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Edited Transcript of BCRX earnings conference call or presentation 4-Mar-19 1:30pm GMT

Q4 2018 BioCryst Pharmaceuticals Inc Earnings Call

BIRMINGHAM Mar 8, 2019 (Thomson StreetEvents) -- Edited Transcript of BioCryst Pharmaceuticals Inc earnings conference call or presentation Monday, March 4, 2019 at 1:30:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Jon P. Stonehouse

BioCryst Pharmaceuticals, Inc. - CEO, President & Director

* Lynne M. Powell

BioCryst Pharmaceuticals, Inc. - Chief Commercial Officer & Senior VP

* Thomas R. Staab

BioCryst Pharmaceuticals, Inc. - CFO, Principal Accounting Officer, Senior VP & Treasurer

* William P. Sheridan

BioCryst Pharmaceuticals, Inc. - Chief Medical Officer & Senior VP

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Conference Call Participants

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* Daniel G. Wolle

JP Morgan Chase & Co, Research Division - Analyst

* Gena Wang

Barclays Bank PLC, Research Division - Research Analyst

* Maurice Thomas Raycroft

Jefferies LLC, Research Division - Equity Analyst

* Owen J. Drinkwater

RBC Capital Markets, LLC, Research Division - Associate

* Serge D. Belanger

Needham & Company, LLC, Research Division - Senior Analyst

* Tyler Martin Van Buren

Piper Jaffray Companies, Research Division - Principal & Senior Biotech Analyst

* John Bluth

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Presentation

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Operator [1]

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Good morning, ladies and gentlemen, and welcome to the BioCryst Fourth Quarter 2018 Earnings Conference Call. (Operator Instructions) As a reminder, this conference call is being recorded for replay purposes.

It is now my pleasure to hand the conference over to John Bluth. Sir, you may begin.

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John Bluth, [2]

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Thanks, Brian. Good morning, and welcome to BioCryst's Fourth Quarter and Full Year 2018 Corporate Update and Financial Results Conference Call. Today's press release and accompanying slides are available on our website.

Participating on the call with me today are: CEO, Jon Stonehouse; CFO, Tom Staab; Chief Medical Officer, Dr. Bill Sheridan; and Chief Commercial Officer, Lynne Powell. Following their remarks, we will answer your questions.

Before we begin, I want to direct your attention to Slide 2, which discusses our use of forward-looking statements and potential risk factors regarding an investment in BioCryst. As detailed on the slide, 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. 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.

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Jon P. Stonehouse, BioCryst Pharmaceuticals, Inc. - CEO, President & Director [3]

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Thank you, John, and thanks to all of you for joining us this morning. BioCryst is off to a very exciting start in 2019, with some exceptional progress over the past few weeks.

Our #1 priority is oral BCX7353 for the prevention of hereditary angioedema attacks. We remain on track to report 24 weeks safety and efficacy data in the second quarter from the APeX-2 trial. We are now gearing up for our regulatory filing by year-end and extensively planning and preparing for the launch of 7353 into the U.S. marketplace next year.

Bill and I attended the recent AAAAI meeting, the largest allergy and immunology meeting in the U.S. in San Francisco, and the excitement from patients and physicians around 7353 continues to build.

Once again, we heard loudly and clearly that patients desperately want a once-daily oral therapy to prevent HAE attacks and a single-dose oral therapy to treat their acute attacks. We presented the full ZENITH-1 clinical trial results at AAAAI. Bill will share more with you in a moment, but the headline is, ZENITH-1 is complete, we plan moving quickly ahead into the Phase III trial with the 750 milligram dose, and we expect to begin the trial over the summer.

We are also very excited to share with you the target and data for BCX9930. Remember, we announced in January we prioritized 9930 to move into the clinic in the first half of the year. 9930 is an oral factor D inhibitor for the treatment of complement-mediated diseases. The beauty of having an oral factor D inhibitor is that there are a number of these diseases already identified and the list is growing. You should think about this program like a pipeline in a molecule as there could be many indications to pursue with this one molecule.

Today, patients with these devastating diseases either have nothing or IV infusion treatments. 9930 would offer an oral option that could improve on existing therapies. Clinical development programs for these diseases can move quickly because the biomarkers are well established, so you can quickly understand whether your drug is working in a given disease in days or weeks of treatment in a very small number of patients.

The opportunity here is bigger than HAE. The preclinical profile of 9930 we have thus far, which Bill will describe to you, is fantastic. We expect to begin our Phase I next quarter and we expect to report out the results by year-end.

Bill and Lynne will provide more details around both the preclinical data profile and commercial opportunity with 9930, and you'll get a better sense of why we're so excited.

The BioCryst discovery team led by Dr. Babu in our Birmingham, Alabama research headquarters has now successfully discovered multiple compounds for 3 rare diseases: HAE, complement-mediated diseases and FOP, where we plan to begin a Phase I trial with BCX9250 in the second half of the year.

We are building a company that will soon have a highly differentiated marketed product and a growing clinical pipeline, all focused on bringing patients with rare diseases an oral therapy and a shot at having a normal life.

We have also recently extended our cash runway further into 2020 with the addition of the $100 million debt facility we announced last month. This provides the company with additional financial flexibility to support these exciting programs.

Now I'd like to hand the call over to Bill for an update on the HAE program and more details about 9930. Bill?

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William P. Sheridan, BioCryst Pharmaceuticals, Inc. - Chief Medical Officer & Senior VP [4]

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Thank you, Jon. I'll start with the HAE program and the data we just reported last week from the ZENITH-1 trial at the AAAAI meeting.

You'll recall that ZENITH-1 was a Phase II, dose ranging, proof-of-concept trial designed to estimate treatment effect, evaluate safety and tolerability, select clinically meaningful endpoints for a Phase III registration trial and identify the best dose to advance. We are thrilled that ZENITH-1 clearly achieved all its objectives. This trial also broke new ground as the first prospective, randomized, placebo-controlled trial of acute HAE treatment administered at home by the patient early in the course of the attack, with a goal of stopping escalation of attack symptoms. This aligns with modern treatment guidelines and is an important element of treatment that limits disease impact. We selected the 3 dose levels to test based on clinical PK profiles.

As you can see on Slide 9, we had previously reported that all HAE subjects in a PK study dose with 750 milligrams had drug levels more than 8x EC50 within 30 minutes sustained through 24 hours post-dose. This long duration of action is important, given the recent evidence of a high-rated re-dosing with short half-life acute HAE treatments.

With ZENITH-1 completed, we now have real-world controlled clinical trial results, confirming its rapid onset of action and 24-hour duration of effect for single oral doses of 7353 and a clear dose response going from 250 to 750 milligrams.

As Jon noted, in September we reported results showing clinically meaningful and statistically significant treatment effects from our 750 milligram dose, together with a favorable safety and tolerability profile, strongly supporting advancing the 750 milligram dose to Phase III.

The most noteworthy additional data from the 250 and 500 milligram cohorts reported last week at AAAAI was the clear dose response we observed across multiple endpoints. This is reflected on Slide 12 with the examples of improvements in Visual Analog Scale scores in a proportion of subjects who used rescue medicine.

As detailed on the safety summary Slide 13, 7353 was generally safe and well tolerated with no notable differentiation from the adverse event profile of placebo.

Our next step, the acute program for 7353, is to meet with regulators to discuss the Phase III trial with a goal of starting patient enrollment over the summer.

The prophylactic program also continues to make excellent progress. As Jon noted, the 24-week safety and efficacy readout from APeX-2 is on schedule for the second quarter. As a reminder, the trial enrolled very quickly, in fact over-enrolled with 121 subjects and is now powered at 99% to detect 50% reduction in attack rate versus placebo. We look forward to sharing the results with you in the second quarter.

Both APeX-2 and our safety trial APeX-S continue to progress well. Patients have now started to enter an extension period beyond 48 weeks of dosing. That means continued daily oral treatment through 96 weeks. In parallel, the team has made an excellent start on our regulatory filings and we remain on schedule to file a New Drug Application with the FDA by the end of the year and the marketing authorization application with the EMA in the first half of 2020.

We recently enrolled our first patient in the APeX-J trial in Japan, which is being conducted to support the J-NDA. This trial is a 24-subject randomized, placebo-controlled trial similarly designed to APeX-2 using the same doses of 7353. Because there are no prophylactic treatments for HAE approved in Japan, the unmet need there for HAE patients is high and clear.

Now I'm very excited to tell you more about 9930, our oral factor D inhibitor for complement-mediated diseases, which is advancing in Phase I clinical development.

Today, patients with complement-mediated diseases either have no specific treatment options or must be treated with lifelong IV infusions. The only approved therapies in this field work to inhibit a terminal component of the complement cascade C5. Factor D is a critical enzyme in the alternative complement pathway that drives amplification of the entire complement system upstream to C5.

With this mechanism of action as a factor D inhibitor, we believe that 9930 is a potential treatment for a broader range of complement-mediated disorders. Potential indications for 9930 include many rare diseases of the kidney, blood and nervous system. Treatment with oral 9930 could fundamentally transform patients' lives and improve on existing therapy.

The preclinical profile of oral 9930 is extremely attractive. And after oral dosing in nonhuman primates, complement activity was immediately and dramatically suppressed. In preclinical studies, this compound was potent, specific and had a very wide safety margin.

Let me now walk you through the data that has us so excited on Slide 18. The left-hand table reports a consistent in vitro potency of 9930 across multiple complement assays. These include measurement of factor D enzymatic action, complement-mediated destruction of red blood cells of hemolysis and deposition of complement enzyme C3 fragment on the surface of red cells for patients with PNH. The specificity values in the right-hand table indicate a low likelihood of off-target effects on other serine proteases.

An important preclinical proof-of-concept test for 9930 was to dose animals orally and measure its effects on the complement cascade. This experiment answers the fundamental question, does enough drug get absorbed to work on the target? We used standard assay in this field, hemolysis of heterozygous red cells.

On Slide 19, you can see that after dosing nonhuman primates, 9930 rapidly suppressed complement activity with near-complete suppression of complement-mediated hemolysis by 24 hours despite the 50% lower potency of 9930 on nonhuman primate factor D compared to human factor D. But note, the drug exposure needed was a fraction of the no observed adverse event level or NOAEL exposure in preclinical safety studies. The preclinical safety margin of 9930 that supports entry into clinical trials is also very encouraging.

On Slide 20, you can see, first, that we saw very high drug exposures proportional to dose and, second, that drug levels for the NOAEL of 9930 were more than 500x greater than the estimated therapeutic target level with an associated human equivalent dose of more than 5,000 milligrams. This dose is so much higher than needed for target pharmacodynamic effects that it will never be necessary to study it in the clinic. The preclinical safety and pharmacology profile of 9930 should provide us with tremendous dosing flexibility.

Based on its preclinical PK-PD and safety profile, we expect that we will be able to safely dose oral 9930 in people and achieve drug levels that block the complement cascade. Proof of concept can be very efficient in this field. Complement assays and many validated and highly predictive disease-related biomarkers are already very well established. By using these tools in our clinical studies, we will be able to see proof of concept in a matter of days or weeks in most cases with very small patient numbers.

We look forward to seeing the results from our single ascending dose and multiple-ascending dose Phase I trial when it reads out in the fourth quarter.

In summary, the body of preclinical evidence for 9930 suggests that we have a great molecule here. We're driving hard to proof of concept in patients, and we can do this very quickly because complement assays and disease biomarkers are so good, needing very few patients to generate convincing evidence. We believe oral 9930 could represent a pipeline and a product with potential to address many different complement-mediated disorders.

Now I'd like turn the call over to Lynne.

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Lynne M. Powell, BioCryst Pharmaceuticals, Inc. - Chief Commercial Officer & Senior VP [5]

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Thank you, Bill. I'm also very excited about the potential of 9930 from a commercial perspective.

As you can see on Slide 22, the single approved IV infusion therapy for complement-mediated disorders has already generated $3.6 billion in annual sales with just 3 approved indications. Interestingly, the majority of these sales come from outside the U.S., primarily from Europe. We believe the future market for complement inhibitors could exceed $10 billion based on the range of potential indications.

An oral factor D inhibitor like 9930 has the potential to capture a significant share of that opportunity because of its upstream inhibitory activity and of course, the significant advantage of oral administration compared to lifelong infusions.

With full global rights to 9930 and the relatively quick proof of concept, we look forward to seeing the data later this year.

In the near term, we are anticipating the readout of our 24-week safety and efficacy data from APeX-2 next quarter. Our key focus is preparing the organization for launch of what will be the first once-daily oral medicine to prevent HAE attacks.

As you track the HAE market and recent competitor launches, you can see on Slide 23, the market mix continues to shift from acute only to prophylactic therapy as better prophylactic agents become available for patients.

Based on our recent conversations with physicians at AAAAI and our own market research, we expect the availability of 7353 will further accelerate the movement of the market from acute to prophylaxis.

Over the past several years, we have conducted market research with HAE patients and their physicians, both prior and post the new therapies entering the market and the results have been remarkably consistent.

On Slide 24 and 25, you can see some of our most recent round of research completed in late 2018. What is striking is that even with the new prophylactic treatment options that are available, patients continue to state their strong preference for an oral option with 89% of patients, including 10 out of 14 TAKHZYRO patients, saying that if an oral option were available, they would try it. The allergists who treat HAE say the same, with 97% expecting their patients would try an oral option.

Our focus will be to deliver on this desire with a product that patients can access and to provide best-in-class customer service.

Now I'd like to turn the call over to Tom.

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Thomas R. Staab, BioCryst Pharmaceuticals, Inc. - CFO, Principal Accounting Officer, Senior VP & Treasurer [6]

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Thank you, Lynne. As Jon mentioned, we took an important step in the first quarter to further extend our cash runway and enhance our financial flexibility by closing a $100 million secured credit facility. This $100 million facility represented a modification and an enhancement of our existing $30 million secured credit facility outstanding at December 31.

This new agreement provided $20 million of immediate additional nondilutive capital to extend our cash runway and provides flexibility for us to draw another $50 million of milestone-based nondilutive capital at our option.

In addition to the nondilutive cash added to the balance sheet in the first quarter, $30 million is available to us at our option following positive APeX-2 data, which is considered sufficient to file a New Drug Application.

We ended 2018 with $128 million in cash and investments. Of course, this amount does not include the $20 million we added upon the first quarter modification of our credit facility.

With our existing cash on hand, the $20 million of proceeds we received in the February closing as well as the contingent proceeds from the modified credit facility, we have a strong cash position that provides us the resources to fund our development programs and commercial preparations deeper into 2020 and well past the readout of APeX-2 and the filing of our NDA application for a prophylactic HAE indication.

Our detailed fourth quarter and year-end financial results can be found in the press release we issued this morning, but I'd like to take some time to highlight some information for you, given the many milestones we anticipate across our programs in 2019.

As you see on Slide 27, revenue for the fourth quarter of 2018 decreased to $2.7 million. As compared to fiscal 2018 levels, we expect slightly more development activity and related revenue from galidesivir in 2019 due to planned clinical activity. In addition, we expect to ship and record just under $7 million of RAPIVAB product sales to the U.S. government under our procurement contract, with the expectation that this shipment will occur before the end of September.

Fourth quarter 2018 R&D expenses increased to $23.4 million from $16.9 million in the fourth quarter of 2017. Specifically, the increase was due to the ongoing APeX-2, APeX-S, APeX-J trials and the completed ZENITH-1 trial as well as wrapping up preclinical activities that allow us to conduct Phase I trials in both our complement and FOP programs in 2019.

Given the significant clinical development activities in our 4 rare disease programs and continued development activity with galidesivir and peramivir, we expect our 2019 R&D expenses will increase from 2018 levels. This increase is reflected in our 2019 guidance that I will discuss in a few moments.

General and administrative expenses were $4.5 million and decreased slightly in the fourth quarter of 2018. However, upon receiving positive APeX-2 data in the second quarter of this year, we anticipate our G&A expenses will increase as we build out the necessary commercial and medical affairs infrastructure to successfully launch 7353 in 2020.

Regarding operating guidance, we expect our 2019 cash utilization to be in the range of $105 million to $130 million and our 2019 operating expenses to be in the range of $120 million to $145 million. This operating expense, as in past years, excludes equity-based compensation due to the difficulty in reliably projecting this expense as it is impacted by the volatility and price of our stock as well as by divesting of outstanding performance-based stock options.

Furthermore, with the modification of our secured credit facility and looking below the operating line, you should expect higher interest expense for 2019 because of higher debt balances than those in 2018.

2019 is off to an outstanding start, with strong clinical data from the full ZENITH-1 dataset, advancement of a very exciting compound 9930 into the clinic and added financial flexibility for the company with our credit facility modification. We look forward to sharing the APeX-2 results with you when the trial reads out next quarter.

This concludes our prepared remarks, and we would now like to take it to your questions or answer your questions. Brian?

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Questions and Answers

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Operator [1]

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(Operator Instructions) And our first question will come from the line of Jessica Fye with JP Morgan.

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Daniel G. Wolle, JP Morgan Chase & Co, Research Division - Analyst [2]

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This is Daniel for Jessica. Can you talk about the technique for confirming attacks in APeX-2? And how this compares to APeX-1? And I have a quick follow-up.

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William P. Sheridan, BioCryst Pharmaceuticals, Inc. - Chief Medical Officer & Senior VP [3]

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Sure. Daniel, it's Bill. The attacks in APeX-2 are confirmed by the site investigator in a telephone call within approximately 2 business days of when they notified that a subject has had an attack electronically. The subjects in the study carry an electronic diary. Each day they record that whether or not they've had an attack. And that gives the site investigator the opportunity to go through a series of standardized questions about symptoms, treatment, follow-up and alike and make a judgment that's recorded then as investigators assess the attacks and that becomes the primary analysis dataset for efficacy for the study. In contrast, in APeX-1, we had a remote expert panel of 3 expert physicians who received a spreadsheet with what was recorded in a diary from the patient that they had no ability, no facility to contact the patient or ask them questions, so that's a significant difference.

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Daniel G. Wolle, JP Morgan Chase & Co, Research Division - Analyst [4]

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Got it. And then for ZENITH-1 for acute attacks, a number of endpoints were assessed. Can you maybe talk about what potential influence for Phase III you're thinking that would best highlight the product profile?

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William P. Sheridan, BioCryst Pharmaceuticals, Inc. - Chief Medical Officer & Senior VP [5]

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Well, we're very pleased that what we saw was rapid onset of action and sustained duration and that's what patients need for acute -- for an acute treatment and we've got a number of endpoints to choose from. It's a highly competitive area. So at this stage, we're not going to disclose what we're advancing as the primary endpoints of Phase III. And as I mentioned on the call, the next step is to meet with regulators to discuss the design and then finalize the design and start the study in the summer. So we're looking forward to that.

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Operator [6]

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And our next question will come from the line of Maury Raycroft with Jefferies.

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Maurice Thomas Raycroft, Jefferies LLC, Research Division - Equity Analyst [7]

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First question is for 9930. I'm wondering if you can comment on what the half-life is? And if you're not disclosing the half-life, is there a strategy here to have a molecule with longer or shorter half-life? And then how does that play into the clinical indications that you're going to pursue?

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William P. Sheridan, BioCryst Pharmaceuticals, Inc. - Chief Medical Officer & Senior VP [8]

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Sure. Maury, we haven't disclosed the half-life. We'll find out what it is in humans, which is what really matters. And we'll find that out pretty quickly, where -- we actively -- in all of our drug development programs, including 9930, we actively work on all of the traditional tactics for formulation development, but the first step here is to find out what its exposure profile is and its PD profile and safety profile is in people, so that will be exciting.

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Maurice Thomas Raycroft, Jefferies LLC, Research Division - Equity Analyst [9]

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Do you have an idea based on the nonhuman primate data?

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William P. Sheridan, BioCryst Pharmaceuticals, Inc. - Chief Medical Officer & Senior VP [10]

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We've got nonclinical experience in several nonclinical species. The predictability of human half-life on the basis of nonclinical findings is rather weak. It's so wide that people in the literature declare success if they get it within threefold either away, so that's not particularly helpful. So I think we really need the human data.

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Maurice Thomas Raycroft, Jefferies LLC, Research Division - Equity Analyst [11]

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Okay. And can you talk about, which indications that you're considering?

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William P. Sheridan, BioCryst Pharmaceuticals, Inc. - Chief Medical Officer & Senior VP [12]

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All of them. So I think that what's fascinating here is that over the last, I'd say, 20 to 30 years, the explosion of understanding of how abnormal activation of the complement system or suppression of its inhibitors leads to disease outcomes that are really very, very significant across a broad range of diseases. And we've seen from the initial indications of IV treatments just what a striking difference adequate treatment can make, so we'll pick things that are the most feasible where the medical need is high and it's very attractive.

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Jon P. Stonehouse, BioCryst Pharmaceuticals, Inc. - CEO, President & Director [13]

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Yes. This concept of pipeline in a molecule is really important for people to understand. You could build a whole company around an oral factor D inhibitor because there's so much opportunity. So we're extremely excited with this program.

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Maurice Thomas Raycroft, Jefferies LLC, Research Division - Equity Analyst [14]

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Great. And I'll ask one more question. Just based on the half-life with 7353 for acute HAE, I guess, how confident are we that you can -- or how confident are you that you can talk about some of the supporting evidence that re-dosing, particularly with FIRAZYR in mind, is because of short half-life or is it because of patients waiting too long to dose?

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Jon P. Stonehouse, BioCryst Pharmaceuticals, Inc. - CEO, President & Director [15]

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Yes. The half-life, Bill, correct me if I'm wrong, is in the 50- to 70-hour range. So -- and you saw from the clinical data that the Kaplan-Meier curve on reaching for rescue medicine got wider and wider as you went across the 24-hour period. So the likelihood that there's re-dosing necessary appears to us to be low with 7353. And what's really interesting is now there are 2 sets of data showing real-world experience with the short half-life acute therapies. The first one was done by the group in Berlin, I think, late last year that was published, showed a 40% re-dose rate with FIRAZYR in the real world and then at the AAAAI meeting the HAE Association had a poster, and I think it was around 30% was the re-dose rate. And so that's a problem. It's a problem from a payer perspective that you've got to pay for an additional dose and it's a problem from a patient perspective because the last thing you want to do is be questioning whether or not you're going to get full coverage with the dose you took. So for emotional reasons, financial reasons, having a long-acting acute therapy is a must.

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Operator [16]

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And our next question will come from the line of Brian Abrahams of RBC Capital Markets.

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Owen J. Drinkwater, RBC Capital Markets, LLC, Research Division - Associate [17]

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This is Owen on for Brian. Just on the market research slide you presented in prophylactic, the question about switching from an injectable to an oral, did that include any explicit assumptions on efficacy? And along those lines, where are you viewing the bar for APeX-2, given the differentiation as an oral? And can you share any learnings on the real-world use you have seen from following the continued TAKHZYRO launch?

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Lynne M. Powell, BioCryst Pharmaceuticals, Inc. - Chief Commercial Officer & Senior VP [18]

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Yes. So in terms of the market research data, we have seen that the -- we have seen that our product was preferred compared to the -- to other products. And if you look at Slide 24, this situation had, had the question asked within a period of showing profiles of drugs, so a profile -- the Phase II profile of 7353 and the marketed profiles of TAKHZYRO and HAEGARDA. And as you can see, very, very good interest in moving to an oral product. And if we look similarly at the physician slide, they really do show an interest in really recommending and allowing patients to move to an oral therapy.

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Jon P. Stonehouse, BioCryst Pharmaceuticals, Inc. - CEO, President & Director [19]

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I think, Owen, one other really important piece that we see is both, when we did this research a while back before the new therapies were on the market and now with the new therapies on the market is a consistency that patients want to try an oral. And so I think our trial usage is going to be really high. That's -- we see that consistently with all the market research we've done. And so then it's a matter of what experience do they have on the drug and will they stay on it. And we think that just -- if you do the simple math of looking at injections with something like TAKHZYRO, where you have 2 -- an injection every 2 weeks, that's many injections over the course of a year versus if you have a breakthrough attack on your oral therapy, it -- and you've got to inject FIRAZYR, for example, it's way less. So we think that the usage -- the trial usage is going to be very high, and we think many patients are going to stay on the therapy because they don't want an injection.

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Operator [20]

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And our next question will come from the line of Tyler Van Buren with Piper Jaffray.

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Tyler Martin Van Buren, Piper Jaffray Companies, Research Division - Principal & Senior Biotech Analyst [21]

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I guess, first question was on 9930 as well. Can you speak a little bit more about the competitive landscape with respect to factor D inhibitors and specifically, what makes you guys so excited? And historically, how's the difficultly been developing a molecule that's selective enough where it doesn't hit the other serine proteases or is the potency or all the above? Some additional thoughts would be helpful.

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Jon P. Stonehouse, BioCryst Pharmaceuticals, Inc. - CEO, President & Director [22]

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Yes. So it's -- I would say complement-mediated diseases is crowded, but the vast majority -- dozens are injectable, and there's only one other oral competitor. And in a market that's as big, we think that's a really nice opportunity for 9930. The second half of your question was, oh, around specificity. This is a tough target. That's why there aren't a lot of oral factor D inhibitors. Like other targets we've gone after, our ability and capability that we have with the group in Birmingham is to identify potent inhibitors, but also specific to that target. And so we can go after things like serine proteases and kinases and the like because we have both potency and specificity.

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William P. Sheridan, BioCryst Pharmaceuticals, Inc. - Chief Medical Officer & Senior VP [23]

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I think that we're thrilled with the data. We've got excellent potency specificity, PK-PD, safety profile in the nonclinical body of evidence. So we're very much looking forward to getting our clinical data.

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Tyler Martin Van Buren, Piper Jaffray Companies, Research Division - Principal & Senior Biotech Analyst [24]

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Based on everything you're seeing clinically, does it compare fairly well to the injectables or how does it compare? And also how do you think the mechanism compares to a C3 inhibitor?

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William P. Sheridan, BioCryst Pharmaceuticals, Inc. - Chief Medical Officer & Senior VP [25]

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So in conversations we've had with expert advisers who we've been having conversations with about the program, as soon as we mention oral factor D inhibitor, we get responses like, wow, that's the holy grail of complement therapeutics. And the reason for that reaction -- and I'm not kidding. That was a direct quote. The reason for that reaction is because the alternative pathway amplifies all of the different mechanisms of initiation of the complement cascade and factor D is absolutely essential to do that. So if you block factor D and block amplification, no matter how complement got stimulated in the first place, then that opens up every disease. So for example, there are great reviews on kidney diseases that are driven by abnormalities of inhibitors of the alternative pathway and they're characterized by deposition of the relevant fragments of complement from that pathway that have nothing to do pretty much with the terminal cascade. It just depends on C5 and C5 inhibitors can't address the fundamental pathology of the disease, whereas a factor D inhibitor could. So I think there are 2 things here. One is you can address all of the current diseases because of the amplification loop, inhibitory aspects, and you can address diseases that are too proximal for distal inhibitors to do anything for them. So both of those aspects are very, very interesting and exciting.

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Operator [26]

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(Operator Instructions) And our next question will come from the line of Serge Belanger with Needham & Company.

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Serge D. Belanger, Needham & Company, LLC, Research Division - Senior Analyst [27]

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A couple of questions on 7353. Now that we're in March and 2Q is just a few weeks away, any possibility that we can get more granularity on when in 2Q we'll see the Phase III data? And then on NDA filing plan for second half of '19, what is the gating item for that? Is it the open-label safety studies or a CMC component?

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Jon P. Stonehouse, BioCryst Pharmaceuticals, Inc. - CEO, President & Director [28]

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So it's second quarter, full stop. No more granularity than that and high degree of confidence that we'll hit that. With regard to the NDA, it is the safety study that's the gating factor because we need -- and Bill has mentioned this numerous times, we need 100 patients for 48 weeks at each dose and that just takes a bit longer time. CMC looks great. No issues there. And so -- in fact, we're starting to write certain sections of the NDA and CMC is one of them, so yes, you're right. It's the safety study that's the gating factor for filing year-end.

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Serge D. Belanger, Needham & Company, LLC, Research Division - Senior Analyst [29]

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Okay. And then now that you have proof-of-concept data in the acute treatment of HAE with 7353, coming out of AAAAI and the feedback you got there, where do you think -- and oral is more of a game-changer, but in the acute treatment or prophylactic? I know your market research definitely supports an oral product for both, but where do you think the key game changer is here?

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Lynne M. Powell, BioCryst Pharmaceuticals, Inc. - Chief Commercial Officer & Senior VP [30]

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I think there's a lot of potential in both of those markets, but I see the prophylactic market as being the biggest market and also the most rapidly growing market. For an oral therapy, we believe that patients who have been on acute therapy because they didn't like to have an injection regularly may look at an oral therapy for prophylaxis. So we believe that is growing fast.

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Operator [31]

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Your final question comes from Gena Wang with Barclays.

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Gena Wang, Barclays Bank PLC, Research Division - Research Analyst [32]

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Just 2. First one is also regarding the 9930 factor D inhibitors. Just wondering how do you see 9930 compared to other factor D inhibitors, particularly, Achillion, the first generation and second generation assets?

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William P. Sheridan, BioCryst Pharmaceuticals, Inc. - Chief Medical Officer & Senior VP [33]

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So -- sure. Happy to take a stab at that. So we're very pleased with the profile we've seen. The history in the field indicates that it can be difficult to develop these types of drugs. And so that's why we're so excited by the in vivo proof-of-concept with PD on complement-mediated hemolysis. The tremendous dose range we've able to dose safely in animals, the very high safety margin, all of those factors give us a lot of confidence that we should be able to see effects in humans. We'll know that very soon. So as Jon mentioned before, this is a huge market, which is -- and as Lynne pointed out, growing. So there's plenty of room for more than one player here.

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Jon P. Stonehouse, BioCryst Pharmaceuticals, Inc. - CEO, President & Director [34]

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Yes. And as a practice, we don't compare ourselves to other therapies other than the fact that there's a bunch of injectables in the clinic and on the market. And so an oral will be a game changer here. Your second question, Gena?

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Gena Wang, Barclays Bank PLC, Research Division - Research Analyst [35]

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Yes. So maybe just follow-up on the 9930 and if you can share any thoughts on the Phase I trial design, limitation in trial design? Anything you can share with us.

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William P. Sheridan, BioCryst Pharmaceuticals, Inc. - Chief Medical Officer & Senior VP [36]

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So in these circumstances, the first thing we need to understand is the drug levels that we get after oral dosing in single ascending dose and multiple ascending dose. So that's step 1. So that's what we'll be doing.

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Gena Wang, Barclays Bank PLC, Research Division - Research Analyst [37]

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Okay. And the next question is just a quick one on APeX-2. I know you mentioned before, just wondering if you can remind us how would you define as one attack.

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Jon P. Stonehouse, BioCryst Pharmaceuticals, Inc. - CEO, President & Director [38]

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How would you define what? We couldn't hear that.

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Gena Wang, Barclays Bank PLC, Research Division - Research Analyst [39]

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One attack.

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Jon P. Stonehouse, BioCryst Pharmaceuticals, Inc. - CEO, President & Director [40]

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One attack. How do you define one...

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William P. Sheridan, BioCryst Pharmaceuticals, Inc. - Chief Medical Officer & Senior VP [41]

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How do you define one attack? I think the question may be getting at, if you had an attack recently and then your symptoms continue, is that two attacks or one attack. So there is a time window element to it. So in the field, typically, experts feel that if symptoms happen on Tuesday, when they already happened on Monday, it's really just one continued attack. So that type of thing is taken into account in the adjudication of the attack by the investigators.

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Jon P. Stonehouse, BioCryst Pharmaceuticals, Inc. - CEO, President & Director [42]

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And that's where I think this investigator-confirmed attack is more important than an adjudication panel because these docs know these patients and having a dialogue with the patient helps get clarity on that point.

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Operator [43]

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This concludes our question-and-answer session for today. So now, I'd like to hand the conference back over to Mr. Stonehouse for any closing comments or remarks.

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Jon P. Stonehouse, BioCryst Pharmaceuticals, Inc. - CEO, President & Director [44]

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Yes. Thank you. So as always, we appreciate your interest. We're off to a fantastic start in 2019. And clearly, there are some very, very important milestones ahead. And you have our commitment to be focused on delivering those and keeping you up-to-date, and we look forward to a very exciting year in 2019. Thank you. Have a great day.

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Operator [45]

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Ladies and gentlemen, thank you for your participation in today's conference. This does conclude our program, and you may all disconnect. Everybody, have a good day.