Q1 2022 BioCryst Pharmaceuticals Inc Earnings Call

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Operator: Good day, and thank you for standing by. Welcome to the BioCryst Pharmaceuticals first quarter 2022 earnings conference call. At this time, all participants are in a listen-only mode.

Good day, and thank you for standing by.

Welcome to the Biocryst Pharmaceuticals first quarter 2022 earnings conference call.

At this time all participants are in a listen only mode.

Operator: After the speaker's presentation, there will 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. If you require assistance during the conference, please press star zero. I would now like to hand the conference over to your speaker today, Jon Bluth, Head of Investor Relations at BioCryst. Thanks, Daniel.

After the speaker's presentation, there will be a question and answer session.

So 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.

You require assistance during the conference Please press Star zero.

I would now like to hand, the conference over to your Speaker today, John Bluth head of Investor Relations at Biocryst.

Jon Bluth: Good morning, and welcome to BioCryst's first quarter 2022 corporate update and financial results conference call. Today's press release and accompanying slides are available on our website. Participating with me today are CEO Jon Stonehouse, CFO Anthony Doyle, Chief Commercial Officer Charlie Geyer, Chief Medical Officer Dr. Bill Sheridan, and Chief R&D Officer Dr. Helen Thackray. Following our remarks, we will answer your question. Before we begin, please note that today's conference call will contain forward-looking statements, including those statements regarding future results on audited and forward-looking financial information, as well as the company's future performance and or achievements.

Thanks, Daniel Good morning, and welcome to Biocryst first quarter 2022, corporate update and financial results Conference call. Today's press release and accompanying slides are available on our website participating.

Participating with me today are CEO , Jon Stonehouse, CFO , Anthony Doyle, Chief Commercial Officer, Charlie Gayer, Chief Medical Officer, Dr. Bill Sheridan and Chief R&D Officer, Dr. Helen Tac rate following our remarks, we will answer your questions.

Jon Bluth: These statements are subject to known and unknown risks and uncertainties, which may cause our actual results, performance, or achievements to be materially different from any future results or performance expressed or implied in this presentation. Consequently, we should not place undue reliance on these forward-looking statements. For additional information, including a detailed discussion of our risk factors, please refer to the company's documents filed with the Securities and Exchange Commission, which can be accessed on our website. I'd now like to turn the call over to Jon Stonehouse. Thanks, Jon.

Before we begin please note that today's conference call will contain forward looking statements, including those statements regarding future results unaudited and forward looking financial information as well as the Companys future performance <unk> achievements. These statements are subject to known and unknown risks and uncertainties, which may cause our actual results performance or achievements to be materially different from any future results or performance.

Expressed or implied in this presentation did not place undue reliance on these forward looking statements for additional information, including a detailed discussion of our risk factors. Please refer to the company's documents filed with the Securities and Exchange Commission, which can be accessed center website I'd now like to turn the call over to Jon Stonehouse, Thanks, Jon with nearly $50 million in net revenue in the first quarter.

Jon Stonehouse: With nearly $50 million in net revenue in the first quarter of this year, Orladeo's quarterly sales continue to provide us with real-world evidence and confidence. After quarter, we remain on track for no less than $250 million in net revenue this year, a billion dollars in global peak sales. What's particularly important this quarter, as we face the expected headwinds from some payers requiring reauthorization, higher copay deductibles, and the impact of the Medicare donut hole, is that our team still tapped into strong patient and physician demand for Orladeo and produced quarter-over-quarter revenue growth.

This year for.

Gordon Dale quarterly sales continued to provide us with real world evidence and confidence quarter after quarter that we remain on track for no less than $250 million of net revenue this year $1 billion in global peak sales.

What's particularly important this quarter as.

As we face the expected headwinds from some payers requiring reauthorization higher co pay deductibles and the impact of the Medicare Donut hole is that our teams still tapped into strong patient and physician demand for orla, Dale and produced quarter over quarter revenue growth.

Jon Stonehouse: Orladeo plays a critical role in our strategy, and the growing revenue stream is creating value by providing evidence that our company can discover, develop, and commercialize successful products and by strengthening our financial position. There's plenty of opportunity to capture, too.

Or Dale plays a critical role to our strategy and the growing revenue stream is creating value by providing evidence our company can discover develop and commercialize successful products and by strengthening our financial position.

There's plenty of opportunity to capture too.

Charlie Geyer: Charlie will go into more detail on this and talk about the things we're doing to get this important medicine to every HAE patient who wants to try it around the world. And why wouldn't they if they had a chance to be controlled on one capsule once a day? So for the remainder of the year, each quarter, we expect that there will be steady revenue growth over the previous quarter, culminating with annual revenue of no less than $250 million.

Charlie will go into more detail on this and talk about the things we're doing to get this important medicine to every H a patient wants to try it around the world and why would they if they had a chance to be controlled on one capsule once a day.

So for the remainder of the year each quarter, we expect that there will be steady revenue growth over the previous quarter, culminating with an annual revenue of no less than $250 million.

Charlie Geyer: That's more than a doubling of first year sales and a quarter of the way to our $1 billion peak sales expectation in just the first two years of launch. Based on what we see so far this year and the trajectory we're on, we remain very confident we can achieve these targets. Our pipeline is another important part of our strategy; our team has made significant progress in the investigation of the serum creatinine increases in patients in our BCX9930 clinical trials since we first identified this a month ago.

That's more than a doubling of the first year sales in a quarter of the way to our $1 billion peak sales expectation in just the first two years of launch.

Based on what we see so far this year and the trajectory. We're on we remain very confident we can achieve these targets.

Our pipeline is another important part of our strategy. Our team has made significant progress in the investigation of the serum creatinine and increases in patients in our <unk> 90, 930 clinical trials since we first identified this a month ago.

Charlie Geyer: While the investigation is not complete, we believe dose is the most likely cause of these elevations, and we'll work with regulators to see if there's a path forward to restarting clinical trials. Bill will share more details on this topic.

So while the investing is not complete we believe dose as the most likely cause of these elevations and we will work with regulators to see if there's a path forward to restarting clinical trials.

Bill will share more details on this topic.

Jon Stonehouse: Regardless of the outcome, patient safety is paramount to us in finding a safe and effective Factor D inhibitor. Factor D inhibitor remains something we are very committed to because we know many patients suffering from complement-mediated rare diseases are waiting. Whether it's 9930 or one of our backups or both, our goal remains to bring a highly competitive oral factor D inhibitor to patients. We will follow the data and make thoughtful decisions on what to invest in and what not to invest in, based on how it helps us reach this goal. Time to market, how the competitive landscape changes, and our product profile will also be important factors in our capital allocation decisions. So when you step back, you look at our company in its entirety.

Regardless of the outcome patient safety is paramount to us and finding a safe and effective factor D inhibitor remains something we are very committed to because we know many patients suffering from complement mediated rare diseases are waiting.

Whether it's 90 930 or one of our backups are both our goal remains to bring our highly competitive oral factor D inhibitor to patients.

We will follow the data and make thoughtful decisions on what to invest in and what not to invest in based on how it helps us reach this goal.

Time to market, how the competitive landscape changes in our product profile will also be important factors in our capital allocation decisions.

So when you step back and you look at our company in its entirety.

Jon Stonehouse: You'll see it's a company with a growing revenue stream coming from a product and a team that's showing they can execute and successfully launch a drug that we believe will grow to a billion dollars at peak. We have a pipeline to create even greater value with the goal of bringing more and more products to the market for patients suffering from rare diseases, and we have a discovery platform that has, and will continue to bring, molecules to fill our pipeline even further. And finally, we have a solid balance sheet to allocate capital to those things we believe create even greater value.

You'll see it as a company with a growing revenue stream coming from a product and a team that's showing they can execute and successfully launch a drug that we believe will grow to $1 billion at peak.

We have a pipeline to create even greater value with the goal of bringing more and more products to the market to patients suffering from rare diseases.

And we have a discovery platform that has and will continue.

If molecules to fill our pipeline even further.

And finally, we have a solid balance sheet to allocate capital to those things, we believe create even greater value.

Jon Stonehouse: When you see all of that, you see meaningful value creation today and even greater value creation for the future. I'll now turn the call over to Charlie to talk about Orladeo. The first quarter was another strong one for Earladale.

When you see all of that you see meaningful value creation today.

And even greater value creation for the future.

Now I'll turn the call over to Charlie to talk about all the data.

Thanks, John .

The first quarter was another strong one for <unk> the patient base continued to grow steadily and even with the headwinds of payer reauthorization, we finished with $49 $7 million in Orla diesel sales and are on track for no less than $250 million in sales for the year.

Charlie Geyer: The patient base continued to grow steadily, and even with the headwinds of payer reauthorizations, we finished with $49.7 million in Orladeo sales and are on track for no less than $250 million in sales for the year. We are confident about the growth trajectory because it is becoming increasingly clear how well patients are doing on Orladeo. We are seeing three cohorts of patients emerge: those who are doing great and stay on therapy, those who are still deciding if this is the best treatment for them, and those who decide it isn't.

We are confident about the growth trajectory because it is becoming increasingly clear how well patients are doing on orla down we.

We are seeing three cohorts of patients emerge those or those who are doing great and stay on therapy.

Who are still deciding if this is the best treatment for them and those who decide it isn't the.

Charlie Geyer: The size of each of these groups is fluid, but the group doing... The group doing well and staying on therapy is by far the largest and is driving our sales growth. What we are seeing is that the patients most likely to do well and stay on Orladeo are those who were well controlled on an injectable prophylaxis before switching. We are getting real-world evidence from our specialty pharmacy showing that patients who were well-controlled on Taxiro at baseline, for example, are staying equally well-controlled on Orladeo.

The size of each of these groups is fluid, but the group doing group doing well and staying on therapy is by far the largest and is driving our sales group what.

What we're seeing.

Is that the patients most likely to do well and stay on Orla, Dale or those who are well controlled on an injectable prophylaxis before switching.

We're getting real world evidence from our specialty pharmacy, showing that patients who are well controlled on tax iroh at baseline for example are staying equally well controlled on <unk>.

Charlie Geyer: These patients switching from taxiro represent a sizable and growing cohort because 50% of all patients on Orladeo in Q1 originally switched from another prophylaxid, and half of those came from taxiro. That switching trend continued for patients starting Orladeo in Q1 and shows no sign of changing. Real-world evidence is consistent with the 96-week data from our pivotal study showing that the median attack rate was zero in 16 out of the last 17 months of the trial.

These patients switching from tax iroh represent a sizable and growing cohort because 50% of all patients on <unk> in Q1, originally switched from another prophage and half of those came from tax IRA.

That switching trend continued for patients starting <unk> in Q1 and shows no sign of changing.

The real World evidence is consistent with the 96 week data from our pivotal studies showing that the median attack rate was zero in 16 out of the last 17 months of the trial.

Charlie Geyer: It is also consistent with data from our long-term safety study showing that patients switching from injectable prophy were attack-free in over 80% of months on Orladeo. Further evidence of how well patients are doing is that after switching to Orladeo and the prior authorization process is complete, 78% of taxiropatients and 73% of Hagarda patients continue on Orladeo for at least six months. Patients switching from acute only therapy have similar retention.

It is also consistent with data from our long term safety study showing that patients switching from injectable prophage were attack free in over 80% of months' on Orla Dale.

Further evidence of how well patients are doing is that after switching to <unk> and the prior authorization process is complete.

78% of tax IRA patients and 73% of Haegarda patients continue on oral <unk> for at least six months.

Patient switching from acute only therapy have similar retention.

Charlie Geyer: We're also seeing that access and reimbursement correlate with long-term patient retention. Overall reimbursement access improved in Q1, and now nearly 80% of patients on Oraldale are on paid drugs, up from about two-thirds in the second half of last year. This improved access is important, not only because more patients are receiving paid therapy but also because we are seeing that 70% of patients who reach paid therapy continue on Orladeo for at least 12 months, compared to 60% retention for patients who remain on long-term free products.

We're also seeing that access and reimbursement correlates with long term patient retention.

Overall reimbursement access improved in Q1, and now nearly 80% of patients on oral or that are on page drug up from about two thirds in the second half of last year.

This improved access is important not only because more patients are receiving paid therapy, but also because we are seeing that 70% of patients who reach paid therapy continue on oral <unk> for at least 12 months compared to 60% retention for patients who remain on long term free product.

Charlie Geyer: We believe the size of the patient cohorts that I described is fluid because some patients are making their decision about Orladeo too quickly. For example, one-third of all discontinuations to date have occurred after just one shipment, and 50 percent overall within the first two shipments.

We believe the size of the patient cohorts that I described are fluid because some patients are making their decision about Orlando too quickly.

One third of all discontinuation to date have occurred after just one shipment and 50% overall within the first two shipments.

Charlie Geyer: Education and expectation setting are critical in the early phase of treatment, and we have added new members to the team to support patients in this process. If a patient has a high probability of doing well, those well-controlled PROFI switchers, for example, we want to make sure they don't give up too quickly after an early breakthrough attack or side effect because they might miss out on the long-term benefits of Orlodeo. The clinical trial and real-world evidence that I described is convincing physicians, leading to greater breadth and depth of Orladeo Perseverance.

Education and expectation setting are critical in the early phase of treatment and we have added new members to the team to support patients in this process.

If a patient has a high probability of doing well those well controlled Profi switchers. For example, we want to make sure. They don't give up too quickly after an early breakthrough attack or side effect, because they might miss out on the long term benefits of oil a day.

The clinical trial in real World evidence that I described is convincing physicians, leading to greater breadth and depth of the Orlando per base.

Charlie Geyer: In the first quarter, new patient prescriptions were evenly split between new prescribers and repeat prescribers. [Inaudible] We also saw an even split in new prescriptions coming from our Tier 1 Top 500 HAE treaters and the broader base of treaters. Our latest quarterly survey with allergists again matches the prescribing trends and tells us how much more opportunity remains. We surveyed another 60 allergists who treat an average of eight HAE. They were already prescribing Orladeo to 13% of their patients and predicted growth to 23% over the next 12 months. It is neck and neck with Tex Iroh for future market leadership.

In the first quarter, new patient prescriptions were evenly split between new prescribers and repeat prescribers.

We also saw an even split in new prescriptions coming from our tier one top 500, HAE treaters and the broader base of treaters.

Our latest quarterly survey with Allergists again matches, the prescribers prescribing trends and tells us how much more opportunity remains.

We surveyed another 60, allergists, who treat an average of eight <unk>.

They were already prescribing oral a day up to 13% of their patients and predicted growth to 23% over the next 12 months neck and neck with tax iroh for future market leadership.

Charlie Geyer: We expect favorable patient outcomes, new prescription trends, and improved reimbursement to drive steady quarterly growth on our way to no less than $250 million this year. The patient growth trends we see give us confidence that, at peak, we will reach a stable base of at least 2,000 patients in the U.S. who have great outcomes on Orlodeo. That's just a 25 to 30 percent share out of the 7,500 diagnosed and treated patients and would generate up to $800 million in annual sales from the U.S. alone.

We expect the favorable patient outcomes, new prescription trends and improved reimbursement to drive steady quarterly growth on our way to note with less than $250 million. This year.

The patient growth trends, we see give us confidence that at peak, we will reach a stable base of at least 2000 patients in the U S who have great outcomes on orla to have that.

That's just 25% to 30% share out of the 7500 diagnosed untreated patients and will generate up to $800 million in annual sales from the U S alone.

Charlie Geyer: As we've noted before, the U.S. will account for the great majority of sales in 2022, but international launches are gaining momentum. We have launched with our own teams in Germany, France, the UK, Norway, Sweden, and Denmark, and with partners in Japan and the UAE.

As we've noticed noted before the U S will account for the great majority of sales in 2022, but international launches are gaining momentum.

We have launched with our own team in Germany, France, the UK, Norway, Sweden, and Denmark, and with partners in Japan and UAE.

Dr. Bill Sheridan: We anticipate several more launches and reimbursement approvals this year, and we are busy preparing multiple regulatory and reimbursement submissions. The favorable reception that Orladeo is getting from regulators, payers, physicians, and patients across countries and regions bodes well for a strategy to bring Orladeo to patients around the world on our way to $1 billion in peak global sales. I'll turn the call over to Bill for an update on our clinical program. Thanks, Charlie.

We anticipate several more launches and reimbursement approvals this year and we are busy preparing multiple regulatory and reimbursement submissions.

Favorable reception that Orla Dale is getting from regulators payers physicians and patients across countries and regions bodes well strategy to bring <unk> to patients around the world on our way to $1 billion in peak global sales.

I will turn the call over to Bill for an update on our clinical program.

Thanks, Charlie.

Dr. Bill Sheridan: While we have not completed our investigation into the serum creatinine elevations we observed in our BCX9930 clinical program, we have made significant progress, and I want to provide an update for you today on what we have learned thus far and what the next steps are. As you may recall, at the time we announced that we were halting patient movement in April, we had four active clinical trials with BCX9930. These are summarised on slide four.

While we have not completed our investigation into the sooner it correctly and elevations we observed.

<unk> hundred 90, 930 clinical program.

We have made significant progress, but I want to provide an update for you today and what we've learned thus far and what the next steps are.

As you may recall at the time, we announced that we were hunting patient month in April we had four active clinical trials with <unk> 90 930.

As summarized on slide four.

Dr. Bill Sheridan: Patients in Redeem I and Redeem II randomized to 9930, and patients enrolled in Renew began the trials by starting immediately at 500mg twice daily. Patients in the long-term extension for our proof-of-concept study had started at lower doses, and all patients were ultimately moved up to the 500 milligram dose. We currently have three patients from our redeemed trials who had severe or moderate elevations in their student creatinine, beginning several weeks after starting B69930 at 500. These lab findings indicated renal injury, which is why we proactively paused enrolment to investigate further.

Patients you can redeem one and redeemed two randomized to 90 930 and patients enrolled in renew began to trials by starting immediately at 500 milligrams twice daily.

Patients in the long term extension for a proof of concept study has started at lower doses and all patients will ultimately moved up to the 500 milligram dose.

We currently have three patients from our redeemed trials.

Severe moderate elevations in their serum creatinine beginning several weeks after starting the 690 930 at the 500 milligram dose level.

These led findings indicated renal injury, which is why we proactively paused enrollment to investigate further.

Dr. Bill Sheridan: Two of the patients were hospitalized for observation and evaluation, and both were discharged after their initial evaluation. These three cases involved a rise in serum creatinine of about two to four times the upper limit of normal.

Two of the patients were hospitalized for observation and devaluation and both were discharged after their initial evaluation.

These three cases involved a rise in serum creatinine of about 2% to four times the upper limit of normal.

Dr. Bill Sheridan: We're pleased to see that kidney function has improved in all three patients, with a fall in their serum creatinine levels during the short period of observation thus far. Consequently, two of these patients have been discontinued from therapy. The patient who had the smallest rise in serum creatinine continues on BCX9930 at this time. Three patients we noted with early onset increases in serum creatinine represent approximately one-third of the patients randomized to 99.30 in the REDEEM studies, and other patients in the Redeem trial for sincretinine have remained similar to baseline.

We are pleased to see the kidney function has improved in all treated patients with a full in assumed threatening levels. During the short period of observation thus far.

These patients have been discontinued from therapy.

The patients who had the smallest horizon serum creatinine continues on <unk> 99 to the at this time.

Three patients we noted with early onset increases in serum creatinine represent approximately one third of the patients randomized to 99 city in the redeem studies.

Another patient seem to redeem trial for <unk> has remained similar to baseline.

Dr. Bill Sheridan: Additionally, during the investigation, we learned that about 40% of the patients in the long-term extension study had slowly evolving, late-onset, mild-to-moderate increases in serum creatinine, which started about 3-12 months after they switched to the 500mg dose. This was not observed during treatment with doses lower than 500 mg, and none of these patients experienced early-onset severe serum creatinine elevation.

Additionally, during the investigation, we learned that about 40% of the patients in the long term extension study has had slowly evolving later onset multimodal increases in serum creatinine, which started about three to 12 months after they switched to the 500 milligram dose.

This was not observed during treatment with doses lower than 500 milligrams and none of these patients have experienced early onset severe serum creatinine elevations.

Dr. Bill Sheridan: So, here is the summary of what we know so far. We are observing an emerging signal of increasing serum creatinine early during treatment and also after chronic treatment. Although there may be other factors contributing to these events, it is prudent to assess this signal as probably related to BCX9930.

So here's a summary of what we notice sofa.

We are observing an emerging signal of increasing serum creatinine early during treatment and also after chronic treatment.

Although there may be other factors contributing to these events. It is prudent to assist the signal is probably related to <unk> 90 930.

Dr. Bill Sheridan: It is noteworthy that we have not seen elevations of C-incretinine at doses lower than 500mg, and we have not seen early onset increases in syncretinine when we start with a lower dose. And in the proof-of-concept study, we have also seen that BCX9930 has encouraging efficacy in PNH patients with increases in hemoglobin and reduced transfusions at both the 400mg BID and 500m Of course, we're very disappointed by these safety observations, especially considering the strong efficacy we have seen with BCX9930 and the unmet need for better treatments for patients. But no one wants patients to experience these types of events in clinical trials.

It is noteworthy that we have not seen elevations of <unk> at doses lower than 500 milligrams.

And we have not seen early onset increases in serum creatinine, when we start with a lower dose.

And in the proof of concept study. We have also seen that <unk> 90, 930 has encouraging efficacy in <unk> patients with increases in hemoglobin and reduce transfusions at both the 400 milligram PID and 500 milligram PID doses.

Of course, we are very disappointed by the safety observations, especially considering the strong efficacy we have seen with the 690 930, and the unmet need for better treatments for patients.

No one wants to patients to experience these types of advanced in clinical trials.

Dr. Bill Sheridan: And the key question for us now is to explore with regulators whether or not there is a path forward for the program from a benefit-risk perspective. Throughout our investigation, we have been and continue to be in active dialogue with the study sites and investigators, our independent data monitoring committee, and the FDA and other regulators. The FDA has placed the BCX9930 program on a partial clinical hold. Under this partial clinical hold, BioCryst may not enrol new patients in its VCX9930 clinical trials.

And the key question for US now is to explore with the regulators whether or not there is a path forward for the program from a benefit risk perspective.

Throughout our investigation, we have been and continue to be in active dialogue with the study sites and investigators are independent data monitoring committee and the FDA and other regulators.

The FDA has placed the <unk> 90, 930 program on a partial clinical hold.

Under this partial clinical hold.

<unk> may not enroll new patients and its VCX 90, 930 clinical trials.

Dr. Bill Sheridan: However, patients already enrolled who are receiving clinical benefit from BCX9930 treatment and have no other available treatment options can continue to be dosed and remain in the trials. BioCryst had already taken this same action voluntarily prior to the partial clinical hold. And we have, of course, provided study sites with updated informed consent language for patients and guidance to investigators to reflect the new safety risk. What comes next?

However, the patients already enrolled who are receiving clinical benefit from <unk> treatment and have no. Other available treatment options can continue to be dosed and reminding the trials.

Biocryst had already taken to sign actually voluntarily prior to the partial clinical hold.

Of course provided study sites with updated informed consent language for patients and guidance to investigators.

Afflict, a new safety risk.

So what comes next.

Dr. Bill Sheridan: We know BCX9930 shows strong clinical efficacy. Clinical efficacy is seen at both 400mg and 500mg, as illustrated on slide 6. These efficacy observations are supported by the PD data from BCX9930 showing complete inhibition of Factor D at both the 400mg and 500mg dose levels.

We now be 690, 980 shows strong clinical efficacy.

Clinical efficacy is seen at both 400 milligram and 500 milligram as illustrated on slide six.

These efficacy observations are supported by the PD data from <unk> 90, 930, showing complete inhibition of factor D. At both the 400 milligram and 500 milligram dose levels.

Dr. Bill Sheridan: Based on what we are learning in the investigation, the preliminary evidence points to both 500 milligrams twice daily dosing and the immediate start of that 500 milligram dose level without a period at a lower dose first as plausible contributory factors for the serum creatinine increases we have observed to date. Since we have also seen similar efficacy with BCX9930 at 400mg and have not seen stream-crackling elevations that this does. We plan to complete the investigation and then consult with regulators regarding a possible path forward with amended protocols using stepped dosing to 400mg. If they agree with an approach like this, we could restart the clinical program. But if they do not, unless we identify another path to pursue, we would likely terminate the program.

Based on what we are learning in the investigation the preliminary evidence points to both 500 milligrams twice daily dosing and the immediate sort of that 500 milligram dose level without a period at a lower dose first as plausible contributory factors for the serum creatinine increase in Sweden.

To date.

Since we have also seen similar efficacy with <unk> 90, 930 at 400 milligrams.

And have not seen elevations at this dose.

We plan to complete the investigation and then consult with regulators regarding a possible path forward with amended protocol using stepped dosing to 400 milligrams.

If they agree with an approach like this we could restart the clinical program pre staging not unless we identify another path to pursuit, we would likely terminate the program.

Dr. Bill Sheridan: We expect to have clarity from regulators on whether or not there is a path forward for BCX9930 by the end of the third quarter. However, we do not plan on providing interim updates as we progress through these interactions. However, we look forward to completing our investigation and regulatory discussions, and we plan to update you once we have clarity on our next steps for the BCX9930 program. Now, I'd like to hand the call over to Anthony.

We expect to have clarity from regulators on whether or not there is a path forward for <unk> 90, 930 by the end of the third quarter.

We do not plan on providing interim updates as we progress through these interactions.

We look forward to completing our investigation and regulatory discussions we plan to update you. Once we have clarity on our next steps for the <unk> 90, 930 program now I'd like to hand, the call over to Anthony.

Anthony Doyle: Thanks, Bill. Given the early stage of our discussions with regulators, it's premature to provide revised guidance for OPEX. However, in the scenario where we recommence enrollment, then spend would likely be at the low end of the $440 to $480 range that we guided to previously.

Thanks Bill.

Given the early stage of our discussions with regulators, it's premature to provide revised guidance for opex in the scenario, where we recommence enrollment than spend would likely be at the low end of the $4 40 to 480 range that we guided to previously if we discontinue the 19 930 program then spend in 2022 would be lower than that.

Anthony Doyle: If we discontinued the 99-30 program, then spending in 2022 would be lower than that. What I can be more certain of is the strong performance of Orladeo and our confidence in our revenue guidance of no less than $250 million for this year and peak global sales of $1 billion. This, as well as our other pipeline assets, gives us a tremendous base to build on. You can find our detailed first quarter financials in today's earnings press release, and I'd like to call your attention to a few items.

What I can be more certain of is the strong performance of Orlando and our confidence in our revenue guidance of no less than $250 million for this year and peak global sales of $1 billion.

This as well as our other pipeline assets give us a tremendous base to build on.

Anthony Doyle: Revenue for the quarter was $49.9 million, of which $49.7 came from the net sales of Orladeo. Having finished 2021 with revenues of $122 million, this puts trailing 12-month revenue for Orladeo at over $161 million, as we progress toward their 2022 guidance of no less than $250 million for the year. Operating expenses, not including non-cash stock compensation for the quarter, were $90.3 million.

You can find our detailed first quarter financials in today's earnings press release, and I'd like to call your attention to a few items.

Revenue for the quarter was $49 9 million of which $49 seven came from the net sales of Orlando.

<unk> finished 2021 with revenues of $122 million. This puts trailing 12 month revenue for Orla diode over $161 million as we progress towards our 2022 guidance of no less than $2 50 for the year.

Operating expenses, not including noncash stock compensation for the quarter were $93 million.

Jon Stonehouse: Quarter 2 of 2022 will likely be higher given the annual guidance that we gave on OPEX previously, with the 9930 investment in CMC and trial expansion being the main driver. Cash at the end of the quarter was about $447 million, and with the $75 million from Ethereum that we've agreed to draw in mid-2022, our balance sheet is very strong. We're deploying this capital towards programs that can create value for the company and for shareholders.

Quarter, two of 2022 will likely be higher given the annual guidance that we gave on Opex previously with 90 930 investment in CMC and trial expansion being the main drivers.

Cash at the end of the quarter was about $447 million with the $75 million from our cerium that we've agreed to draw in mid 2022, our balance sheet is very strong.

We are deploying this capital towards programs that can create value for the company and for shareholders investment in Orlando continues we are investing to strengthen our launch here in the U S. While we also expand our reach and bringing <unk> to patients around the world. We will also continue to invest in our pipeline.

Jon Stonehouse: Investment in Orladeo continues. We are investing to strengthen our launch here in the U.S., while we also expand our reach in bringing Orladeo to patients around the world. We will also continue to invest in our pipeline. The targets that we go after are hard targets, and they're always challenging.

The targets that we go after are hard targets and there are always challenges the challenges that we had with our boral statin Haa paved the way for the success that we are now having with Vale.

Jon Stonehouse: The challenges that we had with Avoralstat and HAE paved the way for the success that we are now having with Dale. We are hopeful that we can continue to move forward with BCX9930, as with the strong efficacy data that we have shown thus far, we think that we can help patients in PNH and beyond, but we will be smart about it. If we can move forward, we will move forward with speed and focus.

We are hopeful that we can continue to move forward with <unk> thousand 930, as with a strong efficacy data that we've shown thus far we think that we can help patients in <unk> beyond <unk>, we will be smart about it if we can move forward, we will move forward with speed and focus if we cannot.

Operator: If we cannot, then we will reallocate capital to programs that can add value in complement and in other rare diseases. With the strength of the Orladeo launch, the Discovery team, our development pipeline, and our strong balance sheet, we are well positioned for future growth. Operator, we'd now like to open it up for Q&A. As a reminder, to ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound key.

Then we will reallocate capital to programs that can add value and complements and in other rare diseases.

With the strength of the <unk> launch the discovery team and our development pipeline and our strong balance sheet, we are well positioned for future growth.

Operator, we'd now like to open it up for Q&A.

As a reminder to ask a question you will need to press star one on your telephone to what.

<unk> Your question press the pound key.

The interest of time, we ask that you. Please limit yourself to one question and one follow up.

Please standby, while we compile the Q&A roster.

Operator: In the interest of time, we ask that you please limit yourself to one question and one follow-up. Please stand by while we compile the Q&A roster. Our first question comes from Ken Cacciatore with Cowan. Your line is now open.

Our first question comes from Ken Cacciatore with Cowen. Your line is now open.

Jon Stonehouse: Hey guys, thanks for the update. Just wondering if we could get a little bit deeper into some of the analysis on the 400 milligram. Just can you talk about duration of treatment or anything that you've learned from that patient group? I know you talked about efficacy, but just wondering as you looked into safety, it seems as if the duration of that when they were moving through was a little bit shorter. So I just want to know any more analysis you could provide on that.

Hey, guys. Thanks for the.

So the update just wondering if we could get a little bit deeper into some of the analysis on the.

400 milligram, just can you talk about duration on treatment or anything that you've learned from that patient group I know you talked about efficacy, but just wondering as you looked into the safety. It seems as if the duration on that.

When they were kind of moving through with a little bit shorter. So just wanted to know any more analysis.

Could provide on that and then also just wondering if we talk about the R&D understanding the commentary on reallocating can you just give us some perspective, however on the percent that's being allocated right now to 90 930, maybe a little bit more color on would it be completely allocated.

Jon Stonehouse: And then also just wondering if we talk about R&D, understanding the commentary on reallocating. Can you just give us some perspective, however, on the percent that's being allocated right now to 99.30? Maybe a little bit more color on whether it will be completely allocated?

Jon Stonehouse: Unfortunately, if we have to stop it, to what degree do you think going forward there will be less adjustments? Thanks so much. Bill, you want to take the first one, Anthony the second?

Unfortunately, we have to stop it to what degree do you think going forward there would be adjustments lower thanks, so much.

Bill you want to take the first one Anthony.

Dr. Bill Sheridan: Thanks for the question. The way that the proof of concept study was done, because this is such a rare disease and to be efficient in that trial, we had a combination of in-trial patient dose escalation as well as starting at higher doses in sequential cohorts of small numbers of people. So the result of that certainly was that, as the trial matured, the duration of treatment with 400 milligrams was substantial, but the duration of treatment with 500 milligrams was quite a bit longer.

Thanks for the question.

The way that the proof of concept study was done.

Because this is such a rare disease and to be efficient in that trial we.

We had a combination of intra patient dose escalation as well as studying at higher doses in sequential cohorts of small numbers of people. So the result of that certainly is that.

As the trial matured the duration on 400 milligrams was substantial but the duration on 500 milligrams was quite a bit longer.

Dr. Bill Sheridan: So, as I mentioned in my remarks, the observations are confined to the 500 milligram period. It's a plausible hypothesis that that's what's driving this, but we can't rule out other factors, obviously, but that's where we stand on the data.

So as I've mentioned in my remarks, the observation is that confined to the 500 milligram period.

It's a plausible hypothesis, that's what's driving this.

We can't rule out other factors, obviously, but that's where we stand on the data.

Anthony Doyle: Yeah, and then in terms of capital allocation, so what we've said is that last year, for example, the Factor D program was around 62-63% of our total R&D spend and that this year was going to be even higher. Now, hopefully, we can move forward, albeit with a delay. If we can't yet, we'll make sure that the areas that we reallocated to have those potentials to create additional value.

And then in terms of capital allocation. So what we've said is that last year for example.

The factor D program was around 62, 63% of our total R&D spend on that this year was going to be even even higher.

Now hopefully we can we can move forward, albeit with a delay if we can't yet we'll make sure that can.

Areas that we reallocated to have those potentials to create additional value and I think we've been clear it will be potentially in both the complement space and in other rare diseases, where we think we have a strong pipeline on a really good discovery team.

Jon Stonehouse: And I think we've been clear, it could potentially be in both the complement space and in other rare diseases where we think we have a strong pipeline and a really good discovery team. Great, thank you. Thank you. Our next question comes from Jon Wolleben with KMT Securities. Your line is now open.

Great. Thank you.

Thank you. Our next question comes from John Wall Oven with JMP Securities. Your line is now open.

Jon Stonehouse: Hey, thanks for the update and taking the questions. Along the same lines on 9930, I just want to make sure I heard this right. Were there nine patients enrolled so far across the REDEEM trials? And then were the three patients with elevations, were they all treatment naive or C5 inadequate responders, or any other common characteristics between the patients with the elevations? Thanks, Jon, for the question.

Hey, thanks for the update and taking the questions.

Along the same lines on 930, I just want to make sure I heard this right where.

Where there are nine patients enrolled so far across there have been trials, and then where the three patients with elevations.

All treatment naive or.

Adequate responders in any other common characteristics between the patients with the elevations.

Thanks, John for the question.

Dr. Bill Sheridan: You know, as I mentioned in the remarks, you know, the... We only unblinded the patients who had the elevations. So it's an estimate that approximately 30% of the enrolled patients had those elevations in the REDEEM studies. And those three patients come from both REDEEM I and REDEEM II. And maybe one for Charlie, if I may.

As I mentioned in the remarks.

The.

We only own blinded the patients who.

The elevations so it's an estimate that approximately 30% of the enrolled patients.

Those elevations in the redeem studies and those three patients do come from both <unk> and redeemed two.

And maybe one for Charlie if I may you.

Charlie Geyer: You mentioned the number of patients switching from TekZyro. Do you have any data on how long those patients were on TekZyro before switching? Hey Jon.

You mentioned the number of patients switching from Tech zero do you have any data on how long those cases were onsite collateral for switching.

Charlie Geyer: No, we don't have that. But what we do have is data showing that they were stable on Taxiro. And most of these patients, when they switch to Orladeo, kind of maintain that same level of control once they switch over to Orladeo. So that's really important.

Hey, John No. We don't have we don't have that.

But what we do have is data showing they were stable on tax sorrow and in most of these patients when they switched to oral or Dale kind of maintain that same level of control once they switch over to early days. So that's what's really important.

Got it okay. Thanks for taking the questions.

Jon Stonehouse: Okay. Thanks for taking the questions. Thank you. Our next question comes from Chris Raymond with Piper Sandler. Your line is now open.

Thank you. Our next question comes from Chris Raymond with Piper Sandler Your line is now open.

Jon Stonehouse: Hey, thanks for taking the question. Also, a question on 9930, or a couple of them, if you may, if I may ask. So I guess, um, I just want to understand the, The patients that were treated with the 400mg BID dose, can you just clarify and specify, Have you not seen any creatinine level elevations at that dose level? At that dose level, I guess what I'm trying to understand is, you know, And I guess this is probably something for your discussions with FDA, but what's the level of evidence you guys have that you won't see that After longer-term treatment at that, and then... Oh, I'm sorry, also in the extension patient, 40% had, and Declare Mulling. When did that start to show up? What was the trigger, I guess, for actually...

Hey, Thanks for taking the question.

Also a question on that 930 <unk> a couple of them if you may.

May I ask.

So I guess.

I just want to understand.

<unk>.

The patients that were treated at the 400 milligram.

Dose.

Can you just clarify specify had.

Have you not seen any creatinine level.

<unk>.

That dose level.

I guess, what I'm trying to understand is.

And I guess this is probably something for your discussions with FDA, but how.

What's the level of evidence I guess, you guys have the impact I see that the same issue.

After longer term treatment at that at that dose level.

And then so.

Oh I'm sorry also in the extension patients.

40% had.

The correct level increases when does that start to show up.

The trigger I guess, we're actually seeing that.

That effect.

Dr. Bill Sheridan: So, Bill, it might be helpful to describe the proof-of-concept study, you know, how we escalated, got to 400, then went to 500. I think that might be helpful for the first part of his question. Sure.

So bill it might it might be helpful to describe the proof of concept study how we escalated got the 400, then went to 500 I think that might be helpful. For the first part of his question.

Dr. Bill Sheridan: So the study was designed so that patients started at a lower dose, and right at the beginning, that was 50 milligrams, and then those few patients stepped through increased doses at 100, 200, and 400 milligrams. At that period, you know, we did the PK and PD modeling, and we had experience at 500 milligrams and higher doses in our healthy subjects, and we put all that together and decided to move forward to the 500 milligram dose level in the pivotals, and so all of those patients were then moved to 500 milligrams.

Sure.

The study was designed so that patients started at a lower dose and right at the beginning that was 15 milligrams and then.

Those few patients step through increased doses at 100, 200 400 milligrams.

Dr. Bill Sheridan: So the period of time that people were on 400 milligrams varies. In some people, it was quite substantial, and all of the observations of increased serum creatinine, as I mentioned earlier, were only seen in the 500 milligram dose period. So does that clarify the question for you? Yes.

At that period did the PK PD modeling.

We had experienced at 500 milligrams on higher doses in healthy subjects, and we put all that together.

Decided to move forward as a 500 milligram dose level in the pivotal since several of those patients within moved to 500 milligrams. So the period of time that people were on 400 milligrams varies.

Some people it was quite substantial and all of the observations as increased serum creatinine as I mentioned earlier.

Only seen in the 500 milligram dose period, so does that clarify the question for you.

Yes. Thank you.

Dr. Bill Sheridan: And then his second question was around the extension and the 40% and the slower rise. You know, it's after many months of 500 milligrams on average, so I think that another part of your question was what level are we talking about? We're talking about any level above the upper normal. And when did you start, when did you first see that?

And then the second question was around the extension in the 40% and a slower rise.

Yes.

After many months of 500 milligrams on average.

I think that.

Another part of your question was what level are we talking about we're talking about any level above the upper level.

Yes.

And when did you start when did you first see that effect in the extension patients.

For quite a long period on drug.

Within several months on average at 500 milligrams.

Thank you.

So there are two patents here as I mentioned in my remarks. This is the patent.

Patent that we saw in the redeem studies in those three subjects and is lighter more mild to moderate pattern that we saw in the long term extension both of those observations are confined to the 500 milligram dose level.

Yes.

Thank you.

Dr. Bill Sheridan: for quite a long period on the drug, but it can, you know, within several months on average at 500 milligrams. So there are two patterns here, as I mentioned in my remarks. There's this early-onset pattern that we saw in the RADEEM studies in those three subjects, and there's this later, more mild-to-moderate pattern that we saw in the long-term extension. Both of those observations are confined to the 500-milligram dose level. Thank you. And our next question comes from Jessica Fye with JP Morgan. Your line is now open. Good morning, guys. This is Daniel for Jessica.

Thank you and our next question comes from Jessica Fye with Jpmorgan. Your line is now open.

Hi, Good morning, guys. This is Daniel for Jessica Thanks for taking my question.

Jon Stonehouse: Thanks for taking our question. First, was the duration of dosing similar between the two patients who discontinued treatment and the one patient who still continues on BCX9930 and Redeem? That is, could that patient get any worse with continued dosing? And the second question is, can you maybe give us more? Sorry, I'll follow up after their first question. Okay. So, hi Danielle.

Chris.

What is the duration of dosing similar between the two patients who discontinued treatment and the one patient who is still continues on <unk> financing zero and redeem that is that patients get any worse with continued dosing and the second question is can you maybe give us mark. Thank you I'll follow up after their first question.

Okay.

Dr. Bill Sheridan: Now all three subjects who had the early-onset rises in creatinine are doing better, and creatinine is falling now. And the one patient who had continued dosing with 99-30, it's come way back down. So the duration of treatment in all is similar, you know, prior to the onset of these events. This was early in treatment. Okay.

Hi, Danielle <unk>.

All three subjects, who had the early onset rises in creatinine are doing better than credit name is falling and the one patient who had continued dosing with 99 city, it's come way back down.

The duration of treatment in all is similar prior.

Prior to the onset of these events. This was early in treatment.

Charlie Geyer: And then I guess one more question on Arlodeo. Can you give us maybe more color on the persistency difference seen between those who are reimbursed versus those who are on free drugs? What could be driving that difference?

Okay got it.

And then I guess one more question on <unk> can you give us a bit more color on the persistency differences between dose core reimbursed versus those.

Those are four on free drug what could be driving that difference.

Charlie Geyer: It's a good question. It's something we're digging into. I think one of the things is that the reimbursed patients are most likely to be good HEE patients who meet clinical criteria for reimbursement. And so that's, you know, that's analogous to the stable taxiro and HICARTA patients that I was describing.

It's a good question, it's something we were <unk>.

Digging into it.

One of the things is that the reimbursed patients are most likely to be.

Good hey, patients, who meet clinical criteria for reimbursement and so that's.

Analogous to the stable tax Ireland haegarda patients that I was describing.

The other thing is that reimbursement is always it's a stressor its a worry that patients and physicians have and as much as we try to help them and make them comfortable through that process. If the payer is not paying.

Jon Stonehouse: The other thing is that reimbursement is always, it's a stressor. It's a worry that patients and physicians have. And, you know, as much as we try to help them and make them comfortable through that process, it's the payer is not paying. It is something that can lead to stress. Stress can cause health problems.

It is it is something that can lead to stress stress can cause attacks stress can cause people to seek other options. So what we're really pleased about is how well we're getting patients onto <unk>.

Jon Stonehouse: Stress can cause people to seek other options, so what we're really pleased about is how well we're getting patients onto reimbursement. And what that's leading to is, you know, launch to date, about two-thirds of the patients who started on Orladeo are still on Orladeo, and we're building this really stable base of patients who are doing great. That's what's going to drive us to 2,000 patients. The other piece, Daniel, is that these are patients early in the process, and that's where we're seeing the bulk of the discontinuation, like Charlie described.

Onto reimbursement and what that's leading to is launched to date.

About two thirds of the patients who started on <unk>.

<unk> are still on <unk> and we're building this really stable base of patients who are doing great and thats whats going to drive us to 2000 patients.

The other piece Daniel this is patients early in the process and that's where we're seeing the bulk of the discontinuation like Charlie described if you stay on longer the chances are youre going to stay on the drug and so that's another factor that plays into this.

Jon Stonehouse: If you stay on longer, the chances are you're going to stay on the drug, and so that's another factor that plays into this. So, does that mean the patients on free drugs don't stay that long? I'm sorry, never mind.

So does that mean the patients on free trials Dawn, Steve outlined exactly right. Okay.

Jon Stonehouse: I got it. If FDA doesn't, you know, allow for the resumption of the trials with an amended protocol, what are the potential paths forward for the program? Is there a backup molecule that you can possibly develop? And if so, what stage is it currently at?

Got it.

I have one more question on 19th trial.

It doesn't allow for a resumption of the trials with the amended protocol what are the potential path forward for the program is there a backup molecule that can possibly develop.

And if so what stages currently at thank you very much.

Jon Stonehouse: Thank you very much. Yeah, we're still in the investigation stage, and so can't comment on any other paths at this point in time, but you can imagine that we're continuing to look and see if there are other paths to pursue. And we're always working on backups. You saw that with Avoralstat and Orladeo with HAE, you know, and in Factor D in the complement area, we do the same thing.

Yes, we're still in the investigation stage and so can't comment on any other pass at this point in time, but you can imagine that we're continuing to look and see if there are other paths to pursue.

And we're always working on backups, you saw that with of oral stat, and Orla Deyoe with HCA.

And factor D. In the complement area, we're doing the same thing so there earlier.

Jon Stonehouse: So they're earlier, and when we're ready to talk about them, we will, but we're always working on backups. Great. Thank you. You're welcome.

When we're ready to talk about them, we will but we're always working on backups.

Okay. Thank you.

Youre welcome.

Jon Stonehouse: Thank you. And our next question comes from Tazeen Ahmad with Bank of America. Your line is now open. Hi, good morning. This is Avi on behalf of Tazeen.

Thank you and our next question comes from <unk> Ahmad with Bank of America. Your line is now open.

Jon Stonehouse: Just one quick question on 9930. So if you move to the 400 mg dose, what do you think are the implications for the efficacy profile? And then if you have not experienced, or not observed any increase in serum creatinine below 500 mg, why not just move to 400 mg versus taking the stepped approach? And then on the stepped approach, like over what time do you plan to move up to 400 mg? I think his first question, Bill, is why did we move beyond 400 milligrams in the proof of concept, and then why did we choose that as the dose for the pivot?

Yes, hi, good morning, this is avi.

<unk>.

Just one quick question on line 930.

So if you move to 400 doors.

What do you think are the implications for the efficacy profile.

And then.

If you have not experienced at not observed any.

The increase in serum creatinine.

Below 500, Meg vie why not just move to 400.

Taking a step approach and then on the SAP approach like over what time do you plan to move up to 400 dose.

So I guess first question Bill is why did we move beyond 400 milligrams.

And the proof of concept and then why do we choose that as the dose for the pivotal.

Dr. Bill Sheridan: On the first point, at the time we designed the Pivotal Studies, we wanted to try to give patients an opportunity to avoid breakthrough hemolysis in the event of sequential missed doses. So, you know, that was a theoretical concern. And at that time, we couldn't distinguish the safety profile of 400 and 500 milligrams or the efficacy profile.

On the first point at the time.

Signs of pivotal studies.

We are.

We wanted to try to give patients an opportunity to avoid breakthrough hemolysis seen the advent of sequential missed doses. So that was a theoretical concern.

And at that time, we Couldnt distinguished the safety profile of 400, 500 milligrams or the efficacy profile. So we thought that that was a reasonable choice.

Dr. Bill Sheridan: So we thought that that was a reasonable choice. You know, with regard to the other aspect of this on efficacy, you know, we're very, you know, I. I have no qualms about stepping back to 400 milligrams in terms of efficacy. There's, you know, very good evidence from the proof of concept study that that's a fine dose from the perspective of increasing hemoglobin and the clone size and controlling hemolysis and so on.

With regard to that.

The other aspect of this on efficacy.

Sorry.

I have no qualms about stepping back to 400 milligrams in terms of efficacy. This very good evidence that from the proof of concept study that that's defined dose from the perspective of increasing the hemoglobin in the close size and controlling the <unk> and so on.

Dr. Bill Sheridan: So, you know, that was the decision at that point. Now we have new information, and it makes sense to propose an alternative dosing strategy consisting of step-up dosing and limiting the dose. The reason for the step-up dosing is that none of the patients in the proof of concept study had early onset rises in creatinine.

So.

That was the decision at that point and then we have new information and it makes sense to.

Propose an alternative dosing strategy, consisting of stepped up stiff up dosing and limiting the dose the reason for the step up dosing is because.

None of the patients in the proof of concept study had Italy on CIT raws and creatinine.

Dr. Bill Sheridan: And all of the patients in the proof of concept study started at a lower dose and then had a step-up in dose. You know, there are other drugs out there on the market where starting at a lower dose avoids early side effects. So, you know, that's a reasonable, plausible hypothesis as a way to move forward. And, you know, we'll discuss that with regulators after we complete our investigation and see whether there's a path forward or not. All right, thank you so much.

And all of the patients in the proof of concept study started at a lower dose and then had a step up in dose.

There are other drugs out there on the market.

Starting at a lowest dose avoids side.

Side effects.

That's a reasonable plausible hypothesis as a way to move forward and we will discuss that with regulators. After we completed our investigation and see what it is.

Oh no.

Alright, thank you so much.

Jon Stonehouse: Thank you. Our next question comes from Serge Belanger with Needham. Your line is now open. Hi, good morning.

Thank you. Our next question comes from Serge Belanger with Needham. Your line is now open.

Jon Stonehouse: Thanks for taking my questions. The first one was on 9930. Can you just describe your FDA interaction since the study was paused and, I guess, when the FDA issued their partial clinical hold? And I believe you mentioned you're planning to have discussions at the end of the third quarter. It seems like a long time to wait, so is that a FDA scheduling limitation or does additional work need to be done before this meeting? We were informed a few weeks ago, and we had already communicated that we put a pause on enrollment and that we'd continue dosing in patients that were receiving a benefit from the drug, and there was no alternative, which is consistent with the partial hold that the FDA had placed.

Hi, good morning, Thanks for taking my questions.

First one on 90 930 can you just describe your FDA interactions since the study was pause and I guess when the FDA issued their partial clinical hold.

And I believe you mentioned youre going to Youre planning to have discussions at the end of the third quarter.

It seems like a long time to wait so is that a FDA scheduling limitation or additional work needs to be done before this meeting.

No.

Informed a few weeks ago, and we had already communicated that we put a pause on enrollment and that we continue dosing in patients that were receiving a benefit from the drug and there was no alternative which is consistent with the partial holes that the FDA had placed and we knew that.

Jon Stonehouse: And we knew that we had an upcoming earnings call and we were in the thick of the investigation, and we thought it was better to have all the information shared at once so that you could have context. So that was the decision. Time to, You know, on the first time, there may be a second go at it and maybe a meeting, all that stuff. So we'll see how that unfolds. But we think that it could happen by the end of the third.

We had an upcoming earnings call and we were in the thick castigation than we thought it was better to have all the information shared at once so that you could have the context.

So that was the decision.

He asked a question about like the timing between now and when we go back to the FDA, Yes, that's a hard one to predict and so we said by the end of the third quarter, we'd be able to get there, but obviously you can imagine we want to work as quickly as we can to get a proposal in front of them and then there is a clock that goes and so we will.

Go through that process, if we get.

On the first time, there may be a second go that and maybe a meeting all that stuff. So we'll see how that unfolds, but we think that it could happen by the end of the third quarter.

Charlie Geyer: Okay, and then just one for Charlie on Arlodeo. I think you mentioned there were some challenges with prior odds in the first quarter. Just curious if those were the results of the usual reset of deductibles, or there was something else impacting those prior odds, and if they've been resolved. No, it was the expected stuff, Serge, so it's... You know, there's always a bolus that happens in the first quarter as payers kind of do the annual reset.

Okay, and then just one for Charlie on Northern Dale. Thank you mentioned there were some challenges with prior ox.

The first quarter.

Curious if those were the result of the usual reset of.

Deductibles or there was something else impacting those prior us and if they have been resolved.

No it.

With the expected stuff surge so.

Theres always a bolus that happens in that in the first quarter, it's as payers kind of do the annual reset. So it was it was what we expected I think John mentioned in his comments it was patient stepping back to free products during the.

Charlie Geyer: So it was what we expected, and I think Jon mentioned in his comments, patients stepping back to free products during the PA process; Medicare, the donut hole, and then commercial deductibles are always higher until those are exhausted early in the first quarter. Thank you. Thank you. Our next question comes from Gina Wong with Barclays. Your line is now open.

Process, it's Medicare.

Donut hole and then commercial deductibles are always higher until those are exhausted early in the first quarter.

Thank you.

Thank you. Our next question comes from Gena Wang with Barclays. Your line is now open.

Jon Stonehouse: Thank you for taking my questions. I also have two questions. One is regarding HAE-9930. Just wondering if, on the other side, FD allows you to resume and under, you know, the lower dose or step up those titration protocols. So, do you need to revisit your clinical trial design and expand the number of patients in order to reach, you know, the assumption of a clinical benefit to reach statistical significance?

Thank you for taking my questions. I also have two questions one is regarding itchy.

So when you feel.

Just wondering.

I will say the other side with SB allow you to resume.

Under the lower dose.

Stepping up dose titration protocol, so do you need to revisit your clinical trial design.

The number of patient in order to.

Lee.

Yeah.

The assumption of a clinical benefit too.

Significance.

Jon Stonehouse: And my second question is regarding Olidayu. For patients who are naive or switch from on-demand, could you give a breakdown of patients that were prescribed by community doctors versus academic doctors? And what is the attack rate when they switch to Olidayu?

And my second question is regarding <unk>.

For the patients.

Naive or switch from.

On demand could you give a breakdown of patients prescribed by community doctors. This is Dan.

Okay.

What is the attack rate.

When do you switch to <unk>.

Thank you.

Charlie Geyer: Yeah, so the first question about what you do to the protocol: if you're changing the dose, that's definitely a major amendment, and so we'd make that, but I can't tell you exactly the other things that'll change because we haven't had those conversations, but I think it would be largely the same study. We think that the efficacy of 400 is similar to 500, and so powering and things like that, at least at this point, we don't think we need to change, but we'll have more information once we talk to the regulators.

Yeah. So the first question about what do you do to the protocol if.

If you're changing the dose.

It's definitely a major amendment and so we'd make that but.

I can't tell you exactly the other things that will change because we haven't had those conversations but I think it would be largely the same study we think that the efficacy of 400 is similar to 500, and so powering and things like that at least at this point, we don't think we need to change but.

We will have more information once we talk to the regulators.

Charlie Geyer: And Tina, on your question about acute-only patients who are switching to Orladeo, and that's consistently since launch been a little less than half the patients coming to Orladeo. From an overall attack rate perspective, you know, those patients are doing well also when they switch to Orladeo and are staying on therapy similarly to what I described with the patients switching from prophylaxis. And as far as where, who's prescribing, to those of you, the acute-only portion of the market has been shrinking, and that's pretty consistent across the board.

And John on your question on an acute only patients who are switching to Orlando and thats consistently since launch, but a little less than half the patients coming to Orlando.

From a from an overall attack rate perspective, those patients are doing well.

Also when they switched to <unk> and are staying on therapy. Similarly to what I described with the prophylactic patients switching from prophylaxis.

And as far as where who's prescribing to those who have the acute only portion of the market has been shrinking.

That's pretty consistent across the board there'll be some doctors here and there that might prescribed more but I wouldn't describe it as an academic versus community I would say overall most patients. These days are on prophylaxis.

Charlie Geyer: There'll be some doctors here and there, you know, that might prescribe more, but I wouldn't describe it as academic versus community. I would say overall, most patients these days are on prophylaxis, and the prophylaxis market continues to shrink as patients switch to Orladeo and other prophylaxis products, while the acute market shrinks.

And.

That prophylaxis market continues to shrink as patients switched to oral <unk> and other prophylaxis products you market shrinks.

Charlie Geyer: Sorry, the acute market is shrinking. Thank you. I'm sorry, just wondering the acute, you know, the attack rate when they switch, what is the annual, if you were giving a rough estimate regarding annualized attack rate, usually what is the range of those patients? I don't want to refer to the 96-week data where they had, what, an average of three attacks or so per patient. For more information, visit www. FEMA.gov Okay, thank you.

The market is shrinking thank you.

So just wondering if acute.

Chuck Li <unk> switch what did you get any skew giving yet.

Rough estimate regarding annualized attack rate, usually what what is the range of dose patients.

So I don't want to refer to the 96 week data, where they had an average of three attacks or so per.

Per month, and they got down to a half attack per month I mean, that's probably the best information. We can give you that's right in these patients what we're seeing is there. Most of these patients are gaining very good control on <unk>, which is the key point.

The other point that Charlie made the median attack rate and what 16 out of the last 17 months was zero and so a lot of people are really controlled.

Okay. Thank you.

Jon Stonehouse: You're welcome. Thank you. Our next question comes from Brian Abrahams with RBC. Your line is now open. Hey, good morning.

Thank you. Our next question comes from Brian Abrahams with RBC. Your line is now open.

Jon Stonehouse: Thanks for taking my questions and I appreciate all the detail, both on Rodeo and 9930. So on 9930, if the FDA greenlights the titration design to 400 mg, would you still be fully investing in this drug in the same way as you did before, including incorporating patients with renal diseases in that study? Or would there be some sort of gated investment or perhaps a focus on certain disease areas or subpopulations or more refractory patients?

Hey, good morning, Thanks for taking my questions.

All the detail both on <unk> and 90 930.

So 90 930, if the FDA Green light penetration titration design to 400 Megs.

Would you still be fully investing in this drug in the same way as you did before including.

Haven't incorporating patients.

With renal diseases in that study or would there be some sort of more gated investment or perhaps.

Focus on certain disease areas, there subpopulations somewhere refractory patients and then for Charlie I'm just curious if during the first quarter there was any impact of the omicron wave.

Jon Stonehouse: And then for Charlie, I'm just curious if, during the first quarter, there was any impact of the Omicron wave on either switching or new patient starts or discontinuation dynamics and anything we might expect to see with respect to that evolving over the course of the rest of the year. Thanks. Yes, I'll take the first one, Brian, that you know, we're not intending to just invest in PNH. And that's the only population we go after.

On.

Either switching or new patient starts are a discontinuation dynamics than anything we might expect to see.

With respect to that evolving over the course of the rest of the year.

Charlie Geyer: If the drug proves to be safe and effective at a 400 milligram dose twice a day, we'll go into every indication that we can get into. And I can't give you the timing on that at this point in time, because there are discussions with regulators and all the other things that we need to do. But it would be too broad if we can determine that it's safe and effective. And then, Brian, your question on Q1 with Omicron.

Yeah, So I'll take the first one Bryan.

We're not intending to just invest in <unk> and that's the only population. We go after if the drug proves to be safe and effective at a 400 milligram dose twice a day will be going into every indication that we can get into and I can't give you the timing on that at this point in time, because there is discussions with regulators and all the other things that we need to do but it would be go abroad.

If we can determine that its a safe and effective dose.

And then Brian your question on Q1 with with Omicron.

Charlie Geyer: Honestly, hard to say. What I can say is our new patient starts were good for the quarter. They were slightly slower earlier in the quarter, but we ended the quarter at the same rate that we saw in the second half of last year, so really good momentum.

Honestly hard to say what I can say is our new patient starts were good for the quarter. They were slightly slower earlier in the quarter.

We ended the quarter.

At the same rate that we saw in the second half of last year. So really good momentum was omicron a part of that.

Jon Stonehouse: Was Omicron a part of that? As we've said before, it's something that we've been operating with COVID all the way through, so I'm not going to pin anything specifically on Omicron. We're happy with our pace right now.

As we've said before it's something that we've been operating with Covid all the way through.

So I'm not going to pin anything specifically on omicron were we're happy with with our pace right now.

Understood. Thanks, so much.

Jon Stonehouse: Thank you. Our next question comes from Liisa Bayko with Evercore. Your line is now open. Hi, thanks for taking my question, and also thanks for all the color.

Thank you. Our next question comes from Lisa <unk> with Evercore. Your line is now open.

Hi, Thanks for taking my question and thank you all.

So thanks for all the color.

Dr. Bill Sheridan: Just to start with 9930, just to follow up on what Brian was saying, do you have any particular concerns about, you know, the idea of moving into renal diseases, you know, just given the serum creatinine? And would we expect some sort of different outcome in that group, maybe lower dosing, perhaps? You know, it's highly suitable. Thanks for the question. I think PNH is a complicated disease. So every patient with PNH has subclinical kidney effects from their PNH because of hemoglobin urea when they're not treated, and hemocytin effects on the renal tubules, whether or not you can see that in any of your clinical chemistry or urinalysis tests.

Just to start with 90 930, just a follow up Brian was saying do you have any particular concerns about.

<unk>.

Idea of moving into renal diseases.

Just given the serum creatinine.

Would we expect some sort of a different outcome in that group, maybe lower dosing perhaps.

<unk>.

Hi, Lisa it's bill Thanks for the question I think.

<unk> is a complicated disease.

Patient with pay NIH has subclinical kidney fix from the P&I, which because of hemoglobin area. When they are not treated.

And the citizen effects on the renal <unk>, whether or not you can see that in any of your clinical chemistry of your analysis tests.

Dr. Bill Sheridan: So it's not like they have pristine kidneys to begin with; they don't. I think that, I don't know the answer to your question, that's going to be the outcome of discussions with regulators and experts and ultimately patients and committees and all the rest of it. What I can tell you is that in the interactions we've had with our nephrology expert advisors through the investigation, when I've asked exactly the same question of them, their response is, "We need complement inhibitors to treat people with no treatments, with these diseases, complement-mediated diseases who currently have no treatments."

So it's not like they have pristine kidneys to begin with I don't.

I think that.

I don't know the answer to your question, that's going to be an outcome of discussions with regulators.

Experts and ultimately patients committees and all the rest of it what I can tell you is that in the interactions we have headwinds in nephrology expert advisors through the investigation when I've asked exactly. The second question is in the responses, we need complement inhibitors to treat people with no treatments, who has with these diseases complement mediated diseases.

We currently have no treatments.

Dr. Bill Sheridan: And you need to complete your investigation and let's see if we can move forward. So that's not the end of the story, but it gives you an idea of what's in the mind of the experts who treat these diseases. I think that the theme of the feedback that we got, too, is really important for everyone to understand. There is real support in the community to continue moving 9930 forward. And so obviously, we're going to do it safely and thoughtfully, but I'm pleased to see the enthusiasm that investigators, key opinion leaders, and others have shown around this molecule. Okay, that's helpful feedback. And then can you just describe the step up to 400 protocol that you're considering? You know, what doses would you start at? How long would it take to get to 400?

And you would need to complete your investigation and let's see if we can move forward.

But that's not the end of the story, but it.

It gives you an idea of what's in the minds of the experts who treat these diseases I think that that theme of the feedback that we got to is really important for everyone to understand there is a real support in the community to continue moving 90 930 forward and so obviously, we're going to do it safely and thoughtfully.

But.

I am pleased to see the enthusiasm that investigators key opinion leaders and others have shown around this molecule.

Okay. That's helpful feedback and then.

The first.

The step up to 400 protocol that you are considering what doses. If you start at how long would it take to get to 400.

Dr. Bill Sheridan: In the proof of concept study, it took a very long time. I think that we need to step through the regulatory discussions first before we can be certain about exactly how that goes. I think, on the basis of the data we currently have, there's flexibility in what might be the approach there, so let's see how that goes. Okay.

In the proof of concept study.

It took a very time I think that we need to step through the regulatory discussions for this before.

Before we can be certain about exactly how that goes I think this.

On the basis of the data that we currently have.

This flexibility.

What might be the approach there so let's see how that goes.

Jon Stonehouse: And then just finally, for Oralidaio, your guidance of 1 billion, do you factor in any potential competition from other oral calicorin inhibitors that are in various stages of development? And do you have an ongoing effort there? It just seems like you've created a really nice market here and I'm wondering if you have any life cycle management. Yeah, no, we definitely consider future competition and the timing of which, you know, is some years out from now. But here's how we get there mathematically, right?

Okay, and then just finally for oral of Danielle.

Your guidance of $1 billion do you factor in any potential competition from other oral.

California have returns that are in various stages of development and do you have an ongoing effort. There. It just seems like you've created a really nice market here and wondering if yes, some lifecycle management plans.

Yes, we definitely consider future competition and the timing of which you know is some years out from now.

But here's here's how we get there mathematically right. Its 2000 patients out of the 7500, Charlie told you that.

Jon Stonehouse: It's 2,000 patients out of 7,500. Charlie told you that that's between 25 and 30% of the market share. So there's still a lot of market to be had by others. And I think the other piece is that if you're controlled by one capsule once a day, why would you switch? What incremental benefit would you see that would cause you to switch? And I mean, we've gotten really smart about what goes on in the minds of patients and doctors. We've done a ton of market research, and we can't find a reason why.

That's between 25% to 30% market share. So there's still a lot of market. She had by others and I think the other pieces if youre controlled on one capsule. Once a day why would you switch what incremental benefit would you see that would cause you to switch and we've gotten really smart.

What goes on in the minds of patients and doctors, we've done a ton of market research and we can't find a reason it's not efficacy because they are controlled and it can't be convenience because you can't get better than one capsule once a day and so.

Jon Stonehouse: It's not efficacy because they're controlled. And it can't be convenient because you can't get better than one capsule once a day. And so we just find it really difficult for people to take our share away from us.

We just find it really difficult for people to take share away from US now they may get share from other injectables that people that weren't controlled on orla Dale that could be a spot and there is room for that so we think it's a very realistic number.

Jon Stonehouse: Now, they may get a share from other injectables that, you know, people that weren't controlled on Orladeo, that could be a spot, and there's room for that. And then what about your lifecycle management plan?

And then what about your lifecycle management plan.

Jon Stonehouse: Yeah, I mean, we're always looking at things to, you know, obviously, we've invested in a meaningful way in HAE, but we are also building a pipeline beyond HAE with complement and, and the like. And, and so, and then we've got a really long patent life with Orladeo as well. So, you know, our focus right now is to get to peak as fast as we can, and, you know, lock in those patients that are well controlled and tolerate the drug. And, and then, you know, continue to advance our pipeline. Okay, so does it seem like there is really difficult to develop oral calocrine inhibitors? Is that what I'm hearing?

Yes, I mean, we're always looking at things to you know obviously, we've invested in a meaningful way in <unk>, but we also are building a pipeline beyond <unk> with complement and and the like and so and then we've got a really long patent life with with or the de <unk> as well so.

Our focus right now is to get to peak as fast as we can and.

In those patients that are well controlled and tolerate the drug and then continue to advance our pipeline.

Okay. So it seems like there is it really difficult to develop oral <unk> inhibitors is that what I'm hearing because it seems like.

Jon Stonehouse: Because it seems like, Um, you know, without 100% relief of attacks in a clinical trial, not I know in real life, the patients who stay on, but in a clinical trial, there's still room to have an even better molecule. And I was wondering if that's something that you're working on? Or is it just so difficult?

Without 100%.

Release of attacks in a clinical trial, not I would now and realize that patients can stay on but in a clinical trial. There is still room to have.

We have an even better molecule and just wondering is that something that youre working on or just.

So difficult I mean.

Jon Stonehouse: I mean, we haven't seen a lot of progress in this front. Yeah, just one thing I want to correct you on, and I agree that the pivotal study results are the pivotal study results, but what we're seeing in the real world is people are really well controlled, right? It doesn't work for everybody, but the ones that it works for, they're really, really well controlled.

We haven't seen a lot of progress.

Just one thing I want to correct, yes, I agree that the pivotal study results are the pivotal study results, but what we're seeing in the real world as people are really well controlled right. It doesn't work for everybody, but the ones that it works for their really really well controlled this is not I'm sacrificing efficacy for convenience no way and so I think thats.

Jon Stonehouse: This is not, I'm sacrificing efficacy for convenience, no way. And so I think that's incredibly important to remember. I forgot the other part of your question. I won't use an expletive, but yeah, it's hard, really hard, and as evidenced by the fact that we're the only one who comes up with it once a day, and others try, right?

Incredibly important to remember I forgot the other part of your question.

Hi, guys.

The difficulty in yeah, Oh, yeah.

I won't use an expletive, but yes, it's hard really hard and as evidenced by the fact that we're the only one who has come up with a once a day and others tried right and you know as we know in this industry, it's tough to come up with drugs period, and it's tough to come up with drugs for hard targets and so nobody's come up with a once a day oral.

Jon Stonehouse: And you know, as we know in this industry, it's tough to come up with drugs, period, and it's tough to come up with drugs for hard targets, and so nobody's come up with a once-a-day oral calocrine inhibitor at this point. And yes, it's extremely hard, and the attrition rate is high. So then just a last question for me. I noticed you got a designation for your FOP program. Are you making any investments there? What how do you think about next steps?

<unk> inhibitor to this point.

Yes, it's extremely hard in the attrition rate is high.

So then just a last question from me I noticed you.

Got it designation for your MLP program are you, making any investments there how it works.

Perfect.

Jon Stonehouse: Yeah, we are. And we're really excited to get that designation. And, you know, our goal is to get inpatients next year. And so we're continuing to move that program. It's a horrible disease without really any real treatments right now.

Yes, we are and we're really excited to get that.

Designation and our goal is to get in patients next year and so we're continuing to move that program with <unk>.

Horrible disease without really any real treatments right now and so we're starting to get to know the community the patient community the doctors, who treat and yes, we're going full speed on that and hope to be in patients next year.

Jon Stonehouse: And so we're starting to get to know the community, the patient community, the doctors who treat them. And yes, we're going full speed on that and hope to be inpatients next year. Thanks, Jon.

Thanks, Sean.

Thank you.

Jon Stonehouse: Thank you. Thank you. And your final question comes from Justin Kim with Oppenheimer. Your line is now open. Hi, good morning. So just maybe a quick one from me.

Thank you and your final question comes from Justin Kim with Oppenheimer. Your line is now open.

Jon Stonehouse: I didn't really see much sort of mention around experience in the renewed population. And, you know, just curious, is there a substantial enrollment there that there will be a crude clinical experience or, you know, just kind of curious, you know, how you will get the evidence to gain confidence in treating this population? Yeah, we just got started enrolling in that trial. So it wasn't a substantial number of patients; it was very few.

Hi, good morning.

Just maybe a quick one from me.

Haven't really seen much sort of mention around experience and the renewable population.

Just curious.

The essential enrollment there that there will be a crude clientelist loans or just kind of curious.

How you will get the evidence to gain confidence in treating this population.

We just got started and enrollment in that trial. So it wasn't a substantial number of patients. It was very few and.

Jon Stonehouse: And you know, I think Bill talked about the process that we'd use in evaluating nephritis disease. Compliment-Mediated Diseases, we've got some more work to do, but I think, again, if you have a safe and effective drug and you find the dose, then you can go into, you know, many different indications, and that's the goal. Okay, I got it. Thank you. And that concludes today's Q&A session. I would now like to turn the call back over to Jon Stonehouse for closing remarks. Yeah, thank you.

I think bill talked about the process that we use in evaluating.

Nephritis diseases.

Complement mediated diseases, we've got some more work to do but.

Again, if you have a safe and effective drug and you find the dose.

Then you can go in many different indications and Thats the goal.

Okay got it thanks.

Thank you and this concludes.

Today's Q&A session I would now like to turn the call back over to Jon Stonehouse for closing remarks.

Jon Stonehouse: So I'm just going to restate something I said earlier, which is, if you take a step back, and you look at our company, you see a company with a highly innovative, once a day oral calicrine inhibitor called Orladeo, that's on its way to $250 million, no less than $250 million this year, and a billion dollars at peak. What is the value of that? The second is that we've got a pipeline, and yeah, we've faced some challenges.

Yes. Thank you so I'm just going to restate something I said earlier, which is if you take a step back and you look at our company you see a company with.

Our highly innovative once a day oral <unk> inhibitor called Orla Deyoe, that's on its way to $250 million no less than $250 million this year and $1 billion at peak, what's the value of that the second is we've got a pipeline and yes, we faced some challenges.

Tech companies have you seen that don't face challenges along the way.

Jon Stonehouse: You know, what biotech companies have you seen that don't face challenges along the way? But we're still really excited about being able to bring more and more products to the market for patients suffering from rare diseases. What's the value of that? And then we have a platform where all this came from, right? Discovery Engine that can repeat it over and over and over again.

But we're still really excited about being able to bring more and more products to the market for patients suffering from rare diseases. What's the value of that and then we have a platform where all of this came from right discovery engine that can repeat it over and over and over again whats the value of that and then lastly, we have a strong balance sheet really strong balance sheet and we're bringing in revenue at the <unk>.

Jon Stonehouse: What's the value of that? And then lastly, we have a strong balance sheet, a really strong balance sheet, and we're bringing in revenue at the same time. What's the value of that? So when you step back, my answer to that is there's a lot of value here today, and there's the potential for even greater value in the future. And so we're going to keep plowing ahead, tackling these challenges as we face them, driving Orladeo sales towards a billion dollars, and we remain very confident that we have what it'll take to build one of the next great biotech companies.

Same time, what's the value of that so when you step back my answer to that is there's a lot of value here today and there is even the potential for even greater value in the future and so we're going to keep plowing ahead.

Tackling these challenges as we face them driving oiler Dale sales towards a $1 billion and we remain very confident that we have what it will take to build one of the next great biotech company. So thanks for your interest and have a great day.

Jon Stonehouse: So thanks for your interest, and have a great day. This concludes today's conference call. Thank you for participating. You may now disconnect. [music]

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

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