Q4 2020 BioCryst Pharmaceuticals Inc Earnings Call
[music].
Ladies and gentlemen, thank you for standing by and welcome to the Biocryst what quarter 'twenty 'twenty earnings call.
Operator: Ladies and gentlemen, thank you for standing by, and welcome to the BioCryst fourth quarter 2020 earnings call. At this time, all participants are in a listen-only mode.
At this time all participants are in a listen only mode.
After the speaker's presentation, there will be a question and answer session.
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 1 on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star zero. I would now like to hand the conference over to your speaker today, Mr. John Bluth of BioCryst. You may begin. Thanks, Daphne.
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 any further assistance. Please press star zero and I would now like to hand, the conference over to your speaker today, Mr. John Bluth with Biocryst you may begin.
John D. Bluth: Good morning, and welcome to BioCryst's fourth quarter 2020 corporate update and financial results conference call. Today's press release is available on our website. Participating with me today are CEO Jon Stonehouse, CFO Anthony Doyle, Chief Medical Officer Dr. Bill Sheridan, Chief Business Officer Megan Snizinski, and Chief Commercial Officer Charlie Geyer. Following our remarks, we will answer your questions. 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 company's future performance and or achievements.
Thanks, Daphne and good.
Good morning, and welcome to Biocryst fourth quarter, 2020, corporate update and financial results Conference call.
Today's press release is available on our website.
Participating with me today are CEO, Jon Stonehouse, CFO, Anthony Doyle, Chief Medical Officer, Dr. Bill Sheridan, Chief Business Officer Officer, Megan Kaczynski, and Chief Commercial Officer, Charlie Gayer. Following our remarks, we will answer your questions before we begin. Please note that today's conference call will contain forward looking statements, including those statements.
Regarding future results and all.
And it and forward looking financial information as well as the company's future performance and our 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 you should not place undue reliance on these forward looking statements for additional information.
John D. 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. You 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, followed by 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.
And 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 Good morning to all of you and thanks for joining us.
Jon P. Stonehouse: Good morning to all of you, and thanks for joining us. Meaningful value is created by companies that translate great science into clinical benefit, leading to approvals and successful market launches of new medicines that patients are waiting for, and the most successful biotech companies are able to repeat this process of discovery, development, and commercialization across multiple drugs in multiple disease areas. Building this capability doesn't happen overnight, but when you make this transformation, you see real change and real value.
Meaningful value is created by companies that translate great science, and the clinical benefit leading to approvals and successful market launches of new medicines that patients are waiting for it.
And the most successful biotech companies are able to repeat this process.
Discovery development and commercialization across multiple drugs and multiple disease areas.
Building this capability doesn't happen overnight.
But when you make this transformation you see real change and real value.
That transformation is happening right now at Biocryst and.
Jon P. Stonehouse: That transformation is happening right now at BioCryst. We know patients with rare diseases are waiting for oral treatments despite having injectable therapy to manage their disease. We've heard that for years in HAE and are hearing the same thing in P&H.
We know patients with rare diseases are waiting for oral treatments, despite having an injectable therapy to manage their disease.
We've heard that for years and H AE and are hearing the same thing and P and H.
Jon P. Stonehouse: We've built an exceptional drug discovery platform to go after challenging targets like calocrine inhibitors, Factor D inhibitors, and L2 inhibitors so that we can take this great science, get drug approvals, and finally get the drugs to the market to put an end to the patients waiting. The approval of Orladeo in the U.S. and Japan is evidence of this change. Charlie and Megan will describe what we are doing and what we are hearing from customers in the marketplace.
We have built an exceptional drug discovery platform to go after challenging targets like <unk> inhibitors factor D inhibitors and <unk> inhibitors.
So that we can take this great signs get drug approvals and finally to the market to put in and to the patients waiting.
The approval of oil and Dale and the U S and Japan is evidence of this change Charlie and Megan will describe what we are doing and what we are hearing from customers in the marketplace.
And while it's early days and the U S launch they will share why we believe we are off to a good start.
Jon P. Stonehouse: And while it's early days for the U.S. launch, they will share why we believe we're off to a good start. Megan will then share with you the even bigger unmet need in Japan for patients suffering from HAE and how Orladeo can have a big impact as the first approved treatment for Preventing Attack. We believe Orladeo has the potential to generate north of $500 million in global peak sales.
Megan will then share with you the even bigger unmet need and Japan for patient suffering from HCA and how all the day Oh can have a big impact as the first approved treatment.
And for preventing attacks.
We believe oiler deyoe has the potential to generate north of $500 million and global peak sales.
Next up is European approval.
We expect that approval and Q2 and Charlie will describe how his team and Europe has been preparing for the launch. So we can hit the ground running just like we have and the U S.
We also have and increasing body of evidence that we can repeat the success and complement mediated diseases with our oral factor D inhibitor.
Jon P. Stonehouse: Next up is European approval. We expect that approval in Q2, and Charlie will describe how his team in Europe has been preparing for the launch so we can hit the ground running just like we have in the U.S. We also have an increasing body of evidence that we can repeat this success in complement-mediated diseases with our oral factor de-inhibitor. Last year, we shared proof-of-concept data from four P&H patients treated with BCX9930.
Last year, we shared proof of concept data and <unk> patients treated with <unk> hundred 90 930.
Bill will update you on the progress of the study and what to expect when we announced the data from our full set of 16 patients, including both treatment naive patients and.
And C five inadequate responders.
What makes our oral factor D program, even more valuable and exciting.
As we plan to go after many complement mediated rare diseases and having one molecule to go after many indications could enable us to have several different approvals for many more patients.
And finally, you can see the change and our balance sheet.
As you will hear from Anthony capital from our December financing has transformed our company and allows us to put our head down to successfully launch or the day all around the world.
And rapidly advance our pipeline.
Jon P. Stonehouse: Bill will update you on the progress of the study and what to expect when we announce the data from a full set of 16 patients, including both treatment-naive patients and C5 Inadequate Responders. What makes our Oral Factor D program even more valuable and exciting is that we plan to go after many complement-mediated rare diseases.
So this transformation is no longer aspirational. It is happening right now and we're focused on going fast because we know patients are waiting.
Now I'll turn the call over to Charlie to share early insights into our launch and Charlie.
Thanks, Jon.
We invested early to be ready for a fast launch to get patients on therapy quickly and to secure reimbursement access for Orlando, what we're seeing so far is very encouraging we are wrapping up clinical trial conversions and the great majority of these patients are choosing to continue with all the data.
We are also seeing strong early demand from new patients.
So far patients on therapy are equally split between clinical conversions and those new to <unk> and our sales and marketing efforts are filling the funnel quickly.
Jon P. Stonehouse: Having one molecule to go after many indications could enable us to have several different approvals for many more patients. And finally, you can see the change in our balance sheet. As you will hear from Anthony, capital from our December financing has transformed our company and allowed us to put our heads down to successfully launch Orladeo around the world and Rapidly Advance our Pipeline. So this transformation is no longer aspirational.
And what's notable is we are also seeing as many new patients switching to early day from injectable profi products as those starting profi on Orlando after previously treating their HLA with only acute medications.
This is right in line with our strategy because we believe <unk> offers significant and sustained attack reduction with the reduced burden of treatment, regardless of the patient's background therapy or attack rate.
And more early evidence that we're off to a good start and addressing the strong pent up demand is that HCA treaters are embracing orla do we have.
<unk> expanded the prescriber base beyond those involved and the apex clinical trials.
Once patients decide to switch to oral and down our empower patient services team works with them to get started on product right away. So.
Jon P. Stonehouse: It's happening right now, and we're focused on going fast because we know patients are waiting. Now, I'll turn the call over to Charlie to share early insights into our launch.
So far most are starting on our quick start program, while empower helps them through the prior authorization process.
Reimbursement approvals are coming mostly through medical exceptions at this stage of our market access team is making significant progress as payers see the strong demand from patients.
Charles K. Gayer: Thanks, Jon. We invested early to be ready for a fast launch, to get patients on therapy quickly, and to secure reimbursement access for Orladeo. What we're seeing so far is very encouraging. We are wrapping up clinical trial conversions, and the great majority of these patients are choosing to continue with Orladeo. We are also seeing strong early demand from new patients. So far, patients on therapy are equally split between clinical conversions and those new to Orladeo, and our sales and marketing efforts are filling the funnel quickly. What's notable is we're also seeing as many new patients switching to Orladeo from injectable prophy products as those starting prophylaxid on Orladeo after previously treating their HAE with only acute medication.
Payers are starting to add oil a day out to their coverage policies and we expect this process to accelerate over the next quarter.
We knew that Covid would require some adjustments and we were and we prepared to launch in this environment faced.
Faith to face meetings with customers have been limited and many areas of the country, but physicians have been receptive to zoom calls because they want to learn about <unk>.
Our team has been very efficient with these interactions by transferring calls directly to colleagues when market access for medical questions come up.
Live meetings and Congresses are not quite the same and FERC and a virtual format, but we've seen a lot of interest and our virtual education events for health care providers and patients for example over 200 patients attended to virtual events earlier this month.
We also see that physicians and their patients are communicating via telemedicine went in person visits are not possible and many physicians have been comfortable prescribing oral a day I'll remotely because starting and oral medicine does not require training.
Our U S launch is off to a strong start and meeting the pent up demand from patients and Hai treaters.
Looking forward to Europe, our market research tells US there is also significant pent up demand for the first targeted oral treatment.
Charles K. Gayer: This is right in line with our strategy because we believe Orladeo offers significant and sustained attack reduction with a reduced burden of treatment regardless of a patient's background therapy or attack rate. More early evidence that we're off to a good start in addressing this strong pent-up demand is that HAE treaters are embracing Orladeo. We have significantly expanded the prescriber base beyond those involved in the APEX clinical trial. Once patients decide to switch to Orladeo, our Empower patient services team works with them to get started on the product right away. So far, most are starting on our Quick Start program, while Empower helps them through the prior authorization process.
The difference in Europe is that Prophage use has been limited by lack of options. So we have a great opportunity to grow the protein market with oil a day.
Just as we did and the U S. We have built a team with deep rare disease experience and passion for launching innovative drugs.
Germany will be our first commercial launch in Q2, and we look forward to reporting on multiple global launches in the coming quarters.
Now I'll pass it to <unk> to provide more color on how we are starting to change the treatment.
Treatment paradigm and to describe launch preparations and Japan.
Thanks, Charlie net.
<unk> affairs, and partnering closely with Charlie team to support a successful launch.
Our efforts are aimed at increasing physician knowledge and understanding of oil a day.
Overall health care providers are embracing the strength of our clinical data and product profile and <unk>.
Particular, the comparisons of how patients do before and while on treatment.
Charles K. Gayer: Reimbursement approvals are coming mostly through medical exceptions at this stage, but our market access team is making significant progress as payers see the strong demand from patients. Payers are starting to add Orladeo to their coverage policies, and we expect this process to accelerate over the next quarter. We knew that COVID would require some adjustments, and we were and are prepared to launch in this environment.
And tack reduction from our baseline of three per month to one per month sustained over time and the attack free period, many patients are experiencing and our longer term safety study.
We continue to generate additional supportive data, including what will share a quad AI, which starts tomorrow.
We'll show the positive outcomes of attack reduction and less on demand and use regardless of prior prophylactic experience or baseline attack frequency.
Charles K. Gayer: Face-to-face meetings with customers have been limited in many areas of the country, but physicians have been receptive to Zoom calls because they want to learn about Orladeo. Our team has been very efficient with these interactions by transferring calls directly to colleagues when market access or medical questions come up. Live meetings and congresses are not quite the same in a virtual format, but we've seen a lot of interest in our virtual education events for healthcare providers and patients.
This adds to the body of evidence, helping physicians and patients understand the breadth of experience and improved outcome koala and Orla day out including from patients who've been on other proceeds before.
Our medical strategy is also focused on the shift towards individualized treatment plans.
Meet the needs of patients with respect to reducing both disease and treatment burden.
The recent publication from Dr. <unk> at mass General outlining a model for share decision, making and ETE is evidence of this movement in the field.
Charles K. Gayer: For example, over 200 patients attended two virtual events earlier this year. We also see that physicians and their patients are communicating via telemedicine when in-person visits are not possible. And many physicians have been comfortable prescribing Orlodeo remotely because starting an oral medicine does not require training.
In addition, our burden of treatment data is resonating.
And to acknowledge injection fatigue and needle phobia is real breakthrough.
Breakthrough attacks will occur while on other proceeds and patients and caregivers wanted to treatment that is easier to administer.
Charles K. Gayer: Our U.S. launch is off to a strong start in meeting the pent-up demand from patients and HAH readers. Looking forward to Europe, our market research tells us there is also significant pent-up demand for the first targeted oral treatment. The difference in Europe is that prophy use has been limited by a lack of options.
Our research research.
Patients want more than only attack reduction this.
And this is why it's so important for physicians to ask about each patient need even if they believe the attacks are under control.
Our work is helping physicians see how all the day offers patients both the attack control they desire and the lifestyle freedom and benefits of the convenient and discreet oral once daily pill.
Megan Snizinski: So we have a great opportunity to grow the profi market with Orladeo. Just as we did in the U.S., we have built a team with deep rare disease experience and passion for launching innovative drugs. Germany will be our first commercial launch in Q2, and we look forward to reporting on multiple global launches in the coming quarter. Now I'll pass it to Megan to provide more color on how we are starting to change the HAE treatment paradigm and describe launch preparations in Japan. Thanks, Charlie.
As Charlie mentioned, we are seeing a balance of switch patients from injectable protein products and those previously only on acute therapy, we are making early progress and shifting the paradigm.
Jon shared how we're supporting multiple launches globally, we were thrilled to receive and Mitel W. Approval last one marketing holiday of this historic milestone as the first approved proceed therapy and Japan.
Megan Snizinski: Medical Affairs is partnering closely with Charlie's team to support a successful launch. Our efforts are aimed at increasing physician knowledge and understanding of Orladeo. Overall, healthcare providers are embracing the strength of our clinical data and product profile, in particular the comparisons of how patients do before and while on treatment, like the mean attack reduction from a baseline of 3 per month to 1 per month, sustained over time, and the attack-free period many patients are experiencing in our longer-term safety study.
We chose Tory our commercial partner given their performance and building the HIV market data.
And they prove they can increase disease awareness and patient identification to grow their HIV business into a $200 million franchise.
As a reminder, only about 580 patients are identified today with prevalence estimates upwards of 2500.
With all the day of Towry has the opportunity to apply their past experience to build the prophylactic market driving patient identification and profi adoption similar to what we've seen in the U S over the last decade with the introductions of new AC therapies.
Megan Snizinski: We continue to generate additional supportive data, including what we'll share at Quad AI, which starts tomorrow, will show the positive outcomes of attack reductions and less on-demand use regardless of prior prophylactic experience or baseline attack frequency. This adds to the body of evidence, helping physicians and patients understand the breadth of experience and improved outcomes while on Orladeo, including from patients who've been on other PROFIs before. Our medical strategies also focused on the shift towards individualized treatment plans that best met the needs of patients with respect to reducing both disease and treatment burden.
With approval Tories Medical Representatives are now able to meet with physicians.
Theyre hearing interest and excitement from physicians to see or the day, who is a major advancement and care for their patients.
Our NHI pricing discussions are in progress and we expect to complete them and early Q2.
After price listing doctors can begin prescribing and Torrey full launch promotion and marketing activities will kick off.
Upon successful completion of the pricing discussion, we'd receive a $15 million milestone and we share and Torrey success with a tiered royalty from 20% to 40% of net sales.
In addition to the commercial launches we're equally focused on advancing our factor D program and pipeline I'll turn the call over to bill for more on our clinical progress.
Megan Snizinski: The recent publication from Dr. Banerjee at Mass General outlining a model for shared decision-making in HAE is evidence of this movement in the field. In addition, our burden of treatment data is responding. Physicians acknowledge injection fatigue and needle phobia are real.
Thanks, Megan and good morning, everyone.
And <unk> 90, 930 development program is making excellent progress and.
We are excited to advance its novel effectively and EBITDA into advanced development trials across multiple indications in 2021.
Megan Snizinski: Breakthrough attacks still occur while on other pro- And patients and caregivers want a treatment that is easier to administer. Our research shows patients want more than only attack reduction. This is why it's so important for physicians to ask about each patient's needs, even if they believe the attacks are under control.
We're looking forward to a big year.
And our overall goal and development of 99 that he is very clear.
To bring forward and oral monotherapy complement inhibitor treatment for both P&I and additional rare and serious and potentially life threatening diseases driven by the alternative pathway.
Megan Snizinski: Our work is helping physicians see how Orladeo offers patients both the attack control they desire and the lifestyle freedom and benefits of a convenient, more discreet oral, once-daily pill. As Charlie mentioned, with us seeing a balance of switch patients from injectable pro-fee products and those previously only on acute therapy, we are making early progress in shifting the paradigm. Jon shared how we're supporting multiple launches globally. We were thrilled to receive MHLW approval last month, marking Orladeo's historic milestone as the first approved prophytherapy in Japan.
Inhibiting <unk> day and P&I. It is important for patients momentum we had prior experience with <unk> inhibitors.
The clinical program.
Support a label for monotherapy treatment and old patients.
Patients.
P&I patients who are naive to <unk> inhibitors patients who have had an inadequate response to <unk> inhibitors, and patient is doing well and medically, but who want to eliminate the burden of therapy from injections or infusions.
And 2020, we showed data from four C. Five inhibitor naive patients treated with <unk> monotherapy with dose escalated through 400 milligrams twice a day.
This data showed that control of hemolysis with both related and at the site.
Profiled six book.
We have since completed enrollment and the study with a total of 16 teenage patients and with treatment naive.
Megan Snizinski: We chose Torrey, our commercial partner, given their performance in building the HIV market. They proved they could increase disease awareness and patient identification to grow their HIV business into a $200 million franchise. As a reminder, only about 500 HAE patients are identified today, with prevalence estimates upwards of 2,500.
99, <unk> as monotherapy and six per patients with inadequate responses to <unk> inhibitors.
We received 99 city in addition to the C five inhibitor treatment.
And our upcoming R&D day, we look forward to sharing the results, we complete phase one dose ranging trial and it.
Is what we plan to head and the data readout.
First we will have data from <unk> patients.
Megan Snizinski: With Orladeo, TORI has the opportunity to apply its past experience to build the prophylactic market, driving patient identification and prophylaxid adoption, similar to what we've seen in the U.S. over the last decade with the introduction of new HE therapies. With approval, TORI's medical representatives are now able to meet with physicians. They're hearing interest and excitement from physicians who see Orladeo as a major advancement in care for their patients. Our NHI pricing discussions are in progress, and we expect to complete them in early Q2.
Five inhibitor naive and 65% EBITDA inadequate responders through at least six weeks of treatment and added.
400 milligrams or 500 milligrams per day.
And the range of both clinical outcomes and laboratory outcomes, including for example.
Hemoglobin transfusion particular slides peanuts coincides and LDH and safety data from dosing for up to 48 weeks.
At the R&D day, we will also share and new market research with you from teenage patients.
What youll see will feel very familiar is the insights are very similar to what we saw and hae's patient there is.
Tremendous burden treatment associated with Injectables and these patients want and oral treatment.
And 2020, we discussed that plant that dose selection and design considerations and future studies.
Both U S and European regulators.
Megan Snizinski: After price listing, doctors can begin prescribing, and TORI's full launch promotion and marketing activities will kick off. Upon successful completion of the pricing discussions, we will receive a $15 million milestone, and we share in Torrey's success with a tiered royalty from 20% to 40% of net sales.
Dose selection for <unk> 99 cities is based on precedent.
PK PD modeling and responses and <unk>.
With completion of this study we will have the information we need to choose the dose for accelerated advanced development programs across all indications and we believe we will be ready to move to strike and phase one to pivotal trials and pay and age.
With the upcoming data readout, we will be ready to finalize the study plans and Pip.
William P. Sheridan: In addition to the commercial launches, we're equally focused on advancing our Factor D program and pipeline. I'll turn the call over to Bill for more on our clinical progress. Thanks, Megan, and good morning, everyone.
Pivotal trials and C&I.
And proof of concept trial and collected nephritis indications later this year.
Announced the details of those trials as we stopped them.
And our strong balance sheet allow us to fully invest and those program.
We are very excited by the progress we made in 2020 and the terrific opportunity, we have and 2021 to bring and oral monotherapy closer to approval for seriously ill patients with complement mediated diseases.
William P. Sheridan: Our BCX9930 Development Program is making excellent progress, and we are excited to advance this novel factor D inhibitor into advanced development trials across multiple indications in 2021. We're looking forward to a big year. Our overall goal for the development of 9930 is very clear, to bring forward an oral monotherapy complement inhibitor treatment for both PNH and additional rare, serious, and potentially life-threatening diseases driven by the alternative pathway. Inhibiting Factor D and PNH is important for patients no matter their prior experience with C5 inhibitors.
Now I'll hand, the call over to Anthony.
Thanks Bill.
What a difference a year makes and we ended 2019 was $138 million of cash and we ended 2020 with $303 million.
And to another $75 million.
And upcoming on a day, our revenues from the U S, Japan and Europe the.
The strengthening of our balance sheet, which takes us into 2023 allows us to focus on creating value for the company and shareholders by investing in areas that will provide maximum efficiency and return.
The main areas that we are investing and continue to be supporting the launch of Orlando globally and and.
And this thing and the development of <unk> 90, 930 across multiple indications while of course, making sure that we have the infrastructure in place to support the pace of progress that we expect.
As the CFO. It's also nice to have significant financial flexibility and levers to pull as we move forward.
And the launch Orlando continues to progress, we can make strategic and financial adjustments that correlate with the pace of the revenues that are being generated are.
And our investments and factor D. Also continues to evolve and our continuing desire to move quickly and broadly with the investment and this program's development.
William P. Sheridan: The goal of the clinical program is to support a label for monotherapy treatment in all TNH patients. This means PNH patients who are naive to C5 inhibitors, patients who have had an inadequate response to C5 inhibitors, and patients doing well medically but who want to eliminate the burden of therapy from injections or infusions. In 2020, we shared data from four C5 inhibitor naive patients treated with 9930 monotherapy at doses escalated through 400 mg twice a day. This data showed that control of hemolysis is dose-related and that the safety profile is excellent.
As I noted we will also have the option, if we need us to drawdown and the additional $75 million from our existing credit facility with a theory.
And as we showed with the financing that we announced in December we have future opportunities to access capital with our growing portfolio of assets.
Because of these many variables we are not providing specific revenue or operating expense guidance and the launch period for Orlando.
But based on our expectations for revenue operating expenses and our option to access the additional $75 million. We believe our current cash runway takes us into 2023.
This position of financial strength allows us to focus on execution to focus on value creation and not on near term cash needs and that's a new and exciting spot for biocryst.
<unk> is transforming and so too is our value proposition, where commercial stage rare disease company and Orlando will generate meaningful revenue across multiple regions with Bcf and $99 30. The development team is working on a drug that has huge potential across multiple indications the team and Birmingham continues to discover and.
William P. Sheridan: We have since completed enrolment in the study with a total of 16 P&H patients. Ten were treatment-naive who received 99-30 as monotherapy, and 6 were patients with inadequate responses to C5 inhibitors who received 99.30 in addition to their C5 inhibitor treatment. At our upcoming R&D day, we look forward to sharing the results of the complete Phase I dose ranging trial in PNH. Here's what we plan to have in the data readout.
Next generation of medicines for rare diseases and.
And we are now and a strong financial position to invest and driving value creation across all of these areas.
That's it from our prepared remarks, and we'll now open it up for your questions.
Okay.
At this time, if you would like to ask a question press star followed by the number one on your telephone keypad.
To withdraw your question press the pound key.
Please standby, while we compile the Q&A roster.
Your first question comes from the line of Jessica Fye with J P. Morgan.
William P. Sheridan: First, we will have data from all 16 TNH patients, the 10C5-inhibitor-naive and 6C5-inhibitor-inadequate responders, through at least 6 weeks of treatment at either 400mg or 500mg PID, and a range of both clinical outcomes and laboratory outcomes, including, for example, hemoglobin, transfusions, reticulocytes, PNH clone size What you'll see will feel very familiar, as the insights are very similar to what we saw in the HIE pictures.
Hey, guys, good morning, and hopefuls law and a few.
Your financial question.
Right.
Orlando consensus for this year is around $35 million are you comfortable with that number.
How should we think about gross to net and the early part of the launch and could that evolve as you get coverage ramped up.
And third where does formulary coverage and now what's your goal for coverage and when do you expect to achieve it.
Yeah.
Alright, Thanks, Jess I'll take the.
First one and.
Charlie you can take the next two so the consensus as we said, we're not going to give guidance. Our goal is to meet or beat the expectations of wall Street and we're excited.
To approach the first quarter and give.
William P. Sheridan: There is a tremendous burden of treatment associated with injectables, and these patients want an oral treatment. In 2020, we discussed our plan for dose selection and design considerations for future studies with both U.S. and European regulators. This selection for BCX9930 is based on precedent for PK-PD modeling and responses in PNA.
And give you a first full quarter and the next earnings call. So.
That answer and you want to take the gross to net and yes, absolutely Hi, Jeff.
As far as growth to net goes.
First of all just a reminder for everyone that oral a day with the lowest whack price in the market and we kind of we expect growth to net to change over time as I said in my remarks early on and we're using the quick start program and we're getting patients on therapy via medical exception, primarily and so we expect this.
The gross to net to evolve in the year as we get more policies out there. So we're being conservative in how we look at gross to net per year, one and we encourage other people to to be conservative and your estimates for year one.
Anthony J. Doyle: With completion of this TNH study, we will have the information we need to choose the dose for accelerated advanced development programs across all indications, and we believe we will be ready to move straight from Phase I to pivotal trials in TNH. With the upcoming data readout, we will be ready to finalize our study plans and start pivotal trials in CNH and proof-in-concept trials in selected nephritis indications later this year. We will announce the details of those trials as we start them.
As far as coverage as I mentioned, we're starting to have some early successes with plans, putting oil and <unk> onto policy and we're getting very good feedback from payers in terms of the value proposition of oil a day.
And understanding.
And the patient demand for <unk>. So we're really expecting coverage to accelerate this quarter, it's going to be a year long process for some payers. So it will continue to evolve, but we expect to make a lot of progress and the next quarter.
And Charlie the other thing you might want to just mentioned is in the interim while we're working through negotiating for policy. What what are we able to do to get paid yes. So absolutely. So the first one.
Anthony J. Doyle: A strong balance sheet allows us to fully invest in this program. We're very excited by the progress we've made in 2020 and the terrific opportunity we have in 2021 to bring an oral monotherapy closer to approval for seriously ill patients with complement-mediated disease. I now hand the call over to Anthony. Thanks, Bill. What a difference a year makes.
Thing, we're trying to do is make sure that patients get right on therapy right away and then we're working through medical exception processes with with payers and we've had some early success with that.
It's a more labor intensive process, but it's one that.
And we're working closely with physicians and patients on and so thats working from any patients and we get more leverage just the more we fill the funnel with new starts. So that's that's a primary focus of Charlie's team.
Great. Thank you and welcome.
Your next question comes from the line of Brian Chin with Bank of America.
Anthony J. Doyle: We ended 2019 with $138 million in cash, and we ended 2020 with $303 million, access to another $75 million, and upcoming Orladeo revenues from the US, Japan, and Europe. The strengthening of our balance sheet, which takes us into 2023, allows us to focus on creating value for the company and shareholders by investing in areas that will provide maximum efficiency in return. The main areas that we are investing in continue to be supporting the launch of Orladeo globally and investing in the development of BCX9930 across multiple indications, while, of course, making sure that we have the infrastructure in place to support the pace of progress that we expect. As the CFO, it's also nice to have significant financial flexibility and levers to pull as we move forward.
Hi team. Thanks for taking my question this morning.
My first question is and I'll, let al can you give me and update on the rate of conversion from your EAP and extension study to the commercial truck.
And when do you expect the conversion to <unk>.
To come to Chipotle.
Totally complete based on what Youre seeing so far and I have and follow up.
Sure. Brian This is Charlie I'll take I'll take that question. So the conversion is just about complete at this point, we set out to make that conversion this quarter and we're really ramping that up at this point and as I mentioned in my remarks, we're seeing the great majority of patients who are on the two clinical trials plus our EAP.
Deciding to continue on and Orlando.
The commercial world and Charlie Theres, two steps and that process right. There is converting them to commercial drug and then there is they have to go through the same prior authorization and the insurance that's right. That's right. So what we what we worked with the.
The clinical sites is getting the the start forms for patients and then they go through the prior authorization and some of those patients just like the brand new ones will go on quick start and then as I just mentioned.
We're working through medical exceptions, and ultimately policies for those patients, but we're really encouraged with the progress on the clinical conversions.
Okay, great. So maybe just one more on 90 930, so it will be getting data.
And with patients getting the high dose at 400 500 for at least next week next month.
Can you remind us that the trial allows you not acquit responders to <unk> five and <unk> 90, 930, as an add on and therapy.
Anthony J. Doyle: As the launch for Lidale continues to progress, we can make strategic and financial adjustments that correlate with the pace of the revenues that are being generated. Our investment in Factor D also continues to evolve, and our continuing desire is to move quickly and broadly with the investment in this program's development. As I noted, we will also have the option, if we need it, to draw down the additional $75 million from our existing credit facility with Ethereum.
And their potential philosophy that you have backup patient weaning down <unk> five while they're on nine 930. Thank you.
Bill do you want to take that one.
Sure.
Hi, Good morning, Thanks for the question, Yes, the protocol does allow.
With patient two and inadequate responders and the C five inhibitor withdrawn.
So we'd like to see everything would be stable can take quite a while for the hemoglobin to plateau out for example.
It takes a long time for the bone marrow to get to a new steady state.
And each individual will be that opportunity.
It's too soon and the study.
Anthony J. Doyle: And as we showed with the financing that we announced in December, we have future opportunities to access capital with our growing portfolio of assets. Because of these many variables, we are not providing specific revenue or operating expense guidance during the launch period for Orladeo.
To see that day.
And yet and it's possible we might have done quite a lot and later this year.
And it's a great question, Brian because again the goal is mono therapy, as Bill said and as a.
<unk> prepared remarks.
Great Alright, great. Thank you so much for.
The answers are looking forward to that data readout.
Alright.
Your next question comes from the line of Gena Wang with Barclays.
Operator: But based on our expectations for revenue, operating expenses, and our option to access the additional $75 million, we believe our current cash runway takes us into 2023. This position of financial strength allows us to focus on execution, to focus on value creation, and not on near-term cash needs. That's a new and exciting space for BioCryst. BioCryst is transforming, and so too is our value proposition. We are a commercial-stage rare disease company, and Orladeo will generate meaningful revenue across multiple regions.
Hi, This is David Farr for Gena so.
I have a couple of questions. The first one is on the <unk> net.
Two zero asset.
So it seems to me that all 60 patients and treat it is there any new cases of a rash and that's been observed and Ah.
Can you just give us some additional thoughts around the mechanisms of the downside rash.
Bill do you want to take share.
Sure.
So as we noted last year.
Had some cases, Inc.
And consequential ranch and.
These events disappear.
The 699 liquidity treatments continued consecutive doses increase on day 15 per the protocol and stable.
Operator: With BCX9930, the development team is working on a drug that has huge potential across multiple indications. The team in Birmingham continues to discover our next generation of medicines for rare diseases. And we are now in a strong financial position to invest in driving value creation across all of these areas. That's it for prepared remarks. We'll now open it up for your questions. To ask a question, press followed by the number one on your telephone keypad. To withdraw your question, press the pound key.
We'll update that.
At the R&D day call.
And the new data coming up.
It hasnt been an issue and with regard to and mechanism.
<unk>.
If you look in the literature and we.
<unk> done extensive consulting actually that started way back in and <unk> development program and we saw a few similar cases.
And so when you actually work these things out.
Fine.
Sure.
Exactly what can make it a day.
So we don't expect that we will rule.
And.
Operator: Please stand by while we compile the Q&A. Your first question comes from the line of Jessica Fye with J.P. Morgan. Hey, guys. Good morning.
Laboratory.
Right.
Litigation.
And capital mechanism exactly that almost never happens.
But the main point is it's benign it goes away and you can keep dosing up so and our view its really non consequential.
Jessica Macomber Fye: Hope all's well. I had a few financial questions. First, on Bloomberg's Orladeo consensus for this year is around $35 million.
Right.
Yeah, that's very helpful.
Another question is around and your Registrational trial for non <unk>, III zero and I understand that you're not going to share. Some additional color on the R&D day I was wondering if you can share some initial thoughts around the execution and trial would likely be a single arm trial or do you need to have.
Jessica Macomber Fye: Second, how should we think about growth channels in the early part of the launch? And could that evolve as you get coverage ramped up? And third, where does formulary coverage stand now? What's your goal for coverage, and when do you expect to achieve it?
Have a.
Arm with C five inhibitor.
And non inferiority or superiority.
Bill you might want to just focus on what's the goal of the label that we're shooting for.
The drug and then that can help give them a central and what we need to study.
Sure.
Charles K. Gayer: All right. Thanks, Jess. I'll take the first one, and Charlie, you can take the next two.
Just to clarify one thing at the R&D day, I won't be going into designs and future studies, when we stopped but it will.
But we'll talk about that later this year.
Charles K. Gayer: So the consensus, as we said, we're not gonna give guidance. Our goal is to meet or beat the expectations of Wall Street. And we're excited to approach the first quarter and give you the first full quarter on the next earnings call. So that's that answer. And you wanna take the gross to net? Yeah, absolutely. Hi Jeff.
At the R&D day, we will go over the data from the ongoing study, which we're very excited about.
To share with you and the goal per treatment here is to make oral drug available for every patient with <unk> as a monotherapy. So that means that we will probably have to be more than one study because there are people who are not currently on <unk> inhibitors from.
Various reasons and there are people who are currently don't see volume inhibitors from.
From a not.
Charles K. Gayer: So as far as gross to net goes, first of all, just a reminder for everyone that Orladeo is the lowest black price in the market, and we expect gross to net to change over time. As I said in my remarks early on, we're using the quick start program, and we're getting patients on therapy via medical exception primarily. And so we expect this gross to net to evolve in the year as we get more policies out there. So we're being conservative in how we look at gross to net for year one.
And not doing so well and having inadequate responses and some of them are doing okay.
But and oral drug has.
Full attraction and we'd like to be able to cover all the bases.
You can have a look at.
Other sponsors.
Studies that are published and there is a history of controlled clinical trials and the field I think.
And that would give you some guidance as to where the standard zone.
I think the most exciting part is we're going from a phase one study and the pivotal and bill and his team have done a fantastic job of being creative and and getting us to accelerate that's going fast.
Alright, thank you for the color.
And welcome.
Your next question comes from the line of Brian Abrahams with RBC capital markets.
Great. Thanks for taking my questions and Steve on for Brian.
Those early there is and the rollout can you share whether or what their uptake is even across the burden with mild and severe patients equally represented there and maybe breakdown and with our new patients are coming from general practitioners and specialists.
Charles K. Gayer: And we encourage other people to be conservative in your estimates for year one. As far as coverage goes, as I mentioned, we're starting to have some early successes with plans putting Orladeo on the market. And we're getting very good feedback from payers in terms of the value proposition of Orladeo and understanding patient demand for Orladeo. So we're really expecting coverage to accelerate this quarter. It's going to be a year-long process for some payers, so it'll continue to evolve, but we expect to make a lot of progress in the next quarter. And Charlie, the other thing you might want to just mention is, you know, in the interim, while we're working through negotiating for policy, what are we able to do to get paid? Yeah, so absolutely.
Sure Hey, Steve as Charlie.
As I said in my <unk>.
Charles K. Gayer: So the first thing we're trying to do is make sure the patients get right on therapy right away, and then we're working through medical exception processes with payers. And we've had some early success with that.
Charles K. Gayer: It's a more labor-intensive process, but it's one that we're working closely with physicians and patients on. And so that's working for many patients. And we get more leverage just the more we fill the funnel with new starts. So that's a primary focus of Charlie's team. Great, thank you.
And you are not in an airplane and so diving deeper and the list I mean, it's Charlie says the initial part of the launch is focused on the high prescribers, but we can work our way through the list over time and and doing it remotely are virtually is real.
A real plus.
Thanks.
You're welcome.
As a reminder to ask a question that star one on your telephone.
Charles K. Gayer: Your next question comes from the line of Ryan Chang with Bank of America. Hi team, thanks for taking my questions this morning. My first question is on Orladeo. Can you give me an update on the rate of conversion from your EAP and extension studies to the commercial drug? When do you expect the conversion to fully complete based on what you're seeing so far? And I have one follow-up question. Sure, Brian. This is Charlie.
And your next question comes from the lineup Laurie right Cross with Jeffries.
Hi, good morning, everyone. Congrats on the progress and and thanks for taking my questions.
My first question was on a 90 990 930 data.
And with your R&D day, I guess, how should we think about hemoglobin variability and the bar per success on hemoglobin measures for the naive and experienced patient populations.
So you want to take that true.
Sure.
Right.
Charles K. Gayer: I'll take that question. So the conversion is just about complete at this point. We set out to make that conversion this quarter, and we're really wrapping that up at this point.
Just and question.
And the.
Leading a physician to treat <unk> patients.
Charles K. Gayer: And as I mentioned in my remarks, we're seeing the great majority of patients who are on the two clinical trials plus our EAP deciding to continue on Orladeo in the commercial world. And Charlie, there are two steps in that process, right? There's converting them to a commercial drug, and then they have to go through the same prior authorization and insurance. That's right.
To think about.
What are the goals of treatment and that your introduction approximal compliment and keep it simple.
Clinical research and there's a lot of publication on that that talks about grades and.
<unk>, sorry, and Ah controlling the transfusions, and having people and not be dependent on transfusions, as a <unk> and <unk>.
Do that and you need to stabilize the hemoglobin and and.
Clearly better for people with their name year is relieved and <unk>.
Charles K. Gayer: So what we worked with the clinical sites on was getting the start forms for patients, and then they went through prior authorization. Some of those patients, just like the brand new ones, will go on Quick Start. And then, as I just mentioned, we're working through medical exceptions and ultimately policies for those patients. But we're really encouraged with the progress on the clinical conversion. Okay, great. So maybe just one more on 9930.
And please so I think the controlling transfusions and having the hemoglobin go up in that and that publication really publication.
Good start up and that there.
Various metrics included the hemoglobin, including I'd Cramps, 10 grams, and 12 grams per deciliter. So I don't think there's a single magic number and stuff you know the Gulf here and control, the transfusions, and and and prove the anemia and improve distinct cause of the day.
Got it Okay. That's helpful in and then and clinical trials Dot Gov be estimated enrollment per P. And age was relatively hi, just wondering if you could provide any insight into the enrollment right for this study and remind non rationale for why you didn't add more sites for this.
Ryan Arnold: So as we'll be getting data with patients getting the high dose at 400 and 500 for at least six weeks next month, can you remind us if the trial allows inadequate responders to wean off C5 since you're using 9930 as an add-on? Is there potential for us to see the effect of patients weaning down C5 while they're on 9930? Bill, do you want to take that one?
Graduate High school and.
So we so.
No. This was innovative design that included.
S P and H patient you know studies, one first and human studies with healthy subjects single us and he does healthy subjects multiple that sending goes and part three to study redesigned and incredibly flexible way because you know when we started we didn't know how many subjects, we would need to complete those French and so what we did day.
It was had potential from multiple cohort starting at different doses like.
William P. Sheridan: Sure. Good morning. Thanks for the question. Yes, the protocol does allow patients who are inadequate responders to have the C5 inhibitor withdrawn. So we'd like to see everything be stable. You know, it can take quite a while for the hemoglobin to plateau out, for example. It takes a long time for the bone marrow to get to a new steady state.
We worked out along the way and we wanted to also to study and number of patients with C. Five and headache inhibitor inadequate response history, and and number with no no history of and they're having a safe to say five and pick it up.
For that flexibility was basically.
There wasn't a particular number and so we had in mind and you know we and we had enough you know in the trial design that you had a good envelope and we needed you know we needed and no more than 16 to get our objectives.
Yeah that that piece is really important and we always put numbers. So we don't have to add amendments to increase the study size 16 was plenty to figure out the dose and the other thing is it's a rare disease. So you don't you can't use these patients and the next study so if you're over enroll and early studies you have a more challenging recruiting for the later studies.
William P. Sheridan: So in each individual, there'll be that opportunity. It's too early in the study to see the data yet, and it's possible we might have that data later this year. And it's a great question, Brian, because, again, the goal is monotherapy, as Bill said in his prepared remarks. Great. Yeah, I agree. Thank you so much for the answers.
Got it that makes sense.
And maybe last quick question too you've talked about providing clarity on additional indications to pursue with 90 930 that you could move directly and to face too with and it sounds like we can learn more about their secure R&D day I guess just clarifying if that's the case if we should expect an update on that and then can you say if you've already reached from alignment with <unk>.
Ryan Arnold: Looking forward to the data readout. Your next question comes from the line of Gina Wang with Barclays. Hi, this is David speaking on behalf of Gina.
<unk> I'm moving directly into base twos.
Bill you Wanna take that.
Sure on the first question with regard to the.
Unknown Executive: So, I have a couple of questions. The first one is on the BPNH-9930 asset. So, it seems to be that all 16 patients are being treated. Are there any new cases of rash that's being observed? And can you give us some additional thoughts around the mechanisms of the onset of rash?
And the products and vacations and other indications Darren day day, we will go out with a field and how exciting it is and what the opportunities My day, we might be specify exactly what we're including you know and the card of studies and two we stop and because we've seen that's.
And that's very competitive and.
And and they don't Wanna advertise exactly what we're doing before it's absolutely necessary uhm.
William P. Sheridan: Joe, do you want to take that? Sure. So, as we noted last year, we've had some cases of inconsequential rash, and these events disappear as BCX9930 treatment is continued, in fact, even as the dose is increased on day 15 for the protocol. So, we'll update that at the R&D day call with the new data cut that's coming up. It hasn't been an issue. And with regard to the mechanism of action, you know, if you look in the literature, and we've done extensive consulting, actually, this started way back in the Barrett Health State Development Program, and we saw a few similar cases.
Uhm with regard to the second question on interactions with regulators, we had very good interaction with last year.
And the two key topics with how do we take a dose for pivotal trials and.
And that's based on P. K P D modeling and we've got a lot and and on that and.
And the second was just general design considerations around a pivotal studies and moving directly from the first one goes range I think the pivotal studies and we got a line that around those general considerations, Sir we need to finalize that designs wrap that up and being later this year will be in a position to stop.
This is another efficiency maury it in terms of being able to do a dose range and study and teenage patients and phase one and then have the Dallas to be able to go into other indications at that really accelerates a program.
William P. Sheridan: It's seldom that you actually work these things out for these benign rashes exactly what the mechanism is. So we don't expect that we'll, you know, that we'll have, you know, laboratory, you know, investigations that work out the mechanism exactly. That almost never happens.
And that's spelled K point, right, Sir and check the day.
Is not the targeted pocket book mutation and any of these diseases and.
There's a whole range and different things can happen that disturbed the complex system and activate the alternative pathway all the way from.
William P. Sheridan: But the main point is it's benign, it goes away, and you can keep dosing up. So in our view, it's really non-consequential. Yeah, that's really helpful. So another question is around your registrational trial for 9930. I understand that you're probably going to share some additional color on R&D day. I'm just wondering if you could share some initial thoughts around the registration trial.
Pigging mutations and pier 19, barnburner stem cells.
Jim one sector, right and mutations and so on so none of those or mutations affected do so effective day is just happens to be the and.
Amazon and that's that's the alternative Parkway and that does the trick is adequate to think if it's back to day and T and H E. The goldfish adequate drink and affected the and everything else.
William P. Sheridan: Would it likely be a single-arm trial, or do you need to have an arm with a C5 inhibitor to show non-inferiority or superiority? Hey, Bill, you might want to just focus on what the goal of the label is that we're shooting for with the drug, and then that can help give them a sense of what we need to study. Transcribed by https://otter.ai. On R&D Day, we'll go over the data from the ongoing study, which we're very excited about sharing with you.
Got it. Thank you very much for the perspective and congrats again.
Thanks Marsh.
At this time and no further questions and I will now trying to call and over to Mister Stonehouse for concluding remarks.
So first off let me again, thank you for joining US. This is a really exciting time at Biocryst and so we look forward first off to be sharing the 90 930 phase one dose ranging data with you at our R&D day on March 22nd and we also look forward to sharing the first full quarter of or.
William P. Sheridan: And the goal for treatment here is to make our oral drug available for every patient with PNH as monotherapy. So that means that we'll probably have to do more than one study because, you know, there are people who are not currently on C5 inhibitors for various reasons, and there are people who are currently on C5 inhibitors. Some of them are not doing so well and having inadequate responses, and some of them are doing okay. But, you know, oral drugs have a powerful attraction.
And the day of sales at our next earnings call. So as I said before the transformation and this company is happening now and we hope that we've gotten your interest and if you'd like to reach out to us we're happy to connect with you in the meantime, so thanks again and have a great day.
This concludes today's conference call. Thank you for participating and you may now disconnect.
[music].
Jon P. Stonehouse: So we'd like to be able to cover all the bases. You can have a look at other sponsors' studies that are published, and there is a history of controlled clinical trials in that field, I think, that would give you some guidance as to where the standards are. I think the most exciting part is we're going from a Phase I study into Pivotals, and Bill and his team have done a fantastic job of being creative and getting us to accelerate. That's going fast.
Jon P. Stonehouse: Thank you for the call. Your next question comes from the line of Brian Abrahams with RBC Capital Markets. Great, thanks for taking my question. This is Steve on behalf of Brian.
Brian Corey Abrahams: Though it's early days in the rollout, can you share whether Orladeo uptake is even across severity, with mild and severe patients equally represented there? And any breakdown on whether new patients are coming from general practitioners or specialists? Thanks. Sure. Hey, Stavis, Charlie.
Charles K. Gayer: You know, as I said in my prepared remarks, we're really pleased with the breakdown of patients thus far. We're getting an equal split with people switching from injectable prosis and those who are treated with acute-only and then coming over to profi for the first time now that Orladeo's available. You know, as far as the profi switches are concerned, we can't comment specifically on the severity of those. They were on profi already, so they're pretty severe.
Charles K. Gayer: But what our clinical data shows is that regardless of background therapy, regardless of treatment rate, patients across the board do well on Orladeo. And then his second question was whether prescribing is a GP specialty. Yeah, I mean, at this point, this is predominantly a market that's treated by allergists and immunologists. And we know where those doctors are, and we're really excited because we're moving well beyond the group that did our clinical trials.
Charles K. Gayer: And we're seeing real uptake in a broadening base of those specialists. Eventually, we'll get some GPs and others too, but right now, we're focusing on the big top treaters. Yeah, your question is a good one. And one of the benefits of COVID is the fact that you're not behind a steering wheel driving to the next clinic or you're not on an airplane.
Jon P. Stonehouse: And so diving deeper into lists, I mean, as Charlie says, the initial part of the launch is focused on the biggest prescribers, but we can work our way through the list over time, and doing it remotely or virtually is a real plus. As a reminder, to ask a question, press star 1 on your telephone. And your next question comes from the line of Maurice Raycroft with Jeffrey. Hi, good morning, everyone.
Maurice Thomas Raycroft: Congratulations on the progress, and thanks for taking my questions. My first question was on 9930 data. It's your R&D day. I guess, how should we think about hemoglobin variability and the bar for success on hemoglobin measures for the naive and experienced patient population? Bill, you want to take that? Sure. Hi, Murray. Interesting question.
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William P. Sheridan: The leading physicians who treat PNH patients have started to think about what the goals of treatment are in the era of the introduction of proximal complement inhibitors into clinical research. And there's a nice publication on that that talks about grades of benefits. So controlling the transfusions and having people not be dependent on transfusions is a big goal. And to do that, you need to stabilize hemoglobin. And it's clearly better for people if their anemia is relieved, and their fatigue improves.
William P. Sheridan: So I think that controlling transfusions and having the hemoglobin go up in that publication, early publication as a thought startup, there were various metrics included for hemoglobin, including 8 grams, 10 grams, and 12 grams per deciliter. So I don't think there is a single magic number that is the answer.
William P. Sheridan: The goals here are to control the transfusions and improve the anemia and improve the symptoms of the disease. Got it. Okay, that's helpful.
William P. Sheridan: And then on clinicaltrials.gov, the estimated enrollment for P&H was relatively high. Just wondering if you can provide any insight into the enrollment rate for this study and remind me of the rationale for why you didn't add more sites for this study for our first one. So we,
William P. Sheridan: This was an innovative design that included PNH patients in a phase one first-in-human study. We started off with healthy subjects, single SNE dose; healthy subjects, multiple SNE doses, and part three of the study was designed in an incredibly flexible way because when we started, we didn't know how many subjects we would need to complete those rates. So what we did there was have the potential for multiple cohorts starting at different doses that we worked out along the way, and we wanted also to study a number of patients with C5 inhibitor inadequate response history and a number with no history of ever having received a C5 inhibitor.
William P. Sheridan: So that flexibility was basically, you know, there wasn't a particular number that we had in mind. We had enough in the trial design that we had a good envelope, and we needed no more than 16 to hit our objectives. Yeah, that piece is really important. We always put numbers in so we don't have to add amendments to increase the study size.
William P. Sheridan: 16 was plenty to figure out the dose. And the other thing is, it's a rare disease, so you can't use these patients in the next study. So if you overenroll in early studies, you have a more challenging time recruiting for later studies.
Maurice Thomas Raycroft: And maybe last quick question. So you've talked about providing clarity on additional indications to pursue with 9930 that you could move directly into phase 2. And it sounds like we could learn more about this at your R&D day. I guess just clarifying if that's the case, if we should expect an update on that. And then can you say if you've already reached some alignment with regulators on moving directly into phase 2? Bill, do you want to take that?
William P. Sheridan: Sure. On the first question with regard to the nephritis indications and other indications, at the R&D day, we will go over the field and how exciting it is and what the opportunities might be. We won't be specifying exactly what we're including in our nephritis studies until we start them because we've seen these very competitive fields and don't want to advertise exactly what we're doing before it's absolutely necessary.
William P. Sheridan: With regard to the second question on interactions with regulators, we had very good interactions last year, and the two key topics were how we pick a dose for pivotal trials, and that's based on PK-PD modeling, and we got alignment on that. And the second was just general design considerations around pivotal studies and moving directly from phase one dose ranging into pivotal studies, and we got alignment on those general considerations.
William P. Sheridan: So, we need to finalize that design, wrap that up, and then later this year we'll be in a position to start. This is another efficiency, Maury, in terms of being able to do a dose-ranging study in PNH patients in phase one, and then have the dose to be able to go into other indications. That really accelerates the program. Let's talk about a key point, Brian. So, Sector D is not the target of mutation in any of these diseases, you know; a whole range of different things can happen that disturb the complement system and activate the alternative pathway all the way from.
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William P. Sheridan: Pigot mutations in P and H in bone marrow stem cells to germline factor H mutations and so on. So none of those are mutations in Factor D. So Factor D just happens to be the enzyme that starts the alternative pathway, and the dose that is adequate to inhibit Factor D in P and H is the dose that's adequate to inhibit Factor D in everything else.
Maurice Thomas Raycroft: Got it. Thank you very much for the perspective, and congratulations again. Thanks, Maurice. At this time, there are no further questions, and I will now turn the call over to Mr. Stonehouse for his concluding remarks.
Jon P. Stonehouse: So first off, let me again thank you for joining us. This is a really exciting time at BioCryst. And so we look forward, first off, to be sharing the 9930 phase one dose ranging data with you at our R&D day on March 22nd. And we also look forward to sharing the first full quarter of Orladeo sales with you on our next earnings call. So, as I said before, the transformation in this company is happening now.
Jon P. Stonehouse: And we hope that we've peaked your interest. And if you'd like to reach out to us, we're happy to connect with you in the meantime. So thanks again, and have a great day. This concludes today's conference call. Thank you for participating, and you may now disconnect.
Operator: Tazeen Ahmad, Brian Abrahams, Jon Stonehouse, William Sheridan, Liisa Bayko, Jonathan Wolleben, Charles Gayer, Franois Brisebois, Ryan Arnold, BioCryst Pharmaceuticals Inc, © The Bulletproof Executive 2013, Thanks for watching!. .. © The Bulletproof Executive 2013, © The Ultimate Parody Site! , , , , , [inaudible] ?? ?? ?? [inaudible] Unknown Executive, Huidong Wang, Stacy Ku, Ryan Arnold, BioCryst Pharmaceuticals Inc, Tazeen Ahmad, Brian Abrahams, Jon Stonehouse, William Sheridan, Liisa Bayko, Jonathan Wolleben, Charles Gayer, Helen Thackray, Anthony Doyle, Brian Arnold, BioCryst Pharmaceuticals Inc
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