Q3 2022 Agios Pharmaceuticals Inc Earnings Call

Yeah.

Good day, and thank you for standing by and welcome to the Q3 2022 odd years Pharmaceuticals, Inc. Earnings Conference call. At this time all participants are in 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 will need to press.

Star one 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 hardly Manny.

Please go ahead.

Thank you operator, good morning, everyone and welcome to <unk> third quarter 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 Brian Goff, our Chief Executive Officer, Dr. Sarah Gubins, our Chief Medical Officer, and head of research and development, Richard <unk>, Our Chief commercial officer, and Cecilia Zhang 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, 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 will turn the call over to Brian .

Thanks, Holly and good morning, everyone.

Joining you today on my first <unk> financial results call as Chief Executive Officer, nearly three months after assuming the role in August .

<unk> has a long standing legacy of scientific excellence and clinical execution and it's on the cost of broadening its ability to change the treatment landscape of rare and genetically defined diseases.

With the recent launch of <unk> and its extensive clinical and preclinical pipeline. The opportunity that lies ahead for <unk> and the patients that serves is exciting.

Yes.

Okay.

Company from the very beginning.

Since joining in August as I dug into the business and that so many of our talented team.

Optimism and excitement for the future of our Geos 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.

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.

22 has been a year of execution with five pivotal studies and two early stage trials underway and ongoing commercial launch in the U S and active filing in the EU in Great Britain, and advancing preclinical pipeline and broad business development efforts to continue to build out our pipeline.

And finally, while the pie refined watch 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 is 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.

<unk> 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 jobs to our Geos and her first quarterly call as our Chief Financial Officer.

So sealy as we 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. Raluca law, and Cynthia Smith relevant Cynthia of our seasoned biopharmaceutical executives with critical expertise that will help us maximize our potential.

Within R&D that clinical and medical teams have been busy securing a positive <unk> opinion for <unk> in EU.

And this meeting the AG 946, Mds Phase Iia trial published new data from our thalassemia in PK deficiency clinical programs and top tier medical journals.

Securing an expansive expensive 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 <unk> 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 Hcp's drive disease education, and urgency to treat and facilitate initiation of pirate kind therapy.

Richard will discuss some of these learnings and tactics shortly.

And finally last week, we completed the monetization of the tip Soho royalties 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 our very clear.

We continue to drive enrollment across our thalassemia and sickle cell disease pivotal trials secure approval of pirate kind for PK deficiency in the EU in Great Britain.

And drive towards continued commercial success for our U S launch.

I'd like to thank each and every <unk> employee for their fantastic work accomplished this quarter and for their support and my own learning and Onboarding. During these first few months with that I'll turn it over to Sarah.

Thanks, Brian .

2022 has been a year of significant execution for the research and development organization.

We have continued pioneered the field of PK expert.

Patients and broaden the potential applicability of this mechanism to a range of diseases with significant unmet needs.

Also advancing our earlier pipeline.

As highlighted on slide nine our clinical focus for PK excavation is to transform the course of hemolytic anemia.

In EMEA by increasing Red blood cell energy health and longevity.

By improving the overall health of the Red blood cell or <unk> impact the downstream consequences of hemolysis and ultimately improve.

Feel and function.

To date, we have demonstrated remarkable consistency in the largest clinical datasets for our PK activator across our three most advanced therapeutic area sickle cell disease thalassemia.

Jesse 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 <unk> and our collaborators were accepted for presentation, which further underscore the clinical consistency across the season as well as a common analysis of the underlying pathophysiology of these diseases.

Specifically, we look forward to sharing new data demonstrating the long term impact of treatment with <unk> in PK deficiency and thalassemia as.

Well at the sat and mat data for our novel PK activator $89.

More to come on our ash abstract when they go online today at nine a M eastern time.

Turning to our cost of SaaS PK activator Mcduffie back known commercially as pilot time became the first FDA approved therapy for PK deficiency in February and we continue our efforts to expand the utility of this medicine to patients with PK deficiency.

This summer we initiated two randomized placebo controlled trials the pilot <unk> in pediatric patients with PK deficiency Hs one up to 18 shown here on slide 11.

Excavated gets will enroll pediatric patients who are not regularly transfused and activate T.

He will enroll pediatric patients who are regularly transfused.

In addition, we have been busy advancing our marketing authorization application for five times in adults with PK deficiency through the EMA process. This year and we're pleased to receive a positive <unk> 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 patients access through our global managed access program. This program provides a pathway for eligible adults receiving care in the EU in Great Britain, who are diagnosed with PK deficiency to have access to prior guidance.

We will provide drug free of charge, regardless of the patient's insurance coverage.

<unk> will not be available under the global managed access program for indications under investigation or outside of the label, including solid senior sickle cell disease in pediatric PK deficiency.

Moving to yourself me now on Slide 12, we are very excited to have the potential to establish <unk> as the first oral therapy to improve hemolytic anemia, and ineffective erythropoiesis across the spectrum.

Also southsea, including transfusion dependent and transfusion independent thalassemia.

The impressive data generated in our core period of our phase two study of non transfusion dependent beta and Alpha thalassemia shown on slide 13 were published in the journal lapses 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 towards enrolling a meaningful portion of patients across two global pivotal trials of pirate time, energized and energized team, which are described on slide 14.

As a reminder, energized with a randomized placebo controlled trials in both alpha and beta thalassemia patients who are not regularly transfused with a primary endpoint of hemoglobin response.

<unk> is a randomized placebo controlled trials in both alpha and beta thalassemia patients who are regularly transfused.

Of the six to 20 Red blood cell unit transfused during the 24 weeks prior to randomization with a primary endpoint of transfusion reduction response.

In sickle cell disease, we are exploring parakiting, an operationally seamless phase two three study known as it rises.

With the goal of being the first potential oral agents to improve anemia, reduce poc's and improved quality of life by increasing native hemoglobin, resulting in reduced thanks.

Moving to slide 16, we are actively enrolling patients in the phase two portion, which will randomized 69 basis. Once the one to one to 60 milligrams Maritime twice daily 100 milligram twice daily or matching placebo.

The primary endpoints are hemoglobin response, that's fine that's equal or more one gram per deciliter, increasing average hemoglobin concentration from weekend through week 12 compared to baseline in safety.

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

Upon completion of the double blind portion of the phase two we will evaluate the totality of the data before triggering the start of phase III.

The outcome of the primary endpoints of the first then we will take into account secondary endpoints from the study, including changes in markers of hemolysis rates of sickle cell pain crisis and patient reported symptoms.

Our collaborators at the NIH and the University of interest continued to treat sickle cell patients with prioritizing extension study, which will also provide longer term treatment data to support our decision.

With phase II success. These data, but also allowed 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 the same clinical trial sites to enroll two distinct sets of page.

<unk> in the phase two and in the phase III, we have the ability to increase the speed at which we can transition from one state to the next.

In addition, we can assess the need for modifications to the phase III based on the outcome of phase two without impactful statistical and regulatory aspects of the trial.

He will share the outcome of the phase two portion of the study and our go no go decisions next year.

I'll now turn to slide 17, and 18 96, our novel PK activator, which provides the opportunity to further build our PK activator, French that 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 AG 900, <unk> profile as a potent PK activator will be presented at the Ash meeting in December .

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

In September we initiated our 18 nine for six lower risk Mds clinical program.

As outlined on slide 18, MBS are a heterogeneous group of rare hematological malignancies characterized by ineffective erythropoiesis abnormal cell maturation dysplasia and progressive Cytopenia.

Anemia is the most common feature of lower risk Mds occurs and approximately 90% of patients and about half will develop red blood cell transfusion dependence.

Primary therapeutic strategies are limited for patients with lower risk Mds anemia and include erythropoiesis stimulating agents or transfusions.

Additional treatments are indicated only in specific Mds subtypes, and generally with limited responses.

We believe $89 six has the potential to attach red blood cell functionality and survival by increasing like Kocis and ACP production and improved differentiation of erythroid itself in bone marrow potentially improving anemia caused by ineffective erythropoiesis in lower risk Mds similar to Dallas senior.

The first step in our clinical program the phase II a component of the phase two <unk> study shown on slide 19, which is an open label proof of concept study of one dose level of $89 six 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 towards our remaining priority for the year with that I will now turn the call over to Richard.

Thanks, Sara 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 40 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 really want proof point for pipeline, we're establishing a strong base of really what evidence and uncovering the opportunities for discipline P. Diaz debated on the market. In addition to being the placebo therapy available for patients with PK deficiency.

While this initial launch will be a modest revenue generator. It establishes our commercial capabilities platform in DRAM in genetically defined diseases.

And importantly, deduction, perhaps to the broader hematology community, but 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 third quarter, which represented the second full quarter of the prior claim launch we generated net U S sales of $3 5 million, which is indicative of increased patient demand offset by modest inventory build in the prior quarters up your lunch.

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 pipeline prescription enrollment forms a 64% increase over total P. S. At the end of Q2.

Of these P F.

Net of 56 patients on <unk> therapy, which includes those patients with new prescriptions and those continuing treatment of 51% increase since quarter two.

It continues to take approximately four to six weeks to convert a P F.

Description a trend that is unlikely to show them in the near term.

This continuation 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 the label.

As we absorb non responding patients come off therapy, we would be able to make better assessments of adherence and persistence, but those who stay on therapy.

As we saw last quarter. These patients are coming from abroad unique prescriber base of physicians diversified across the country.

Patients coming on therapy represents a range of demographics and disease characteristics that is consistent with the adult PK deficiency population.

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

<unk> to date aligns with our prelaunch expectations as outlined on slide 23.

The payer policies being developed online to the indication statement on the clinical trial eligibility criteria as anticipated.

In addition, Brian authorization criteria are 92 that specialty medicine and typically include the need for genetic testing consultations with the specialist and baseline hemoglobin in transfusion history.

Moving to slide 24, we are pleased with the continued interest in anemia, IV kit, which is a free genetic testing program designed to help patients with the general diagnosis of hemolytic anemia unknown etiology.

To receive an accurate diagnosis as of September 30th more than 5300 kits have been ordered a 26% increase since Q2.

Consistent with last quarter, approximately 25% of kids have been completed and the PK deficiency positivity rate produced completed tests remains in the mid single digit percentages.

After positive tests, approximately 60%, what it does and 40% pediatrics.

In taking a pass blew view of launch progress to date their 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 positions 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 Pilocarpine. 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 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 is equally if not more important and effective to empower and activate patients a sense advocate for diagnosis and treatment.

Looking ahead to the fourth quarter, we have been focused on evaluating tactical shifts and localized experiment to increase initiatives that are working and fill gaps in our loan strategy based on these new learnings importantly, the impact <unk> has on the lives of patients is evident NBA encouraged with these early launch successes and a positive experience.

We are creating with our 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 and knowledge base and the connections. We are making are setting us up for success as we continue to expand the applicability of cytokine to own and then you put patients with PK deficiency as well as longer term for other genetically defined diseases.

With that I'll now turn it over to Sylvia to review third quarter financials.

Thanks Richard.

Third quarter 2022 financial results found in the press release, we issued this morning, which has this summer.

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

Turning to slide 27 at Vishay pilot ninth net revenue for the second quarter with city 5 million got it.

Pilot on inventory levels on a weeks basis remained slightly lower throughout the quarter from where we ended Q2.

As a reminder, we anticipate no doubt what kind of inventory given our limited distribution network, which consists of one specialty pharmacy and one specialty distributor.

Gross to net continues to be in the 10% to 20% range as expected based on other rare disease launches.

Cost of sales for the quarter was $517000.

Turning to operating expenses research and development for the third quarter was $65 million, an increase of one <unk> compared to the first quarter of 2021.

Selling general and 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.

If someone royalty revenue, which is recorded under royalty income from gain on sale of audits you place and that's one of our income statement was $4 4 million tonnes.

It is somewhat royalty income will cease in 2022 due to the fate of these really a few bryce to Qatar has been part of it.

We ended the quarter with cash cash equivalence and marketable securities of approximately $1 billion, which.

Which excludes the $131 8 million of cash received from <unk> for the sale of our royalty rights to do so.

With this cash balance we expect to be able to execute our current operating plan through major academies and took us don't want activity without the need to raise additional equity.

In the current environment, we are grateful for our strong balance sheet, but also mindful to maintain this advantage and ensure the capital necessary to execute on our promising clinical program and we changed that seem to be key for BD. We continue to be laser focused on capital allocation to only our highest priorities proactively managing them.

Expenses and evaluating opportunities to add to our pipeline.

I'll now turn the call back to Brian to close us out.

Thanks, Cecilia to summarize we're pleased with the continued progress across the organization and our priorities for Q4 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 Biofuels with that operator, please open the line for questions.

And thank you.

As a reminder to ask a question you will 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.

One moment, while we queue up for questions.

And one moment for our first question.

And our first question comes from Gregory <unk> from RBC capital markets. Your line is now open.

Okay.

Hi, This is Neil on for Greg Congrats on the quarter and thank you for taking our questions.

Maybe first on <unk> wondering if you could help us think about how the prescription enrollment forms convert to patients on prior kind of.

What are the pushes and pulls to think about in this process and then maybe another one for us is cilia as.

As we've had two full quarters since the park high launch how are you thinking about forecasting and potentially providing revenue guidance.

You.

Yeah.

Great. Thanks for the question, maybe we'll have rich I'll start with the first one.

So thanks again for the questions first five P. S conversions to fill is concerned.

Thanks.

I was kind of enrollment form the prescription enrollments himself as an enrollment into operational support services. So that's how those logos they get and going into my audio is get connected to a patient support manager who help them navigate through the benefits investigation process is why does get them access to therapy, and then you navigate through the prior authorization.

<unk> that have been established by the past to help them and figure it out.

What is needed in order to get them get them built so when they reported the 84% and 50 656 other patients that have received at least one Phil.

Thinks about four to six weeks to get from a PDF to fail and that's really driven by the P. A criteria that have been established by the pit.

And I turn it over to see that this is the second but think of it.

I think it's early yet and we're going to we're not going along but we do we are considering and went to provide guidance and we can provide it went up a bit.

Yeah.

Great. Thank you.

Thank you.

And thank you.

And one moment our next question.

Okay.

And our next question comes from Marc Frahm from Cowen. Your line is now open.

Hi, Thanks for taking my questions.

Richard I realize it's early in this process, but can you.

Characterize the typical reauthorization criteria youre expecting to be applied.

I guess, how much broader do you think that could be on average versus.

The primary endpoint in the trial.

Yeah, Mark Thanks for the for the question. So the way to think about it is again as you said that PM did it it is a little bit early to comment on the specifics because they'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 that is.

He authorization in fact, you are going to be a board is to really help payers. Appreciate it understand how I mean, but this setup. So that's what our goal is with them, which is to say no to just look at people globally not transfusion burden, but also look at chronic hemolytic parameters, which influence how patients feel and function. So that is.

Part of the dialogue that is happening right now so it's totally comment on not specifics around that.

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 kept the category because it's on the ultra rare size.

And the team I must say is making really good progress with the payers as well.

Okay. That's helpful and then.

Maybe just on the patients that are that are getting added kind of in the last quarter or more recently.

Can you characterize these more recent adds in terms of is it wins its successes on kind of what you spoke to in the prepared remarks each of.

Youre getting these patients who maybe haven't been an under active care, but have been diagnosed previously.

<unk> therapy or is that more being driven by.

Things like anemia idea and stuff.

Actually making the new differential.

Differential diagnosis.

So the.

The specifics around that mark would be a little bit hard to characterize that as we've looked at before and yes. It is designed to test for hemolytic anemia up unknown etiology, so it's not specific to <unk>.

And therefore, he cant directly tie that back to which patients have been identified through an EBIT our goal and our focus has been on driving education from the physician standpoint to help them appreciate the need and urgency to diagnose it and raise that.

So the diagnostic triage process, which currently Florida, the diagnostic triage sponsors, saying so that disease education from a physician standpoint needs to continue and continues to remain a focus for us.

In both of you on the other end, we also want to make sure that patients are educated about their disease and know how have those conversations but that physician. So that they can be empowered to take a more active role in that.

So send treatment. So that's pushed pulled the born out of my strategy is what's driving demand and will continue to remain a focus for now and forever locked into disease space.

Okay. Thank you.

Thank you.

And one moment our next question.

And our next question comes from Mark Breidenbach from Oppenheimer. Your line is now open.

Hey, good morning, just a couple of quick ones for me.

First of all I'm wondering how we should be thinking about pricing.

In Europe , what are you guys seeing as maybe the most appropriate comps for for this drug in Europe in terms of pricing.

And also in light of the recent topline phase III data from hydro set in low and intermediate risk Mds.

Is that impacting or influencing your plans for developing <unk> in Mds in any way and maybe you can just take an opportunity to highlight there.

The main differentiator between 946 in pet.

Thank you.

Sure Good morning bark, Bryan I'm going to start with the first one and then Sarah can certainly comment on on MTS and our thoughts there for.

For ex U S and I won't get into specifics about pricing at this stage.

I would like to emphasize is that while we are waiting and expecting the final approval of partner kind in Europe and Great Britain as we noted on the call.

So that'll be an important win for PKU patients near term.

We've decided to do is focus on ensuring access for the PK D patients that we know and very much like to have access to <unk> and so as Sarah mentioned on the call.

Proud of the fact that we have a global managed access program in place that's not commercial obviously just to make sure that adult PKU 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. We're when we think about ex U S Euro.

Europe , specifically, we're continuing to access 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 private one launches, namely polishing in sickle cell disease.

I'll just add that.

We're not at this stage when you're thinking about commercialization, we're not looking too.

To build out.

On our own or Salesforce or commercial team ex U S. We're looking at partnering opportunities.

But we're going to be very selective in how we do that in all of that is what will guide us on how to commercialize and to your question, what's the appropriate pricing would be.

Okay and as far as the second.

And therefore, the second question around the spot or Sip data so.

We don't believe the recent outcome of those sputter step trial that has any impact on our clinical development plans. We are continuing as they start very excited about them I think the biggest differences are of course, there is a very different routes of administration. We havent oral convenience that is very important, especially also in elderly part.

Collation, but then most importantly, there was a very different mechanism of action and we believe that the activation in the context of enhancing read lots of functionality and survival is very important in the context of this disease.

And our clinical development program is really set up to income class Esa naive patients in Esa refractory patients. So basically all commerce with lower risk Mds, which we believe is an advantage of how we designed our program today.

Okay. Thanks, so much.

Taking the questions and congrats on the quarter.

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.

Mostly because that's really the leading predictor for housing launches going on to the story of breath rats in terms of the kinds of physicians prescribing the drug as well as breath, and so kind of patients that I'm being prescribed drugs. So in the second quarter up launch will continue to see that dynamic laying out that being said the two things that we have to get right in.

It'll take time is one is diagnostic efficiency that is a sort of triage process that happens from a diagnostic standpoint, where if he could he gets lost in that funnel and our God is with the availability of treatment to raise that urgency from a physician standpoint, so that they are testing for diagnosing P. G D.

More early in the in the diagnostic funnel then they ought to be so that's one and the second component is given the rat and do you have the disease and the fact that this is a chronic condition that does not have centers of excellence and it's a diffuse speech in population, having the patient be a very active role in the diagnosis and treatment and bobbing them with a tool.

<unk> and educating them to ensure that they know how to have those conversations with the health care provider 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 and you also indicated in the past. This is going to be affluent said. He launched this is not going to be some magical like hockey stick inflection point in them yet.

So it's going to be slow and steady, but it's really the foundation for a commercial capability building as Brian alluded to in his opening remarks for what's to come in the future with Tennessee musicals, though.

And then somebody will convince who did see some inventory version of what you would expect from the first couple of corners, but we anticipate no mountains of inventory going forward. As a reminder, we might have a limited network.

Because one specialty pharma, sorry, my specialty pharmacy to one specialty distributor.

Britain.

Inventories solution different too scrambled.

New patient builds as as we go for the next quarter. So.

Yes.

Perfect. Thanks, so much for taking my questions.

Thank you.

And one moment for our next question.

And our next question comes from Andy Burns from S. C. B. Your line is now open.

<unk> <unk> between a couple of calls I'm wondering if you could give us some color on the <unk>. So the patients that are using the drug uhm.

Maybe those that are not actually using the drugs and it's early but let me comment on assistance, where we appreciate.

And then just warm over here on behalf of opportunity.

A number of patients to the depot.

So just wondering we should talk about a particular drug <unk>.

Treatment paradigm.

Uhm, So hi, Andy Thanks for the text to 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 in patients irrespective of age splenectomy status and.

Symptomology regularly trying to use driving that he's trying to do is get drunk you. A specific question around genotype. We haven't provided specifics by the way to think about it is from appear prior off the criteria. If the pay a policy does not include the <unk> mutated patients then named those patients wood.

Not be able to get therapy, <unk> financial eligibility criteria and couldn't get on our feet drug program. So that's the one caveat of of states, depending on the pier policy, but in general the announcing possessions and emitting use of the drug based on a specific disease disease patient characteristics.

Maybe I'll just leave it for persistent C. We're in the period right now where we're starting to get initial data I would say, we're we're on track with what we'd expected, but it's too early to make too many projections from that.

From the standpoint, where we are at this stage of the launch you may recall from the clinical trial. There were the response rate was about 40% to 45% with pie recon and moving forward in the real world. What we'll be looking at is how to payers respond at the six month Mark a treatment.

To 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 it's six months and we'll just have to monitor that over time, but we feel good with our progressing with excellent so far.

Okay.

Question.

Yeah, you bet and Sarah can cover Embo's sore throat at a the question around April an off label use for April so the way we have designer program right. Now is really studied fabaceous, who may be naive to any area stimulated agents or who have been refractor.

<unk>. We currently are not planning this proof of concept study do enrolled patients who are on April actively.

Because we are truly looking for efficacy at this point specifically to our our drug.

Okay.

Thank you.

Thank you.

And if you have a question that is star one one again if you have a question that is star one one.

And one moment for our next question.

And our next question comes from Salve Richter from Goldman Sachs New lines now open.

Good morning. This is andrea on for solving thanks for taking our questions for the first one and recognizing that it's early but maybe another question on pricing for pure kind. How are you thinking about this for indications such as Palestinian sickle cell do you expect that to be in line with with houses priced at four P. K D.

Yeah. Thanks.

Thanks for the question I'll take that one again I think with pricing.

We're not going to go into specifics at this stage, but I'll, just say that Directionally whoa wait 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 fallacy me to energize the energized T trials as well as the phase two portion of <unk>.

<unk> 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 P. J D.

And then sickle cell is you know is another step up from even <unk>, we're talking about.

In Dallas, EMEA 18 to 23000 patients in the U S and the you five sickle cell disease in the U S alone or in the neighborhood of 100000 patients. So that plus the data will guide us on the appropriate pricing decisions.

And I know that as a non specific answer.

As far as I think it should take it for now.

No problem. Thanks, so much and then maybe just a broader question just wondering if you could provide some updated thoughts here and how you're thinking about potential business development activities for the future and how this would interface with your existing pipeline. Thanks, so much.

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 tips of loyalty mum's monetization deal with cigars.

And what that does is obviously further strengthen our balance sheet, which is already as we described in an enviable position, particularly in this market. So that will add to our optionality as to what we do with our our.

Capital deployment for B D. We have an ambition to further strengthen our pipeline as well as Ah diversified.

Particularly diversification from PK are activation.

And internally because we believe vd is so important for us over the long term. We've also enhanced the size of our <unk> team internally and that should give US you know more quality Moore.

<unk> capacity from a search and evaluation diligence standpoint.

The way I think about it as our sweet spot for business development would be potentially synergy with a rare non malignant hematology disease areas, where we're currently focus that could be one part in or leverage of the building rare disease capabilities that we're working on on the foundation of our.

T V launches, which is talked about and then lastly of course for us and rare diseases. Whatever we do will have to have line of sight to transformational benefit for patients. That's mission critical from our perspective, so we're not timed bounding.

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.

Okay. Thank you so much for the car.

Sure. Thank you.

And one moment for our next question.

And then next question comes from Danielle Brill from Raymond James Your line is now open.

Hi, guys. Good morning, Thanks for the question I'm I'm curious what percent of patients that have been diagnosed with your anemia Ivy cats are actually asking to go on treatment. Thank you.

Hi, Daniel this is fantastic. Thanks again to the question I have noted this anemia. These designs like humidity academia of unknown etiology, such not specific for the diagnosis of P. K D. So there's really no way for us to know Compliantly, what patients diagnosed to any 90 have been put.

<unk> the way, we think about message I hope it continues to remain an on demand generation of that envelope with a top down approach enjoying that the health care provider that appropriately.

And the meeting P K D and the diagnostic triage process, but also and popping and activating patients. So that they know to have those conversations with that has kept providers to ensure that they can get diagnosed and treated so that continues to be asked to open the specifics of Ralph translation of an email I D. Two patients is not possible.

I see I guess are the dogs that are ordering me I <unk> the same as the doctor prescribing the drug.

They certainly can be yeah.

And as we have noted we.

We believe anemia I D is one of the.

You select tools that are really important for our continued progress and watched we believe that we have that with a D V. I D, but I would not categorize it as it's exclusive.

For those who prescribed.

Perfect. Thank you for the question.

Sure. Thank you.

And I am showing no further questions I would now like to turn the call back over to Brian Golf CEO for closing remarks.

Alright, Thanks, a lot Justin and thanks, everyone for your questions and your continued interest in our progress as always I want to thank my <unk> 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 Ross.

With us rather in so many ways and especially those who participate in our clinical trials across indications are connections across stakeholders and our collective efforts fuel our ongoing innovation impact for peapack for peace.

Defying diseases. So thanks, a lot for joining us today and you may now disconnect.

This concludes today's conference call thing can participate in you may now disconnect.

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Good day, and thank you for standing by and welcome to the Q3 2022 odd years Pharmaceuticals, Inc. Earnings Conference call. At this time all participants are in a listen only mode. After the speaker's presentation there'll be a question and answer session.

Ask a question during the session you will need to press star one 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 hardly Manny.

Please go ahead.

Thank you operator, good morning, everyone and welcome to odd year since third quarter 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 Brian Goff, our Chief Executive Officer, Dr. Sarah Gubins, our Chief Medical Officer, and head of research and development, Richard <unk>, Our Chief commercial officer, and Cecilia Zhang 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, 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 will turn the call over to Brian .

Thanks, Holly and good morning, everyone. It's a privilege to join you today on my first <unk> financial results call as Chief Executive Officer, nearly three months after assuming the role in August .

<unk> has a long standing legacy of scientific excellence and clinical execution and is on the cost of broadening its ability to change the treatment landscape of rare and genetically defined diseases.

With the recent launch of <unk> and its extensive clinical and preclinical pipeline. The opportunity that lies ahead for <unk> and the patients that search is exciting.

Sure.

Okay.

The company from the very beginning.

Since joining in August as I dug into the business and that so many of our talented team my optimism and excitement for the future of Antunes has grown for several reasons first the strength of the culture and patient orientation is even better than I perceived during my diligence process.

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 and ongoing commercial launch in the U S and active filing in the EU in Great Britain.

And advancing preclinical pipeline and broad business development efforts to continue to build out our pipeline.

And finally, while the pie refined launch was always attractive based on my experience and passion for rare diseases.

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 is the first ever treatment available for patients with PK deficiency and 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.

<unk> 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 Celia jobs to our Geos and her first quarterly call as our Chief Financial Officer.

So sealy as we 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. Raluca law, and Cynthia Smith relevant Cynthia of our seasoned biopharmaceutical executives with critical expertise that will help us maximize our potential.

Within R&D that clinical and medical teams have been busy securing a positive <unk> opinion for pirate kind in the EU.

Initiating the <unk> 94, six Mds phase Iia trial publishing data from our thalassemia in PK deficiency clinical programs and top tier medical journals.

Securing an expansive expensive set of data for presentation at Ash in December and making progress on enrollment for our thalassemia and sickle cell of these trials with several will cover in more detail.

On the commercial front with just two full quarters under our belt since the approval of <unk> earlier. This year, we continue to make important progress and are very much in the dynamic learning phase at 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 Hcp's drive disease education, and urgency to treat and facilitate initiation of pirate kind therapy.

Richard will discuss some of these learnings and tactics shortly.

And finally last week, we completed the monetization of the <unk> royalties 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 our very clear.

Continue to drive enrollment across our balance EMEA in sickle cell disease pivotal trials secure approval the pirate kind for PK deficiency in the EU in Great Britain.

And drive towards continued commercial success for our U S launch.

I'd like to thank each and every <unk> employee for their fantastic work accomplished this quarter and for their support and my own learning and Onboarding. During these first few months with that I'll turn it over to Sarah.

Thanks, Brian .

2022 has been a year of significant execution for the research and development organization.

We have continued pioneered the field of PK activation and broaden the potential applicability of this mechanism to a range of diseases with significant unmet need.

Advancing our earlier pipeline.

As highlighted on slide nine our clinical focus for PJ excavation 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 or <unk> impact of 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 our PK activator across our three most advanced therapeutic area sickle cell disease thalassemia.

Patiency can 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 <unk> and our collaborators were accepted for presentation, which further underscore the clinical consistency across seasons as well as a common analysis of the underlying pathophysiology of these diseases.

Specifically, we look forward to sharing new data demonstrating the long term impact of treatment with <unk> in PK deficiency, and thalassemia as well as SaaS and mass data for our novel PK activator $89.

More to come on our ash abstract when they go online today at nine a M eastern time.

Turning to our booked SaaS PK activator mcduffie back known commercially pirate time became the first FDA approved therapy for PK deficiency in February and we continue our efforts to expand the utility of this medicine to patients with PK deficiency.

This summer we initiated two randomized placebo controlled trials of pirate <unk> in pediatric patients with PK deficiency Hs one up to 18 shown here on slide 11.

Excavated gets will enroll pediatric patients who are not regularly transfused and excavation.

We will enroll pediatric patients who are regularly transfused.

In addition, we have been busy advancing our marketing authorization application for five times in adults with PK deficiency through the EMA process. This year and we're pleased to receive a positive <unk> 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 authority by year end.

If approved we are committed to providing patients access through our global managed access program. This program provides a pathway for eligible adults receiving care in the EU in Great Britain, who are diagnosed with PK deficiency to have access to prior guidance we.

We will provide drug free of charge, regardless of the patient's insurance coverage.

<unk> will not be available under the global managed access program for indications under investigation are outside of the label, including solid senior sickle cell disease in pediatric PK deficiency.

Moving to sell senior on Slide 12, we are very excited to have the potential to establish <unk> as the first oral therapy to improve hemolytic anemia, and ineffective erythropoiesis across the spectrum of Delta in 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 as shown on slide 13 were published in the journal lapses 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 towards enrolling a meaningful portion of patients across two global pivotal trials of pilot time energized and energized team, which are described on slide 14.

As a reminder, energized with a randomized placebo controlled trials in both alpha and beta thalassemia patients who are not regularly transfused with a primary endpoint of hemoglobin response.

<unk> is a randomized placebo controlled trials in both alpha and beta thalassemia patients who are regularly transfused defined at the 6% to 20 Red blood cell unit transfused during the 24 weeks prior to randomization with a primary endpoint of transfusion reduction response.

In sickle cell disease, we are exploring parakiting, an operationally seamless phase III studies known asset right.

With the goal of being the first potential oral agents to improve anemia, reduce ceoc's and improved quality of life by increasing native hemoglobin, resulting in reduced thanks.

Moving to slide 16, we are actively enrolling patients in the phase II portion, which will randomized 69 patients one to one to one to 60 milligrams Maritime twice daily 100 milligram twice daily or matching placebo.

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

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

Upon completion of the double blind portion of the phase III, we will evaluate the totality of the data before triggering the start of phase III.

The outcome of the primary endpoints. The first then we will take into account secondary endpoints from this study, including changes in markers of hemolysis rates of sickle cell pain crisis and patient reported <unk>.

Our collaborators at the NIH and University of speed today continued to treat sickle cell patients with prioritizing extension study, which will also provide longer term treatment data supports our decision.

With phase two success. These data will also allow us to make it the termination of 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 the same clinical trial sites to enroll two distinct sets of patients in the phase II and into phase III, we have the ability to increase the speed at which we can transition from one state to the next.

In addition, we can assess the need for modifications to the phase III based on the outcome of phase two without impact on statistical and regulatory aspects of the trial.

He will share the outcome of the phase two portion of this study and our go no go decisions next year.

I will now turn to slide 17, and 18 96, our novel PK activator, which provides the opportunity to further build our PK activator franchise and pursue multiple potential therapeutic impact.

We have completed the phase one single ascending and multiple ascending dose cohorts of healthy volunteers and initial results supporting AG 900, <unk> 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 the hemolytic anemia.

September we initiated our <unk> $9 six lower risk Mds clinical program.

As outlined on slide 18, MBS are a heterogeneous group of rare hematological malignancies characterized by ineffective erythropoiesis abnormal cell maturation dysplasia and progressive Cytopenia.

In EMEA the most common feature of lower risk Mds occurs and approximately 90% of patients and about half will develop red blood cell transfusion dependence.

<unk> therapeutic strategies are limited for patients with lower risk Mds anemia, and includes erythropoiesis stimulating agents or transfusion.

Additional treatments are indicated only in specific Mds subtypes, and generally with limited responses.

We believe $89 six has the potential to enhance red blood cell functionality and survival by increasing glycolysis in ACP production and improved differentiation of erythroid self in bone marrow potentially improving anemia caused by ineffective erythropoiesis in lower risk Mds similar to <unk>.

The first step in our clinical program is the phase II a component of the phase two <unk> study is shown on slide 19, which is an open label proof of concept study of one dose level of <unk>.

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 towards our remaining priorities for the year with that I will now turn the call over to rich.

Thanks, Sara 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 40 days of launch.

Seth 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 proof point for pipeline, we are establishing a strong base of really one evidence and uncovering the opportunities for <unk> debated on the market. In addition to being disclosed <unk> available for patients with PK deficiency.

While this initial launch will be a modest revenue generator. It establishes our commercial capabilities platform in DRAM in genetically defined diseases, and subs and importantly deduction 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 prior client launch we generated net sales of $3 5 million, which is indicative of increased patient demand offset by modest inventory build in the prior quarters of launch.

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 pipeline prescription enrollment forms a 64% increase over total P. S. At the end of Q2.

These P. S. They were a net of 56 patients on <unk> 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 p/e asked two of those prescription trend that is unlikely to shorten and the near term.

Discontinuation 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 absorbed non responding patients come off therapy, we will be able to make better assessments of materials and persistence, but those who stay on therapy.

As we saw last quarter. These patients are coming from abroad unique prescriber base of E&P 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 payer dynamics on National account directors continue to have positive interactions with <unk>.

The payer mix to date aligns with our prelaunch expectations as outlined on slide 23.

The payer policies being developed a line to the indication statement on the clinical trial eligibility criteria as anticipated.

In addition, prior authorization criteria of 92 rare specialty medicine and typically include the need for genetic testing consultation with a specialist and baseline hemoglobin in transfusion history.

Moving to slide 24, we are pleased with the continued interest in anemia, I'd kit, which is a free genetic testing program designed to help patients with a general diagnosis of hemolytic anemia unknown etiology to receive an accurate diagnosis as of September 30th more than 5300 guests have been ordered.

96% increase in Q2.

Consistent with last quarter, approximately 25% of kids have been completed and the PK deficiency positivity rate put those completed tests remains in the mid single digit percentages.

After positive tests, approximately 60%, what it does and 40% pediatrics.

In taking a pass through 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 your positions 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 Pilocarpine. 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 inaction, therefore, continuing to educate on the critical nature of differential diagnosis through genetic testing.

Can use to be of utmost importance.

We are also recognizing that beyond the physician is equally if not more important and effective to empower and activate patients with sense advocate for diagnosis and treatment.

Looking ahead to the fourth quarter, we have been focused in evaluating tactical shifts and localized experiments to increase initiatives that are working and fill gaps in our loan strategy based on these new learnings importantly, the impact <unk> has on the lives of patients is evident NBA encouraged with these early launch successes and the positive experience.

We are creating with the broader PK deficiency community.

We have much more work ahead of us on behalf of these patients.

As I laid out at the beginning these learnings and knowledge base and the connections. We are making are setting us up for success as we continued to expand the applicability of cytokine to own and did you book patients with PK deficiency as well as longer term for other genetically defined diseases.

With that I'll now turn it over to Sylvia to review third quarter financials.

Thanks, Richard a third quarter 2022 financial results.

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 Richard sure private ninth net revenue for the second quarter with $3 $5 million.

<unk> inventory levels on a weeks on hand basis remains slightly lower throughout the quarter from where we ended Q2.

As a reminder, we anticipate no delinquent inventory given our limited distribution network, which consist of one specialty pharmacy and one specialty distributor.

Gross to net continues to be in the 10% to 20% range.

Based on other rare disease launches.

Cost of sales for the quarter was $517000.

Turning to operating expenses research and development for the third quarter was $65 million.

An increase of $1 million compared to the first quarter of 2021.

Selling general and administrative expenses were $29 $1 million for the third quarter, representing a $1 $90 million increase over third quarter 2021.

The increase in SG&A expense was primarily due to an increase in workforce related expenses.

Did someone royalty revenue, which is recorded under royalty income from gain on sustainable energy place net on our income statement was $4 4 million tonnes.

So our royalty income will cease in 2022 due to the sale of these really on <unk> two <unk> has two partners.

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

If you exclude the 171 8 million of cash received from <unk> for the sale of our <unk> two pivotal.

With this cash balance we expect to be able to execute our current operating plan through major academies and to cash flow positivity without the need to raise additional equity.

In the current environment, we are great for us.

Some final sheet personal mindful to maintain this advantage and ensure the capital necessary to execute on our promising clinical program and we changed that seem to be key 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.

Thanks, Cecilia to summarize we're pleased with the continued progress across the organization and our priorities for Q4 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 Biofuels with that operator, please open the line for questions.

And thank you.

As a reminder to ask a question you will 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 <unk> from RBC capital markets. Your line is now open.

Hi, This is Neil on for Greg Congrats on the quarter and thank you for taking our questions maybe.

Maybe first on <unk> wondering if you could help us think about how the prescription enrollment forms convert to patients on prior kind of what are pushing close to think about in this process and then maybe another one for us is cilia.

As we've had two full quarters since the prior kind launch how are you thinking about forecasting and potentially providing revenue guidance. Thank you.

Okay.

Great. Thanks for the question, maybe I'll have Richard start with the first one.

Thanks again for the questions first five P. M conversions two of those is concerned so our prior guidance.

I was kind of enrollment form the prescription enrolled nickel himself as an enrollment into operational support services. So that's how the logos they get and going into my audio is get connected to our patient support manager who help them navigate through the benefits investigation process is why does get them access to therapy, and then you navigate through the prior.

Asian criteria that have been established by the pit to help them to figure out.

What is needed in order to get them into the field. So when we reported the 84% and 50 656 of the patients that have received at least one Phil.

Takes about four to six weeks to get from a P. F to fail and that's really driven by the P. A criteria that have been established by the pit.

And I turn it over to see that this is the second but thank you vishal.

I think it's early yet in Arlington.

But we do we are.

When center and went to provide guidance on what you provided went up a bit.

Alright, Thank you alright, thanks, guys.

Thank you.

And thank you.

And one moment our next question.

Okay.

And our next question comes from Marc Frahm from Cowen. Your line is now open.

Hi, Thanks for taking my questions.

Hey, Jay.

Early in this process, but can you.

Characterize the typical reauthorization criteria youre expecting to be applied.

I guess, how much broader do you think that could be on average versus the.

The primary endpoint in the trial.

Yeah. Thanks for the for the question. So the way to think about it is again as you said that PM did it it is a little bit early to comment on the specifics because they'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 they are.

The authorization in fact, you are going to be our goal is to really help payers. Appreciate it understand how I D. But this setup. So that's what our goal is with them, which is to say no to just look at hemoglobin transfusion burden, but also look at chronic hemolytic parameters, which influence how patients feel and function. So that is.

Part of the dialogue that is happening right now so scheduling comment on not specifics around that and 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 kept the category because it's on the ultra rare size.

And the team I must say is making really good progress with the payers as well.

Okay.

Helpful and then.

Maybe just on the patients that are that are getting added kind of in the last quarter or more recently.

Can you characterize these more recent adds in terms of is it wins successes on kind of what you spoke to in the prepared remarks each of.

Getting these patients who maybe haven't been at under active care, but have been diagnosed previously.

<unk> therapy or is it more being driven by.

Things like anemia idea and stuff.

Making the new.

Differential diagnosis.

So.

The specifics around that mark would be a little bit hard to characterize that as we looked at before and yes. It.

He is designed to test for hemolytic anemia up unknown etiology, so it's not specific to <unk>.

Therefore.

One directly tie that back to which patients have been identified through an EBIT our goal and our focus has been on driving education from the physician standpoint to help them appreciate the need and urgency to diagnose a PK beat and raise that sort of diagnostic triage process.

Which currently floor the diagnostic triage processing, so that disease education from a physician standpoint needs to continue and continues to remain a focus for us.

In Brazil 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 the diagnosis and treatment. So that's pushed full component of our strategy is what's driving demand and will continue to remain a focus for now and forever.

And the disease space.

Okay. Thank you.

Thank you.

And one moment our next question.

And our next question comes from Mark Breidenbach from Oppenheimer. Your line is now open.

Hey, good morning, just a couple of quick ones for me.

First of all I'm wondering how we should be thinking about pricing how are they playing in Europe .

Or 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 topline phase III data from hydro set in low and intermediate risk Mds.

Is that impacting or influencing your plans for developing <unk> six and Mds in any way and maybe you can just take an opportunity to highlight.

The main differentiator between nine six and with.

Thank you.

Sure. Good morning, Barton, it's Brian I'm going to start with the first one and then Sarah can certainly comment on on MTS and our thoughts there for.

For ex U S and I won't get into specifics about pricing at this stage.

I would like to emphasize is that while we are engaging in expecting the final approval of partner kind in Europe and Great Britain as we noted on the call.

So that'll be an important win for PKU patients near term.

We've decided to do is focus on ensuring access for the PKU patients that we know with very much like to have access to <unk> and so as Sarah mentioned on the call.

Proud of the fact that we have a global managed access program in place that's not commercial obviously this to make sure that adult PKU 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. We're when we think about ex U S Euro.

Europe , specifically, we're continuing to access 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 <unk> in sickle cell disease.

I will just add that.

We're not at this stage when you're thinking about commercialization, we're not looking too.

To build out.

On our own sales force or commercial team ex U S. We're looking at partnering opportunities.

We're going to be very selective in how we do that in all of that is what will guide us on how to commercialize and to your question, what's the appropriate pricing would be.

Okay and as far as the second.

And therefore, the second question around the spot or Sip data so.

We don't believe the recent outcome of those sputter trial would it have any impact on our clinical development plans. We are continuing as these are very excited about them I think the biggest differences are of course, there is a very different routes of administration. We havent oral convenience that is very important, especially also in elderly pop.

Malaysia, but then most importantly, there is a very different mechanism of action and we believe that peak 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 income class.

Yes, they are naive patients in Esa refractory patients. So basically all commerce with lower risk Mds, which we believe is an advantage of how we've designed our program today.

Okay. Thanks, so much.

Taking the questions and congrats on the quarter.

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.

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 Viracon is the initial demand matching your expectations.

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.

Sure.

I'll kick us off here, Jason and that has to see that comment on the inventory component. So from an initial demand standpoint, the way to think about it is we are poised to continue to remain laser focused on demand generation because that is going to be really important in this disease space a couple of points to highlight about the disease itself. I think we are encouraged with what we saw this quarter.

And the growth we saw in the new prescription enrollment forms because that's really the leading predictor for housing, let's just wait until a story of breadth breadth in terms of the time.

Physicians prescribing the drug as well as breadth and so 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 E C.

Is it a triage process that happens from a diagnostic standpoint, where PTT gets lost in that funnel and our goal is with the availability of treatment to freeze that urgency from a physician standpoint, so that they are testing for diagnosing PGD more early in the in the diagnostic funnel than they are today. So that's one and the SEC.

<unk> component is given the <unk> 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 would be a very active role in the diagnosis and treatment involving them with the tools.

And educating them to ensure that they know how to have those conversations with it has to get provided.

Very very important and that's part of our tactical pivot that we've made as well as the focus on demand generation will continue.

Also indicated in the past this is going to be a tier one cities launched 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 Palestinians Hotel.

And then in terms of inventory, we did see some inventory management as you would expect in the first couple of quarters, but we anticipate nellix of inventory going forward. As a reminder, we validated. This network. This is Jim Mitchell, one specialty pharma, alright, my specialty pharmacy, and one specialty niche David.

Great and so that inventory is sufficient to think too to handle that.

New patient builds as we go forward in the next quarter or so.

Yes.

Perfect. Thanks, so much for taking my questions.

Thank you.

And one moment our next question.

And our next question comes from Andy Berens from Seb. Your line is now open.

Thanks, and sorry, if I missed this because I was bouncing between a couple of calls.

I'm wondering if you could give us any color on the June the types of the patients that are using the drug.

Yes.

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 to get IPOH off label. So just wondering how we should think about acute care of drug entering that treatment paradigm.

So hi, Andy Thanks for the thanks for the question so in terms of the patient characteristics.

Had used across the board.

In terms of the kinds of patients that have been prescribed drug. So we have seen in patients irrespective of age colectomy status and some commodity regularly transfused Robyn. They tried to do is get drugs to your specific question around.

Genotype, we haven't provided specifics, but the way to think about it is from a payer.

I don't have the criteria.

If the payout policy does not include the double nondefense mutated patients that named 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 depending on the payer policy, but in general the announcing positions limiting use of the drug.

Based on a specific disease disease patient characteristic.

And then 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 that.

From the standpoint of where we are at this stage of the launch you may recall from the clinical trial. There were the response rate was about 40% to 45% with pilocarpine.

Moving forward in the real World, what we'll be looking at is how the payers respond at the six month mark of treatment.

To the other criteria that they put in place as well as <unk>.

Is the synchronization of patient visits with their doctor to do the appropriate monitoring is it exactly at six months and we will just have to monitor that over time, but we feel good with our progressing on that front so far.

Okay.

Question on <unk>.

Yes, you bet and Sarah can cover MBS sure. So.

The question around equal an off label use for April so the way we have designed our program right now is to really study the patients who.

Maybe naive to any aerie towards stimulated agent or who have been refractory. We currently are not planning in this proof of concept study to enroll patients who are on people actively.

Because we are truly looking for efficacy at this point.

Typically too.

Our drug.

Okay.

Thank you.

Thank you.

And if you have a question that is star one one again if you have a question that is star one one.

And one moment our next question.

And our next question comes from Salvino Victor from Goldman Sachs. Your line is now open.

Good morning. This is Andrew on for Sylvia and thanks for taking our questions.

For the first one recognizing that it's early but maybe another question on pricing for pure kind. How are you thinking about this for indications such as Dallas EMEA sickle cell do you expect that to be in line with with how you've priced it for P. J D.

Yes, Andrew Thanks for the question I'll take that one again I think that with pricing.

Not going to go into specifics at this stage, but I will 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 to energize T trials as well as the phase II 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 will take a thoughtful look at pricing.

In General Dallas EMEA is a step up in terms of patient prevalence from where we are with TKD and then sickle cell as you know is another step up from even fallacy that we're talking about.

Dallas EMEA 18 to 23000 patients in the U S and EU five in sickle cell disease in the U S alone.

Or in the neighborhood of 100000 patients so that plus the data will guide us on the appropriate pricing decision.

And I know Thats, a non specific answer but as far as I think we should take it for now.

No problem. Thanks, so much and then maybe just a broader question just wondering if you could provide some updated thoughts here on how youre thinking about potential business development activities for the future and how this would interface with your existing pipeline.

Thanks, so much.

Yes, you bet.

Combined that as well with at least the acknowledgment of what we had in our comments earlier that we're really pleased to have completed the social royalty monetization deal with regard.

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 diversified.

Particularly diversification from Teekay or activation.

Internally because we believe <unk> 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 one on the capacity from a search and evaluation of the diligence standpoint.

The way I think about it is our sweet spot for business development would be potentially synergy with.

Rare non malignant 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 TKD launches Richard 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.

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.

Okay. Thank you so much for the color.

Sure. 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.

Hi, guys. Good morning. Thanks for the question I'm curious what percent of patients that had been diagnosed with your anemia IV kits are actually opting to go on treatment. Thank you.

Hi, Danielle this is rich asked so thanks again for the question. So as noted before in EMEA. These design for hemolytic anemia of unknown etiology. So it's not specific for the diagnosis of <unk>. So theres really no way for us to know compliance Lee what patients diagnosed to an EBIT have been put.

On therapy. The way we think about this is our focus continues to remain around demand generation in that envelope with a top down approach ensuring that the healthcare provider that appropriately.

<unk> <unk> JV and the diagnostic triage process.

Also empowering and activating patients so that they know to have those conversations with that has kept provider to ensure that they can get diagnosed and treated so that continues to be a focus but specifics around transformation of in EMEA IV into patients is not possible.

I see but I guess are the docs that are ordering the <unk> the <unk>.

The docs prescribing the drug.

They certainly can be.

And as we have noted.

We believe in EMEA.

One of the few select tools that are really important for our continued progress in March we believe that we have that with the DVD I D.

But I would not categorize it as its exclusive.

For those who are prescribed.

Understood. Thank you for the question.

Sure thing.

<unk>.

And I am showing no further questions I would now like to turn the call back over to Brian <unk> CEO for closing remarks.

Alright, Thanks, a lot Justin and thanks, everyone for your questions and your continued interest in our progress as always I want to thank my <unk> 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 us pardon.

With us rather than so many ways and especially those who participated in our clinical trials across indications our connections across stakeholders and our collective efforts fuel our ongoing innovation impact for <unk> for Pete.

Defined disease. So thanks, a lot for joining us today and you may now disconnect.

This concludes today's conference call. Thank you for participating you may now disconnect.