BioCryst Pharmaceuticals Inc (BCRX) 2008 Q1 法說會逐字稿

Good morning, and welcome to BioCryst's First Quarter 2008 Financial Results conference call. Before we begin, let me read a formal statement regarding risk factors associated with today's call. Today's conference call and accompanying slides will contain forward-looking statements regarding future events and the future financial performance of BioCryst. Such forward-looking statements may include predictions regarding current and proposed clinical trials of forodesine HCL, BCX-4208 and peramivir, potential development of compounds not in clinical testing, and cash flow projections, including the benefit of the U.S. Department of Health and Human Services funding of peramivir. These statements involve known and unknown risks, uncertainties and other factors that may cause the actual future of events or actual future financial performance to be significantly different from those expressed or implied by the forward-looking statements.

Please refer to the section "Risk Factors" in the Company's most-recent press releases and the documents that accompany files from time to time with the SEC. Specifically, you may refer to the Company's most recent Form 10-K, Form 10-Q, and Form 8-K, all of which are readily available on our website at www.biocryst.com. These documents contain and identify additional information regarding important factors that could cause the actual results to differ from those contained in the forward-looking statements. Such information can typically be found in the section marked "Risk Factors" or "Forward-Looking Statements." These statements may reflect the Company's views with respect to future events. BioCryst has no obligation to update or revise these statements. BioCryst cautions that you should not place undue reliance on these forward-looking statements.

Joining me on the call today are Jon Stonehouse, CEO of BioCryst, and Dr. Thomas Simon, our Interim Chief Medical Officer. We are also pleased to have Dr. William Sheridan, former Vice President of Product Development to Amgen, who is currently consulting with us on our PNP development program.

Before I turn the call over to Jon, who will provide you with an update on our clinical programs, let me give you a brief update on our first quarter financials. I will refer you to slide number two.

For the first quarter ended March 31, 2008, BioCryst reported revenues of $10.8 million, compared to $9.2 million for the first quarter of 2007. The increase in revenues is primarily due to revenues with our contract with the U.S. Department of Health and Human Services for the development of peramivir and the continuing amortization of deferred revenue from our collaborative agreements.

The net loss for the quarter was $13.1 million, or $0.34 per share, compared to a net loss of $8.8 million, or $0.30 per share, for the quarter ended March 31, 2007. R&D expenses for the first quarter were $21.9 million compared to $16.2 million in the first quarter of 2007. The increase in R&D expenses is attributable to an increase in clinical trial related expenses, manufacturing costs for our lead product candidates and cost related to an increase in the personnel supporting the development of our product candidates.

G&A expenses for the first quarter 2008 were $2.9 million compared to $2.4 million in the first quarter of 2007. The increase in G&A expenses is based on an increase in professional fees and personnel related costs.

As of March 31, 2008, the Company had cash, cash equivalents and investments of $81.2 million. 4208, we expect our net cash used to be between $25 million and $30 million, and this is in line with our previous guidance. This [burn] rate could vary significantly depending on the timing of reimbursement from HHS.

That concludes our financial report, and I will turn the call to Jon.

Thank you, Stuart. First off, I would like to discuss the recent decision by Roche to terminate its license to develop BCX-4208 for autoimmune diseases. This means that although Roche and BioCryst will complete the ongoing Phase IIa trial, BioCryst will regain full worldwide rights to the BCX-4208 compound.

While we are disappointed to no longer have Roche as our partner for the development of BCX-4208, we are encouraged by the safety and tolerability profile, pharmacokinetic characteristics and pharmacodynamic dose response effect demonstrated in both the Phase I multiple ascending dose study, at doses up to 1040mg administered once daily for 7 days, and an interim analysis from the ongoing Phase IIa study. Top line data from the completed Phase IIa trial is expected in the second half of 2008.

After reviewing the full data set, we will be able to make an informed decision regarding the next steps in the development of BCX-4208. Roche believes the results to date do not preclude further clinical exploration in autoimmune diseases. Roche has indicated that its decision was based in part on the continued inability to model effects in preclinical species. Roche believes that this issue, coupled with the absence of striking efficacy in the Phase II interim analysis, makes development of BCX-4208 challenging in transplantation, which was the main driver for Roche.

As a reminder, the Phase IIa study is a randomized, double blind, placebo controlled, dose ranging trial in which patients were dosed once daily for six weeks with 20mg of BCX-4208, 120mg of BCX-4208 or placebo. The primary objective is safety and tolerability. The secondary objectives are pharmacodynamic effect and clinical response. A planned interim analysis has been completed on 30 subjects of whom 18 completed the full six weeks of treatment.

The interim analysis showed that BCX-4208 was safe and well-tolerated. A dose-dependant reduction in peripheral blood lymphocyte counts was observed including CD4+, CD8+, CD56+, and CD20+ cells. The observed reductions in lymphocyte counts are similar to the percentage reductions with other currently marketed therapies for autoimmune diseases.

No clinical efficacy was observed in the interim analysis. However, it is important to understand the context of how this trial was designed. Through discussions with the FDA, Roche and BioCryst designed the trial that was focused on safety. This trial in 66 patients with psoriasis was confined to doses of 20mg and 120mg therapy given for six weeks rather than the standard 12 weeks in typical psoriasis efficacy studies.

In addition, the study required subject discontinuation for a CD4+ count less than 350 cells per milliliter of blood. This rule may have interfered with the assessment of efficacy. The trial has already reached full enrollment. The trial is ongoing and we are looking forward to reviewing the complete data set.

So, switching gears, this quarter we continued to advance our forodesine HCL program. Our pivotal trial of forodesine HCL in patients with cutaneous T-cell lymphoma is progressing as planned. Regarding chronic lymphocytic leukemia or CLL, we have also shown that forodesine HCL may be a helpful treatment option. Data presented at the December 2007 ASH meeting, revealed the potential of forodesine HCL to be an effective therapy for patients with CLL. As the graph on slide four displays, cells from 15 of 29 patients showed cytotoxicity effects from forodesine HCL in over 60% of CLL cells. In addition, cells from 11 cases demonstrated cytotoxicity in 40% to 60% of the cells.

During the quarter, we initiated another single-arm Phase II trial evaluating the effects of forodesine HCL in patients with previously treated CLL. The primary endpoint is response rate. The first patient has already been dosed, and we will provide an update on the programs by year end.

Now, I would like to discuss the recent progress within our peramivir program. In early January, we initiated a Phase III trial of peramivir in subjects with influenza. This study was voluntarily discontinued in January after 82 subjects were enrolled because of a decision to evaluate higher doses in a Phase II setting. The Phase III trial was a randomized, double blind, placebo controlled study in subjects with influenza A or B with a target enrollment of 600 patients. Patients were to be dosed with either placebo or 300mg of i.m. peramivir. The primary endpoint was timed to alleviation of symptoms with safety and viral shedding as a key secondary endpoint.

Slide 6 shows preliminary data on the primary endpoint of time to alleviation of symptoms. The study was designed to demonstrate a difference in the time to alleviation of symptoms between subjects receiving 300mg of peramivir and subjects receiving placebo. In the subjects with a confirmed influenza A infection and who had received peramivir 300mg, we saw an average improvement of 30 hours in time to alleviation of symptoms compared to subjects who had received placebo.

In the overall studied population, a 14 hour difference in symptoms alleviation was observed between subjects who received 300mg of peramivir and subjects who received placebo. Very large confidence intervals were associated with these results, as would be expected given the small sample sizes. The small sample size was due to the trial not being carried out to completion. The observed treatment differences were not statistically significant.

Slide seven shows drug levels for peramivir from multiple studies. The first two bars show results from Phase I clinical studies in a highly controlled environment. The third bar shows the results from the Phase III study. The Cmax values are similar from the Phase III study and the Phase I studies indicating that following these needle length guidelines in the Phase III setting leads to plasma levels that are comparable to the Phase I setting.

Virology data were also measured in this discontinued study. The magnitude of reduction in viral load and the percentages of subject shedding influenza were consistent with the data seen in the previous Phase II study. [Basing] data from this discontinued Phase III study continue to demonstrate an excellent safety profile for peramivir at doses evaluated to date.

The data from our previous Phase II study, together with these preliminary data from the discontinued Phase III study, suggest that a 300mg dose of peramivir may be at the low end of the dose response curve, and evaluation of higher doses may result in increased clinical benefit. In preparation for a new Phase II trial of evaluating a dose of peramivir higher than 300, we are developing a new formulation, which may allow doses of up to 900mg.

The chart on slide eight provides a comprehensive comparison of actual PK data from our i.m. peramivir studies and model PK data. The graph compares Cmax levels achieved at different doses ranging from 150mg to 600mg across Phase I studies 111 and 117 and the Phase III study 311. Based upon PK modeling using Phase I study data, doses up to 900mg may lead to much high drug exposure. By the end of the second quarter, we will have completed a pharmacokinetic analysis comparing the new and old formulations, which will allow us to initiate a trial of peramivir at higher doses this summer.

This final slide provides an overview of our upcoming milestones. Later this summer, we are expecting an update from our partner, Shionogi. For our on trial and hospitalized patients receiving i.v. peramivir, we will provide an update by year end. As mentioned previously, we are also preparing to initiate a Phase II i.m. trial within the third quarter. Later in the year, we are expecting full data from the BCX-4208 Phase IIa trial with Roche and preliminary data from our forodesine HCL trial in CLL.

So, in conclusion, it has been an active quarter. We continue to learn a lot about our late stage programs. We have multiple programs moving forward with important data from each of them coming within the year. We look forward to providing you with further updates as the year progresses.

Thank you for joining us today, and we will open it up to questions now.

(OPERATOR INSTRUCTIONS.) Joseph Schwartz of Leerink Swann. Please go ahead.

Hi, good morning. Thanks for taking the questions. I was wondering if you could, first of all, give us your thoughts on the reasons to think that 4208 would work better in other autoimmune diseases. How do you view the profile of these lymphocyte reductions versus the sequelae in other diseases?

Thanks, Joe. This is Jon. Let me turn that question over Bill Sheridan. Let me just elaborate a little bit more on why he is on the call. As Stuart said, he is a consultant with us, and one of the things that we are doing is getting the best experts to help us think through -- look at the data, understand the data, and then figure out the path forward. And Bill brings a lot of experience in the industry and in particular in oncology and autoimmune disease. So, I will turn it over to Bill.

Thank you. The first comment to make is that is has not been determined yet whether BCX-4208 works in psoriasis or not. And as Jon explained in his remarks, this Phase IIa study was designed primarily as a safety and tolerability and PK and TD exploration study. Efficacy was not a primary endpoint. It is not sized to make a determination that is definitive, so we are looking for signals.

So, what BioCryst will need to do given the encouraging drop in lymphocytes and various substance of lymphocytes that we are seeing, is to evaluate various autoimmune diseases and make a decision about how to explore this compound. So, it remains to be determined whether or not the drug works in psoriasis. You cannot draw a conclusion yet about that.

Okay. And what else has Roche been doing with the drug since they have had it in their hands? I mean, it has been a long time now that we have waited for the data. Some patients have received the drug, but have they worked on the formulation? Has that changed in any way?

Yes. They have actually done a lot of work. A lot of preclinical work, a lot of additional Phase I work, multiple ascending dosing work beyond what BioCryst had started, and a lot of very good work on API and formulation work. So, in general, the molecule is in very good shape to continue to do further development.

Okay, and then just one question on peramivir, the i.m. formulation in particular, the new formulation. How does the relative viscosity look at this point for the more concentrated form, and what does that imply for the needle girth since there were issues before with the length?

I will let Tom Simon answer that.

Viscosity is based -- first of all, thanks for the question. The viscosity is basically the same as the new and old formulations. Needle lengths will be comparable.

And the gauge will be the same.

Yes.

Okay. And is there any reason to think that you could not more than triple the dose beyond 900mg if you need to?

You start run into volume issues if you go up too far with this.

Okay, great. Thanks so much.

Reni Benjamin of Rodman & Renshaw. Please go ahead.

Hi, this is Dr. Ling on behalf of Ren. Good morning, and thank you for taking my questions.

So, my first question is about the forodesine program in CLL. You mentioned you are probably going to give an update later this year. I was wondering whether it is going to be presented at some medical conference.

So, as I said, we have got two studies going on with CLL. We had a study with M.D. Anderson and then another one that we recently initiated. Enrollment is progressing and depending on where we are with enrollment, we will decide whether or not we have got enough information to present at upcoming meetings.

Okay. My second question is regarding the peramivir program. So, you mentioned you will probably start a new trial in the summer. I was wondering, what are the other steps you need to take before a decision of this trial and whether you need to submit another IND for this new formulation.

Tom Simon. So, the steps before this trial will be first to complete the ongoing investigations with the new formulation as selected and make sure we have got the dosage nailed down, the formulation nailed down. We do not need to file a new IND, and our plan would be to go ahead and start that in the summer.

I am sorry. So, you do not need to or you do need to?

Do not.

Do not need to, okay.

Do not need a new IND.

All right, great. And then, I probably have missed this, but when you talk about the preliminary data from the discontinued Phase III trial, how many patients were treated there?

A total of 82 patients were enrolled.

Uh-huh.

And they were randomized 2 to 1 in favor of the peramivir, a similar split between men and women, also just within the Northern hemisphere. Keep in mind that only 14% of the total plan population was enrolled, so that is why those confidence intervals are so broad, and it is very hard to go beyond just the data we are showing you.

Okay. And then last I just want to make sure, for the new trial you are going to test both higher doses apparently, and then regarding the needle length, you are going to sort of use the proper needle length for people with different BMI index. Am I understanding it correctly?

Yes, absolutely. And I think that one of the nice things about the data that Jon showed you is that we have shown that using those needle guidelines, we can get drug levels that are comparable to what we get in the very well-controlled Phase I setting.

But, then -- yes, I guess by increasing both tests at a higher dose and also sort of increase the drug exposure by using the proper needle lengths, I guess, are you concerned maybe at some point you are going to give patients too much drugs, because you apparently you increase the drug exposure from two prong?

No. We are not concerned about that. We have very good margins in terms of our preclinical safety data, so we really are fine by that score. The very reason to think this will work just fine.

So, based on your preclinical study, what is the corresponding maximum dose you can push in humans?

So, can you repeat that question? What is the corresponding Cmax?

No. Actually, I guess I try to get a sense of the therapeutic window based on your preclinical data. What is sort of the highest [MT], the highest tolerated dose you can push in humans?

We can go to doses higher than 900. The rate limiter for us now is the volume of drug. And so, at least from what we can see thus far, and again we had a complete to Phase II study with the new and old formulations, from a volume perspective 900 looks like the top.

Okay. All right, thank you very much for taking my questions.

(OPERATOR INSTRUCTIONS.) Seeing that there are no additional questions, I would like to turn the call back over to Jon Stonehouse, CEO of BioCryst, for closing comments.

So, again, we appreciate your participation. We appreciate the questions. One thing that I just want to remind everybody is BioCryst is a company of multiple products with a pretty deep pipeline for a company our size. And we feel that this is a very exciting year because we are moving a number of these compounds forward, and as I said in my prepared remarks, this year we will get data on each of them. And so, we are really looking forward to continuing to push forward and to get more information on our compounds as the year progresses. So, again, thank you for your interest, and have a good day.

Thank you again for joining BioCryst's First Quarter 2008 Financial Results and Corporate Update conference call. The conference has ended. You may now disconnect your lines. Thank you.