Rigel Pharmaceuticals, Inc. (RIGL) Q4 2016 Earnings Report, Transcript and Summary

Good afternoon, and welcome to Rigel Pharmaceutical's Earnings Conference Call for the Fourth Quarter and Year End of 2016. All participants are in listen-only mode. We will be facilitating a question-and-answer session at the end of today's conference. [Operator Instructions] I would like to remind you that this call is being recorded for replay purpose from Rigel's website. [Operator Instructions] And now, I will turn this conference over to our first speaker, Dolly Vance, who is Rigel's Executive Vice President, Corporate Affairs and General Counsel. Go ahead.

Hello and welcome to our financial results and business update conference call. The financial press release for the fourth quarter and year end of 2016 was issued a short while ago and can be viewed in the news and events section of our Investor Relations page on our website, www.rigel.com. Joining me on the call today from Rigel are Raul Rodriguez, our CEO; Ryan Maynard, our CFO; and Anne-Marie Duliege, our Chief Medical Officer. As a reminder, during today's call, we may make forward-looking statements regarding our financial outlook and our plans and timing for regulatory and product development. These statements are subject to risk and uncertainties that may cause actual results to differ from those forecasted. A description of these risks can be found in our most recent Annual Report in Form 10-K on file with the SEC. Any forward-looking statements are made only as of today's date, and we undertake no obligation to update these forward-looking statements to reflect subsequent events or circumstances. At this time, I would like to turn the call over to our CEO, Raul Rodriguez.

Thanks, Dolly, and welcome everyone. Thank you for your time this afternoon. As most of you know 2016 was a pivotal year for Rigel. We achieved significant milestones with our lead product candidate fostamatinib and restructured our company which positioned us for success as we move fostamatinib through the regulatory process and we hope to a commercial launch. Looking ahead our goal is to transform Rigel with a specialized focused commercial organization aimed at providing new therapeutics with patients with chronic immune thrombocytopenia also known as ITP as well as other indications. We've been very encouraged by the completion of our FIT Phase 3 clinical program of fostamatinib and ITP because the studies are remarkably consistent across all three trials. In a subset of patients, fostamatinib was shown to have a clear clinical benefit which is important as these are difficult to treat patients with chronic ITP. I'll share a summary of a more recent accomplishments related to fostamatinib and ITP. Later Anne-Marie will provide additional background on the three FIT Phase 3 clinical trials, which include the pivotal 047 and 048 studies as well as our open label long-term extension study of 049. In August and October of 2016, Rigel reported results from the three FIT Phase 3 clinical trials, which demonstrated that patients who responded to fostamatinib have a timely, robust and sustained response to treatment. The rapid response provides an early feedback as to whether fostamatinib maybe a viable treatment option for that patient's ITP. The enduring benefit gives patients and their clinicians confidence that their disease is under control in the long term. During the post study, our post study analysis of the FIT data for our NDA submission, we characterized an additional patient population in the fostamatinib group that shows a meaningful platelet response, but did not meet the defined stable platelet response in the trial. Using this group as well as the stable responders, we calculated the overall response rate from studies 047 and 048. We found that the overall response rate for fostamatinib was 29%, 29 of 101 patients compared to 2% for placebo, one out of 49 with a P value of less than 0.0001. Anne-Marie will give you further information on this calculation in her section. We also found that those patients who were stable responders to fostamatinib continue to maintain their benefit for a medium of sixteen months and increasing, and notably the FIT Phase 3 clinical program confirmed that fostamatinib had a consistent, tolerable and predictable safety profile. This profile aligned with the safety database of approximately 5,000 patient used. Given the totality of the FIT Phase 3 clinical program, we remain committed to submitting the new drug application to the U.S. Food and Drug Administration by the end of the first quarter of 2017 within a matter of weeks. Should regulatory milestones progress as anticipated, we hope to advance our vision of evaluating of evolving fostamatinib into a profitable biotech company. I also would like to briefly review a few additional fourth quarter activities before turning the call over to Anne-Marie and who will give you more detail about our ITP study results. In the fourth quarter, we expanded our commercial and regulatory capabilities with new hires that would support the advance of fostamatinib and potential commercial launch in the first half of 2018. We look forward to the contributions of these new management members and expect to add more in commercially related areas in the coming months. Now to the rest of our pipeline, we have an ongoing Phase 2 study of fostamatinib in IgA nephropathy. IgA nephropathy is chronic autoimmune disease associated with the inflammation in the kidneys that may diminish their ability to filter the blood. The condition affects an estimated 82,000 to a 165,000 cases in the U.S. Outside of controlling blood pressure with angiotensin blockade there are no therapies for this condition. In January, we reported results from the first cohort of this Phase 2 study which evaluated the safety and tolerability of a lower dose of fostamatinib 100 milligram BID. The study found that at 24 weeks fostamatinib is well tolerated and no new safety signals were detected. The data suggests the trend towards the greater reduction in proteinuria in fostamatinib treating patients relative to placebo. We expect the second cohort a 150 milligram BID will finish enrollment in 2017 with results in 2018. Beyond ITP and IgA nephropathy, we're continuing our investigation of fostamatinib in patients with autoimmune hemolytic anemia affecting approximately 40,000 adult patients. Autoimmune hemolytic anemia is a rare serious blood disorder where the immune system produces antibodies that result in the destruction of the bodies' own red blood cells. We expect to have results from this proof-of-concept study in 2017. In addition Rigel plans on selecting a molecule from its IRAK program for preclinical development in 2017. It is expected that this program will include clinical evaluation in immunology areas such as lupus, gout and/or psoriasis. I will now turn the call over to Anne-Marie. Following her presentation slide, we'll report on fourth quarter and year end financials. Anne-Marie?

Thank you, Raul. As Raul stated earlier, we have continued our analysis of results from the FIT Phase 3 clinical program. Overall, we believe that the predictable efficacy profile of fostamatinib combined with the safety profile will make fostamatinib, if approved and a trusted treatment option for those patients with chronic ITP that are in need of [indiscernible] therapy. This data will be presented to the FDA in the new drug application that we're currently preparing. Fostamatinib's unique mechanism of action provides a potential benefit to people with chronic ITP. As a reminder, fostamatinib is a SYK inhibitor and targets the underlying cause of ITP. SYK kinase is a key player in the immune system destructions of platelets in ITP. ITP patients can have platelet counts that for below 30,000, the level at which they are generally considered at risk for spontaneous or trauma induced hemorrhage. And chronic ITP is difficult to treat disease. This patient population is very heterogeneous, so it is hard to predict which patient will respond to which of the currently available treatment, if any. There are approximately 60,000 to 125,000 patients with chronic ITP in the U.S. and it qualifies as an orphan disease. Turning towards the slide presentation, I will now review some of the key data points related to fostamatinib in ITP. Let's look at Slide 10, the FIT Phase 3 program consisted of two identical placebo control studies, 047 and 048, combined 150 adult patients with chronic or persistent ITP were enrolled with 49 of them assigned to placebo. Patients indeed were randomized into fostamatinib or placebo in a two to one ratio and then dose for up to 24 weeks. The primary endpoint was the achievement of the stable platelet count equal to greater than 50,000 per microliter on at least four of the last six clinic visits from which 14 to 24. At the conclusion of the participation in either of the two studies, patients were invited to enroll in an open label long-term extension study 049 where all patients received fostamatinib. Moving to Slide 11, overall the population suffered with very severe chronic ITP as reflected in, one the median platelet count at baseline of 16,000 per microliter, and two a median duration of ITP of 8.5 years prior to study entry. And all the subjects had received one or more prior ITP treatment option with the majority of them being steroid, 35% of them had a splenectomy and close to 50% of patients had tried TPO agent. Moving to Slide 12, previously we announced the results of both the FIT 047 and 048 studies, which showed a consistent stable platelet response of plus 18% in the fostamatinib group in both studies. With those studies complete, we have all the data in order to provide additional insight. As Raul explained when patients respond to fostamatinib, they respond quickly with a robust and sustained response. If you look at this chart on Slide 13, it shows how quickly the median platelet numbers to the fostamatinib responder in green began to climb within a few weeks and the platelet counts continue to rise to approximately 100,000 per microliter where they held steady through the balance of the 047 and 048 studies. Turning now to Slide 14, during our post-op data review for the NDA filings, further analysis was done to characterize fostamatinib in patients who may not meet the very high bar set for the stable response criteria in 047 and 048, but who may have achieved a meaningful platelet count or benefit. We specifically look at patients who had achieved at least two consecutive platelet counts over 50,000 per microliter during the trough without rescue. Initially defined that transient, these responders in fact had a platelet response with a median of approximately 50,000 per microliter overtime and so we have renamed these as intermediate responses, intermediate between no response and a stable response. There were 11 of these patients in the fostamatinib group and none in the placebo group. By contrast, the non-responders and the placebo patient median platelet count remained at or below 30,000 per microliter over time. So, when adding the stable and intermediate response rate, the overall response rate for both studies again shown on this slide 14, is 29%, 29 out of 101 patients for the fostamatinib group compared to 2% for placebo, and the difference is of course highly significant at 0.0001. But the important point is that the primary endpoint is the stable response, this is the predefined endpoint in our NDA submissions. The intermediate response is the post study analysis that supports the clear treatment of set of fostamatinib. Coming back to the analysis of the primary endpoint we conclude on Slide 15 that fostamatinib works effectively for certain ITP patients and the benefit was consistent across all subgroup analyzed including exposure to TPO agents previously, this blood platelet producing booster who have limited treatment options remaining. Moving to Slide 16 with over 5,000 patients worth of data including previous trial in RA, we feel comfortable about the safety profile of fostamatinib. The results during the placebo control studies are summarized in this table. Adverse events in the fostamatinib group in studies 047 and 048 were generally mild or moderate with GI gastrointestinal, blood pressure and LFT adverse events reported most frequently. All adverse events are manageable and reversible. Of note, there were more assays of bleeding in the placebo group then in the fostamatinib group. In the fostamatinib group inside these assays, the serious adverse events of bleeding occurred in the non-responders and not in the stable or in the intermediate response rate. Now the next three slides describe our ongoing open label long-term extension study also known as 049. All patients in the FIT 047 and 048 studies were invited to enroll in 049 wherein they had completed the participation of the parent test. When the data was collected up to in September 2016 which is the interim analysis of this long-term extension, there were 123 patients enrolled and receiving fostamatinib in 049. 17 stable platelet responders from 047 and 048 studies had enrolled into the 049 study and the median platelet count for those responders were over 100,000 per microliter after a total median exposure to fostamatinib of approximately 16 months. This is actually a very good result because it shows that for the majority of patients have better response. This response is sustained overtime. In the 049 study, we also assessed the percentage of patients who were initially randomized to the placebo group in the parent study and responded in the 049 Study. There were nine of these patients and 9 out of 41, is 22% with a P value of 0.0078. So, 22% of the former placebo patients now newly exposed to fostamatinib for a minimum of 12 weeks achieved a prospectively defined stable response. And this result is consistent with the response rate of 18% achieved in the parent trial. So our analysis of the FIT Phase 3 study will continue, and we plan to share additional information at upcoming scientific meetings and in publication. On Slide 21, we want to remind you of our regulatory path forward where using the current available data to prepare the NDA dose here for fostamatinib in ITP to provide to the FDA. Our submission could potentially lead to an FDA Advisory Committee review later in the year and of course we will continue to communicate about all regulatory milestones. Moving to Slide 22, Raul mentioned our study of fostamatinib in IgA nephropathy the most common glomerulonephritis worldwide. Because it causes inflammation and scarring of the kidney, people with this rare condition are at risk of serious complications from kidney dysfunction including high blood pressure and renal failure. The first cohort in the Phase 2 study, outlined on Slide 23 was completed at various centers throughout Asia, the US and Europe. This cohort evaluated the efficacy, safety and tolerability of lower dose of fostamatinib 100 milligram BID with 26 patients assigned to fostamatinib and 12 patients to the placebo actually randomized, and the measure of change in proteinuria renal function and histology which were the efficacy parameters. In fact, the primary efficacy endpoint was the main change of proteinuria from baseline to 24 weeks and it is shown on Slide 24. The study found that at 24 weeks fostamatinib was well tolerated with no new safety signal detected. The initial data suggested trend towards a greater reduction in proteinuria in fostamatinib-treated patients relative to placebo. Given this initial data, we began enrollment of cohort 2. Rigel expects that the second cohort evaluating a higher dose of fostamatinib 150 milligram BID for IgA nephropathy will finish enrollment in 2017 with results in 2018. I will now turn the call over to Ryan to provide our financial reporting.

Thanks, Anne-Marie. For the fourth quarter of 2016, we reported a net loss of $15.6 million or $0.16 per share compared to a net loss of $12.7 million or $0.14 per share in the fourth quarter of 2015. Revenues from collaboration were 3 million in the fourth quarter which was comprised of a milestone payment received from Bristol-Myers Squibb. We reported total cost and expenses of 18.8 million in the fourth quarter of 2016 compared to 21.3 million in the fourth quarter of 2015. This decrease was primarily due to reduction in workforce in September of 2016 offset by an increase in stock-based compensation expense as well as increasing costs related to the NDA submission with fostamatinib in ITP. For the year ended December 31, 2016, we reported contract revenues from collaborations of 20.4 million and a net loss of 69.2 million or $0.73 per share compared to contract revenues from collaborations of 28.9 million and a net loss of 51.5 million or $0.58 per share in 2015. Contract revenues from collaborations in 2016 were mainly comprised of the upfront payment amortization and a milestone payment from our collaboration with BMS. As of December 31, 2016, we had cash, cash equivalents and short-term investments of 74.8 million compared to 126.3 million as of December 31, 2015. In February of 2017, we completed an underwritten public offering that brought in 43.0 million in cash proceeds after discounts commission and offering expenses. We also received a milestone payment of 3.3 million in February of 2017 from BerGenBio due to their advancement of BGB324, its small molecule AXL kinase inhibitor into a Phase 2 clinical study. Therefore, we expect that our current cash amounts will be sufficient to support our projected spending requirements including preparation of the potential commercial launch of fostamatinib for at least the next 12 months. We also continue to evaluate ex-U.S. partnerships for fostamatinib and other partnering opportunities across our pipeline. Now I'll turn it back over to Raul who'll provide some concluding thoughts before we open up the call for questions.

Thank you, Ryan. So, before turning the call over to questions, I'd like to just take a minute and step back a bit and make a few observations. So as we've got in the detail and need to take a breath and see where we're. The last 13 months have really been monumental for Rigel, and we made a major transition. We completed a Phase 3 program that showed that fostamatinib may be a viable treatment for ITP patients. So, we actually feel like we've a product here. We met with ITP patients also last year and what they told us is that this disease places a tremendous burden on their lives and that they have a need for new treatment options, and this made us all the more determined about doing what we're doing. So, we refocused the Company and that allowed us to invest in regulatory and commercial readiness. We completed a fundraise which gave us additional resources to execute on that plan. So, all this positions us very well for moving forward. This year, we're going to manage the NDA towards the potential approval. We're going to get ready for our commercial launch in the U.S. in the first part of next year, and we're going to work on expanding our pipeline. So, we're really excited about where we're at this point in the Company’s history. So, at this time I'll open your calls up for questions.

[Operator Instructions] Our first question comes from the line of Josh Schimmer from Piper Jaffray.

Anne-Marie, the color on bleeding events in the Phase 3 FIT trials was very interesting, wondering if you had data on either minor bleeding events in the FIT trials or more serious bleeding in the extension trials that would further support the clinical benefit of the drug? Thank you.

So, there were definitely more minor bleeding episodes, more in the form of minor [indiscernible] petechiae. That would be expected to see in both groups. And then in the long-term extension program, there were some serious adverse events of bleeding that were truly expected and did not change our analysis that happened in the non-responder groups and did not change our analysis of what I've provided on the slide.

So just to be clear in the long-term extension those bleeding as they used were in patients who switched over from the placebo arm and did not respond or were there any that this current in responder population?

So, those one [indiscernible] that occurred on day one of fostamatinib treatment. You wouldn't expect that fostamatinib worked as quickly on day one. So, we start comment on a responder that was early and another patient who had a gastric abnormality that led to bleeding even in the context of a response, but that was again totally expected. Fostamatinib doesn't always prevent all form of bleeding, but prevents few of these at very low platelet count.

Thank you. Our next question comes from the line of Eun Yang from Jefferies. Your line is open.

So, you're planning to on your own track to file an NDA this quarter. I'm wondering, if you have had a recent interaction with the FDA, and if so, do they tell you that there is going to be an outcome moving in the fourth quarter?

So, the answer is we're definitely planning to file an NDA on time. Second is we have not had any additional contact with the FDA. The FDA is aware of our filings and aware of our filing timelines that's all. We would not expect at this time that they would provide any comments.

And we've incurred nothing on a potential outcome.

So, is that kind of normal that you file in NDA without kind of some sort of agreement with the FDA or discussion? I mean, you mentioned that they are aware of your potential filing, but is that how you normally have it done?

So, we had met with FDA back prior to the results to discuss the nature and the content of the filings should the results support the filing. That was on prior results. In addition and as we put it, we have sent our top line results to the FDA in writing shortly after we got both trial results. And we indicated to them that we were planning to file in NDA based on these results. And they have not gotten back to us specifically with any comments or questions about our results, but they have acknowledged our e-mail and they understand that we will be filing at the end of Q1.

So, you haven't got any response from the FDA after you submitted the data, that FDA said, hey we received the data, we're okay with your filing?

You're correct. You're correct the FDA did not make any comment on our data. We're always expecting them to make comments. They are very busy with other submission and right now they just know that we're filing based on 2.12 that have showed a clear treatment effect.

Okay, so when you file, do you think that there is a -- and I don't understand, is there a possibility that FDA would say, hey, refusal to file and they show letter?

We don't want to -- I don't want to speak on behalf of the FDA. Really, I will never try to do that. But the FDA usually will issue a refusal to file, if they believe there was no enough substance in this, in the document or there were major problems with the organization of the filing. We have made sure and will continue to make sure that none of these two circumstances happened. We have also shared our results with consultant on a regulatory perspective who agreed with us that there's a clear and consistent treatment effect across three files. With two of them having met the formal P value of significant that we have a well defined safety profile and that we're addressing an orphan drug disease with a population of severe patients with chronic ITP that have an unmet medical need, and that in this context it is very reasonable for us to submit on these data and engage in a dialogue with the FDA.

And then autoimmune hemolytic anemia, I mean you're just saying, hey, your data in 2017. Can you give us kind of status to how many patients in Phase 1 are you planning to enroll by '17, how many patients have been enrolled to date?

The goal of that stage is as you were corrected 17 patients, more important is that we feel confident we'll enough patients in our belt 17 or whatever even if it's short of that to make a call this calendar year, and we'll be able to release that for you. So, we're not going to where we were and give updates on a regular basis, but simply wait we have enough to make something definitive, and then we'll make that statements. But we're confident that it'll happen this year.

And then last question is on cancer immunotherapy with the Bristol. In the first quarter of last year, Bristol identified a TGF beta receptor kinase inhibitor for IND enabling toxic studies. When do you think you would move into Phase 1 and along the way is there any milestone payment from Bristol and if so how much would that be?

Fortunately that they collaborated -- you're actually right they did select the molecule and we did receive a payment, but in terms of future we really can't comment on that. Really, it's their program and they have shared with us confidential information on the plan. And unfortunately, we're not allowed to disclose that to others. But they're working very hard, I can say that, I think it's an excellent collaboration, and we and I believe they're very enthusiastic about the program. And we'll keep you updated as dated as we receive milestones or able to disclose something.

[Operator Instructions] We'll be taking our next question from the line of Anupam Rama from JPMorgan.

It's Eric in for Anupam this evening. Thanks for taking the questions. Just the first on the NDA, just wondering, if you could walk us through the remaining kind of gating factors here ahead of the following this quarter, and whether given the fact that you have accrued some refractory patients in the FIT study whether you see tend to seek priority review in your filing? And then I have a follow-up.

So, what I did -- thanks for your question. This is going to be one of the largest NDAs that the FDA will submit in I think certainly in this division will be monumental in terms of the size because we have so much legacy data. And that's really what's taking up a fair amount of work. I think we're very confident that we're in very good shape to file it. I mean there's a lot of QC-ing going on, et cetera, in terms of doing all of that work and it's a tremendous effort. And I'd like to just take a minute, if I can just to commend our folks in regulatory here who have been working 7 days a week to get this accomplished. And they lead a broad effort that this is undertaken by the entire company in support of that. So really a tremendous amount of work, but as you can imagine, there's still the rest of this month to get work done and they're extraordinarily busy. There's really to characterize it as the key this and that step, there's just so many steps that are required, it would be unfair to so diminish it. So a fair amount of work a lot of work here is remaining to still be done, but we're confident on our ability to meet that target.

Maybe, if I could just follow up with a question on IgA nephropathy. I'm just curious to know what kind of feedback you're getting from docs on the initial data disclosure in January? And whether there are any learnings from kind of the first cohort that in execution might allow for kind of better patient randomization in the second cohort?

So, we have shared the data with few key opinion leaders in IgA nephropathy and they are encouraged because they don't see too many situations of decrease in proteinuria. One of the strengths of the trial that we're looking for mostly in for the second cohort, actually right now the results are very limited is having a histology, so a renal biopsy at study entry and at 24 weeks, which is something that the nephrologists will look for with great interest. In terms of the randomization, there's hardly anything that one can do when we there's so small numbers. We know that randomization doesn't work very well. And so we hope that the second cohort will sort of decrease a little bit this imbalance, but these are small numbers and there's hardly anything we can do about it.

Our next question comes from the line of Do Kim from BMO. Your line is open.

This is Al. A quick follow-up on the timeline, it's hard to believe this is a little bit, but the comments for fostamatinib in ITP. Just to clarify. Is there a specific time by which you should hear from the FDA regarding the possibility of an outcome?

Yes, so, we first rendered the first two months after submission of our and NDA will be through the FDA to review and make sure that they truly actually themselves want to formally review it. That will be the acceptance of our submission. We expect that within two to three months after that, we may have some indications as some of the FDA's questions about the organizing of the file and then start getting into more discussions that with us. So, that should be mostly something over the summer that we would expect to hear about potential ODAC. Clearly, we'll be there for in ODAC prior to that anyway.

And then moving a little bit later could you talk about how you think physicians will use fostamatinib given the Phase 3 study population and whether it could be ahead of TPO agents immediately or how long it'll take to sort of get to an expanded patient population?

I think the label that the trial that we did allows for a broad label for the product and I think one thing that we learned from this Phase 3 program is that the product works about equally well across a wide range of patients with clinical, different clinical backgrounds that is TPO experience as well as TPO naïve, splenectomized, not splenectomized with toxin experience, not experience as well, I mean though that's not approved. So, really across a wide range of patient populations, and so it's available to benefit all those types of patients, I think our exact positioning of the product and how we'll be used at launch might be one thing and certainly our effort would be to expand the utility of the product so that clinicians and their patients have access to this product. Because keep in mind if it works for you it works really well and I think patients who benefit from the product do so quite profoundly, and so that's something that we want to communicate, exactly where it'll be used is yet to be defined depending on a variety of different things. But we'll keep you up-to-date in terms of our thoughts on that. I think as this year progresses and our positioning of the product and forecast becomes a bit more refined, we'll be able to share some of thoughts with you with more detail.

And maybe just one more question on IgA trial. If you could provide any more details on the strength of the positive trend you're seeing and as it appears the fostamatinib benefitted on some patients or was it fairly consistent across all patients?

It was definitely some patients had more of a decrease in proteinuria and others had none. So, it didn't not -- was not a consistent decrease for all patients and this represented average across all our patients. We were not -- we are not part of the study -- we intended for the study to show anything significant in terms of asset, but just even this indication of the trend was for us encouraging enough in the context of no new safety signal to then support the continuation and the completion of enrollment of the second cohort in which by of course we hope to see more of efficacy treatment.

Keep in mind we usually see a stronger efficacy signal or a more robust signal at 150 milligram BID than we do at a 100 milligram, which is kind of the basis of what have been researched. We expect to see something more robust in the currently enrolling cohort.

Thank you. That's all the questioners that we have in the queue at this time. So, I'd like to turn the call back over to Raul Rodriguez for closing remarks.

Well, thank you very much, and thank you for your questions. It's been a very productive quarter and year for Rigel. I think the either upcoming year will be exciting as well and we'll continue to make substantial transition for the Company. We'll give you regular updates on our regulatory milestones and on our pipeline as appropriate. And we thank you, as always, for your support and interest in the Company.

Ladies and gentlemen, thank you again for your participation in today's conference. This now concludes the program and you may now disconnect at this time. Everyone have a great day.