Rigel Pharmaceuticals Inc (RIGL) 2020 Q2 法說會逐字稿

Greetings, and welcome to Rigel Pharmaceuticals Financial Conference Call for the Second Quarter 2020. (Operator Instructions) As a reminder, this conference is being recorded.

It is now my pleasure to introduce our first speaker, Dolly Vance, who is Rigel's Executive Vice President, Corporate Affairs and General Counsel. Thank you, Ms. Vance. You may begin.

Welcome to our second quarter 2020 financial results and business update conference call. The financial press release for the second quarter was issued a short while ago and can be viewed along with the accompanying slides for this presentation in the News & Events section of our Investor Relations page on our website at www.rigel.com.

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 risks and uncertainties that may cause actual results to differ from those forecasted. A description of these risks can be found in our annual report on Form 10-K for the year ended December 31, 2019, and subsequent filings with the SEC, including our Q1 quarterly report on Form 10-Q. 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.

Thank you, Dolly, and thank you for joining us on our second quarter 2020 financial and business update call. Also joining me today are Tarek Sallam, our Vice President of Marketing; our Chief Medical Officer, Wolfgang Dummer; and Dean Schorno, our CFO.

Now turning to Slide 5. We would like to introduce you to our key value drivers. For those of you already familiar with our story, there is a new value driver that we are excited to discuss. Rigel's 4 key value drivers are growing global sales of TAVALISSE in ITP; creating and capitalizing on the opportunity in warm autoimmune hemolytic anemia; exploring TAVALISSE or fostamatinib in the treatment of COVID pneumonia and COVID ARDS and subsequently looking at other pneumonias and ARDS caused by other health problems; and lastly, expanding our pipeline of programs based on key opportunities in immune-associated diseases.

In Q2, we continued to make good progress across all of these areas despite the challenges of the COVID pandemic. We are very proud today to tell you about these. In the recent quarter, we continued to grow TAVALISSE sales on a year-over-year basis and reported today a 47% increase compared to the second quarter of 2019. We are very pleased with this given the external challenges. This is also a testament to the perseverance of our commercial organization and the highly differentiated and effective product we provide. Tarek will tell you more in a few minutes.

As a reminder, outside of the U.S., we received approval for the use of fostamatinib in ITP in Europe in Q1 of this year. And as recently announced, our product is now available in Germany and the U.K. by our partner, Grifols, under the brand name TAVLESSE.

Another potential opportunity -- commercial opportunity in hematologic disorders is with warm autoimmune hemolytic anemia or AIHA, which we feel it to be a very large opportunity for Rigel. AIHA is also an autoimmune disease like ITP, where the body produces antibodies against a certain hematologic cell type, in this case, red blood cells. There is a real unmet need given that there are no approved products for this indication. Based on the progress we have made to date, Rigel is in a position to potentially be the first approved product in AIHA. In addition, this indication is very synergistic with ITP, both indications sharing the same prescribing hem/onc physicians, thus giving us the ability to leverage the TAVALISSE experience and knowledge currently being built by the Rigel field force.

As we shared recently, we are exploring the opportunity for TAVALISSE in the treatment of COVID-19 pneumonia and associated conditions. TAVALISSE and SYK inhibition may provide a unique and effective treatment to address the overreaction of the immune system and the destruction unleashed by the virus. Wolfgang will describe the scientific rationale, our compelling preclinical data and our recently announced investigator-sponsored trial in this -- in his section.

Lastly, our RIP1 inhibitor and our IRAK1/4 inhibitor programs are both in Phase I trials and we are very excited about the potential for both of these assets. IRAK and RIP are very attractive immune targets. And based on early data, our molecules have demonstrated characteristics that give us a great deal of optimism for their potential.

We continue to make progress in our discussion to secure a co-development/co-promotion agreement with these assets, and we believe that we will be able to do so by year-end. All of these key value drivers are extraordinarily attractive market opportunities that we are well positioned to advance.

Tarek will now give us a commercial update. Tarek?

Thank you, Raul. Today, I will provide a review of our commercial efforts. As a reminder, TAVALISSE is indicated for the treatment of thrombocytopenia in adult patients with chronic ITP, who have had an insufficient response to a previous treatment. Additionally, as Raul mentioned, our product has been successfully launched by Grifols, our European collaborators, under the brand name of TAVLESSE. We are excited to see the initial European markets come online, particularly with a broad indication that positions the product as a competitive alternative to the older standards of care.

So moving on to Slide 8. We continue to gain momentum in the U.S., which accounts for over half of the approximately $2 billion global ITP market. We achieved net product sales of approximately $15 million for the quarter, which is an increase of 47% year-over-year and 18% over the previous quarter. This is our highest quarter of sale to date, which is especially encouraging given the challenges that our field teams have been faced with. Additionally, we see continued strength in our persistency rate, which should improve as health care providers become more familiar with the product and utilize it in earlier lines of treatment.

We are pleased with this quarter's performance and the execution of our commercial efforts particularly in these challenging times. Physicians continue to express receptivity to TAVALISSE, highlighting the recent second-line data analysis, the unique mechanism of action and having an alternative oral option. All said, we believe that over time, enhanced physician access will allow us to accelerate our selling efforts to unlock incremental opportunity.

So I'm on Slide 9. Central to these efforts will be the recent post hoc analysis of our Phase III trial in ITP. We have previously presented the 78% response rate of TAVALISSE when utilized in the second-line setting. And here, you can see this analysis of the data further broken down in more detail.

As a reminder, the initial presentation of response from our Phase III program focused on the entire overall study population, which had an average duration of disease of 8.5 years and a median of 4 previous treatments. While many health care practitioners were impressed at the overall response rate in this clinical setting, the additional information reflected on this graph highlights that TAVALISSE and its differentiated mechanism of action can achieve response rates similar to other treatment options when used earlier in the treatment cycle. We believe this more refined look at the data will enable clinicians to make decisions focused more on therapeutic approach and individual patient needs and less on clinical trial response rates.

So let's transition to how we are educating health care providers on this new information and providing support for their patients during this unique and unprecedented environment due to the COVID-19 pandemic. Slide 10, please. As recent data suggests, unfortunately, it seems that the COVID-19 pandemic is not abating in the U.S. Like other organizations, we have not seen improvements in terms of our opportunities to have face-to-face interactions with physicians. That said, our teams have been doing a fantastic job utilizing virtual engagements to stay connected with our customers and to continue educating on TAVALISSE.

The new data analysis we just reviewed is a valuable tool that we have integrated into our selling materials and is being used by our field teams in clinical conversations with the physician community. Due to its recency, awareness of the data is relatively low amongst our customer base right now. But it is growing, and we are encouraged by the positive feedback from physicians.

Importantly, this post hoc analysis was recently published in the British Journal of Haematology. This is a highly respected journal, and we believe this recognition can help improve the awareness and conversation about this data amongst treating physicians. We believe this is a growing opportunity, supported by the endorsement of KOLs and now a highly respected peer-reviewed publication that reinforces the benefits of using TAVALISSE in earlier lines of treatment.

So turning to Slide 11. We are very excited to have a product that is now launched in markets outside of the U.S., namely Germany and the U.K. Our European collaborator, Grifols, is planning a phased rollout over the next 18 months across the rest of Europe. We also continue to make progress with our other partners listed on it and look forward to increasing the global footprint of TAVALISSE/fostamatinib. And finally, with a solid foundation in place that will support our commercial success in ITP, we are excited to execute on our strategy to make fostamatinib a franchise product, specifically the opportunity to have a potential indication in warm autoimmune hemolytic anemia or AIHA.

To give us an update on the progress we are making on this development program, I will now hand the call over to my colleague, Wolfgang Dummer, our Chief Medical Officer. Wolfgang?

Thank you, Tarek. Good afternoon, everybody.

I'd like to begin on Slide 13. With regards to our program in warm autoimmune hemolytic anemia, we continue to be well positioned to become the first approved drug for this indication. We're the only company currently in a Phase III pivotal trial, and we have currently 44 patients randomized, which is approximately half of the study. I'd also like to add that we are the only company that has Phase II clinical data already in warm AIHA.

We view AIHA as an attractive opportunity due to important synergies with our commercial ITP business. We're continuously educating physicians on mechanism of action, efficacy, safety and best clinical use of TAVALISSE in the ITP market. And these doctors are generally the same that treat AIHA patients. This should generate broad awareness of TAVALISSE as a treatment option for AIHA right upon launch.

Turning to Slide 14. Here's a brief update on our ongoing Phase III trial. As mentioned, we have currently 44 patients randomized, and sites have reopened recently after the pandemic shutdown. It is too early to precisely predict timing of enrollment completion at this point. We will update as we get a better understanding how the pandemic affects recruitment over the coming months. However, I would like to emphasize that we now have over 90 sites activated in 22 countries, and having an established operational foundation in this environment is very important. Since some countries are likely to normalize more quickly than others, we will be able to ramp enrollment on a country-by-country basis as the situation permits. So we believe that as soon as the COVID-19 situation normalizes, we should regain momentum rather quickly and efficiently.

Slide 15. Switching to COVID-19, let me talk you through our program with TAVALISSE or fostamatinib in COVID-19.

Moving to Slide 16. There is still a strong need to effectively treat COVID-19 and its disease complications. Fostamatinib can have a modulatory effect in several ways on the hyperreactive immune system, which causes the severe and life-threatening cases at a point where the viral load itself is already decreasing or eliminated. While a vaccine would be important to generate broader immunity, there still is and there will continue to be a strong need for safe and effective treatment options, including possibly fostamatinib. Fostamatinib is a great candidate to study as it is an approved, well-understood product, easy to take as a pill with a large safety database of over 4,500 patients treated in clinical trials.

On the next 3 slides, I will lead you through the clear scientific rationale for SYK inhibition in COVID-19 before I speak about the clinical trial at Imperial College.

The Slide 17 provides a simplified overview of the role of SYK signaling in the COVID-19 pathogenesis. Please have a look at the virus particle at the top middle of the image. In the early stages of the infection, the replicating virus causes lung epithelial cell destruction and release of so-called damage-associated molecular patterns, DAMS; and pathogen-associated molecular patterns, PAMS, which binds to C lectin receptors, on the right of the image. Signaling through C lectin receptors can lead to excessive inflammatory cytokine release and coagulopathy from vascular endothelial cells as well as to neutrophil activation and cytotoxicity by a process called mitosis. All these events can damage the lung and even other organs such as the kidneys or the heart. SYK inhibition with fostamatinib can reduce this highly inflammatory process.

On the top left of the image, you can see the second main reason for a hyperreactive immune system. As a response to the viral infection, our immune systems begin to make anti-SARS-Cov-2 antibodies. These antibodies then form immune complexes with the virus, which binds to Fcgamma receptor-expressing cells such as macrophages, dendritic cells, monocytes and, in some patients, can induce excessive release of inflammatory cytokines, such as IL-1 beta, IL-6, IL-8. Tier 2 SYK inhibition with fostamatinib can ameliorate the cytokine storm and prevent organ damage.

Fostamatinib is the only SYK inhibitor that may -- is the only SYK inhibitor approved that may interfere with the pathology of COVID-19 at multiple points through multiple cell types and could therefore work in COVID-19-related organ damage, pneumonia and also ARDS of viral and other etiology. This is not an entirely new concept as we have preclinical data from our model in ARDS.

On Slide 8 -- 18, you see an executive summary of those experience with R406, which is the active metabolite of fostamatinib. On the left, you see the histology of lung tissue under 4 different experimental circumstances. Upper left, healthy lung tissue with clear alveoli where transport of oxygen into the blood happens. On the top right, you see the same thing when only fostamatinib is administered with no negative impact on the lung. On the lower left, you see ARDS induced by LPS, which led to massive inflammation, fluid and cell debris in the alveoli, making oxygenation of the blood difficult or insufficient. On the lower right, you can see that fostamatinib had a clear beneficial effect on this pathology. And not surprisingly, as depicted on the panel to the far right, this led to survival of the mice with ADRS that were treated with fostamatinib.

On Slide 19, I show you 2 additional references recently published independent of Rigel that further support the scientific rationale for fostamatinib. The first on the left comes from MIT and Harvard. They screened 3,713 compounds to identify any that are FDA-approved and reduced Mucin-1. Mucin-1 is a biomarker which predicts the development of acute lung injury and ARDS and correlates with poor clinical outcomes. Of all those compounds screened, fostamatinib was the only to decrease expression of mucin-1 and is already FDA approved and therefore was proposed by the authors for rapid repurposing for patients with COVID-19 lung disease.

The other paper on the right referenced is from Amsterdam University Medical Center. The researchers there demonstrated that R406, the active metabolite of fostamatinib, blocked macrophage hyperinflammatory responses to a combination of immune complexes formed by anti-spike IgG from severely ill COVID-19 patients. Anti-spike IgG levels correlated with the severity of COVID-19. Thus, the ability of R406 to inhibit anti-spike IgG-mediated hyperinflammation suggests that it could play a role in the prevention of cytokine storm, pulmonary edema as well as thrombosis associated with severe COVID-19.

My last slide, 20, depicts the Imperial College investigator-sponsored trial that has been opened recently. This is a 3-arm randomized trial with fostamatinib or ruxolitinib plus standard of care versus standard of care alone. The first page will randomize 57 patients per arm for a total of 171 patients, at which point an interim analysis will be conducted. Based on that, the second stage will enroll an additional 95 patients per arm for a total study size of 456. The treatment duration is 14 days, and patients will be followed to day 28. We're excited to have this IST up and running because we expect this could provide initial clinical data in the relatively near future.

With that, I'll hand the call over to Raul Rodriguez. Raul?

Thank you, Wolfgang. On Slide 21, please. We wanted to give you our view of the opportunity for fostamatinib in the treatment of progression of COVID pneumonia and ARDS as well as pneumonias more broadly. It is incredibly exciting to provide -- potentially provide a much needed therapy to address the ravages of the worst pandemic in our lifetimes. As you know, it's the overactive immune system which causes the majority of fatalities in COVID-infected patients. And as Wolfgang shared, we believe that fostamatinib may have a unique and beneficial immunomodulatory impact.

This is a near-term opportunity that can be quite sizable given the large number of patients impacted. The Imperial College ISTs and other potential ISTs can provide an early read on the potential benefit of fostamatinib and do so in a broad range of hospitalized patients from COVID, from mild to more severe and with a broad range of treatment backgrounds. It's exciting to possibly provide a benefit in this extraordinarily large and near-term opportunity.

This also sets us up towards exploring fostamatinib in the treatment of pneumonia and ARDS from other sources, other origins, beyond COVID, both viral and nonviral. There are currently no approved agents for this. Every year in the U.S., there are over 1.3 million patients hospitalized for pneumonias. Approximately 200,000 of these progress to ARDS. With the same rationale that we laid out today, we believe that fostamatinib may have a benefit here. The COVID clinical experience would further confirm this and position us to pursue this large and enduring opportunity.

Let me move on to Slide 23. On Slide 23, I'd like to tell you about our fourth key value driver: expanding our pipeline. At Rigel, we have a very rich history of discovery and developing attractive molecules. These includes all of the opportunities we are discussing today. We focus on the inhibition of key signaling pathways that are critical to many immune-mediated diseases. This includes both immune diseases as well as nonimmune diseases, such as in areas as hematology/oncology. We have 3 in-house programs that we have discussed today: TAVALISSE, our oral SYK inhibitor; an IRAK1/4 inhibitor; and a RIP1 inhibitor program.

Our IRAK 1/4 inhibitor is the only molecule that inhibits both the IRAK1 and IRAK4 pathways and therefore is more profoundly immunosuppressive than other IRAK4-only programs. In preclinical studies, we have shown to block inflammatory cytokine production in response to toll-like receptor, TLR, and IL-1 receptor family signaling. And in the Phase I healthy volunteer study, we achieved proof-of-mechanism results lowering inflammatory cytokines from LPS challenge and demonstrated favorable P/K profile. We also had 4 posters on this program presented at the recent EULAR meeting this past quarter.

With our RIP1 program, we recently completed the multiple ascending dose stage of our Phase I study. Importantly, we have identified a dose range that we believe is safe and well within the expected clinical efficacy range. As previously mentioned, we are making progress identifying -- also identifying a CNS RIP -- a RIP inhibitor molecule for our CNS indications and moving it into the clinic next year.

In addition to these, we have 4 partnered clinical programs, which include 2 JAK inhibitors, another key immune signaling pathway. As you can see, these assets provide us with many options to develop and create value for Rigel, including moving our programs forward ourselves, partnering in various structures, dividing the opportunities geographically or by size of indication.

For our RIP1 and IRAK1/4 program, we are currently in discussions with potential large pharma partners and plan on concluding a co-development/co-promotion agreement by year-end. In addition, we are putting in place further ISTs to allow us to explore the broad utility of our immune-modulated inhibitors.

And speaking of which, on Slide 24, you see the broad range of possible co-indications that are available to these molecules. Some of these we will explore with partners, say, with RIP or IRAK inhibitors. Some, we will explore for ourselves with ourselves alone, such as ITP, AIHA, potentially COVID pneumonia. Our broad portfolio of immune modulators provide us with significant opportunities.

Now with that, I will turn the call over to Dean for our quarterly financial update. Dean?

Thank you, Raul. Turning to Slide 26. For the second quarter of 2020, we shipped 1,632 bottles to our specialty distributors. 1,515 of those bottles were shipped to patients and clinics while 117 bottles remained in our distribution channels at the end of the quarter. As of June 30, a total of 708 bottles remained in our distribution channels.

We reported net product sales from TAVALISSE of $15 million, a 47% increase compared to the second quarter of 2019. Our net product sales from TAVALISSE were recorded net of estimated discounts, chargebacks, rebates, returns, copay assistance and other allowances of $3.4 million, our gross to net adjustment, which is approximately 18.3% of gross product sales.

Before we move on to net product sales, let me comment briefly on our expectations for the third quarter. While we're pleased with the continued growth in our TAVALISSE sales in the second quarter and expect to see continued growth in the third quarter of 2020, the impact of COVID-19 on our business that started in the latter part of the first quarter continues and remains uncertain. As we've highlighted, we've made great strides in optimizing our ability to access our physician community remotely and to provide the many patients suffering from chronic ITP in the U.S. with access to TAVALISSE. Once the significant impact and restrictions caused by COVID-19 are behind us and the future begins to normalize, we expect to see continued strength and growth in our business.

On to the next slide. In addition to net product sales, Rigel's contract revenues from collaborations was $1 million for the 3 months ended June 30, 2020, which consist of deferred revenue from our collaboration with Grifols related to the performance of certain research and development services.

Moving on to costs and expenses. Our cost of product sales was approximately $279,000 for the second quarter of 2020. Total costs and expenses were $33.4 million in the second quarter of 2020 versus $31.7 million in the second quarter of 2019. The increase in total costs and expenses was primarily due to the third-party costs related to Rigel's ongoing pivotal Phase III study in warm autoimmune hemolytic anemia, research and development costs related to other clinical programs and personnel-related costs, partially offset by stock-based compensation expense.

As we look towards the back half of 2020, we continue to expect our full year total costs and expenses to increase by approximately 15% to 20% as compared to 2019 as we continue our commercial expansion and further our research and development pipeline inclusive of the COVID-19 efforts that our team has discussed.

We ended the quarter with cash and short-term investments of approximately $92.5 million. During the second quarter, we accessed the second $10 million tranche from our $60 million term loan credit facility with MidCap Financial. This facility provides the company with access to an additional $40 million, which is subject to the achievement of certain conditions.

With that, I'd like to turn the call back over to Raul. Raul?

Thank you, Dean. Moving on to Slide 28. The COVID pandemic has clearly impacted our business, but it's also presented opportunities for us to potentially contribute to a solution. And I cannot tell you how energized we are about this prospect.

Let me summarize our efforts going forward in each of the 4 key value drivers for the company. We will continue to grow TAVALISSE in the U.S. ITP market, and we're excited about the use of TAVALISSE in earlier lines of therapy and the data that we have to support this position. Similarly, we look forward to supporting our partner, Grifols, as they continue -- as they introduce physicians and patients to -- in Europe to TAVLESSE. We will work to complete the enrollment of our AIHA Phase III study with the re-initiation of screening, and we look forward to enrollment increasing. We will expand our current lead in this area and move forward to completion of that trial and filing an NDA. We will explore how TAVALISSE could provide -- potentially provide patients with COVID-related pneumonia a much needed therapy. And we will continue to advance our RIP1 and IRAK1/4 programs, putting in place a partnership by year-end.

Now before I turn the call over to your questions, I wanted to just make a quick note. I wanted to highlight an addition to our management team. Dave Santos will be joining Rigel as our Chief Commercial Officer. Dave brings over 30 years of experience in hematology/oncology areas in various commercial leadership roles with numerous successful companies. I think he'll be a great addition to the team, and we look forward to his contributions in helping us advance our commercial efforts. And in that, I also want to thank Tarek for his contributions and look forward to those as well.

So with that, I'd like to open up the call to your questions.

(Operator Instructions) Our first question today comes from Eun Yang of Jefferies.

This is [Nalin] on for Eun. Just a couple of questions, particularly on the COVID-19 pneumonia questions -- sorry, on COVID-19 trials. Could you give us some details on what the pathway for getting an approval to non-COVID-19 pneumonia might look like following running a trial in COVID-19 pneumonia? Which type of trial would have to run? Which patient populations might be recruited? And how big might the trial be?

Thank you, [Nalin]. I'll make a couple of comments and ask Wolfgang to also add other comments. So we were very interested in pneumonia and ARDS prevention some time ago and that publication that Wolfgang shared published in '19 before this COVID pandemic came upon us. And so it's an area where we thought that our product could have real potential. And broadly speaking, because there are several different key sources of pneumonias: viral, nonviral, bacterial, others, autoimmune, for example, so there's several different pockets of those. We think there's a great opportunity for our product to meaningfully contribute to stop that progression. And as I mentioned, I think this is an annual ongoing issue that we could have a tremendous opportunity to benefit patients.

Exactly, there's nothing approved in this area. So there isn't a playbook that's all readily written that we could simply copy, but we may have to look at other proximate models for such a circumstance. And b, work with the FDA closely in order for us to pursue that. I think the COVID pneumonia experience will be very helpful because it has the same mechanism as some of these others. And so that might itself maybe a very useful precedence for how we go about it. Wolfgang?

Yes. No...

Yes, go ahead.

We have 1-second delay. So I support what Raul is saying. Obviously, our first step would be to generate solid data in COVID-19. Then as always, depending on how large the effect size is, you can take your learnings on to the design of non-COVID ARDS trials. So in other words, the larger the effect size, the smaller the potential trial needed. So at this point, probably a little bit too premature to determine what the sample size that such a trial would look like.

Just one more question if I may. So the question's for Dean. So you previously mentioned that the funding for the COVID-19 trials would come out of funding intended for further work on TAVALISSE. Could you please clarify if there were other indications beyond ITP and wAIHA that the company had intended to explore?

Yes. So let me start, and then I'll ask Raul to wrap up the comments on this with any incremental thoughts. But what we've described always is that we have exclusivity with fostamatinib/TAVALISSE through into 2032. And with that long runway, we've always had the intention to explore incremental opportunities with this asset. We believe that -- and therefore, we've always planned, from a cost perspective, from an operating expense perspective, to make investments in those areas.

We believe that today, an optimal way to utilize resources is to explore COVID, COVID-related pneumonia and then the extension to ARDS, non-COVID that we've talked about. And so today, those are really the focus of our -- of at least our near-term operating expense. We may make choices into the future to invest in fostamatinib in other ways. But today, it's really focused on the COVID-related opportunity and then the possibility into non-COVID ARDS.

The only thing to add there is to highlight, SYK inhibition has a very broad role. It's not solely Fc receptor signaling as it is in autoimmune diseases like AIHA or ITP, though it's quite beneficial there. But it has a broader role in immune modulation in other cell types and via other mechanisms. And this COVID opportunity helps highlight that. And we'd like to take advantage of that because I think it provides us with a really useful tool. I think we've only begun to scratch the surface of the potential for SYK inhibition.

The next question comes from Yigal Nochomovitz of Citigroup.

I guess you may have seen that Denali and Sanofi announced plans to do a COVID trial with their RIP1 inhibitor. Obviously, you have one as well. Have you given any thoughts to whether you would take R552 into a COVID study in addition to fostamatinib?

Yigal, thank you for your question. What's very interesting about that, it's absolutely right, and it may have potential as well in RIP inhibitors in the treatment of COVID. We are excited about TAVALISSE since we think the mechanism should work here. The proof-of-concept data that we shared today, not just in our hands but really in the hands of independent collaborators, is really compelling. And it has a difference from other development-stage products such as our own 552, our RIP inhibitor, is that it's approved. It's on the market. It's commercially available today. If doctors wanted to use it, they very well could even today. We've manufactured large amounts of the product. Should it show a benefit, we could immediately deploy it to that effect.

And that's a real difference over something that is in the pipeline and, say, in Phase I clinical study. If those work, the hurdles from there to actually getting to -- in the hands of a patient is very challenging. There are many of them. For us, if a doctor wants to use TAVALISSE in a patient with COVID today, he or she could write a script, and that patient would receive TAVALISSE in a matter of hours because most hospitals have a bottle. And if they didn't have a bottle, we could send them the product overnight and that patient would get the product tomorrow. That's a real difference from a development-stage product and something that is commercially available.

In addition to the -- as I mentioned, the preclinical support is outstanding for this opportunity. So it's clear what we would do. But in the future, of course, we'll consider other things, including a RIP program or even a JAK molecule as well. We have those.

Okay. Yes. I just thought it was interesting that you could potentially pursue 2 molecules for COVID. But that certainly...

Absolutely.

And then, Raul, I just wanted to ask a question about the BJH paper. You have a very nice swim chart there showing the responses in the patients with -- the second-line patients, 78% response. But I was curious about the duration of response. It looks like about half of the 32 patients, maybe a little less than half, had duration of response of 2 years or longer, which looked pretty good. Can you comment, to what extent -- how does that compare with some of the other second-line ITP therapies, like the TPOs and Rituxans, specifically on duration of response? How does TAVALISSE stack up there?

Good. I'll ask Tarek and Wolfgang to also contribute to this. But I think it compares nicely. I think that's a very nice result. Keep in mind the following is that we and they did our studies in different places. And it's always difficult to compare one study to the other -- another study done effectively almost a decade apart, if not more. And so it's challenging to compare that way. But I think having that type of durability is actually quite helpful because if you succeed in our product and you stay on it, you're likely to continue to succeed for a very long time. 2 years is a very long time in the treatment scheme of something like ITP. Tarek? Wolfgang?

Sure. Thanks, Raul. This is Tarek. And Yigal, appreciate the question. So one of the exciting parts of the analysis, and you actually honed on it quite acutely, is actually the other side of the coin, which is we see that the second-line patients respond well. But frankly, from a clinical perspective, it's about maintaining that response. And if you look at the paper in that setting, if you use 50,000 as the barometer, it's about 83% -- excuse me, and 83% and about 92% maintain their response if you use 30,000.

So to get to your question, though, as kind of Raul was alluding to about an apples-to-apples comparison, as you're probably familiar with, unfortunately, across all the different ITP trials, there's really no universal definition from an end point design of durability. Almost every trial you come across, even with the other TPO mimetic agents, it's, frankly, a varied definition. But given that we saw upwards of 80% to 90% durability based on how long these patients had been on therapy, what I can tell you is that when we presented this data in market research and advisory boards, this more than exceeds expectations from clinicians because their biggest fear is that they're going to take somebody out of harm's way, but it's going to be a transient effect. And they have a lot of confidence based on this data because the way the response was defined in this is it was based on a number of treatment days. So however long that individual patient was on fostamatinib, on TAVALISSE, that is how the response rate was determined. So that's the denominator there.

And so essentially, what it's saying is for the majority of time they're on a product, they're in that really great threshold and window of response. And so that really alleviated any of those concerns about any sort of transient effect. And so I can tell you, the response has been pretty, pretty positive and affirmative about this data analysis.

Okay. And just one final question for Dean. Dean, with respect to the cash runway, could you just remind us what the runway is currently? And are you planning to access this credit facility again this year?

Thanks, Yigal. So we haven't given any guidance into the future, but let me answer your question in this way. So we ended the quarter with about $93 million of cash. From a top line perspective, as we look into the future, we expect the continued growth of our TAVALISSE net revenues. And as Raul highlighted, we also expect an IRAK or RIP deal later this year, which could result in a significant milestone, significant inflow of cash. So the top line, in combination with the cash we have on hand, is significant for us.

From an operating expense perspective, we continue to expect to be able to create increasing leverage in the business from the clinical programs we've described as well as our sales and marketing efforts, where when we look forward to autoimmune hemolytic anemia, we expect to see significant leverage, no new sales force, those types of opportunities.

So within that context, the $93 million, the $40 million available in our credit line and other sources of financing leave us in a solid position where today, we don't have any intent to raise incremental capital. That said, we will continue to monitor our needs and opportunities and we'll make sure that the business is adequately funded.

Chris Raymond of Piper Sandler.

This is Nicole Gabreski on for Chris. So maybe just to start, on Amgen's recent Nplate commentary. So the second quarter was the first quarter that Amgen cited slowing Nplate new patient starts due to oral alternatives in ITP. I guess does that match the TAVALISSE ITP market trends you guys saw during the quarter? And I guess is it your sense that, that was driven in part by COVID-19, the ASH data update or other factors?

Sure. I'll ask Tarek to comment on that and I'll add some color after.

Yes. Appreciate it, Raul. And thank you, Nicole, for the question. So I would say yes, it does sync up with our data. We're seeing a decrease of Nplate presence in the overall marketplace. I would say causality, frankly, is something we've been tracking over time. I think the COVID-19 -- and this is just really our impressions, Nicole, but our impressions are essentially that really, what we've been hearing from clinicians treating this disease, as well as, frankly, from patients and patient advocates, has been the need for more flexibility and certainly having oral therapeutics adds to that to be able to be an amenable therapy and really cater to patients' needs.

So certainly, in the COVID-19 pandemic, with individuals either sheltering in place or, frankly, just trying to remove themselves from health care contact, that's not necessary. Having an oral option where they don't have to go in for weekly injections is certainly a benefit. And these are things that we've heard from providers in our research and our discussions and dialogues. So I would say it's a trend that we saw before the pandemic and only more so accelerated during.

Raul, did you want to add some color?

The only further color to add, I think, is that once these trends become normalized, they go from -- in and post-pandemic world, they may very well stick. And that's something that we'll also continue to monitor.

Okay. Great. And then maybe just as a follow-up, I know from your previous commentary, your sales reps have had the earlier-line TAVALISSE clinical data in hand since about February. And I know there's been some, I guess, transition -- well not some. There's been a lot of transition to virtual communication just with the pandemic. But I guess I was just curious to get your thoughts on why awareness of this earlier-line data is still relatively low and how you're working to remedy that.

Tarek?

Sure. Raul, if you don't mind, I'll jump in there again. So great question, Nicole. So as we previously presented in other forums, Nicole, we trained our sales force in February and launched the data into their selling materials towards the end of Q1 and going into Q2 really with the momentum from that data.

But the reality, Nicole, is the data was presented and obviously at an esteemed meeting at ASH as a poster. But when -- in order for data to be disseminated, as I'm sure you well understand, is you're also hoping that third-party outlets, trusted sources, a number of vehicles, not just our own commercial efforts, are picking up on that information, communicating it, educating it, whether that's our promotional efforts, CMEs, et cetera. And certainly, having an article now in a publication as esteemed as the BJH, we just see that as an accelerator, if you will.

And so while the teams have been doing a fantastic job, and I really do have to commend them on their commitment and tenacity of looking for opportunities for virtual communication with our providers, as you well can imagine, without having the live medical conferences and other opportunities, it's something that we're just progressing and building momentum. And we really see this publication as an opportunity to pull that forward, if you will. Hopefully, that answers your question.

The next question is from Joe Pantginis of H.C. Wainwright.

Two questions or sets of questions, one on U.S. and one in Europe. I guess starting with the U.S., I guess my question really focuses on the current patients that are mostly targeted, second-line patients, post-TPOs, et cetera. So I guess when you look at the current 54% persistency rate, which is great, I guess how much are you looking to -- or your goal, how much to increase that in that type of population versus how much bang for the buck, sorry for the pun, that you can get as you're looking to expand further into the first-line setting?

Sure. So let me make a few words and ask Tarek to also comment on this. Persistency is something where we monitor very carefully, as you can see. And as we launched the product, it was used primarily in more refractory lines, a bit more -- a bit in earlier line but primarily more refractory. And because they have a lower response rate naturally, your persistency is going to be lower. And as we move into earlier lines, it has the dual benefit: there's more patients there; and two, the response rates are higher, substantially higher, as you saw in Tarek's slide. And we expect, as a result of that, persistency to continue to trend upward. Tarek?

Yes. I think you covered a lot of the key points there, Raul. So Joe, I don't think we're really giving guidance right now in the sense of what our aspirational persistency rates are. We believe that there's improvements as patients and, frankly, practitioners become more familiar with the product. We know that the prognosis of patients, as you articulated, as we move it up, we know these patients are, frankly -- they have a better prognosis. They potentially have less comorbid conditions earlier in the stage of the disease. And we believe the patients can overall have a better outcome on our product, represented not only by our own data analysis but, frankly, just even anecdotally from talking to clinicians.

And so as we move, whether it's from patients from third line to second line or just earlier into care with those individual physicians, we're hearing on a case-by-case experience that physicians are finding greater utility for the product.

Got it. No, that's helpful. And then my EU question, I know things are early right now with regard to the launch that Grifols is conducting. But I guess maybe 2 parts. Number one, can you highlight sort of the blocking, tackling that needs to go? What are the types of hurdles that you would see obviously from a geographical standpoint? Is it more of just reimbursement in particular geographical areas or just the variability of types of treatments in geographical areas or a combination of both, number one?

And then the second part is, maybe for Dean, are you guys going to look to eventually break out the royalty streams versus the actual revenues in the P&L?

Tarek, why don't you make some comments on the European launch and mention TAVLESSE...

Sure, and then I'll hand it off to Dean. It's perfect. And Raul, feel free to add any color. So Joe, great question. And not surprising because it's obviously exciting news for us to now have a global footprint and, frankly, to know that our product is providing benefit to patients outside of the U.S., essentially to say, across the globe. So that's obviously a fantastic milestone that we're very, very proud of.

It is early days. So it is premature to kind of share any sort of outcomes yet. It's only been a few weeks since Germany and the U.K. have started treating patients. But from the strong collaboration that we have with Grifols, obviously, we see this as a huge opportunity. As you're well aware, it represents almost $900 million market opportunity.

As far as the hurdles, again, I think they're facing the COVID pandemic just like we are. They're launching in the midst of this. I can tell you they've been very committed to their virtual engagements. And frankly, we've been very impressed with their executional plans to get the word out. And they have serendipity on their hands in the sense that their timing of the launch does coincide with the availability of the second-line data analysis. And so they're able to provide -- assuming it's permissible in their marketplace, to provide all the information that's part of the comprehensive story of TAVALISSE or TAVLESSE in that market that we have here in the U.S. today.

So I want to make sure I covered all the aspects of your question. Was there anything else that you would specifically ask before I hand it over to Dean?

No, you really addressed it. I guess the other thing is, I guess, you have a country-by-country reimbursement aspect, too, that's going to be part of the blocking and tackling, sort of rhetorical.

Of course.

Yes.

Absolutely, yes.

Okay. Great.

And you may realize that in Europe, the launch happens in different countries in different sequences. It doesn't all happen at once like it does here in the U.S. So you'll see France, Italy, Spain, other countries come in, in some order depending on how quickly those negotiations take place.

And with respect to the reporting, Joe, the launch just happened. And therefore, we haven't determined exactly how we'll provide color and detail on breaking that out and specifically reporting it.

I would remind everyone that in the $20 million milestone payment we got in Q1, $2.5 million of that milestone was an advance royalty payment. So we've already been paid and even recognized that $2.5 million of the first tranche of royalty payments we'll receive from Grifols. But stay tuned. As Grifols starts to now sell, we'll provide incremental clarity and detail around that revenue source and those revenues.

The next question is from Do Kim of BMO Capital Markets.

This is [D. K.] on for Do. First and foremost, congratulations on the quarter for increase in sequential quarter-over-quarter sales there for TAVALISSE. My question is about TAVALISSE, but more so for -- in terms of wAIHA. I know you mentioned that it's a little bit too early to definitively say what the time lines are given the COVID situation. But is it possible to kind of give us a better sense, like maybe a base-case, worst-case scenario here? Are we simply tacking on additional months that were lost while the enrollment was suspended? Or do we have to account for potential ramp-up for each site just to kind of get operations going again before they're actually up and fully enrolling patients? But a little more color on that would be helpful for us.

Sure. I'll ask Wolfgang to make a few comments on that.

Yes. Thanks for the question. First of all, let me reassure that we have a great team in place both at Rigel as well as our CRO. As you have heard, we have 90 sites open now to contribute to the additional 45 patients that we need. That said, to your point, we are still in a pandemic. And our clinical trial sites, just like any other clinical practice, do need to work around social distancing, avoiding COVID-19 infections and focus in severe cases and things like that. But since technically, we only need one new patient from half of the sites, we are still very optimistic that enrollment can pick up suddenly and rather rapidly. But I want to stay away from giving you a precise date other than reassuring you and giving you those encouraging facts.

Okay. That's fair. And this is not going to have any type of implications on the data integrity, correct?

Yes. No, I'm very happy to tell you that we -- immediately with the shutdown, we had a laser-sharp focus on the potential of missing data or bad-quality data. And we were able to have the amount of missing data for the patients that we already have to a really small minimum. So this went actually better than I was originally afraid of.

Okay. Good deal. And my last question has to do with the pipeline. Is there a potential where you take the IRAK1/4 inhibitor and develop it a little bit further to get better economics on the deal, co-pro and co-development deal, as opposed to licensing it out at the end of the year? And in addition to that, what type of indications have you discussed with your partner or just what you've been thinking about in terms of pursuing for this type of deal?

Yes. I'll take -- I'll answer that. Sure, absolutely. I'll answer that. It's absolutely, in fact, almost likely, we'll partner one and not the other. We're pursuing both. We might partner both. That's what we want to say. But we're confident we'll be able to put a partnership in place and that partnership will achieve some very important goals.

One is to bring a substantial amount of resources, economic, clinical resources, that a large pharma partner has to bring to bear on these both opportunities because they both have tremendous opportunities in a wide range of areas, big areas like rheumatoid arthritis, for example, psoriasis; small areas as well, in some cases, like ALS. And so we're interested in bringing to bear that level of commitment in a partner because the opportunities are really quite sizable. And -- but we want to also be able to share in that and contribute in co-development. And we think that with our commercial effort, we can contribute to the commercialization of these products in certain aspects and in certain circumstances. And we're going to model that with those partners.

And so we think it's an attractive proposal for them, obviously a very attractive proposal for us. Beyond those features, obviously, the economics are very useful, and we think that we can get a very attractive economic deal done as well. And so we look forward to putting that in place. It could well be that we decide that we partner one of these 2. And the other, as you suggest, we may take it forward yourselves to the next stage and partner it then and then continue to add value. That is very much a possibility and we do that, but on the basis of having done a very attractive deal if we decide to go that route. But the opportunities are so large that, frankly, having more muscle, more resources is very helpful.

Congrats again on the quarter.

Thank you so much.

The next question is from Tessa Romero of JPMorgan.

Congratulations from me as well on the progress this quarter. Just one on COVID-19 impact for the quarter for TAVALISSE. We're trying to get a better understanding of the dynamics that you saw with respect to refill rate versus sequential patient adds. So anything you would note there for the quarter and maybe also into July as we think about our third quarter estimates?

Sure. I'll ask Tarek to comment on refill and new patient starts with TAVALISSE and COVID commercial.

Sure. Thanks, Raul. So appreciate the question, Tessa. As you can imagine, this was an area for us that we were highly concerned about, like any organization going into the shelter-in-place. But I think as we've just kind of commented earlier about, even just, frankly, the discussions in regards to injectable versus orals and having advantages there, our clinicians very much quickly adapted to telemedicine in supporting their patients remotely.

I think the fact that our patients have tolerated the drug, the offices that are currently utilizing the products are familiar with the product, without getting into the specifics of the numbers, I would say that we were actually very pleasantly surprised from an operational aspect how not only were they able to maintain and, frankly, be able to manage their patients currently on TAVALISSE remotely, but more importantly -- and I think we talked about this in the previous quarter's earnings call, these patients were also looking for other options, particularly if they were on an injectable or needing an alternative therapy, and physicians were comfortable in this remote environment especially given our value proposition to identify new patients and switch them to an alternative oral therapy.

And so I think frankly speaking, our value prop has actually served us quite well during this pandemic, not to say that we're capitalizing on this but to say that physicians are seeing value, physicians are seeing opportunity and are receptive to our messaging.

The only thing to add there, Tessa -- this is Raul, is that both ITP, and this applies to AIHA as well very serious conditions. And while patients are -- have some hesitation to go see a doctor all the time, as things become more normalized, that is, this continues on per month, they do need additional therapies when their platelet counts are very low or, frankly, their hemoglobin levels are very low in the case of AIHA. And they do go out and seek new treatments. And it's good that TAVALISSE with the second-line data can be part of that discussion. And I think for some patients, maybe that will be the right agent.

The next question is from Kristen Kluska of Cantor Fitzgerald.

Congrats on a very productive quarter. So you discussed the importance of tracking the duration of response for TAVALISSE from the British Journal of Haematology publication. And I wanted to touch on the other side of that on the onset or time to initial effect. So I know you've commented before that real-life experience has been different than what was observed in trials. So are you starting to see any trends or hypothesize why some patients respond quickly, whereas others take longer? And then on that note, how does your sales team market this to make sure physicians are giving TAVALISSE a real shot before discontinuing if not seeing any effect?

Sure. So Raul, I can...

Thank you, Kristen. I'll ask Tarek. Thank you. Go ahead, Tarek.

Sure. Thanks. Sorry, Raul. I didn't mean to step all over you there. But what I would say is -- feel free to add color, or Wolfgang, on the clinical aspects. I can talk about the sales force as well as our physician response.

And so you're absolutely spot on, Kristen, which is in our initial clinical trials in our FIT 1, FIT 2 programs, we presented it. We published it even prior to the second line. We talked about the median time to first response was 15.5 days. But we've also previously talked about -- there is variability. That was a clinical trial versus real world. There's all sorts of things that happen in the real-world setting that clinicians and patients have to face.

I think what benefited us, to be honest, from a messaging as well as a learning and education platform, is that early on in the launch, we started hearing from clinicians about some of these varied responses. And if you look at the product label, it actually endorses and supports giving patients at least 3 months to adjudicate or reconcile if this patient is having an adequate response. And given the heterogeneity of this disease, the heterogeneity of response to our agent as well as other agents out there in the marketplace -- and really, I think the guidelines speak to this, which is about the customization of treatment approach. Our sales force was able to utilize that language in the product insert from our clinical trial experience to both share the potential upside and benefit that there are some patients that are going to have a rapid response, but that consistent with our label, consistent with our findings, you really need to give the patients the best shot possible at having a good outcome on the product and really meeting those goals of therapy that the physicians identified and that the patients identified because it varies amongst physicians and patients.

One physician might be satisfied with the platelet level of going from 10,000 to 25,000, whereas another physician may want it to get to 35,000. And I think that variability really speaks to the customization of treating the patient in front of you. And so given that full 3 months of response as ascribed to by our PI, I think, really helps us drive that notion, drive that messaging and education that you need to give the product a chance to meet your objectives. So does that answer your question, Kristen?

Yes, very helpful. And if I may ask a follow-up related to the COVID-19 study. So the first part of the question is just based off of the standard of care. Obviously, this is a new indication that everyone is trying to understand, and I know you list dexamethasone as a potential for one. But given that your lead investigator, as I know, has presented some of your results in ITP and is very knowledgeable about the drug, do you think that there are any therapies in general that are being studied for COVID that have the best shot to be used as a combination with fostamatinib?

Sure. Why don't I ask Wolfgang to make comments on that on standard of care?

Yes. So in general, we have to allow the combination with standard of care if there is compelling data to suggest that the drug works. Otherwise, physicians would just not participate in your trial. That said, for example, if you look at the dexamethasone data more closely, the data is not that earthshaking. So there is some benefit, in particular for the more severe patients. And quite sure given the cheap price and this existing data, many physicians will want to use dexamethasone in the background. But I think there's still a lot of room to grow to accomplish much better effect sizes than what we have seen so far.

The other drug that's emergency-approved of, as you know, is remdesivir. I have a similar comment on this. I think the mechanism of action in the patients who are already hospitalized is not as strong as a rationale because I've shown you that you get these really severe cases mostly when your viral load is already on the downturn, and then it's the immune system that causes the severe cases. So reduction of viral load may not be all that beneficial in that setting. That said, again, if you say on top of standard of care, if an institution says this is our standard of care, we will allow it. But we will -- but we still do see a lot of upside for fostamatinib. Hope that helps.

Yes. And then just quickly on that front, I know that this study is, of course, much shorter than the trials you're primarily used to running. But could you talk about the rationale for just utilizing the 150-milligram dose here?

Yes. As you know, in ITP, we advise to start on 100 milligrams. And then after four weeks, at the discretion of the PI, you can increase the dose to 150. So that is what we have in the label. Now we have used up to 200 in CLL trials, in chronic lymphatic lymphoma. So given that you will treat those patients in a very severe condition for 2 weeks, maybe up to 4 weeks, you don't want to err at a dose that is too low and start with a higher dose. Also, these patients are hospitalized under supervision and all these things, so that -- which alleviates any type of concerns. And we don't want to go to the 200 because again, the 150 is the currently labeled dose and is the higher dose of the 2 they're generally using. And therefore, we're going with the 150.

There are no further questions at this time. I would like to turn the floor back over to Mr. Raul Rodriguez for closing comments.

Thank you, everyone. I'd like to thank you for your -- for listening. I'd like to thank you for your support and your help. We have some incredible opportunities ahead of us. Some of the areas that we're looking at right now, I think, will add tremendous value and in the short term. And so thank you for your support in allowing us to do that. We'll keep you informed of further updates in the coming months. Take care and stay safe.

This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.