your support of <unk> now and in the future.

Richa: So I think that's the underlying sort of thing to think about with regards to anemia ID itself.

Richa: When it comes to diagnosis, again, this is, I think it's just important, this pyrokine deficiency, it's a rare chronic condition, and it is not concentrated in specific centers of excellence. It is diffused throughout the country.

With that I'll turn it over to Sarah.

Thanks Jackie.

Speaker: In May, we made the tough decision to evolve our research organization, which has led to the ongoing integration of our R&D teams and enhanced our research focus and business development activities.

Back in May we announced the evolution of our research organization to focus our people and resources on existing validated preclinical program and shifts our pipeline growth strategy through in licensing or acquiring well characterized high potential effort.

Speaker: And in June, we had a robust presence at the European Hematological Association meeting in Vienna with broad preclinical, translational, and clinical updates across the programs.

This approach enables us to retain a strong internal research team focused on moving our most promising internal programs forward, while also pursuing opportunities that complements our scientific expertise in cellular metabolism and growing clinical and commercial capabilities.

With this evolution and excited to step into my new role as head of research and development.

Richa: It is largely managed in the community. And so our efforts, which have taken the disease understanding into consideration, are around raising awareness of the disease, continue to educate on the burden of disease, working very closely with our medical colleagues to continue to ensure that we are sharing our knowledge as we learn about the disease with the broader community, and ensuring that we continue to drive diagnosis.

It is my focus and priority to seamlessly integrate our research and development functions in a way that increases the coordination and efficiency of the organization and deepens the impact of patient insights on R&D decision, making.

Sarah: Sarah will review our preclinical and clinical programs momentarily.

Richa: This is going to be paramount.

Speaker: A highlight for me occurred a few weeks ago when Agios employees came together for our, first company off-site since the start of the pandemic two and a half years ago. It was an incredible reminder of the expansive talent we have at Agios and the interconnected, culture that continues to thrive through the dynamic evolution of our business.

As shown on slide eight we have a fully built research and development organization encompassing all functions needed to drive our preclinical and clinical programs forward and we have an incredible amount of balanced across each of these functions.

Richa: It's not just going to be a launch thing, but it's going to be a forever thing in this disease space, and it's true for rare diseases in general.

Richa: And so what we are seeing is slow and steady progress in ensuring that we get patients diagnosed and for those that are eligible.

It has been truly gratifying to see the ways. This new structure has already had a positive impact on communication and collaboration within the R&D organization.

Speaker: Turning to slide five, a few weeks ago we announced that as of Monday, August 8, I will, transition to the role of Chair of the Board of Directors and Brian Goff will become the new Chief Executive Officer of Agios. Brian has vast experience in hematology, rare diseases, and commercial and operational leadership, cultivated over the course of 30 years at global biopharmaceutical companies.

Richa: And then with regards to single status, I have Sarah comment actually specifically on, the phase 3 trial design because that will be a nice segue to how we think about differentiating our product in that space as well.

Speaker: I strongly believe that he is the right leader to guide Agios through its next chapter.

Sarah: Sarah, did you want to talk about Rise Up?

Turning to slide nine while our research leaders are focused on helping us thoughtfully evaluate the underlying science and fit of potential business development opportunities. They are also hard at work advancing our internally discovered preclinical program.

Speaker: As I reflect on my time as CEO, I'm proud of the bold, strategic decisions that we made, as a team, our resiliency in the face of a global pandemic, and the individual lives that we have touched through the medicines we've created.

Speaker: My confidence in the Agios team and its ability to make a positive impact on the world remains, steadfast and it's for that reason that I'm so excited to continue to play a role in that mission as Chair of our Board.

Sarah: Sure.

Speaker: Starting on Monday, I'll be focused on helping Brian orchestrate a smooth transition into, his role as CEO, serving as a founding board and point of reference while also giving him space to learn and make decisions.

Speaker: I also look forward to working with my colleagues on our board to fully leverage and evolve, our collective board skill set so that we can continue to be a great resource for Agios and the management team as we move into a bright future as a rare and genetically defined diseases focused company.

Speaker: Standing here today, Agios is operating from a position of immense strength with a first, in class commercial launch, five pivotal trials underway, multiple early stage clinical studies planned or underway, a promising preclinical pipeline, and an enviable balance sheet that provides significant optionality for the future growth of the business.

Sarah: So Rise Up is an operationally seamless trial design with a phase 2 component that we just, discussed and then moving into phase 3. The operationally seamless component of it is actually giving us a lot of flexibility, because it allows us to bring sites on early and get them ready for enrollment as quickly as possible.

Sarah: But it also still allows us to interpret the phase 2 data and make any adjustments as needed, without having an impact on the statistical or regulatory components of the trial.

As shown on slide 10, our earliest program is a branch chained amino acid aminotransferase inhibitor known as <unk> two for the treatment of propionic acid vignette call E and nickel malonic academia also known as enemy.

These <unk> are a group of inherit the inborn errors of metabolism in which the body's cannot breakdown branched chain amino acids, leading to a toxic accumulation.

<unk> two inhibition may reduce the formation of these metabolites, which has the potential to enable patients to have fewer dietary and other restrictions and improve their quality of life.

Our <unk> two inhibitor is currently in the fleet optimization.

Turning to slide 11, our most advanced preclinical program is a sanofi <unk> hydroxylase or ph stabilizer for the treatment of phenylketonuria or PKU.

<unk> is a rare inherited lifelong disease that causes <unk> to accumulate.

Normalizing plasma pheno alanine concentrations may allow patients to increase natural protein intake normalizing their diets and improving their quality of life.

The program is approaching the development candidate milestone and we expect to achieve an IND next year.

As you can see on slide 12 on the clinical side, we have broad clinical development program for both our PK activator fire kind of an 89 six.

Turning to slide 13, $89 six is our novel TCR activate are currently being evaluated in a phase one study with a healthy volunteer and of sickle cell disease component.

We have completed the single ascending and multiple ascending dose healthy volunteer cohorts.

And hope to present these data at the Ash annual meeting later this year.

We recently initiated the sickle cell disease part of the study in order to obtain data for this molecule in hemolytic anemia.

In addition, we believe speak activation has the potential to improve risk loss cell health in both to intermediate Myelodysplastic syndrome, or Mds, where there is a significant unmet needs.

As shown on slide 14, we are working through operationalize them with two eight parts of our 89 for six phase II <unk> study in Mds.

Phase Iia component of the study is an open label proof of concept study of one dose level of $89 six in patients with lower risk Mds.

The study will enrol 20 patients who will receive <unk> nine first fixed once daily for the 16 week core period.

Patients, who complete the core period will be eligible to continue in an extension period.

Sarah: And then for the phase 3, it's set up with two primary endpoints, the hemoglobin response, and an analyzed sickle cell pain crisis endpoint, which if one or both are positive, allows us to move on to secondary endpoint testing, which gives us the totality of the data that we would need to make a meaningful story for patients and physicians and regulators.

The primary endpoints for the study are hemoglobin response defined as equal or more one five gram per deciliter increase from baseline in the average hemoglobin concentration from week eight through week 16, and transfusion independent defined this transfusion free for equal or more eight consecutive weeks during the core period in patients.

Bluecrest fusion Bergen only.

Secondary endpoints include safety additional measures of anemia, and <unk> biomarkers.

Speaker: I look forward to continuing to be part of this amazing team and I thank each of you, for your support of Agios now and in the future.

Sarah: It's very similar in that sense to our other trials, right?

We look forward to initiating the trial by the end of the year.

Speaker: With that, I'll turn it over to Sarah.

Sarah: The beauty of the trial Rise Up is that it does allow us to basically hit on anemia and, on VOC, both very important in the context of sickle cell disease.

Turning to slide 16 for our most advanced PK activator Mcduffie thoughts known commercially as Viracon. Our clinical focus is to transform the course of hemolytic anemia by increasing red blood cell energy health and longevity, and we are well positioned to be the first company to do this across three distinct hemolytic anemia.

Sarah: Thanks, Jackie.

Sarah: Back in May, we announced the evolution of our research organization to focus our people, and resources on existing validated preclinical programs and shift our pipeline growth strategy to in licensing and or acquiring well characterized high potential assets. This approach enabled us to retain a strong internal research team focused on moving our, most promising internal programs forward while also pursuing opportunities that complement our scientific expertise in cellular metabolism and growing clinical and commercial capabilities.

Sarah: With this evolution, I'm excited to step into my new role as head of research and development. It is my focus and priority to seamlessly integrate our research and development functions, in a way that increases the coordination and efficiency of the organization and deepens the impact of patient insights on R&D decision making.

Sarah: As shown on slide 8, we have a fully built research and development organization encompassing, all functions needed to drive our preclinical and clinical programs forward, and we have an incredible amount of talent across each of these functions.

Sarah: It has been truly gratifying to see the ways this new structure has already had a positive, impact on communication and collaboration within the R&D organization.

As shown on slide 16, we are exploring <unk> in an operationally seamless phase II III study known as a writeup in adults with sickle cell disease with the goal of being the first potential oral agents to improve anemia, reduce <unk> and improve quality of life by increasing native hemoglobin, resulting in reduced pain.

Sarah: Turning to slide 9, while our research leaders are focused on helping us thoughtfully evaluate, the underlying science and fit of potential business development opportunities, they are also hard at work advancing our internally discovered preclinical programs.

Sarah: As shown on slide 10, our earliest program is a branched-chain amino acid, aminotransferase, 2 inhibitor, known as BCAS2, for the treatment of propionic acidemia, called PA, and methamelonic acidemia, also known as MMA. These acidemias are a group of inherited inborn errors of metabolism in which the body cannot, break down branched-chain amino acids, leading to a toxic accumulation. BCAS2 inhibition may reduce the formation of these metabolites, which has the potential, to enable patients to have fewer dietary and other restrictions and improve their quality of life.

Sarah: And we're hopeful that that data allows us to bring forward the treatment for sickle, cell disease as a disease mixed entirety.

Sarah: And the one thing I would add to everything that Sarah just said, right, we've designed, the clinical studies and are thinking about how we differentiate based on input from what the community has told us, the broader sickle cell community, physicians and patients, to understand what the needs are and then design the study accordingly.

And fatigue.

The phase II portion will randomize 69 patients once the one to one to <unk> 60 milligram tablets up twice daily 100 milligram capital twice daily or matching placebo.

The primary endpoints arguable globin response defined as equal or more than one gram per deciliter increase in average hemoglobin concentration from week to week 12 compared to baseline.

Sarah: Our BCAS2 inhibitor is currently in lead-late optimization.

Our goal is to complete enrollment in the phase II portion by the end of this year.

Sarah: Turning to slide 11, our most advanced preclinical program is a phenylalanine hydroxylate, or, PAH, stabilizer for the treatment of phenylketonuria, known as PKU. PKU is a rare inherited lifelong disease that causes phenylalanine to accumulate. Normalizing plasma phenylalanine concentrations may allow patients to increase natural protein, intake, normalizing their diet, and improving their quality of life.

Richa: As far as the commercialization is concerned, it will depend on the totality of the data, before we make any determination around that, but we are designing the study to ensure that we are set up for success.

Upon completion of the double blind portion of the fix too we will evaluate the totality of the data before triggering the startup of the C. III.

Sarah: The program is approaching the development candidate milestone, and we expect to achieve, an IND next year.

Richa: Thank you.

Operator: And as a reminder, if you would like to ask a question, press the star, then the one key on your touchtone telephone.

Sarah: As you can see on slide 12, on the clinical side, we have broad clinical development programs, for both our PK activators, pyrokines and HE946.

Operator: We have a question from Danielle Brill with Raymond James.

The outcome of the primary endpoints as the first step then we will take into account changes in markers of hemolysis rates of sickle cell pain crisis patients reported fatigue and other secondary endpoints.

Sarah: Turning to slide 13, HE946 is our novel PKR activator currently being evaluated in a phase, one study with a healthy volunteer and a sickle cell disease component. We have completed a single ascending and multiple ascending dose healthy volunteer cohort and, hope to present these data at the ASH annual meeting later this year. We recently initiated the sickle cell disease part of the study in order to obtain data, for this molecule in a hemolytic anemia.

Danielle Brill: Your line is open.

Sarah: In addition, we believe PK activation has the potential to improve red blood cell health, in low to intermediate myelodysplastic syndrome, or MDS, where there is a significant unmet need.

Sarah: As shown on slide 14, we are working through operationalizing the 2A part of our HE946, phase 2A, 2B study in MDS. The phase 2A component of the study is an open-label proof-of-concept study of one dose, level of HE946 in patients with lower risk MDS. The study will enroll 20 patients who will receive HE946 once daily for the 16-week core, period. Patients who complete the core period will be eligible to continue in an extension period.

With phase II success. These data will also allow us to make a determination on the dosing paradigm for the phase III portion of <unk>.

Suffice in the protocol.

As an operationally seamless study we have the ability to increase the speed at which we can transition from one phase to the next.

Well as to assess the need for modifications to the phase III based on the outcome of the phase two without impact on statistical and regulatory aspects of the trial.

Moving to solid senior on Slide 18, we are very excited to have the potential to establish <unk> as the first oral therapy to improve hemolytic anemia, and ineffective erythropoiesis across desktop and alpha thalassemia as well as transfusion dependent and transfusion independent policy at.

At the end of last year, we initiated our two global placebo controlled pivotal trials with private client energized and energized.

As a reminder, <unk> will evaluate 171 patients randomized two to one to 100 milligrams of mix up about twice daily or placebo in both alpha and beta thalassemia patients who are not regularly transfused.

Sarah: The primary endpoints for the study are hemoglobin response defined as equal or more 1.5 grams, per deciliter increase from baseline in the average hemoglobin concentration from week 8 through week 16, and transfusion independence defined as transfusion free for equal or more, 8 consecutive weeks during the core period in patients with low transfusion burden only.

Finally endpoint is hemoglobin response defined as an equal or more than one gram per deciliter increase in average hemoglobin concentration from week to week 24 compared with baseline.

Sarah: Secondary endpoints include safety, additional measures of anemia, and PK and PD biomarkers.

Energized team will evaluate <unk> 240 patients randomized two to one to 100 milligrams of misstep about twice daily or placebo in both alpha and beta thalassemia patients who are regularly transfused defined a 6% to 20 Red blood cell unit transfused during the 24 weeks prior to randomization.

The primary endpoint of transfusion reduction response defined as a 50% or greater reduction in transfused red blood cell units with a reduction of equal or more than two units of transfused red blood cells in any consecutive 12 week period through week 48, compared with baseline.

Sarah: We look forward to initiating the trial by the end of the year.

Sarah: Turning to slide 16, for our most advanced PK activator, Mitapizat, known commercially, as SpiroKind, our clinical focus is to transform the course of hemolytic anemia by increasing red blood cell energy, health, and longevity, and we are well-positioned to be the first company to do this across three distinct hemolytic anemias.

Sarah: As shown on slide 16, we are exploring SpiroKind in an operationally seamless phase 2-3 study, known as RISEUP in adults with sickle cell disease with the goal of being the first potential oral agents to improve anemia, reduce COCs, and improve quality of life by increasing naked hemoglobin, resulting in reduced pain and fatigue.

Sarah: The phase 2 portion will randomize 69 patients one-to-one-to-one to 50 milligram Mitapizat, twice daily, 100 milligram Mitapizat twice daily, or matched placebo.

Our team is focused on continuing global site activation and patient enrollment efforts in order to enroll a meaningful portion of patients in both studies by the end of the year.

Finally in February Viracon became the first FDA approved therapy for pyruvate kinase deficiency, and we continue our efforts to expand utility of this medicine to all PK deficiency patients.

In June we initiated two studies of pirate <unk> in pediatric PK deficiency patients ages, one up to 18 as shown on slide 19.

Sarah: The primary endpoints are hemoglobin response, defined as equal or more than 1 gram per deciliter, increased in average hemoglobin concentration from week 10 through week 12 compared to baseline and safety.

Activate kits will randomize 30, not regularly transfused patients two to one for either <unk> or placebo and evaluate hemoglobin response over the 12 week period.

Sarah: Our goal is to complete enrollment in the phase 2 portion by the end of this year.

Activate 50 will randomize 45 regularly transfused patients two to one to either <unk> or placebo and evaluate transfusion reduction over the 24 week period.

Sarah: Upon completion of the double-blind portion of the phase 2, we will evaluate the totality, of the data before triggering the start of the phase 3. The outcome of the primary endpoints is the first step, then we will take into account, changes in markers of hemolysis, rate of sickle cell pain crisis, patient-reported fatigue, and other secondary endpoints. With phase 2 success, these data will also allow us to make a determination on the dosing, paradigm for the phase 3 portion as pre-specified in the protocol.

Sarah: As an operationally seamless study, we have the ability to increase the speed at which, we can transition from one phase to the next, as well as assess the need for modifications to the phase 3 based on the outcome of the phase 2 without impact on statistical and regulatory aspects of the trial.

Sarah: Moving to thalassemia on slide 18, we are very excited to have the potential to establish, pyrokines as the first oral therapy to improve hemolytic anemia and ineffective erythropoiesis across beta and alpha thalassemia, as well as transfusion-dependent and transfusion-independent thalassemia.

Sarah: At the end of last year, we initiated our two global placebo-controlled physical trials, of pyrokines, ENERGIZE and ENERGIZE-C. As a reminder, ENERGIZE will evaluate 171 patients randomized 2-to-1 to 100 milligrams, of metapipa twice daily or placebo in both alpha and beta thalassemia patients who are not regularly transfused. The primary endpoint is hemoglobin response, defined as an equal or more than 1 gram per, deciliter increase in average hemoglobin concentration from week 12 through week 24, compared with baseline.

Sarah: ENERGIZE-C will evaluate 240 patients randomized 2-to-1 to 100 milligrams of metapipa twice, daily or placebo in both alpha and beta thalassemia patients who are regularly transfused, defined as 6-to-20 red blood cell units transfused during the 24 weeks prior to randomization. The primary endpoint is transfusion reduction response, defined as a 50% or greater reduction, in transfused red blood cell units with a reduction of equal or more than 2 units of transfused red blood cells in any consecutive 12-week series through week 48, compared with baseline.

In parallel our marketing authorization application for <unk> in adult PK deficiency remains under review in the EU and we remain on track to receive a decision from the EMA by year end.

Sarah: Our team is focused on continuing global site activation and patient enrollment efforts, in order to enroll a meaningful portion of patients in both studies by the end of the year.

In summary, as shown on slide 20, we are pleased with the progress made against our 2022 key milestones this quarter across all program.

Danielle Brill: Hi, guys.

With that I will now turn the call over to rich our chief commercial officer.

Thank you Sarah in the second quarter, which represented the first full quarter of the prior kind launch be generated net U S sales of $3 1 million.

Sarah: Finally, in February, PyroKind became the first FDA-approved therapy for pyruvate kinase, deficiency, and we continue our efforts to expand utility of this medicine to all PK deficiency patients.

Danielle Brill: Good morning.

Danielle Brill: Thanks so much for the question.

Danielle Brill: I guess a follow-up to a couple prior.

As we've said before our commercial launch strategy outlined on slide 22 aimed to connect with the provider and facilitate access to appropriate disease and product information for the patient or focus as uninsured <unk> such that the approximately one 5% to 4000 PK deficiency patients in the U S are accurately diagnose.

Danielle Brill: Maybe I'll just ask another way.

Sarah: In June, we initiated two studies of PyroKind in pediatric PK deficiency patients ages 1, up to 18, as shown on slide 19.

Sarah: Activate KITS will randomize 30 not regularly transfused patients, 2 to 1, to either PyroKind, or placebo, and evaluate hemoglobin response over the 12-week course period.

Sarah: Activate KITS-T will randomize 45 regularly transfused patients, 2 to 1, to either PyroKind, or placebo, and evaluate transfusion reduction over the 24-week course period.

Two efforts like EMEA.

Second physicians understand the urgency to prescribe and eligible patients advocate for treatment and finally patients connect you might argue support services to optimize disease understanding ensure access and drive long term medication adherence.

Sarah: In parallel, our marketing authorization application for PyroKind in adult PK deficiency remains, under review in the EU, and we remain on track to receive a decision from the EMA by year end.

Danielle Brill: Given your expectations on potential discontinuations at the six-month mark, I'm just wondering, if there was a bullet of patients added in 1Q that might impact growth in 3Q.

With our first full quarter under our belt.

Courage by the early launch metrics as well as a meaningful feedback we have received from patients and their physicians.

Sarah: In summary, as shown on slide 20, we are pleased with the progress made against our 2022 key, milestones this quarter across all programs.

Richa: I guess if you could provide some more color on how we should be thinking about sequential, revenue growth, that would be great.

Start with what we view as the key metrics, we have observed so far as outlined on slide 23 as.

Sarah: With that, I will now turn the call over to Richa, our Chief Commercial Officer.

Richa: Thank you.

Richa: Thank you, Sarah.

As of June 30th our team of hemolytic anemia specialists have continued to engage with customers and have been successful in driving script and then now with total of 52 unique patients with completed by the time prescription in government bonds.

Richa: In the second quarter, which represented the first full quarter of the PyroKind launch, we generated net U.S. sales of $3.1 million.

Richa: So, as we've noted, we have 52 patients that have been prescribed Paratine. It's taking about four to eight weeks for the prescription to be filled.

Richa: As we've said before, our commercial launch strategy, outlined on slide 22, aims to connect, with the provider and facilitate access to appropriate disease and product information for the patient.

Richa: We have 37 on therapy right now, which include those that have initiated therapy as well, as those that have refills, so as in they're titrating through the drugs.

This converted to 37 total patients in pipeline, which includes those with new prescription and those continuing treatment in.

Richa: Our focus is on ensuring, first, that the approximately 1.5 to 4,000 PK deficiency patients, in the U.S. are accurately diagnosed through efforts like Anemia ID.

Richa: Second, physicians understand the urgency to prescribe, and eligible patients advocate, for treatment.

Richa: So, we're not going into any more specifics than that at this point.

Fortunately at this early stage of launch these patients are coming from the unique prescriber base of 50 positions diversified across the country validating our view that the majority of patients are treated in the community versus academic medical centers or centers of excellence.

Richa: Again, this is our first full quarter of launch, and a lot more is to be learned. We are learning a lot already from what messages are working, what messages are not working.

The breadth of prescribing across states and practices the indication of early launch out.

Richa: We're seeing how physicians, patients are responding to our strategy, and we are continuing, to hone and continuing to learn, so that will be an ongoing process.

Richa: And finally, patients connect to MyArduous support services to optimize disease understanding, ensure access, and drive long-term medication adherence.

Richa: So, very early to comment.

As we saw in the first quarter patients coming on therapy represents a range of demographics and disease characteristics very representative of the adult <unk> patient population.

These include splenectomy and non connect my patients patients that are regularly add not regularly transfused young in all patients and patients that have a range of various levels of hemoglobin.

In terms of payer dynamics on National account directors continue to have positive interactions with payers to date.

Richa: And I think we can also just remind everybody there was no bolus of patients in Q1.

As we saw in Q1, the majority of scripts have been approved through the medical exception process as payer policies I developed payer policies are starting to be developed with the few in place aligned to indication statement or the clinical trial eligibility criteria.

Richa: With our first full quarter under our belt, we are encouraged by the early launch metrics, as well as the meaningful feedback we have received from patients and their physicians.

Turning to slide 24.

We are pleased with the continued interest in <unk> anemia, I D kit, which is a free genetic testing program designed to drive an accurate diagnosis for patients with a general diagnosis of hemolytic anemia unknown etiology.

Richa: I'll start with what we view as the key metrics we have observed so far, as outlined on slide, 23.

Richa: As of June 30th, our team of hemolytic anemia specialists have continued to engage with, customers and have been successful in driving scripts, as there are now a total of 52 unique This is converted to 37 total patients in pyrokine, which includes those with new prescriptions, and those continuing treatment.

Richa: Importantly, at this early stage of launch, these patients are coming from a unique prescriber, base of 50 physicians diversified across the country, validating our view that the majority of patients are treated in the community versus academic medical centers or centers of excellence.

As of June 30th more than 40 to 100 kits have been ordered a 20% increase since Q1 consistent with last quarter approximately 25% of kits have been completed and the PK deficiency positivity rate for those complete attached remains in the mid single digit percentages.

After positive test they are split evenly between pediatric and adult patients.

Richa: The breadth of prescribing across states and practices is an indication of early launch, health.

Looking to the second half of the year. There are several factors to consider as we continue to evaluate early launch trends.

Richa: As we saw in the first quarter, patients coming on therapy represent a range of demographics, and disease characteristics, very representative of the adult TKD patient population. These include splenectomized and non-splenectomized patients, patients that are regularly and not, regularly transfused, young and old patients, and patients that have a range of various levels of hemoglobin.

Richa: In terms of payer dynamics, our national account directors continue to have positive interactions, with payers to date.

I leave it suggests patients continue on treatment for six months at which point an assessment of response can be meet base.

Richa: As we saw in Q1, the majority of scripts have been approved through the medical exception, process as payer policies are developed. Payer policies are starting to be developed with a few in place aligned to indication, statement or the clinical trial eligibility criteria.

Richa: Turning to slide 24, we are pleased with the continued interest in our Anemia ID kit, which, is a free genetic testing program designed to drive an accurate diagnosis for patients with a general diagnosis of hemolytic anemia of unknown etiology. As of June 30th, more than 4,200 kits have been ordered, a 20% increase since Q1.

Based on our clinical trial experience, we believe approximately 40% to 45% of patients will be considered responders based on hemoglobin levels markers of hemolysis and individual assessment of steel and function as we reached the six month Mark of launch we will start to see the non responding patients come off therapy for the patient.

Richa: 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. After positive tests, they are split evenly between pediatric and adult patients.

Richa: Looking to the second half of the year, there are several factors to consider as we continue, to evaluate early launch trends.

Richa: First, our label suggests patients continue on treatment for six months, at which point, an assessment of response can be made. Based on our clinical trial experience, we believe approximately 40 to 45% of patients, will be considered responders based on hemoglobin levels, markers of hemolysis, and individual assessment of feel and function.

Richa: As we reach the six-month mark of launch, we will start to see the non-responding patients, come off therapy.

Richa: For the patients who stay on therapy, we will be able to make better assessments of adherence, and persistence.

To stay on therapy, we will be able to make better assessments of adherence and persistence second as we said prior to launch it will take approximately a year to achieve optimal payor coverage. We will continue to track their policies as they are developed including the criteria for initial coverage, which could be based on clinical trial eligibility the.

Richa: Second, as we said prior to launch, it will take approximately a year to achieve optimal, peer coverage.

Richa: We will continue to track peer policies as they are developed, including the criteria, for initial coverage, which could be based on clinical trial eligibility, the exclusions for which are noted in the second right-hand box on slide 25, and not the indication statement, as well as how the individual peers define response as part of the reauthorization process.

Exclusions for which are noted in the second grade 10 box on slide 25, and not the indication statement as well as how the individuals. He has defined this bonds as part of the reauthorization process.

Richa: And finally, it is important for us to remember that PK deficiency is a rare chronic condition, which is poorly understood.

And finally, it is important for us to remember that PK deficiency is a rare chronic condition, which is poorly understood. Our efforts around disease education, and encouraging accurate diagnosis continue to be paramount to ensuring long term success. The commercial team is laser focused on these initiatives given that PK deficiency does.

Richa: Our efforts around disease education and encouraging accurate diagnosis continue to be paramount, to ensuring long-term success.

Richa: The majority of patients actually joined in Q2, and so I think what we're starting to, see is we've always talked about this being a slow and steady launch and building this market and the terrific work of our commercial team is starting to pay off as we're gaining that traction with disease awareness and diagnosis and getting patients on, and I think it's going to continue to be a steady progression.

Richa: The commercial team is laser-focused on these initiatives, given that PK deficiency is a, disease that requires multiple interactions to both educate on disease to create urgency and also ensure accurate diagnosis.

That requires multiple interaction.

Educate on disease to create urgency and also ensure accurate diagnosis.

Richa: We are very encouraged with these early launch successes and the positive experiences we, are creating with the broader PK deficiency community. We have built a passionate commercial organization with significant rare disease experience that, is fully capable of executing our launch strategy and be excited and grateful for the impact we are making on the lives of PK deficiency patients.

We are encouraged with these early launch successes and the positive experiences we are creating with the broader PK deficiency community.

Built a passionate commercial organization with significant rare disease experience that is fully capable of executing our launch strategy and we are excited and grateful for the impact we are making on the lives of PK deficiency patients.

Richa: Importantly, what we are seeing from this launch is that our commercial strategy, 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 PK deficiency patients, as well as longer-term for other genetically-defined diseases.

Importantly, what we are seeing from this launch is that our commercial strategy, our knowledge base and the connections. We are making are setting us up for success as we continue to expand the applicability of private <unk> to all eligible PK deficiency patients as well as longer term other genetically defined diseases with that I'll now turn.

Jonathan: With that, I'll now turn it over to Jonathan to review second quarter financials.

Richa: But no bolus back in Q1.

It over to Jonathan to review second quarter financials.

Jonathan: Thanks, Richa.

Danielle Brill: Understood.

Thanks, Richa, our second quarter 2022 financial results can be found in the press release, we issued this morning, which I'll summarize.

More detail will be included in our 10-Q filing later today.

Turning to slide 28, as Richard shared I Recon revenue for the second quarter was $3 $1 million in.

We recognize revenue of $2 $5 million in the quarter with respect to an upfront payment associated with the licensing of intellectual property for our Friedrich <unk> ataxia, a preclinical program, which we discontinued in 2020.

Cost of sales for the quarter was $435000.

Turning to operating expense research and development for the second quarter was $74 5 million.

An increase of $12 5 million compared to the second quarter 2021.

Year over year increase in R&D was driven primarily by increased headcount and workforce related expenses.

<unk> increased activity associated with the ph preclinical program.

Startup costs for the AG 946 phase II Mds study increased spend for the AG 946 phase one trial and startup costs with the pilot pivotal study for sickle cell disease in pediatric PK deficiency.

Selling general and administrative expenses were $28 3 million for the second quarter, representing a $1 million decrease over second quarter 2021.

The decrease in SG&A expense was primarily due to the completion of the Reimbursable transition related services provided to third related to the sale of the oncology business, which concluded in the first quarter of 2022.

<unk> royalty revenue, which is recorded under royalty income and gain on sale of oncology business on our income statement was $2 $7 million.

We ended the quarter with cash cash equivalents and marketable securities of approximately $1 $1 billion.

This cash balance we expect to be able to execute our current operating plan major catalysts and.

<unk> cash flow positivity without the need to raise additional equity.

Operator: Thank you.

With that operator, please open the line for questions.

Operator: We have a question from Greg Harrison with Bank of America.

Thank you as a reminder to ask a question. Please press star one one on your telephone please standby, while we compile the Q&A roster.

Jonathan: Our second quarter 2022 financial results can be found in the press release we issued this morning, which I will summarize.

Operator: Your line is open.

Our first question.

It comes from Marc Frahm with Cowen Your line is open.

Jonathan: More detail will be included in our 10-2 filing later today.

Mary Skidon: Good morning.

Jonathan: Turning to slide 28, as Richa shared, Iroquoian revenue for the second quarter was $3.1 million.

Jonathan: In addition, we recognize revenue of $2.5 million in the quarter with respect to an upfront payment associated with the licensing of intellectual property for our Friedrichs Ataxia preclinical program, which we had discontinued in 2020.

Yes, thanks for taking my questions and congrats on the quarter.

Jonathan: Cost of sales for the quarter was $435,000.

Jonathan: Turning to operating expense, research and development for the second quarter was $74.5 million, an increase of $12.5 million compared to the second quarter of 2021. A year-over-year increase in R&D was driven primarily by increased headcount and workforce-related expenses, planned increased activity associated with the PAH preclinical program, startup costs for the AG946 Phase 2a MDS study, increased spend for the AG946 Phase 1 trial, and startup costs for the pyrokine pivotal studies in sickle cell disease and pediatric PK deficiency.

Jonathan: Selling general and administrative expenses were $28.3 million for the second quarter, representing a $1 million decrease over second quarter 2021. The decrease in SG&A expense was primarily due to the completion of the reimbursable transition-related services provided to Servier related to the sale of the oncology business, which concluded in the first quarter of 2022.

Jonathan: Chisovo royalty revenue, which is recorded under royalty incomes and gain on sale of oncology business on our income statement, was $2.7 million.

Jonathan: We ended the quarter with cash, cash equivalents, and marketable securities of approximately $1.1 billion. 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.

Maybe this is for Richard can you speak to kind of fill time that youre seeing in those 50 to start forms that have come in versus the 37 patients.

On drug and how do you expect that trajectory to kind of change through the rest of the year.

Yes, Mark Thanks for the question. So we are encouraged as we said with the trends that we're seeing in regards to.

Getting patients on.

Yes.

On the drug.

Getting the drug getting access to the drug as well.

So we expect those to converge over time, it's taking about four to eight weeks at this point for patients to get on therapy, given that extra transitioning through the medical exception process is being quite a feat that think about that.

As we've said in the past.

Sydney is the way that any anticipated going into the second half I think two things to keep in mind.

Patients have to tighten.

Titrated to their therapy. According to on April and we have six models.

Assessment Wang.

The weighted response will be made to the patient and depending on the activities from a kind of a second it's about 40% to 45% of patients expected to respond.

We'd have some patients drop off and then ask appear policies in the authorization and Nevada.

As well in terms of what that second half looks nice, but those are the two patients to take into consideration as we think are going to.

To the second half, but we are very encouraged with disappointing on strategy in terms of what you're most of your patients who are getting prescribed drugs as well as the breadth of prescribing across the country.

Okay.

That's helpful and then.

I know the authorization utilization management criteria processes pretty early there.

Early.

Back that youre getting on the reauthorization process.

How strictly are you seeing those plans adhere to the response criteria in the trial versus being open to maybe a broader interpretation of what our response looks like.

So I think if you have any pieces of abb's rate that is so I think no.

Conversation between the physician and the cloud.

Our continued engagement with the payers, which we have continued to do well.

Can you do with reorganization and utilization management. Thank you guys. Good luck.

It's going to be very important so those interactions thus far have been positive.

Plenty to comment like I said.

It continues to trend in the direction of the whole thing.

Okay alright, thank you.

Operator: With that, operator, please open the line for questions.

Mary Skidon: This is Mary Skidon for Greg.

Our next question comes from Gregory <unk> with RBC. Your line is open.

Operator: Thank you.

Mary Skidon: Thanks for taking our question.

Mary Skidon: So you mentioned that the awareness and the diagnosis rate of CKD could increase with, the awareness of the treatment, such as chiropractic, maybe have you been seeing this increase?

Hi, This is <unk> on for Greg. Thank you for taking our questions and congrats on the quarter.

Maybe just a follow up question on the patient's prior kind just wondering among the 37, how many were new patients added this quarter.

And what is your expectation around the <unk> growth in the second half and what are some of the headwinds and tailwind that we should think about.

Operator: As a reminder, to ask a question, please press star 11 on your telephone.

Mary Skidon: How are you planning to quantify this?

And then secondly, just on the diagnostic kit in EMEA I D.

Wondering is the positivity rate a function of prevalence or there are other factors that could increase the positivity rate and where do you see that rate evolve to a long time.

Operator: Please stand by while we compile the Q&A roster.

Mary Skidon: And maybe how long would you expect this increase to take?

Mary Skidon: Thank you.

Thank you, yes, so long term thanks.

Operator: Our first question comes from Mark Fram with Cowen.

Sure. So I'll ask the answer the anemia any questions to ask so just be reported the positive debate because we believe we are at.

At the point, where it's pretty steady and has been pretty steady for a while as a reminder, I mean, yes. It is not designed for PK deficiency.

Designed with the needs of.

Physician and healthcare professional base as well as what we knew was needed to help improve diagnosis for hemolytic anemia period, so designs attached for hemolytic anemia.

<unk> and to aid <unk>.

Kept professionals to understand what the underlying cost is for the hemolytic anemia.

It's just being specific to peak efficiencies either dismissed.

We don't have any information to suggest we would expect any upward.

And the positivity rate associated with it.

To give you specifically so that somebody in EMEA.

<unk> and <unk> again, it's really early to comment I think what is important is that we are seeing slow and steady growth.

We're seeing patients across a wide variety of demographics, we are not seeing patients obligate specific kind of being prescribed the drug we are seeing across hemoglobin levels across.

These characteristics based representatives at the adult PKU population, which is encouraging and across the country, which is also encouraging but just how you would expect this is a rare disease chronic in nature that is not concentrated in any centers of excellence. So you would expect that correct.

Richa: So this is, so when you think about awareness, right, again, I think it's a rare disease, ultra-rare disease, chronic, that's not focused in centers of excellence, so it's going to take a lot of effort and time before we see, we are able to provide any specific trends around where the disease awareness is going.

Richa: I think what we have is leading indicators that we've talked to you guys about today, at today's call.

Richa: One is we are seeing a broad swath of PKD patients, adult PKD patients get on therapy.

In general.

Richa: We are seeing that this is spread out throughout the country, so that means our awareness efforts, are working and we are able to get physicians across the country, healthcare professionals across the country, as well as patients, get on therapy and raise awareness with them.

Again as a reminder, as I said as well in the second half a lot of this is our first full quarter so schedule anybody on.

We have to see what happens with the six month assessment.

Because he looks like which is going to take a long time for us to figure out but is that kind of go drive was 40% to 45% and then we also have to see how the payer policies Victoza reauthorization utilization management guys do you guys have shaped up.

In fluids.

That as well so we'd have more sense of trends more than adequately or under that as opposed to just a couple of quarters, but it is headed in the right direction, which is encouraging.

Great. Thank you.

Yeah.

Mark Fram: Your line is open.

We have a question from Andrew Burns with SVP Leerink. Your line is open.

Mark Fram: Yes, thanks for taking my questions and congrats on the quarter.

Hi, Congrats on the launch progress and thanks for giving US all the color on your addressable market.

I was wondering if you could also give us some color on the genotype of the PK D patients that are on commercial <unk>.

One on the balance sheet any opportunity any thoughts on the transfusion independent opportunities now the Bristol stopped their program in that cohort.

Okay.

Yeah. So.

The genotype.

As a reminder, Ada PK deficiency diagnosis can be obtained two enzymes testing or genetic testing. So we don't always have genotype information off board.

For all of our <unk>.

But we are not seeing physicians at this moment and as you remember from my Ebola in April it's pretty broad tactical what's got the clinical and regulatory teams have done. So it is prescribed for adults.

PKU patients as long as you already have 18 Youre currently eligible for a private guy in and that's what we're seeing in <unk>.

Prescription trends. So that's good news, but not seeing physicians say, oh, I'm only going to give it to a certain kind of genotypic genotype or not give it towards a genotype. So we're not seeing that.

And then to your question around Paris EMEA.

So a couple of things right on that and then ask Sara to comment I'll add from a clinical counseling as well, but very encouraging that we see is starting to generate these positive experiences with <unk> because it's the same physician and healthcare professional base.

So be looking at patents EMEA and.

Abid drugs photography, so the more experience they get the battery experience, we have with the drug.

Better set up we will be where do we have.

And approval.

Telus EMEA space a program itself is designed to address both alpha and beta thalassemia as well as non transfusion dependent and transfusion dependent thalassemia and we know that.

Only a small proportion of establishing a patient population that <unk> dependent beta Tod Scott It yourself by this factor second necessarily a lot of people that don't respond and you really need something that is an oral therapy that's convenient.

From physicians that there is tremendous value in that as well as with beef design, a clinical program itself, but just looking at the totality of Anita including benefits across a wide spectrum of England function as well.

We've seen consistency of benefit from a proof of concept data across all three hemolytic anemia, which we believe that's what that is.

Very good.

So we are very encouraged with what we're seeing but I can comment more on the status of your clinical development.

Thanks.

Yeah, great. Thanks, Richard So yes from the clinical development perspective, we remain encouraged and on track with our program for policy now we do not see this recent decision as having an impact on our program or on our probability of success.

A couple of reasons we've always.

Our plan to deliver on the totality of data package for the transfusion nonregulated.

Population as rich described earlier and then on top of that our mechanism of action is very different I mean, both drugs do increase hemoglobin, but because of the mechanism of action different and the data that we've been generating across our different clinical programs, including also seeing starting to see signs.

Assigned to have an impact on iron overload.

Overload.

We continue to.

Believing in.

In our programs and continue to move forward with the same probability of success.

Great. Thanks, Thanks for that Matt maybe a question for Jeff here I'll, maybe you guys aren't.

During requiring JBT are ya.

Just a quick question Joe Thanks for taking my question I appreciate it.

How about if I laugh in response to that model.

[laughter].

Our next question comes from.

Sorry, Mark.

Mark.

Greenberg with Oppenheimer. Your line is open.

Richa: This is for Richard.

Good morning. This is Jacqueline Mark from Oppenheimer, Congrats on the quarter and thanks for taking our questions.

First one is how many new scripts.

The monthly retention over into Q.

And have you seen any prescription abandonment due to payer related machines.

And I have until I think.

Yes, I didn't hear the first part of your question, but maybe I'll answer the second part and then.

Come back to you.

First question. So I think you had asked about would abandon mcvie.

So again what is there any we haven't seen.

Patients that have been prescribed drug necessary I did not want to take therapy would be better.

Being rollout patients once they've been prescribed therapy in July our high touch patient support program.

Which is really helpful. In terms of getting patients started on therapy and then also.

<unk> one therapy, what we have seen with a few patients anecdotally is that some patients are denis start of therapy, while they have a life event like already Moura holiday. So they don't they are waiting on stopping that RFP, but we are not seeing abandonment that facility stage.

I don't know what your first question was I'm sorry, So if you could repeat that I didn't quite catch.

Yeah, So how many new script and what was the monthly retention rate for the second quarter.

Richa: Can you speak to the kind of still time that you're seeing on those 52 start forms that have come in versus the 37 patients on drug?

So we haven't provided specifics I'll take this new scripts.

We have said is.

We have 52 prescriptions in 37 of those have been filled which includes both those patients that had initiated in this quarter as well as those that are continuing on from the previous quarter.

Richa: And how do you expect that trajectory to kind of change through the rest of the year?

Alright.

Hum.

And then my other question is on the rise that trial with the enrollment in the phase two portion of rise up study on track to complete by year end can we expect a dose selection decision in the first half of 2023.

Richa: Yeah, Mark, thanks for the question.

Initial data from the trial solely focus on the safety and the hemoglobin response or could we see some of the secondary endpoint data as well.

Richa: So we are encouraged, as we said, with the trends that we are seeing in regards to both getting patients on on the drug, but also getting the drug, getting access to the drug as well.

Hi, This is Paulo, so you will not see data in the first quarter of 2023, because the trial. The phase two has a follow up period of 12 weeks. So all patients need to complete that go to their safety follow up that we need to do the data base lock and review the data.

It's not possible for that to happen in Q1.

And then in regards to the data that you will be seeing so we do have.

More than just the hemoglobin response, and the safety that we're collecting in that space through obviously.

Because it's we're going to collect all of the data and our pipeline for secondary endpoints in our presentation and so we will be analyzing all of the data to them to inform our go no go decisions to phase III and then there are pre specified criteria for the dose selection.

Well.

We will be very much focused on moving from phase II to phase III, but we will be presenting the data that we have at an upcoming medical conference win.

When ready.

We'll hope to be more towards the end of the year.

Great. That's helpful. Thank you so much and I'll correct again on the quarter.

Thank you.

Richa: So we expect those to convert over time.

We have a question from Salvino Victor with Goldman Sachs. Your line is open.

Richa: It's taking about four to eight weeks at this point for patients to get on therapy, given that we are still transitioning through the medical exception processes.

Hi, This is Tom yawn for solving and thank you for taking my question could you expand on the launch trajectory of prioritizing PK do you are you planning to continue the same effort to identify patients or are you utilizing new efforts to expand patient identification and how many patients that are positive with the anemia IV so actually.

Richa: They are policies that we developed, as we've said in the past, slow and steady is the way that we anticipate this launch going, including the second half.

Richa: I think two things to keep in mind here, the patients are still titrating through their therapy.

Move to prioritize treatment and lastly on the PK data in sickle cell. How are you thinking about the market opportunity, specifically, which group of patients do you think are most suitable for Parker.

Richa: So according to our label, we have the six months assessment where the assessment response will be made for the patient.

Richa: In addition, we are also seeing slow and steady growth on our Anemia ID kits, which is one, of our key ways to help with diagnosis of hemolytic anemia of unknown etiology, which again is designed with the hopes to help improve diagnosis over time.

Yes.

Richa: And depending on that, at least from our clinical studies, we know it's about 40 to 45 percent of patients expected to respond.

Richa: We'd have some patients drop off.

Yes.

Richa: And then as the peer policies and the authorization criteria developed, we know more as well in terms of what that second half looks like.

With <unk> IV and then work backwards. So first of all I think it's just really important to remember that from a compliance standpoint, there is no way for us to know which patients that had been identified at the beginning patient, which physician that patient along so it's just really important that we continue to drive disease as well as get improved diagnosis.

Richa: So those are the two things just to take into consideration as we go into the second half.

Richa: Both of those things will help in the long term.

Richa: But we're very encouraged with this early launch trend in terms of both diversity of patients who are getting prescribed drugs, as well as the breadth of prescribing across the country.

Richa: Okay, that's helpful.

Richa: As a reminder, 30% of, we believe today that 30% of PKD patients are diagnosed and we expect, that number at peak to be about 70% and to take about five to seven years to get there.

In EMEA. It again, it's not specific to <unk> kinase deficiency, but has been designed with the needs of the community wishes to help do a differential diagnosis on the hemolytic anemia unknown etiology and Thats, where the value comes in and its being utilized 15 continued growth in the tax because there is that you've seen from the community.

Utilization of the Jackson doing that differential diagnosis or they can tailor the treatment.

Tuesday outpatient depending on the kind of hemolytic anemia, the patient had and now for at least one of those hemolytic anemia to pyruvate kinase deficiency, we have a treatment. So I think that's the thing to think about with regards to EMEA D itself when it comes to diagnosis.

Richa: Given the nature of the disease and the fact that it's not concentrated, it'll be a while, before you see any number that we could reasonably comment on.

Again. This is I think it's just important to pyruvate kinase deficiency is a rare chronic condition and it is not concentrated in Asia and specific centers of excellence in a diffused throughout the country.

It is largely managed through the community and so our efforts, which have taken the disease understanding into consideration.

Richa: But the trends are in the right direction.

Around raising awareness of the disease continue to execute on the burden of disease working very closely with our medical colleagues to continue to ensure that we are.

Sharing our knowledge as we learn about the disease with the broader community.

Ensuring that we continue to drive diagnosis liquidity patent challenges going to be as well I'm, just saying that it's going to be putting in this disease space and it's true for rare diseases in general.

Richa: Great.

Richa: Thank you.

And so what we are seeing is.

Lewis steady progress in ensuring that we get patients diagnosed and for those that are eligible and get them on treatment and that's going to continue to be our focus.

Richa: And then, you know, I know the authorization and utilization management criteria process is pretty early, but the early feedback that you're getting on the reauthorization process, you know, how strictly are you seeing those plans adhere to the response criteria in the trial versus being open to maybe a broader interpretation of what a response looks like?

Throughout.

And then with regards to just take those that have happened there I'll comment actually specifically on the phase III trial design, because that will be a nice segway to how we think about differentiating our product in that space as well. So I didn't want to talk about rise up.

Richa: So, I think it's really, this is a rare disease, right?

Richa: That is, so I think here's the conversation between the physician and the plans as well as our continued engagement with the payers, which we have continued to do and will continue to do as those reauthorization and utilization management criteria develop is going to be really important.

Richa: So, those interactions thus far have been positive.

Operator: There's no other questions in the queue.

Speaker: I'd like to turn the call back for management for any closing remarks.

Speaker: Thank you, operator, and thank you, everyone, for the questions this morning.

Sure. So the phase III well right is an operationally seamless Ah trial design from with a phase two component that we just discussed and then moving into phase three the operationally seamless component of it is actually giving us a lot of flexibility because it allows us to be.

<unk> sites on early and get them ready for enrollment that as quickly as possible, but it also still allows us to interpret the phase two data and make any adjustments as needed without having an impact on the statistical or regulatory components of the trial and now for the phase III setup with two primary end.

Points, the hemoglobin response and annualized sickle cell pain crisis.

End points.

Which.

If one both are positive allows us to move on to secondary endpoints testing, which gives us.

You have the data that we would need to make.

A meaningful story for patients and physicians and regulators very similar in that sense.

Our other trials right.

<unk> of the trial rise up is that it does allow us to basically.

Hits.

<unk> and <unk>, both are very important in the context of sickle cell disease, and we're hopeful that that data allows us to bring forward to treatment for sickle cell disease.

As the disease in its entirety.

And the one thing I would add to everything that Sarah just said right. We've designed the clinical studies and I'm thinking about.

How do we differentiate based on input from the community has told us the broadest sickle cell community physicians and patients.

To understand what their needs on it and design the study accordingly as far as the commercialization is going to depend on the totality of the data before we make any determination around that would be a design of the study to ensure that we are set up for success.

Thank you.

And as a reminder, if you would like to ask a question press. The Star then the one key on your Touchtone telephone.

We have a question from Danielle Brill with Raymond James Your line is open.

Hi, guys. Good morning. Thanks, so much for the question I guess, a follow up to a couple of prior maybe ill just ask another way given your expectations on potential discontinuation at the six month Mark I'm. Just wondering if there was a bolus of patients added in <unk> that might impact growth in Threep Q.

I guess, if you could provide some more color on how we should be thinking about sequential revenue growth that would be great. Thank you.

Yeah.

So as Vince noted right. We have 52 patients that have been described private guy and it's taking that route for two weeks for the prescription to be fully we have 2007 on therapy right now which include those that have initiated therapy as well as dose.

<unk> had some refills. So I think this is leading to the drops.

So that's we are not going into any more specifics than that at this point again. This is our first full quarter of launch and lot more to be learned we're learning a lot already.

What messages I'm walking one messages are not walking this scene.

How are physicians patients are responding and.

Two.

Strategy, and we are continuing to own and continue to launch so that will be an ongoing process. So they already to comment anymore.

Richa: It's still early to comment, like I said, but it continues to trend in the direction we hope it would.

Richa: All right, thank you.

And I think we can also just remind everybody there was no bolus of patients in Q1, the majority of patients actually joined in Q2, and so I think what we're starting to see as we've always talked about this being a slow and steady launch and building this market and the terrific work of our commercial team is starting to pay off as we are gaining.

That traction with disease awareness and diagnosis and getting patients on and nothing thats going to continue to be.

A steady progression, but no bolus back in Q1.

Operator: Our next question comes from Gregory Renza with RBC.

Understood. Thank you.

We have a question from Greg Harrison with Bank of America. Your line is open.

Operator: Your line is open.

Ying Luan: Hi, this is Ying Luan for Greg.

Ying Luan: Thank you for taking our questions and congrats on the quarter.

Good morning. This is Mary Kate on for Greg. Thanks for taking my question. So you've mentioned that the awareness and the diagnosis rate of TKD could increase with the awareness of the treatments such as private client maybe have you been seamless increase how are you planning to quantify this and maybe how long would you expect this increase to take thank you.

Richa: Maybe just a follow-up question on the patients of the prior kind.

So this is so when you think about it Dan Thats right again, I think it's a rare disease.

Chronic that's not focused in centers of excellence, so it's going to take.

A lot of effort and time with what we see.

We are able to provide any specific trends around rare diseases and this is going I think what we have as leading indicators that we've talked to you guys about today at today's call is one is we are seeing a broad swath of PKU.

<unk> patients <unk> patients get on therapy.

We are seeing that this is spread out throughout the country. So that means our business excellence, our king and we are able to get to.

Physicians across the country have skipped professionals across the country as well as patients.

Get on therapy and rigor that next wisdom. In addition, we are also seeing still a steady growth on <unk>.

<unk>, which is.

One of our key way.

Ways to help with diagnosis of hemolytic anemia, unknown etiology, which again.

It's designed with the hopes to help improve diagnosis overtime. So both of those teams.

Withheld.

In the long term.

Mind, you are up 40%.

We believe today that 30% up to TD patients are diagnosed and we expect that nickel.

At peak to be about 70% going to take about five to seven years to get that so given the nature of the disease and the fact that it's not concentrated it'll be a while.

What do you see any like.

Any number that we could reasonably comment on.

But the transaction metrics.

Great. Thank you.

Thank you there's no other questions in the queue I would like to turn the call back for management for any closing remarks.

Richa: Just wondering among the 37, how many were new patients added this quarter?

Thank you operator, and thank you everyone for the questions. This morning, as always I would like to wrap up by thanking my <unk> colleagues for their dedication and passion for making a difference for patients.

Richa: And what is your expectation around the NRX growth in the second half?

Speaker: As always, I would like to wrap up by thanking my Agile colleagues for their dedication and, passion for making a difference for patients.

Richa: And what are some of the headwinds and tailwinds that we should think about?

Richa: And then secondly, just on the diagnostic kit, anemia ID, just wondering, is the positivity rate a function of prevalence or there are other factors that can increase the positivity rate?

Richa: And where do you see that rate evolve to in the long term?

Speaker: I also want to thank all of the patients, caregivers, and physicians who partner with, us in so many ways, and especially those participating in our clinical trials across indications.

I want to thank all of the patients caregivers and physicians, who partner with us in so many ways and especially those participating in our clinical trials across indications.

Richa: Thank you.

Richa: Sure.

Richa: So, I'll answer the anemia ID question first.

Speaker: Our connections across our stakeholders and our collective efforts fuel our ongoing innovation, and impact for people with genetically defined diseases.

Our connections across our stakeholders and our collective efforts fuel.

<unk> innovation and impact for people with genetically defined diseases and also need to take just a second and memorialize. This moment is my last quarterly results call for Joseph in the CEO role and just express again, my gratitude to our terrific team.

Richa: So, we reported the positivity rate because we believe that we are at the point where it's pretty steady and has been pretty steady for a while.

Speaker: I also need to take just a second and memorialize this moment as my last quarterly results call, for Adios in the CEO role, and just express again my gratitude to our terrific team for everything that they're doing.

Richa: As a reminder, anemia ID is not designed for PK deficiency specifically, right?

Speaker: It's amazing to have such a great quarter with our first full quarter of launch for, PowerKind and PKD in adults in the U.S., and there are just so many things that are amazing about this moment.

For everything that they're doing it's amazing to have such a great quarter with our first full quarter of launch for power Com and PK data in adults in the U S. And there are just so many things that are amazing about this moment and I'm very grateful for Brian joining the team as I view this as being an additive thing for <unk> as he comes in as the new <unk>.

Richa: We designed it with the needs of our physician and healthcare professional base as well as what we knew was needed to help improve diagnosis for hemolytic anemia period.

Richa: So, designed to test for hemolytic anemia of unknown etiology and to aid healthcare professionals to understand what the underlying cause is for the hemolytic anemia as opposed to being specific to PK deficiency.

Richa: So, as of this minute, we don't have any information to suggest we would expect any upward mobility in the positivity rate associated with PKD specifically.

Richa: So, that's from the anemia ID.

Richa: Great, thank you.

Richa: To your question on NRX versus TRX, again, really early to comment.

Richa: I think what is important is that we are seeing slow and steady growth as we anticipated.

Richa: We are seeing patients across a wide variety of demographics.

Richa: We are not seeing patients of a very specific kind being prescribed the drug.

Richa: We are seeing across hemoglobin levels, across disease characteristics, very representative of the adult PKD population, which is encouraging, and across the country, which is also encouraging, which is how you would expect.

Operator: We have a question from Andrew Behrens with SVB Lyrinc, your line is open.

Richa: This is a rare disease, chronic in nature, that is not concentrated in any centers of excellence. So, you would expect that breadth with the disease in general.

Richa: Again, as a reminder, as I said earlier as well, the second half, this is our first full quarter, so it's still really, really early.

Operator: Hi, congrats on the launch progress and thanks for giving us all the color on the addressable, market.

Speaker: And I'm very grateful for Brian joining the team as I view this as being an additive thing, for Adios as he comes in as the new CEO with a terrific skill set to bring into our team and as I transition into the role of chair of the board and remain part of the team.

Richa: We have to see what happens with the six-month assessment, what the real-world efficacy looks like, which is going to take a long time for us to figure out.

Richa: But in our clinical trial, it was 40% to 45%, and then we also have to see how the payer policies in terms of reauthorization and utilization management criteria get shaped up, which will influence that as well.

Richa: So, we'll have more sense of trends, more like once we have a full year under us as opposed to just a couple of quarters, but it's headed in the right direction.

Andrew Behrens: I was wondering if you could also give us some color on the genotypes of the PKD patients, that are on commercial pyrokine, and then one on the thalassemia opportunity.

Andrew Behrens: Any thoughts on the transfusion independent opportunity now that Bristol has stopped their, program in that cohort?

Richa: Yes, so in terms of the genotype, so as a reminder, right, a PK deficiency diagnosis, can be obtained through enzyme testing or genetic testing, so we don't always have genotype information for all of our pyrokine patients, but we are not seeing physicians at this moment.

Richa: And as you remember from our label, our label is pretty broad, thanks to the work that the, clinical regulatory teams have done, so it is prescribed for adult PKD patients.

Richa: So as long as you're over the age of 18, you're currently eligible for pyrokine, and that's, what we're seeing in terms of our prescription trends.

CEO with a terrific skill set to bring into our team and as I've transitioned into the role of chair of the board to remain part of the team so with that.

Richa: So that's good news.

Richa: We're not seeing physicians say, oh, I'm only going to give it to a certain kind of genotype, or not give it to a certain type of genotype, so we're not seeing that, at least on the data that we have.

Richa: And then to your question around thalassemia, as we always maintain, so a couple of things, right, and I'll ask Sarah to comment on it from a clinical standpoint as well, but very encouraging that we see, we're starting to generate these positive experiences with PKD, because it's the same physician and healthcare professional base that will also be looking at thalassemia and prescribing drugs for thalassemia.

Richa: So the more experience they get, the better experience they have with the drug, the better, set up we will be when we have an approval in the thalassemia space.

Richa: Our program itself is designed to address both alpha and beta thalassemia, as well as, non-transfusion-dependent and transfusion-dependent thalassemia, and we know that only a small proportion of the thalassemia patient population, the transfusion-dependent beta thal, is currently served by mispatricept, and there's still a lot of people that don't respond, and you really need something that is an oral therapy that's convenient.

Richa: We've heard from physicians that they feel a tremendous value in that, as well as the, clinical program itself, which is looking at the totality of the data, including benefits across a wide spectrum of field and function, as well, and we've seen consistency of benefit from our proof-of-concept data across all three hemolytic anemias, which we believe will hold us in really good stead overall.

Richa: So we're very encouraged with what we're seeing, but Sarah can comment more on the, thalassemia clinical development plan.

Speaker: So, with that, look forward to all of your ongoing support.

Sarah: Yep, great.

Sarah: Thanks, Richa.

Sarah: So, yeah, from the clinical development perspective, we remain encouraged and on track with our, program for thalassemia.

Look forward to all of your ongoing support. Thank you for your support in the past and looking forward to a terrific.

Sarah: We do not see this recent decision as having an impact on our program or on our probability, of success, and for a couple of reasons.

Speaker: Thank you for your support in the past and looking forward to a terrific future and many, good quarters to come for Adios.

Sarah: We've always, you know, planned to deliver on the totality of data package for the transfusion, – non-regularly transfused population, as Richa described earlier, and then on top of that, our mechanism of action is very different.

Sarah: I mean, both drugs do increase hemoglobin, but because of the mechanism of action difference, and the data that we've been generating across our different clinical programs, including also starting to see signs of an impact on iron overload, we continue to believe in our programs and continue, you know, to move forward with the same probability of success.

Andrew Behrens: Great.

Andrew Behrens: Thanks.

Andrew Behrens: Thanks for that.

Andrew Behrens: Maybe a question for Jackie on BD.

Andrew Behrens: You guys aren't considering acquiring GBT, are you?

And many good quarters to come for Jess Thanks, very much for joining US today you may now disconnect.

Andrew Behrens: Just, that's a joke.

Andrew Behrens: Thanks for taking the question.

Operator: Okay.

Speaker: Thanks very much for joining us today.

Andrew Behrens: Appreciate it.

Operator: Our next question comes from, sorry, Mark Breedenbach with Oppenheimer.

Andrew Behrens: How about if I laugh in response to that?

Operator: You may now disconnect.

Operator: Your line is open.

Jackie: That's my response.

Jacqueline: Good morning.

Jacqueline: That's helpful.

Operator: This concludes today's conference call.

Jackie: Okay.

Jacqueline: This is Jacqueline from Mark from Oppenheimer.

Jacqueline: Congrats on the quarter and thanks for taking our questions.

Jacqueline: The first one is how many newsgroups and what was the monthly retention rate in 2Q?

Richa: And have you seen any prescription abatement due to payer-related issues?

Richa: Yeah, I didn't hear the first part of your question, but maybe I'll answer the second part and then come back to your first question.

This concludes today's conference call.

Richa: What we have seen with a few patients anecdotally is that some patients are delaying start of therapy while they have a life event, like a wedding or a holiday.

Richa: So they are waiting on starting their therapy, but we are not seeing abatement at this early stage.

Richa: I don't know what your first question was.

Thank you for participating you may now disconnect.

Richa: I'm sorry.

Richa: So if you could repeat that, I didn't quite catch.

Jacqueline: So how many new scripts and what was the monthly retention rate for the second quarter?

Richa: So, we haven't provided specifics on the new scripts.

Richa: What we are, what we have said is, you know, we have fifty two prescriptions and thirty seven of those have been filled, which includes both those patients that have initiated in this quarter as well as those that are continuing on from the previous quarter.

Jacqueline: Okay, thanks.

Okay.

Sarah: And my other question is on the Rise Up trial with the enrollment in the phase two portion of Rise Up study on track to complete by year end.

Sarah: Can we expect a dose selection decision in the first half of 2023?

Sarah: And what initial data from the trial solely focus on the safety and hemoglobin response, or could we see some of the secondary endpoint data as well?

The conference will begin shortly to raise your hand during Q&A you can dial star one one.

Sarah: So, you will not see data in the first quarter of 2023 because the trial, you know, the phase two has a follow up period of twelve weeks.

Sarah: So, all patients need to complete that, go through their safety follow up.

Sarah: Then we need to do the database lock, review the data.

Sarah: So, it's just not possible for that to happen in Q1.

Sarah: And then in regards to the data that you will be seeing, so we do have more than just the hemoglobin response and the safety that we're collecting in that phase two, obviously, you know, because we're going to collect all of the data.

Sarah: And I've outlined the secondary endpoints in our presentation.

Sarah: And so we will be analyzing all of the data to inform our go, no-go decisions to phase three. And then there are pre-specified criteria for the dose selection as well.

Sarah: We will be very much focused on moving from phase two to phase three, but we will be presenting the data that we have at an upcoming medical conference when ready, which we'll hope will be more towards the end of the year.

[music].

Jacqueline: Great.

Okay.

Okay.

Okay.

Uh huh.

Thank you.

Hum.

Okay.

[music].