Good morning, ladies and gentlemen, and welcome to the BioCryst fourth quarter 2018 earnings conference call. At this time, all participants are in a listen-only mode. Following management's prepared remarks, we will host a question and answer session, and our instructions will be given at that time. If during your conference that you require operator assistance, press star then 0, and an operator will be happy to assist you. 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.
Thanks, Brian. Good morning, and welcome to BioCryst 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, John 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 two, 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 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 John Stonehouse.
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 number one priority is oral BCX7353 for the prevention of hereditary angioedema attacks. We remain on track to report 24-week 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. The headline is ZENITH-1 is complete. We plan moving quickly ahead into the phase III trial with the 750 milligram dose. 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 BCX9930 to move into the clinic in the first half of the year. BCX9930 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. 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. BCX9930 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. 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 BCX9930 we have thus far, which Bill will describe to you, is fantastic.
We expect to begin our phase I next quarter. 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 BCX9930. 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 three 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 BCX9930. Bill?
Thank you, John. 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 to identify the best dose to advance. We are thrilled that ZENITH-1 so 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 nine, we had previously reported that all HAE subjects in a PK study dosed with 750 milligrams had drug levels more than eight times EC50 within 30 minutes, sustained through 24 hours post-dose. This long duration of action is important given the recent evidence of a high rate of 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 BCX7353, a clear dose response going from 250 to 750 milligrams. As John 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 and the proportion of subjects who used rescue medicine.
As detailed on the safety summary slide 13, BCX7353 was generally safe and well-tolerated, with no notable differentiation from the adverse event profile of placebo. Our next step for the acute program for BCX7353 is to meet with regulators to discuss the phase III trial, with the goal of starting patient enrollment over the summer. The prophylactic program also continues to make excellent progress. As John 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 a 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 permits continued daily oral treatment through 96 weeks. In parallel, the team has made an excellent start on our regulatory filings, we remain on schedule to file a new drug application with the FDA by the end of the year and a marketing authorization application with the EMA in the first half of 2020. We recently enrolled our first patients in the APeX-J trial in Japan, which is being conducted to support the JNDA. This trial is a 24-subject randomized placebo-controlled trial, similarly designed to APeX-2, using the same doses of BCX7353. Because there are no prophylactic treatments for HAE approved in Japan, the unmet need there for HAE patients is high and clear.
I am very excited to tell you more about BCX9930, our oral factor D inhibitor for complement-mediated diseases, which is advancing into 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 its mechanism of action as a factor D inhibitor, we believe that BCX9930 is a potential treatment for a broader range of complement-mediated disorders. Potential indications for BCX9930 include many rare diseases of the kidney, blood, and nervous system. Treatment with oral BCX9930 could fundamentally transform patients' lives and improve on existing therapies.
The preclinical profile of oral BCX9930 is extremely attractive. After oral dosing in non-human 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 the consistent in vitro potency of BCX9930 across multiple complement assays. These include measurement of factor D enzymatic action, complement-mediated destruction of red blood cells or hemolysis, and deposition of complement enzyme C3 fragment on the surface of red cells from 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 BCX9930 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 use a standard assay in this field, hemolysis of heterologous red cells. On slide 19, you can see that after dosing non-human primates, BCX9930 rapidly suppressed complement activity with near complete suppression of complement-mediated hemolysis by 24 hours, despite the 50% lower potency of BCX9930 on non-human primate factor D compared to human factor D. Of note, the drug exposure needed was a fraction of the No-Observed-Adverse-Effect 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 NOAELs of BCX9930 were more than 500 times 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 BCX9930 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 BCX9930 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 BCX9930 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 of disease biomarkers are so good, needing very few patients to generate convincing evidence. We believe oral BCX9930 could represent a pipeline and a product with the potential to address many different complement-mediated disorders. Now I'd like to turn the call over to Lynne.
Thank you, Bill. I'm also very excited about the potential of BCX9930 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 three 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 BCX9930 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 BCX9930 and a 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 slides 24 and 25, you can see some of our most recent rounds 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 Staab.
Thank you, Lynne Powell. As Jon Stonehouse 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 31st. This new agreement provided $20 million of immediate additional non-dilutive capital to extend our cash runway and provides flexibility for us to draw another $50 million of milestone-based non-dilutive capital at our option. In addition to the non-dilutive 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 four 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. 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-$130 million and our 2019 operating expenses to be in the range of $120 million-$145 million.
This operating expense, as in past years, excludes equity-based compensation due to difficulty in reliably projecting this expense, as it is impacted by the volatility and price of our stock, as well as by the vesting of outstanding performance-based stock options. 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 data set, 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. We would now like to answer your questions. Brian?
Thank you, sir. Ladies and gentlemen, at this time, if you would like to ask a question over the phone lines, please press star and then one on your telephone keypad. We ask everyone who is participating in today's Q&A session to kindly limit yourself to one question and one follow-up. If your questions have been answered or you wish to move yourself in the queue, simply press the pound key. Our first question will come from Jessica Fye with J.P. Morgan. Your line is now open.
Thanks for taking our questions. This is Daniel for Jessica. Can you talk about the technique for confirming attacks in APeX-2 and how this compares to APeX-1? I have a quick follow-up. Thanks.
Sure. Hi, Daniel. It's Bill. Yeah, the attacks in APeX-2 are confirmed by the site investigator in a telephone call within approximately two business days of when they're notified the subject has had an attack electronically. The subjects in the study carry an electronic diary. Each day they record whether or not they've had an attack. That gives the site investigator the opportunity to go through a series of standardized questions about symptoms, treatment, follow-up, and the like, and make a judgment that's recorded then as investigator-assessed attacks, and that becomes the primary analysis data set for efficacy for the study. In contrast, in APeX-1, we had a remote expert panel of three expert physicians who received a spreadsheet with what was recorded in a diary from the patient, but they had no facility to contact the patient or ask them questions. That's a significant difference.
Got it. Thank you. For ZENITH-1, for acute attacks, a number of endpoints were assessed. Can you maybe talk about what potential endpoint for phase III you're thinking that would best highlight the product profile?
Well, we're very pleased that what we saw was rapid onset of action and sustained duration. That's what patients need for an acute treatment. We've got a number of endpoints to choose from. It's a highly competitive area. At this stage, we're not going to disclose what we're advancing as the primary endpoint for phase III. As I mentioned on the call, the next step is to meet with regulators to discuss the design, finalize the design and start the study in the summer. We're looking forward to that.
All right. Thank you very much.
Thank you. Our next question will come from the line of Maury Raycroft with Jefferies. Your line is now open.
Hi, everyone. Congrats on the progress and thanks for taking my questions. First question is for BCX9930. 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? How does that play into the clinical indications that you're going to pursue?
Sure. Hi, 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. In all of our drug development programs, including BCX9930, we actively work on all of the traditional tactics for formulation development. The first step here is to find out what its exposure profile is and its PD profile and safety profile is in people. That'll be exciting.
Do you have an idea based on the non-human primate data?
No. We've got non-clinical experience in several non-clinical species. The predictability of human half-life on the basis of non-clinical findings is rather weak. It's so wide that people in the literature declare success if they get it within threefold either way, that's not particularly helpful. I think we really need the human data.
Okay. Can you talk about which indications that you're considering?
All of them. 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. We've seen from the initial indications of IV treatments, just what a striking difference that adequate treatment can make. We'll pick things that are the most feasible, where the medical need is high and it's very attractive.
Yeah, this concept of a 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. We're extremely excited with this program.
Great. I'll ask one more question. Just based on the half-life with 7353 for acute HAE, how confident are you that you can and talk about some of the supporting evidence that redosing, particularly with FIRAZYR in mind, is because of short half-life, or is it because the patient's waiting too long to dose?
Yeah, the half-life, Bill, correct me if I'm wrong, is in the 50-70-hour range. 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. The likelihood that there's redosing necessary appears to us to be low with 7353. What's really interesting is now there are two sets of data showing real-world experience with the short half-life acute therapies. The first one was done by the group in Berlin, late last year, that was published, showed a 40% redose rate with FIRAZYR in the real world. At the AAAAI meeting, the HAE Association had a poster, and it was around 30% was the redose rate. That's a problem.
It's a problem from a payer perspective that you've got to pay for an additional dose. 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. For emotional reasons, financial reasons, having a long-acting acute therapy is a must.
Got it. Okay, thanks, and congrats again.
Thanks.
Thank you. Our next question will come from the line of Brian Abrahams with RBC Capital Markets. Your line is now open.
Hey, guys, this is Owen on for Brian. Thanks for taking the questions, and congrats on the recent progress. 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? Along those lines, where are you viewing the bar for APeX-2, given the differentiation as an oral? Can you share any learnings on the real-world use you have seen from following the continued TAKHZYRO launch? Thank you.
Yes. In terms of the market research data, we had seen that our product was preferred compared to other products. If you look at slide 24, this situation had the question asked within a period of showing profiles of drugs. A profile of the phase II, profile of BCX7353, and the marketer profiles of TAKHZYRO and HAEGARDA. As you can see, very, very good interest in moving to an oral product. 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.
Oh, one other really important piece that we're seeing 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. I think our trial usage is going to be really high. We see that consistently with all the market research we've done. Then it's a matter of what experience do they have on the drug, and will they stay on it. We think that, if you do the simple math of looking at injections with something like TAKHZYRO, where you have an injection every two weeks, that's many injections over the course of a year, versus if you have a breakthrough attack on your oral therapy, and you got to inject FIRAZYR, for example, it's way less.
We think that 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.
Got it. Thank you very much.
Thank you. Our next question will come from Tyler Van Buren with Piper Jaffray. Your line is now open.
Hey, good morning, guys. Congrats on the progress. 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? Historically, has the difficulty been developing a molecule that's selective enough where it doesn't hit the other serine proteases, or is it potency or all the above? Some additional thoughts would be helpful.
Yeah. I would say complement-mediated diseases is crowded, but the vast majority, dozens, are injectable, and there's only one other oral competitor. In a market that's this big, we think that's a really nice opportunity for 9930. The second half of your question was 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 the capability that we have with the group in Birmingham is to identify potent inhibitors, but also specific to that target. We can go after things like serine proteases and kinases and the like, because we have both potency and specificity.
Yeah. I think that we're thrilled with the data. We've got excellent potency specificity, PK/PD safety profile in the non-clinical body of evidence. We're very much looking forward to getting our clinical data.
Based on everything you're seeing clinically, does it compare fairly well to the injectables? How does it compare? Also, how do you think the mechanism compares to a C3 inhibitor?
In conversations we've had with expert advisors 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." 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. If you block factor D, you can block amplification no matter how complement got stimulated in the first place, and that opens up every disease.
For example, there are great reviews on kidney diseases that are driven by abnormalities of inhibitors of the Alternative Complement 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, which depends on C5. C5 inhibitors can't address the fundamental pathology of the disease, whereas a factor D inhibitor could. I think there are two 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. Both of those aspects are very interesting and exciting.
Great. Thanks for taking the questions.
Thank you. Just as a reminder, ladies and gentlemen, if you would like to ask a question at this time, please press star and then one on your telephone keypad. Our next question will come from the line of Serge Belanger with Needham & Company. Your line is now open.
Hi, good morning. A couple questions on 7353. Now that we're in March and Q2 is just a few weeks away, any possibility that we can get more granularity on when in Q2 we'll see the phase III data? On the NDA filing plan for second half of 2019, what is the gating item for that? Is it the open label safety studies or a CMC component?
It's second quarter, full stop, no more granularity than that, 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's mentioned this numerous times, we need 100 patients for 48 weeks at each dose, and that just takes a little bit longer time. CMC looks great. No issues there. In fact, we're starting to write certain sections of the NDA, and CMC is one of them. Yeah, you're right, it's the safety study that's the gating factor for filing your end.
Okay. Now that you have proof of concept data and the acute treatment of HAE with 7353, coming out of AAAAI and the feedback you got there, where do you think an oral is more of a game changer? Is it in the acute treatment or prophylactic? I know your market research definitely supports an oral product for both, where do you think the key game changer is here?
I think there is a lot of potential in both of those markets, 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. We believe that is growing fast.
Okay. Thank you.
You're welcome.
Thank you. Your final question comes from Gena Wang with Barclays. Your line is now open.
Thank you for taking my questions. Just two. First one is also regarding the 9930 effect, the Factor D inhibitors. Just wondering, how do you see 9930 compare to other Factor D inhibitors, like particularly Achillion's first generation and the second generation assets?
So-
Yeah.
Sure. Happy to take a stab at that. We're very pleased with the profile we've seen. The history of the field indicates that it can be difficult to develop these types of drugs. That's why we're so excited by the in vivo proof of concept with the PD on complement-mediated hemolysis. The tremendous dose range we've been able to dose safely in animals, the very high safety margin, all those factors give us a lot of confidence that we should be able to see effects in humans. We'll know that very soon. As John mentioned before, this is a huge market, and which is, and as Lynne pointed out, growing. There's plenty of room for more than one player here.
Yeah, 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. An oral will be a game changer here. Your second question, Gena?
Yeah. Maybe just follow up on the BCX9930, and if you can share any thoughts on the phase I trial design, indication and trial design, anything you can share with us?
In this circumstance, the first thing we need to understand is the drug levels that we get after oral dosing and single ascending dose and multiple ascending dose. That's step one. That's what we'll be doing.
Okay. 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?
How would you define what? We couldn't hear that.
One attack.
One attack. How do you define one attack?
How do you define one attack?
I think the question may be getting at, if you've had an attack recently and then your symptoms continue, is that two attacks or one attack? There is a time window element to it. 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. That type of thing is taken into account in the adjudication of the attack by the investigators.
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.
Very helpful. Thank you.
You're welcome.
Thank you. This concludes our question and answer session for today. Now, I'd like to hand the conference back over to Mr. Stonehouse for any closing comments or remarks.
Yeah. Thank you. As always, we appreciate your interest. We're off to a fantastic start in 2019. Clearly, there are some very important milestones ahead, and you have our commitment to be focused on delivering those and keeping you up to date.