BioCryst Pharmaceuticals (BCRX) Q4 2020 Earnings Call Transcript

BioCryst Pharmaceuticals (BCRX -1.19%)
Q4 2020 Earnings Call
Feb 25, 2021, 8:30 a.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

Operator

Ladies and gentlemen, thank you for standing by, and welcome to the BioCryst fourth-quarter 2020 earnings call. [Operator instructions] Please be advised at today's conference is being recorded. [Operator instructions] I would now like to hand the conference over to your speaker today, Mr. John Bluth, with BioCryst.

You may begin.

John Bluth -- Senior Vice President, Investor Relations and Corporate Communications

Thanks, Daphne. 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 Sniecinski, 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 on audited and forward-looking financial information, as well as the company's future performance and/or 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 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.

Jon Stonehouse -- Chief Executive Officer

Thanks, John. 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. 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 PNH.

We've built an exceptional drug discovery platform to go after challenging targets like kallikrein inhibitors, Factor D inhibitors, and L2 inhibitors so that we can take this great science, get drug approvals, and finally to the market to put an end to the patients waiting. The approval of ORLADEYO in the US 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 in the US 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 ORLADEYO can have a big impact as the first approved treatment for preventing attacks. We believe ORLADEYO has the potential to generate north of $500 million in global peak sales. 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 US.

We also have an increasing body of evidence that we can repeat the success in complement-mediated diseases with our oral Factor D inhibitor. Last year, we shared proof of concept data for PNH patients treated with BCX9930. Bill will update you on the progress of the study and what to expect when we announced 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 we plan to go after many complement-mediated rare diseases.

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 allows us to put our head down to successfully launch ORLADEYO around the world and rapidly advance our pipeline. So this transformation is no longer aspirational.

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. Charlie?

Charlie Gayer -- Chief Commercial Officer

Thanks, Jon. We invested early to be ready for a fast launch to get patients on therapy quickly and to secure reimbursement access for ORLADEYO. What we're seeing so far is very encouraging. We are ramping up clinical trial conversions and the great majority of these patients are choosing to continue with ORLADEYO.

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 ORLADEYO 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 ORLADEYO from injectable prophy products as those starting prophy on ORLADEYO after previously treating their HAE with only acute medications. This is right in line with our strategy because we believe ORLADEYO offers significant and sustained attack reduction with a reduced burden of treatment regardless of the patient's background therapy or attack rate.

More early evidence that we're off to a good start in addressing the strong pent-up demand is that HAE treaters are embracing ORLADEYO. We have significantly expanded the prescriber base beyond those involved in the APeX clinical trials. Once patients decide to switch to ORLADEYO, our EMPOWER patient services team works with them to get started on product right away. 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, but our market access team is making significant progress as payers see the strong demand from patients. Payers are starting to add ORLADEYO 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. Face-to-face meetings with customers had been limited in many areas of the country, but physicians have been receptive to Zoom calls because they want to learn about ORLADEYO.

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. For example, over 200 patients attended two virtual events earlier this month. We also see the physicians and their patients are communicating via telemedicine when in-person visits are not possible, and many physicians have been comfortable prescribing ORLADEYO remotely because starting an oral medicine does not require training.

Our US launch is off to a strong start in meeting the pent-up demand from patients and HAE treaters. 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 lack of options, so we have a great opportunity to grow the prophy market with ORLADEYO. Just as we did in the US, 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 Megan to provide more color on how we are starting to change the HAE treatment paradigm and to describe launch preparations in Japan.

Megan Sniecinski -- Chief Business Officer

Thanks, Charlie. 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 ORLADEYO. 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 three per month to one per month sustained over time and the attack-free periods many patients are experiencing in our longer-term safety study. We continue to generate additional supportive data including what we'll share at AAAAI which starts tomorrow. We'll 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 ORLADEYO including from patients who've been on other prophies before.

Our medical strategy is also focused on the shift toward individualized treatment plans that best meet the needs of patients with respect to reducing both disease and treatment burden. The recent publication from Dr. Banerji 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 resonating.

Physicians acknowledge injection fatigue and needle phobia is real. Breakthrough attacks still occur on other prophies 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.

Our work is helping physicians see how ORLADEYO 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 prophy 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 ORLADEYO historic milestone as the first approved prophy therapy in Japan.

We chose Torii, our commercial partner, given their performance in building the HIV market. They've 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. With ORLADEYO, Torii has the opportunity to apply their past experience to build the prophylactic market driving patient identification and prophy adoption similar to what we've seen in the US over the last decade with the introductions of new HAE therapies.

With approval, Torii's medical representatives are now able to meet with physicians. They're hearing interest and excitement from physicians who see ORLADEYO as a major advancement in care for their patients. Our any type pricing discussions are in progress and we expect to complete them in early Q2 after price listing doctors can begin prescribing and Torii's 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 in Torii's 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.

Bill Sheridan -- Chief Medical Officer

Thanks, Megan, and good morning, everyone. 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 in development of 9930 is very clear, to bring forward an oral monotherapy complement inhibitor treatment to both PNH and additional rare, serious, and potentially life-threatening diseases driven by the alternative pathway.

Inhibiting Factor D in PNH is important for patients no matter their prior experience with C5 inhibitors. So our goals with clinical program is to support a label for monotherapy treatment in all PNH patients. This means PNH 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 with doses escalated through 400 milligrams twice a day.

This data showed that controlled hemolysis was dose related and that the safety profile was excellent. We have since completed enrollment in the study with a total of 16 PNH patients, 10 with treatment-naive to receive 9930 as monotherapy, and six for patients with inadequate responses to C5 inhibitors who received 9930 in addition to their C5 inhibitor treatment. In our upcoming R&D day, we look forward to sharing the results of the complete Phase 1 dose-ranging trial with PNH. This is what we plan to have in the data readout.

First, we will have data from all 16 PNH patients, the 10 C5 inhibitor-naive, and six C5 inhibitor inadequate responders through at least six weeks of treatment at either 400 milligrams or 500 milligrams BID. And the range of both clinical outcomes and laboratory outcomes including, for example, hemoglobin transfusions, reticulocytes, PNH granulocytes, and LDH, and safety data from dosing for up to 48 weeks. At the R&D Day, we will also share new market research with you from PNH patients. What you'll see will feel very familiar as the insights are very similar to what we saw in HAE patients. There's a tremendous burden of treatment associated with injectables and these patients want an oral treatment.

In 2020, we discussed that plan for dose selection and design considerations for future studies with both US and European regulators. This selection to BCX9930 is based on precedent for PKPD modeling and responses in PNH. With completion of this PNH 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 1 to pivotal trials in PNH. With the upcoming data readout, we will be ready to finalize our study plans and start pivotal trials in PNH and proof of concept trials and selected nephrotic indications later this year calling out the details of those trials as we start them.

Our strong balance sheet allows us to fully invest in this program. We are very excited by the progress we made in 2020 and the terrific opportunity we have in 2021 to bring an oral monotherapy closer to approval for serious renal patients with complement-mediated diseases. I'll now hand the call over to Anthony.

Anthony Doyle -- Chief Financial Officer

Thanks, Bill. What a difference a year makes. We ended 2019 with 138 million of cash and we ended 2020 with 303 million, access to another 75 million and upcoming ORLADEYO 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 and return.

The main areas that we are investing in continue to be supporting the launch of ORLADEYO 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 flexibilities and leverage to pull as we move forward. As the launch of ORLADEYO 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 to move quickly and broadly with the investment in this program's development.

As I noted, we will also have the option if we needed to draw down the additional 75 million from our existing credit facility with Athyrium. 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 in the launch period for ORLADEYO. 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 but for new and exciting spot for BioCryst. BioCryst is transforming and so too is our value proposition. We are a commercial-stage rare disease company and ORLADEYO will generate meaningful revenue across multiple regions. 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 our prepared remarks. We'll now open it up for your questions.

Questions & Answers:

Operator

OK. [Operator instructions] Your first question comes from the line of Jessica Fye with J.P. Morgan.

Jessica Fye -- J.P. Morgan -- Analyst

Hey, guys. Good morning. Hope all's well. I had a few financial questions.

First, on Bloomberg. ORLADEYO's consensus for this year is around 35 million. Are you comfortable with that number? Second, how should we think about gross to net 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?

Jon Stonehouse -- Chief Executive Officer

All right. 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, give you a first full quarter in the next earnings call. So that's that answer, and you want to take the gross to net?

Charlie Gayer -- Chief Commercial Officer

Yeah. Absolutely. Hi, Jess. So as far as gross to net goes, first of all, just a reminder for everyone that ORLADEYO is the lowest flat price in the market and we kind of -- 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 to -- 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 for year one and we encourage other people to be conservative in your estimates for year one. As far as coverage, as I mentioned, we're starting to have some early successes with plans putting ORLADEYO onto policy and we're getting very good feedback from payers in terms of the value proposition of ORLADEYO and understanding the patient demand for ORLADEYO.

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.

Jon Stonehouse -- Chief Executive Officer

And, Charlie, the other thing you might want to just mention is, in the interim, while we're working through negotiating for policy, what are we able to do to get paid?

Charlie Gayer -- Chief Commercial Officer

Yes. So -- absolutely. So the first 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 payers and we've had some early success with that.

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.

Jon Stonehouse -- Chief Executive Officer

And we get more leverage, Jess, the more we fill the funnel with new starts. So that's a primary focus of Charlie's team.

Jessica Fye -- J.P. Morgan -- Analyst

Great. Thank you.

Jon Stonehouse -- Chief Executive Officer

You're welcome.

Operator

Your next question comes from the line of Brian Cheng with Bank of America.

Brian Cheng -- Bank of America Merrill Lynch -- Analyst

Hi, team. Thanks for taking my question this morning. My first question is on ORLADEYO. 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 be fully complete based on what you're seeing so far? And I have one follow-up.

Charlie Gayer -- Chief Commercial Officer

Sure, Brian. This is Charlie. 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. 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 ORLADEYO in the commercial world.

Jon Stonehouse -- Chief Executive Officer

And, Charlie, there's two steps in that process. Right? There is converting them to commercial drug and then there's they have to go through the same prior authorization and the insurance.

Charlie Gayer -- Chief Commercial Officer

Yeah. That's right. That's right. So what we worked with, the clinical sites is getting the start forms for patients and then they go through the 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 conversions.

Brian Cheng -- Bank of America Merrill Lynch -- Analyst

OK. Great. So maybe just one more on 9930. So we'll be getting data with patients getting the high dose at 400 and 500 for at least next week, next month.

Can you remind us that the trial allows the inadequate responders to wean off C5s using the 9930 as an add-on. Is there a potential for us to see that your stack of patients winning down C5 while they're on 9930? Thank you.

Jon Stonehouse -- Chief Executive Officer

Bill, you want to take that one?

Bill Sheridan -- Chief Medical Officer

Sure. Good morning. Thanks for the question. Yes.

The protocol does allow the patients with inadequate responders to have the C5 inhibitor withdrawn. So we'd like to see everything be stable. It can take quite a while for the endoglin to plateau out, for example. It takes a long time for the bone marrow to get to a steady-state.

So in each individual, there'll be that opportunity. It's too soon in the study to see that yet, and it's possible we might have this later this year.

Jon Stonehouse -- Chief Executive Officer

And it's great question, Brian, because again the goal is monotherapy as Bill said in his prepared remarks.

Brian Cheng -- Bank of America Merrill Lynch -- Analyst

Correct. Yeah. I agree. Thank you so much for the answers.

I'm looking forward to the data readout.

Jon Stonehouse -- Chief Executive Officer

Great.

Operator

Your next question comes from the line of Gena Wang with Barclays.

David Dai -- Barclays -- Analyst

Hi. This is David for Gena. So I have a couple questions. The first one is on the PNH and the 9930 assets.

So it seems to me that all 16 patients have been treated. Is there any new cases on rash and that's being observed? And can you give us some additional thoughts around the mechanisms of the downside rash?

Jon Stonehouse -- Chief Executive Officer

Bill, you want to take that?

Bill Sheridan -- Chief Medical Officer

Sure. So the -- as we noted last year, we've had some cases of inconsequential rash and the -- these events disappear as BCX9930 treatments continue and in fact even if the dose is increased on day 15 of the protocol. So we'll update that at the R&D day call with the new data that's coming up, but it hasn't been an issue. And with regard to the mechanism of action, if you look in the literature and we've done extensive consulting -- actually, this started way back in the berotralstat development program when we saw a few similar cases.

It's seldom that you actually work these things out for these benign rashes. It's exactly what the mechanism is. So we don't expect that we'll have laboratory investigations that work out the mechanism exactly. That almost never happens.

Jon Stonehouse -- Chief Executive Officer

But the main point is it's benign, it goes away, and you can keep dosing up. So --

Bill Sheridan -- Chief Medical Officer

Yeah.

Jon Stonehouse -- Chief Executive Officer

In our view, it's really not inconsequential.

Bill Sheridan -- Chief Medical Officer

Yes. Yes.

David Dai -- Barclays -- Analyst

Yes. That's really helpful. So another question is around your restoration trial for 9930. I understand that you're probably going to share some additional color on the R&D day.

I'm just wondering if you can share some initial thoughts around the restoration trial. Would it likely be a single-arm trial? Or do you just have an arm with C5 inhibitor to show no inferiority or superiority?

Jon Stonehouse -- Chief Executive Officer

It -- 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 sense of what we need to study.

Bill Sheridan -- Chief Medical Officer

Sure. So just to clarify one thing. On -- at the R&D day, I won't be going into design of future studies when we start studies or -- we'll talk about that later this year. The R&D day will go over the data from the ongoing study which we're very excited about to share with you.

And the goal of treatment here is to make an oral drug available for every patient with PNH as a monotherapy. So that means that we'll probably have to be more than one study because 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 OK. But oral drug has a powerful attraction, 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's a history of controlled clinical trials in the field I think that would give you some guidance as to where the standards are.

Jon Stonehouse -- Chief Executive Officer

I think the most exciting part is we're going from a Phase 1 study into pivotal, and Bill and his team have done a fantastic job of being creative and getting us to accelerate. That's going fast.

David Dai -- Barclays -- Analyst

Great. Thanks for the color.

Bill Sheridan -- Chief Medical Officer

You're welcome.

Operator

Your next question comes from the line of Brian Abrahams with RBC Capital Markets.

Steve Daddeo -- RBC Capital Markets -- Analyst

Great. Thanks for taking my questions. This is Steve on for Brian. Those early days in the rollout, can you share whether ORLADEYO uptake is even across severity with mild and severe patients equally represented there? And any breakdown on where the new patients are coming from general practitioners or specialists? Thanks.

Charlie Gayer -- Chief Commercial Officer

Sure. Hey, Steve. It's Charlie. As I said in my prepared remarks, the -- we're really pleased with the breakdown of patients thus far.

We're getting an equal split with people coming from switching from injectable prophies and those who are treated with acute only and then coming over to prophies for the first time now that ORLADEYO's available. As far as the prophy switches, yeah, we can't comment specifically on the severity of those. They were on prophy already so they're pretty severe. But what our clinical data shows is that regardless of background therapy, regardless of treatment rate, patients across the board do well on ORLADEYO.

Jon Stonehouse -- Chief Executive Officer

And then a second question was the doc prescribing, is it GP or specialty?

Charlie Gayer -- Chief Commercial Officer

Yeah. At this point, this is predominantly a market that's treated by allergists, 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 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.

Jon Stonehouse -- Chief Executive Officer

Yes. 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 into the next clinic or you're not in an airplane. And so diving deeper in the list -- I mean, as Charlie said, the initial part of the launch is focused on the high prescribers, but we can work our way through the list over time, and doing it remotely or virtually is a real plus.

Steve Daddeo -- RBC Capital Markets -- Analyst

Thanks.

Jon Stonehouse -- Chief Executive Officer

You're welcome.

Operator

[Operator instructions] And your next question comes from the line of Maury Raycroft with Jefferies.

Maury Raycroft -- Jefferies -- Analyst

Hi, good morning, everyone. Congrats on the progress, and thanks for taking my questions. My first question was on 9930 data at your R&D day, I guess how should we think about hemoglobin variability and the bar for success on hemoglobin measures for the naïve and experienced patient populations?

Jon Stonehouse -- Chief Executive Officer

Bill, you want to take that?

Bill Sheridan -- Chief Medical Officer

Sure. Hi, Maury. Thank you. It's an interesting question.

The leading physician to treat PNH patients have started to think about what are the goals of treatment in the era of 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 the hemoglobin.

And it's clearly better for people if their anemia is relieved and their fatigue improves. So I think the -- controlling transfusions and having the hemoglobin go up in that publication, early publication is a good start-up. There are various metrics included for hemoglobin, including eight grams, 10 grams, and 12 grams per deciliter. So I don't think there is a single magic number, is the answer.

The goal here is to control the transfusions and improve the anemia and improve the symptoms of the disease.

Maury Raycroft -- Jefferies -- Analyst

Got it. OK. That's helpful. And then on clinicaltrials.gov, the estimated enrollment for PNH was relatively high.

Just wondering if you can provide any insight into the enrollment rate for this study and remind on rationale for why you didn't add more sites for this.

Bill Sheridan -- Chief Medical Officer

For our Phase 1, so -- now this was an innovative design that included PNH patients in our Phase 1 first-in-human study, which started off with healthy subjects, single-ascending dose, healthy subjects multiple-ascending dose. And part three, the study redesigned in an incredibly flexible way. Because when we started, we didn't know how many subjects we would need to complete dose ranges. So what we did there was have 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 a C5 inhibitor.

So that flexibility was basically -- 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.

Jon Stonehouse -- Chief Executive Officer

Yes. That piece is really important. We always put numbers so we don't have to add amendments to increase the study size. Sixteen 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 in the next study. So if you over-enroll in early studies, you have a more challenge in recruiting for the later studies.

Maury Raycroft -- Jefferies -- Analyst

Got it. That makes sense. 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 with, 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? I'm moving directly into Phase 2s.

Jon Stonehouse -- Chief Executive Officer

Bill, you want to take that?

Bill Sheridan -- Chief Medical Officer

Sure. On the first question with regard to the products 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 very competitive figures and don't advertise exactly what we're doing before it's absolutely necessary. With regard to the second question on interactions with regulators, we had very good interactions last year.

And the two key topics were how do we pick a dose for pivotal trials, and that's based on PKPD modeling, and we've got alignment on that. And the second was just general design considerations around pivotal studies and moving directly from the Phase 1 dose ranges into pivotal studies in we've got alignment around those general considerations. So we need to finalize that design, wrap that up, and then later this year we'll be in a position to start.

Jon Stonehouse -- Chief Executive Officer

This is another efficiency, Maury, in terms of being able to do a dose-ranging study in PNH patients in Phase 1 and then have the dose to be able to go into other indications. That really accelerates the program.

Bill Sheridan -- Chief Medical Officer

Yes. That's also a key point. Right? So activity is not the targeted mutation in any of these diseases. There's a whole range of different things can happen that disturb the complement system and activate the alternative pathway all the way from Piga mutations and PNH in bone marrow stem cells, to germline Factor H mutations and so on.

So none of those are mutations effect to do. Effectively, it just happens to be the enzyme that starts the alternative pathway, and the goal is to treat this inadequate inhibitor Factor D and PNH is the dose that's adequate to Factor D and everything else.

Maury Raycroft -- Jefferies -- Analyst

Got it. Thank you very much for the perspective, and congrats again.

Jon Stonehouse -- Chief Executive Officer

Thanks, Maury.

Operator

At this time, there are no further questions. And I will now turn the call over to Mr. Stonehouse for concluding remarks.

Jon Stonehouse -- Chief Executive Officer

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 1 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 ORLADEYO sales at our next earnings call.

So as I said before, the transformation in this company is happening now, and we hope that we've gotten your interest. And if you like to reach out to us, we're happy to connect with you in the meantime. So thanks again, and have a great day.

Operator

[Operator signoff]

Duration: 40 minutes

Call participants:

John Bluth -- Senior Vice President, Investor Relations and Corporate Communications

Jon Stonehouse -- Chief Executive Officer

Charlie Gayer -- Chief Commercial Officer

Megan Sniecinski -- Chief Business Officer

Bill Sheridan -- Chief Medical Officer

Anthony Doyle -- Chief Financial Officer

Jessica Fye -- J.P. Morgan -- Analyst

Brian Cheng -- Bank of America Merrill Lynch -- Analyst

David Dai -- Barclays -- Analyst

Steve Daddeo -- RBC Capital Markets -- Analyst

Maury Raycroft -- Jefferies -- Analyst

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