Q3 2020 Rigel Pharmaceuticals Inc Earnings Call

Greetings and welcome to the Rigel Pharmaceuticals financial conference call for the third quarter Twentytwenty.

Unknown Executive: Greetings and welcome to the Rigel Pharmaceuticals financial conference call for the third quarter of 2020. At this time, all participants are in a listen-only mode.

At this time all participants are in a listen only mode. A brief question and answer session will follow the formal presentation.

Unknown Executive: A brief question and answer session will follow the formal presentation. At that time, if you have a question, please press the 1 followed by the 4 on your telephone. If at any time during the conference you need to reach an operator, please press star zero.

At that time, if you have a question. Please press the one followed by the four on your telephone.

If at any time during the conference you need to reach an operator, please press the star zero.

Unknown Executive: 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.

As a reminder, this conference is being recorded it is now my pleasure to introduce our first speaker Dolly Vance who.

His rigel executive Vice President Corporate Affairs, and General Counsel. Thank you Ms. fats you may begin.

Dolly Vance: You may begin. Thank you. Welcome to our third quarter 2020 financial results and business update conference call. The financial press release for the third quarter was issued a short while ago and can be viewed, along with the accompanying slides for this presentation, in the news and events section of our Investor Relations page on our website, 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.

Thank you.

Welcome to our third quarter 2020 financial results and business update conference call.

The financial press release for the third quarter, which gets you to a short while ago and can be viewed along with the accompanying slides for this presentation and the news and events section of our Investor Relations page on our website Www Dot Rigel dotcom after.

As a reminder, during today's call we 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.

Dolly Vance: 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 Q3 quarterly report on Form 10-Q. Any forward-looking statements are made only as of today, 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.

A description of these risks can be found in our annual report on form 10-K for the year ended December 31st 2019, and subsequent filings with the FCC, including our Q3 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.

Raul R. Rodriguez: And thank you for joining us for our third quarter 2020 financial business update. Also joining me today are Wolfgang Duner, our Chief Medical Officer, and Dean Schorno, our CFO. I also have the pleasure of introducing Dave Santos, our new Chief Commercial Officer, who joined Rigel in August. Dave has significant commercial experience and has been involved in the successful launch and marketing of several pharmaceutical products, and we look forward to benefiting from his vast experience. Beginning on the slide.

Raul R. Rodriguez: I would like to highlight the success we are having across all of our key value drivers as a result of the continued execution by the entire Rigel team. While we still face headwinds due to COVID-19, we are continuing to make very good progress. We continue to grow Tavalli sales and have set new highs this year. We are successfully positioning Tavilis as an attractive option for ITP patients and enhancing our supporting database with new studies. We have now launched a new observational study called FORTE, focused on second-line patients that Dave will touch on during his presentation. And our partner Griffiths has commercialized the product in Germany and the UK with a phased rollout plan for the rest of Europe.

Raul R. Rodriguez: I am very pleased with the ability of our team to advance our Phase III trial in warm autoimmunity hemolytic anemia, or AIHA. Our product is the furthest along in clinical development for AIHA, and our goal is to be the first approved product for the syndication. Actually, I think during this year we have expanded on our lead, owing to the diverse geographic spread of our sites, as well as our oral administration, which facilitates patient trial participation. As you may have seen, we announced our intention to launch a phase three trial in hospitalized COVID-19 patients this quarter. This will be the third trial launch for fostamatinib in COVID-19, including one sponsored by the National Heart, Lung, and Blood Institute, NHLBI, part of the NIH, and one with Imperial College London.

The furthest along and clinical development for a IHA and our goal is to be the first approved product for this indication.

Actually I think during this year, we have expanded on our lead owing to the diversity of graphics spread of our sites as well as the our oral administration, which facilitates patient trial participation.

You may have seen we announced our intention to lots of phase three trial and hospitalized COVID-19 patients this quarter.

This will be the third try a large for past Imatinib and COVID-19, including one sponsored by the National Heart lung and Blood Institute N H L. B I part of the NIH.

And one with Imperial College, London.

Raul R. Rodriguez: Both of those trials are enrolling patients as we speak. We are excited about the potential to play a role in aiding those affected by COVID-19. And based on our own preclinical data and research from well-regarded institutions, we believe that there is a significant rationale to explore fostamatin in this disease.

Put the those trials are enrolling patients as we speak.

We're excited about the potential to play a role in aiding those affected by COVID-19, and based on our own preclinical data and research from well regarded institutions. We believe that there is a significant rationale to explore foster <unk> in this disease.

Raul R. Rodriguez: Wolfgang will provide more details on both the AIHA trial and our new COVID-19 program in a few minutes. In addition, I'd like to point out that we've continued to develop our earlier stage. This includes our programs in the inhibition of both IRAC-1-4 and RIP-1 pathogen. These are two very important immune signaling pathways that impact a wide range of diseases and provide substantial opportunity.

Wolfgang will provide more details on both the AAJ trout, and our new COVID-19 program in a few minutes.

In addition, I'd like to we continue to develop our earlier stage assets. This includes our programs in the inhibition of both Iraq, one four and Rip one pathways. These are two very important immune signaling pathways that impact a wide range of diseases and provide substantial opportunities.

We continue to make progress in our discussions to secure code development co promotion agreement for one or both of these assets and we believe that we will have a partnership near year and.

Raul R. Rodriguez: We continue to make progress in our discussions to secure a co-development and co-promotion agreement for one or both of these assets, and we believe that we will have a partnership near year-end. I will now pass the call over to Dave, who will provide a commercial update. Thank you, Raul.

I will not pass the call over the day will provide a commercial update <unk>.

Thank you I will.

David A. Santos: It's been great to join Rigel. It's such an exciting time as we work together to execute on our key value drivers. I've now been with Rigel for a full quarter and have been so impressed by the commitment of the commercial team and my colleagues across Rigel to continue making a meaningful difference for patients with chronic ITP, particularly as we deal with the impact of the global pandemic. I want to express my sincere thanks to our entire team for their hard work and persistence during the third quarter, as we continue to grow sales and build awareness of Tavalisse for the treatment of I On slide 7, you will see our FDA-approved indication, which is for adult patients with chronic immune thrombocytopenia, or ITP, who have had an insufficient response to a previous treatment. I would like to begin my discussion on slide 8.

It's been great to join Rigel, it's such an exciting time as we work together to execute on our key value drivers I've.

I've now been with Rachel for a full quarter and have been so impressed by the commitment of the commercial team and my colleagues across Rachel to continue making a meaningful difference for patients with chronic I T P, particularly as we deal with the impact of the global pandemic I want to express my sincere thanks to our enter.

Fire team for their hard work and persistence during the third quarter as we continue to grow sales and build awareness of tabla lease for the treatment of I T. P.

On slide seven you'll see R. F D. A approved indication which is for adult patients with chronic immune thrombocytopenia, our I T. P. Who've had an insufficient response to a previous treatment.

I would like to begin my discussion on slide eight.

We are continuing to grow tolly sales in the U S. In fact in the third quarter, we surpassed the 100 million dollar milestone in total net sales since launch and we are excited about the growth trajectory. We have created during the second and third quarters of 2020, particularly as we have faced the.

David A. Santos: We are continuing to grow Tavalee's sales in the U.S. In fact, in the third quarter, we surpassed the $100 million milestone in total net sales since launch, and we are excited about the growth trajectory we have created during the second and third quarters of 2020, particularly as we have faced the unique challenges of this year. We are beginning to see patients and physicians truly realize the compelling value proposition that Tavalese brings to the $1.1 billion U.S. ITP market as a differentiated targeted therapy with a novel mechanism of action addressing the underlying cause of it, which is platelet destruction, an often overlooked aspect of our product. In the third quarter, we continued to gain momentum, growing sales to $16.3 million, a 39% increase over the third quarter last year.

Unique challenges of this year.

David A. Santos: That growth has been the result of new patients starting total lease therapy, as well as continued improvement in our persistency rate, which now shows that 55% of patients are receiving their four-month refund. We are also making progress expanding our global access for ITP patients, with collaboration agreements in the EU, Asia, Canada, and Israel. The third quarter saw the initial rollout of the product in Germany and the UK.

David A. Santos: And as I said before, even though we have already crossed the $100 million net sales mark, we are just at the beginning of our journey to provide patients with a differentiated treatment for ITP. We're positioned to take advantage of the significant opportunity ahead, having launched our new messaging, highlighting higher response rates in earlier line therapy. And we are also beginning our efforts to compile a broader base of qualitative data with the recent initiation of our new observational study, FORTE, which will provide real-world evidence for the use of Tavalese in earlier lines. That is why we are so enthusiastic about the potential of TAVA. Moving to slide nine, as you may know, there are approximately 81,000 adult patients in the U.S. who have chronic IT.

Sales Mark we're just at the beginning of our journey to provide patients with a differentiated treatment for TP.

We're positioned to take advantage of the significant opportunity ahead, having launched our new messaging highlighting higher response rates in earlier line their therapy and we have also we're also beginning our efforts to compile a broader base of qualitative data.

With the recent initiation of our new observational study Forte, which will provide real world evidence for the use of top police in earlier lines.

That is why we are so enthusiastic about the potential of Cavalese.

Moving to slide nine as you May know there are approximately 81000 adult patients in the U.S., who have chronic eye TP in.

David A. Santos: In light blue, this chart depicts more than 37,000 patients being actively treated on an annual basis with either steroids or later-line therapy. And it is when they switch that they can become a candidate for Tavalee. Additionally, in the dark blue... The chart depicts nearly 44,000 patients in a group we refer to as "watchful waiting" because their disease is being monitored, and they're not actively being treated. However, a portion of these patients will, during the year, also need to switch from watchful waiting to active treatment. And when that happens, Tavalese can become their therapist.

In the light Blue This chart depicts more than 37000 patients being actively treated on an annual basis with either steroids or later line therapy and they did when they switch that they can become a candidate for top Elise.

In addition, only in the dark blue.

Chart depicts nearly 44000 patients in a group we refer to as watchful waiting because their disease is being monitored and they're not actively being treated however, a portion of these patients during the year, we'll also need to switch from watchful waiting the active treatment and when that happens tali.

So it can become their therapy. So we have many opportunities to impact patients who need a new therapy throughout the continuum of chronic eye TP treatment.

David A. Santos: So we have many opportunities to impact patients who need a new therapy throughout the continuum of chronic ITP treatment. Since launch, we've made good progress with patients who are switching in the later line, just as we had anticipated. And that's because these patients are hard to treat, have limited options, and so there is a much higher perceived need by both patients and clinicians.

Since launch we've made good progress with patients who are switching in the later lines just as we had anticipated and that's because these patients are hard to treat have limited options and so there is a much higher perceived need by both patients and clinicians we.

David A. Santos: We have patient case studies that provide compelling evidence to use Tavalese in these late-line patients, showing durable responses in some of the patients who have failed multiple therapies. So, for patients who've yet to try Tavalese, this could be a great option. That said, the greater opportunity to impact patients is in the earlier lines, either when they're switching off steroids or moving to the third line setting. In fact, these early line patients represent approximately 75% of the post-steroid market.

We have patient case studies that provide compelling evidence to use taliesin. These late line patients showing durable responses in some of the patients who failed multiple therapies.

So for patients who have yet to try talia this could be a great option.

That said the greater opportunity to impact patients is in the earlier lines, either when they're switching off steroids or moving to the third line setting in.

In fact these early line patients represent approximately 75% of the post steroids market.

David A. Santos: It certainly is a more challenging cell, as clinicians have developed habits with other options. And that's why it's so important for us to demonstrate to physicians that Tavalese can be as effective as the other post-teroid treatments they've used historically, and importantly, that the responses they get can be durable. To do this, we're leveraging the data from our post-hack analysis that you see on slide 10. These bar graphs are from a new promotional piece we launched in Q3 based on a British Journal of Hematology article that was published in July. The left bar graph on this slide depicts response rates at both the 50,000 and 30,000 platelet count levels in each line of therapy, and it shows the 78 percent overall response rate in the second line compared to the responses seen in later lines. The higher response rates have been a key message for us to deliver to clinicians. Additionally, although the response rates varied by line of therapy, the right bar graph shows that once a response was achieved, it was maintained irrespective of the line of therapy. This durability of response is meaningful to clinicians and patients when choosing therapy.

It certainly is a more challenging sell as clinicians have developed habits with other options and that's why it's so important for us to demonstrate to physicians that toggle lease can be as effective as the other post steroids treatments they've used historically and importantly that the response.

Until they get can be durable.

To do this we are leveraging the data from our post hoc analysis that you see on slide 10.

These bar graphs or from a new promotional piece, we launched in Q3 based on the British Journal of Hematology article that was published in July.

The left bar graph on this slide depicts response rates at both the 50030 thousand platelet count levels in each line of therapy and it shows the 78% overall response rate in second line compared to the responses seen in later lines.

The higher response rates have been a key message for us to deliver to clinicians.

Additionally, although the response rates varied by line of therapy, the right bar graph shows that once the response was achieved it was maintained irrespective of line of therapy.

This durability of response is meaningful to clinicians and patients when choosing therapy.

To augment this existing data. We've also re launched recently launched an observational trial in up to 45 second line patients to collect additional evidence in the real world setting.

David A. Santos: To augment this existing data, we've also recently launched an observational trial in up to 45 second-line patients to collect additional evidence in the real-world setting. So with our existing and future data in earlier line patients, we're confident we can capture more of the significant opportunity ahead in IT. On slide 11.

So with our existing and future data in earlier line patients. We're confident we can capture more of the significant opportunity ahead in I. TP.

On slide 11.

David A. Santos: I will briefly highlight our expanding virtual commercial efforts. Well, we have great data to share from the British Journal of Hematology publication. Our challenge has been getting messages out to clinicians with limited access during COVID.

I will briefly highlight our expanding virtual commercial efforts well.

While we have great data to share out of the British journal of Hematology publication.

Our challenge has been getting messages out to clinicians with limited access during Cove it.

David A. Santos: Our sales team has made excellent progress in creating virtual opportunities to impact clinicians. This graph shows how we have continued to increase our effectiveness in both scheduling and executing virtual interactions with our customers. While the pandemic has certainly challenged our ability to see customers, strong execution with these virtual interactions has helped even the playing field of reach and frequency for smaller sales teams with larger geographies like ours. Although it's still early in using the data from the publication in our virtual efforts with ClinShare.

Our sales team has made excellent progress in creating virtual opportunities impact clinicians. This graph shows how we have continued to increase our effectiveness in both scheduling and executing virtual interactions with our customers well.

While the pandemic has certainly challenged our ability to see customers strong execution with these virtual interactions has helped even the playing field of reach and frequency for smaller sales teams with larger geographies like ours.

Although it's still early in using the data from the publication in our virtual efforts with clinicians we are confident that it will add to our story of the unique emo a if tava lease on platelet destruction and provide a strong reason to use top police in earlier line patients who are switching from their stair.

David A. Santos: We are confident that it will add to our story of the unique MOA of Tavolese on platelet destruction and provide a strong reason to use Tavolese in earlier-line patients who are switching from steroids or to a third-line therapy. We are doing everything possible to ensure that physicians understand the benefits of Tavalese, and it stays top of mind for clinicians when they see patients in any line of therapy who are switching treatments. And I am confident we will continue to add more patients to the Tavalese journey. Finally, turning to slide 12, we are now well on our way to expanding the impact of fostamatinib beyond the U.S. market. Our partner, Griffles, launched Tovles in Germany and the U.K., and we expect to hear from Health Canada on our new drug submission in early 2021 and from the Israel Ministry of Health in the second quarter, enabling Medicine to begin commercial efforts in two markets.

Right or to a third line therapy.

We're doing everything possible to ensure that physicians understand the benefits of top police and it stays top of mind for clinicians when they see patients in any line of therapy, who are switching treatment.

And I am confident we will continue to add more patients to the top Elise journey.

Finally, turning to slide 12, we're now well on our way to expanding the impact of Fostamatinib beyond the U.S. market our partner Griffith launch to have less in Germany and the UK.

And we expect to hear from health, Canada on our new drug submission in early 2021 and from the Israel Ministry of health in the second quarter, enabling medicine to begin commercial efforts in two markets.

The phase three study in Japan is also ongoing with key say.

Wolfgang Duner: The phase three study in Japan is also ongoing. I look forward to providing quarterly business updates to you as we continue to broaden our impact with Tavalese in the future. Thanks for your attention, and now I will turn the call over to Wolfgang. Thank you, Dave.

I look forward to providing quarterly business updates to you as we continue to broaden our impact with top at least in the future. Thanks for your attention and now I will turn the call over to Wolfgang.

Thank you Dave.

Wolfgang Duner: I'll begin on slide 14 with a recap of our warm autoimmune hemolytic anemia phase 3 pivotal trial and our progress over the past few months. This is a very exciting opportunity for us and maybe even greater than ITP given the lack of an FDA-approved therapy and our potential to be first to market. As you know, our trial sites temporarily paused patient enrollment during the lockdown, just like most clinical trials worldwide. In recent months, we began to see sites reopen, and screening activity has picked up.

I'll begin on slide 14, with a recap of our warm all the immune hemolytic anemia phase three pivotal trial and our progress over the past few months.

This is a very exciting opportunity for us and maybe even greater than <unk>, given the lack of an if DEA approved therapies and our potential to be first to market.

As you know our trials sites, hence temporarily paused the patient enrollment during the Locdown took like most most critical trials worldwide.

In recent months, we began to see side three open and screening activity has picked up.

Wolfgang Duner: As of today, we have 57 patients randomized, which is approximately 63% of our target of 90 patients. And note that in October, we enrolled seven patients, which is close to the pre-pandemic pace of eight to nine patients a month. On another positive note, our trial sites have developed procedures and routines to deal with the pandemic and are better prepared to safely enroll and conduct clinical trials than they were earlier this year. Also, we believe the Oral Administration of Cavaliers provides an advantage over other trials as it allows for outpatient visits and does not require in-hospital treatment, which makes things easier. We are also leveraging FDA guidance on how to conduct clinical trials during the pandemic and taking advantage of local labs or remote study visits to keep patients as safe as possible while participating in our trials. Of course, COVID-19 is not over yet. So we are unable to reliably predict enrollment completion at this point.

As of today, we have a 57 patients randomized, which is approximately 63% of our target of 90 patients.

And note that in October we enrolled seven patients, which is close to the pre pandemic pace of eight to nine patients a month.

On another positive note our trial sites have developed procedures into routine to deal with the pandemic and all better prepared to safely enroll and conduct a clinical trials than they were earlier this year.

Also we believe the oral administration of cover these provides an advantage over other throat.

As it allows for outpatient visits and does not require in hospital treatment, which makes things easier.

We are also leveraging if the guidance on how to conduct clinical trials during depend they make and take advantage or local labs or remote study visits to keep the patients as safe as possible while participating in our trial.

Of course, corporate banking is not over yet so we are unable to reliably predict enrollment completion at this point.

With over 90 sites established in 22 countries. We believe we are well positioned to keep or even expand the need for cavalese to become the first drug approved for this indication.

Wolfgang Duner: With over 90 sites established in 22 countries, we believe we are well positioned to keep or even expand the lead for Tavalis to become the first drug approved for this indication. Switching gears on slide 16, to our efforts in COVID-19. As we elaborated in previous calls, there is a strong scientific rationale for sicken inhibition in COVID-19 patients to inhibit hyper-inflammatory cytokines, hypercoagulation, and thrombosis, as well as neutropenia.

Switching gears on slide 16.

Through our efforts in COVID-19.

As we elaborated on previous calls there's a strong scientific rationale to seek inhibition in COVID-19 patients to inhibit the hyper inflammatory cytokine.

Hyper coagulation and thrombosis as well as mid ptosis.

Wolfgang Duner: There have been recent published reports, which we have shared with you before, from MIT and Harvard and the University of Amsterdam proposing Tavalis as a highly suitable drug to treat COVID-19. And we also have in-house preclinical data from a mouse model of acute respiratory distress syndrome in which Tavalis performs well. And as a commercial product with a well-established safety database of more than 4,500 patients treated in clinical trials, Cavalisse is readily available and could be quickly adopted as a treatment for COVID-19. As a result of all of this, we have now taken Tavalis into the clinic for COVID-19. We have shared with you before two investigator-initiated trials at the NIH and Imperial College of London. We are also pleased to announce our Rigel-led Phase 3 trial in COVID-19 to start later this quarter. On slide 17, I'll remind you where Tavalis fits in the course of COVID-19. Tavalis is an immunomodulator that can treat an overreactive immune system. Typically, the immune system overreacts in about 20% of patients after about one week when they develop more serious symptoms and need to be hospitalized.

There has been recent published a report we.

Which we have shared with you before from MIT and Harvard and the University of Amsterdam, proposing how the lease is a highly suitable drug to treat the COVID-19 and.

And we also have in house preclinical data from a mouse model acute respiratory distress syndrome, and we just haven't these performed well.

And as a commercial product with a well established safety database of more than 4500 patients treated in clinical trials. How these is readily available and could be quickly adopt it's a isn't treatment broker with 19.

As a result of all of this we have now taken problem. These into the clinic for COVID-19.

We have shared with you before two investigator initiated trial at the NIH and Imperial College of London.

We're also pleased to announce our right to live phase three trial included 19 to start later this quarter.

On slide 17.

Mind, you were have a lease fleets in the course of COVID-19.

How about lease is an immunomodulator that can threed and overreact to the immune system.

Wolfgang Duner: Tavares could prevent the progression of mild disease to severe disease that puts patients on ventilators and ultimately can lead to death. If we were successful, then we would have a well tolerated, widely available treatment option that could alleviate much of the fear of this disease, even before effective vaccines become available. And at this point, we do not know for sure when safe and effective vaccines will be approved and become available on a large scale. You may have seen this before.

Wolfgang Duner: The only thing I want to re-emphasize is that Tavalis mechanistically could interfere with the disease pathogenesis on multiple levels, not just one. For example, it can inhibit excessive cytokine production. It can prevent hypercoagulation with macro and micro thrombosis, and it can inhibit a process called mitosis, which is accused of playing a major role in COVID-19. That makes Tavalis a really unique candidate for effective treatment of COVID-19 complications. On slide 19.

Wolfgang Duner: You can see a schematic of our right to respond phase three clinical trial. We plan to select hospitalized patients with mild disease who have certain risk factors to develop more severe disease. We expect to randomize approximately 308 patients one-to-one to either Fosformatinibs plus standard of care or placebo plus standard of care. The primary outcome measure is prevention of progression to severe disease as measured with an ordinal scale.

Patients with mild disease, who have certain risk factors to develop more severe disease.

We expect to randomize approximately 308 patients one to one to either for some ethnic plus ended up here.

Or a placebo because he ended up here.

The primary outcome measure is prevention of progression too severe disease as measured with an ordinance scale if.

Wolfgang Duner: If positive, this trial could be the basis for approval of foster maternity to treat COVID-19. Slide 20 shows the Phase II trial design conducted by the National Heart, Lung, and Blood Institute at NIH in collaboration with Inova Health Systems. This study focuses on more severe patients who may be on mechanical ventilation or even ECMO, which supplements very well the rice response trial.

If positive just try it could be the basis for approval, a first and last name to treat the COVID-19.

Slide 20 shows you the faith to trial design conducted by the National Heart lung and Blood Institute at NIH, and <unk> collaboration with Inova Health systems.

This study focuses on more severe patients who may be on Mckinney to ventilation or you can make more.

Wolfgang Duner: Also, NIH has very powerful translational research tools that can generate valuable new mechanistic data on the foster market in COVID-19. For example, they have established a netosis assay that can directly study the effect of prostamatinib on that aspect of the disease. The trial randomized the first patient on October 9th and has already enrolled nine patients, reflecting the great enthusiasm that the NIH and Inova teams have for their study. And just to remind you, there is a third foster maternity trial ongoing in the UK, which has enrolled five patients. This is a phase two study sponsored by Imperial College London studying prostamatinib and ruxolitinib on top of standard of care in patients with COVID-19 pneumonia. So, in summary, we have a multi-pronged approach to COVID-19, and we're excited by the possibility to come up with a safe and effective treatment that is desperately needed. With that, I'd like to turn the call back over to Raul. Okay?

Raul R. Rodriguez: Thank you, Wolfgang. Before Dean reviews our financials for the quarter, I wanted to take a quick look at our pipeline. As you know, we are focusing on the inhibition of immune signaling. The graphics on slide 22 provide a simplified view of that process for each of our three main targets, starting on the left side of the screen.

Raul R. Rodriguez: We have had and are having success with sick inhibition in ITP. Our goal now is to create further attractive opportunities with sick inhibition in other indications. These include warm autoimmune hemolytic anemia and COVID-19, which we've discussed with you today, but also acute respiratory distress syndrome and pneumonia, similar to COVID-19 but from other origins than COVID-19.

Goal now is to create further attractive opportunities with TICC inhibition in other indications. These include warm autoimmune hemolytic anemia, and COVID-19, which we've discussed with you today, but also acute respiratory distress syndrome, and the ammonia similar to COVID-19, but from other origins that.

EBIT margin.

Going forward our plan is to replicate the success with our two earlier stage programs that target Iraq, Onefour and the grip pathways.

Raul R. Rodriguez: Going forward, our plan is to replicate the success with our two earlier stage programs that target IRAC 1-4 and the GRIP 1 path. There's been a great deal of interest in the industry in targeting the IRAC4 pathway, and we have the only molecule in the clinic that inhibits both IRAC1 and IRAC4 timings.

Theres been a great deal of interest in the industry in targeting the Irakfour pathway.

Raul R. Rodriguez: Our research has demonstrated that inhibiting both of these can achieve a much more robust response, providing what we think is a key differentiator over IRAC-IV alone. This allows us to block both innate and adaptive immune responses and so have a broad, robust effect on chronic inflammation. We believe this could represent potential in many disease areas, as shown on the slide. Our RIP-1 program is also very exciting, and there has been a great deal of interest in this area in our industry. RIPA inhibition has the potential to treat multiple inflammatory diseases mediated by the Th2 and TNF pathways, including psoriasis, psoriatic arthritis, ankylosing spondylitis, IBD, and rheumatoid arthritis.

Raul R. Rodriguez: To give you an idea of the potential of this space, there are numerous drugs that generate billions of dollars in revenue annually that block TNF and or TH2 pathways. If our molecule were to show benefit in these patients with these indications, the opportunity is tremendous. The convenience of our administration, which we provide, may also prove to be very attractive. In addition, there is a broader opportunity with RIFNF. While our Phase I product is systemic, we are also exploring a CNS molecule that can cross the blood-brain barrier to potentially treat a variety of neurodegenerative diseases, including Alzheimer's and ALS.

Dean L. Schorno: We have done a significant amount of work on these molecules and plan to select a lead candidate to take into the clinic. We are very excited about these opportunities and exploring them further. So with that, I'll turn the call over to you. Thank you, Raul. Turning to slide 24, for the third quarter of 2020, we shipped 1,727 bottles to our specialty distributors. 1,625 of those bottles were shipped to patients at clinics, while 102 bottles remained in our distribution channels at the end of the quarter. As of September 30th, a total of 810 bottles remained in our distribution channels.

Come these molecules and plan to select a lead candidate to take into the clinic.

We are very excited about these opportunities and exploring them further.

So with that I'll turn call over to Dean.

Thank you Raul turning to slide 24 for the third quarter 2020, we shipped 1727 bottles to our specialty distributors 1625 of those bottles were shipped to patients at clinics.

Well 102 bottles remained in our distribution channels at the end of the quarter.

As of September Thirtyth, a total of 810 bottles remained near distribution channels, we reported net product sales from top lease of $16.3 million, 39% increase compared to the third quarter of 2019, our net product sales from top lease were recorded net of estimated discounts charge back.

Dean L. Schorno: We reported net product sales and tabloids of $16.3 million, a 39% increase, compared to the third quarter of 2019. Our net product sales and tabloids were recorded net of estimated discounts, chargebacks, rebates, returns, copay assistance, and other allowances of $4.1 million. Our gross to net adjustment, which is approximately 19.8% of gross product sales.

Rebates returns co pay assistance and other allowances of $4.1 million, our gross to net adjustment, which is approximately 19.8% of gross product sales before we move on from net product sales, let me comment briefly on our expectations for the fourth quarter.

Dean L. Schorno: Before we move on from net product sales, let me comment briefly on our expectations for the fourth quarter. While we're pleased with the continued growth of Tavolis since the start of the pandemic, the impact of COVID-19 on our business is expected to persist. Within this uncertain environment, we expect to see our sequential growth impacted in the fourth quarter of 2020. However, once the significant impact and global restrictions 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 were $2.1 million for the three months ended September 30, 2020, which relates to a milestone payment under our collaboration agreement with Betty Chang. Moving on to costs and expenses, the cost of product sales was approximately $140,000 for the third quarter of 2020.

While we're pleased with the continued growth takeaways since we started the pandemic the impact of Kobe 19 in our business is expected to persist within this uncertain environment, we expect to see our sequential growth impacted in the fourth quarter of 2012.

The significant impact and global restrictions are behind us and the future begins to normalize we expect to see continued strength and growth in our business onto the next slide.

In addition to net product sales Rogers contract revenues from collaborations was $2.1 million for the three months ended September Thirtyth, 2020, which relates to a milestone payment under our collaboration agreement with Daiichi.

Moving on to costs and expenses on a cost of product sales was.

It was approximately $140000 for the third quarter of 2020 total costs and expenses were $32.2 million for the third quarter of 2020 versus $32.9 million in the third quarter of 2019.

Dean L. Schorno: Total cost and expenses were $32.2 million for the third quarter of 2020 versus $32.9 million in the third quarter of 2019. This small decrease in total costs and expenses was primarily due to reduced or delayed commercial activities resulting from the COVID pandemic, offset by increases in personnel-related and consulting costs. As we look towards the fourth quarter of 2020, we expect our fourth quarter total cost and expenses to increase compared to the third quarter as we continue to increase our commercial activities 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 $72.8 million.

The small decrease in total cost and expenses was primarily due to reduced or delayed commercial activities, resulting from the cobot pandemic offset by increases in personnel related and consulting costs as we look towards the fourth quarter of 2020, we expect our fourth quarter total cost and expenses to increase compared to the.

Third quarter as we continue to increase our commercial activities and further our research and development pipeline inclusive of the COVID-19 efforts that our team has discussed.

Dean L. Schorno: With that, I'd like to turn the call back over to Raul. Thank you, Dean. Looking at slide 26... you will see that we are focusing on our four key value drivers, and we're well positioned to advance or capitalize on each of these opportunities. While our sales force is operating in a very unique environment, our creativity and flexibility have enabled us to implement a virtual approach. We are providing the team with the resources that they need to educate patients and physicians on the benefits of tablis, including its use in earlier lines of treatment. And as you've heard here, more support is coming. This work will also aid Griffith's efforts in Germany and the UK and other European markets as they continue to roll out the product.

Dean L. Schorno: We continue to make good progress on our warm autoimmune hemolytic anemia trial as we enroll the final third of our phase three. Having the wide breadth and reach of our clinical sites, as well as an oral agent, is an advantage during these times. The advance of our COVID-19 program is also very exciting. With our phase 3 trial set to launch, we will be one step closer to potentially helping patients that are suffering from the hyperactive immune response and destruction caused by this virus. And finally, as we continue to make, as we mentioned, progress in our discussions to secure a co-development and co-promotion agreement, and we believe that we will have a partnership near your end. With all of that, I'd like to turn the call over to your questions. If you would like to register a question, please press the 1 followed by the 4 on your telephone. You will hear a three-tone prompt to acknowledge your request. If your question has been answered and you would like to withdraw your registration, please press 1, followed by 7.

Uhm.

You will hear three tone promptitude knowledge your request.

If your question has been answered and you would like to withdraw your registration. Please press the one followed by the three.

One moment please for the first question.

Raul R. Rodriguez: One moment, please, for the first question. Our first question comes from the line of Yigal Nochomovitz of City.

Our first question comes from the line of he go.

No Cho moments of city.

Yigal Dov Nochomovitz: Please go ahead with your question. Hi, this is Carly on behalf of Yigal. Can you hear me?

Please go ahead with your question.

Great Hi, this is Carly on for you all can you hear me okay.

Carly Nicole Kenselaar: Okay. Yeah. Okay, great. The first question we had was about the Phase 3 trial in COVID-19 patients that you announced today. Can you clarify if the decision to start that study was made based on any emerging data from the ongoing investigator-sponsored trials? And if not, can you just provide some color on why you decided to take the step to start Phase 3 before seeing any of the data from the ongoing trials? Thank you, Carly. I'll ask Wolfgang to comment on... Yeah, so as you heard in my presentation, there are pretty compelling data for fostamatinib in a mouse model of acute respiratory distress syndrome, which we shared with you in the previous earnings call. And so we have pretty good preclinical confidence that the drug may work in COVID-19. In addition, there have been some reports from other animal models that strongly suggest a very strong rationale for fostamatinib in COVID-19.

Yep.

Okay, Great. The first question. We had was the phase three trial in COVID-19 patients that you announced today can you clarify if the decision to start that study was made based on any emerging data from the ongoing investigator sponsored child and if not can you.

Provide some color on why you decided to take the step to start the phase three before seeing any of the data from the I S. P.

<unk>.

<unk> I'll ask we'll send to to come at on that.

Yes, or as you heard in my presentation, there or pretty compelling data for post them up <unk> in a mouse model or for acute respiratory distress syndrome, which we have shared with you in the previous earnings call.

And so we we we have pretty good preclinical confidence that's a drag me broken COVID-19. In addition, there's been some reports from from other animal models. That's highly suggest a very strong rationale for for both of them.

<unk> been COVID-19 that has a has led us to stop this multipronged approach. So we were we were approached by the N I H N. The Imperial College, London, who were very enthusiastic about taking <unk> into COVID-19, and those studies have started and to this is how you do it these days.

Wolfgang Duner: That has led us to start this multipronged approach. So we were approached by the NIH and the Imperial College of London, who were very enthusiastic about taking Tavalis into COVID-19. And those studies have started. And this is how you do it these days.

<unk>, we have started conversations with the agency and the F D, a and or working the plane too long to pay three study mm mm later this quarter.

Wolfgang Duner: We have started conversations with the agency and the FDA and are working out a plan to launch a phase three study later this quarter. Okay, great. That's a lot. Go ahead, Carly.

So okay, great how about yourself.

Carly Nicole Kenselaar: No, sure, sure. Go ahead. What I was going to add to that is that these trials are supportive, but if we want to at some point get a label to include this, we have to do a larger trial than the 60 patient trial. We're working on it at NIH. And so this allows us to potentially do that, this larger trial, and I think we'll be in a solid position to do so sometime as early as next year.

So I'd probably.

Oh sure sure.

Go ahead.

Oh, what I was gonna Wednesday to add to that is that these these calls are are supportive, but if we want to at some point get a label to include this we have to do a larger trialled in the sixties patient trial, we're working on it and NIH and so this allows us to potentially do that this larger trial and I think.

Will be in a solid position to do so sometime as early as next year.

Raul R. Rodriguez: Okay, great. That's helpful. And then we had a follow-up question. Can you just provide any further details on how quickly you expect the study will be able to enroll, when we might expect to see some data, and also how much you estimate it will cost to conduct the trial? I'll let you go.

Wolfgang Duner: Yeah, I can take that. So, as we told you on the call, NIH has enrolled nine of 60 patients in their study. So it's fair to assume the study should be enrolled and have data in the first half of 2021. That's going to be the first robust placebo-controlled data set.

Wolfgang Duner: And, you know, if that looks very compelling, then we would certainly seek initial conversations with FDA as to what it takes to get this commercially available and get the drug to patients quickly. Regarding our own study, phase three, I told you we target to initiate that later this quarter. We are working with an experienced CRO to execute this study, and we plan to have a large number of sites to enroll patients in the United States, as well as in several places in Latin America. So I'm confident that we can complete the trial in an expeditious fashion. Uh, Raul, do you want to add to that?

In Latin America, So I'm confident that we can complete the trial in an expeditious fashion.

I'll do you Wanna to that yeah.

Raul R. Rodriguez: Yeah. We've not disclosed the dollar numbers associated with this, but keep this in mind. Our exclusivity period for Tavalisse Foster Matinib goes to 2032, so quite a long time. We feel it's useful to invest in this area further, in the product further, given that it is commercially available already, and we can leverage that with more ease. Also, we were always planning on launching an additional study. We were working on several alternative indications before COVID. COVID came about, and this is the perfect indication, not perfect, a very good indication to pursue with this product. The fit mechanistically, as Wolfgang said, is really very excellent.

Raul R. Rodriguez: There's tremendous interest in novel mechanisms that are very well suited to the disease process. And, in addition, given that we have the product already available and we can make substantial, provide substantial amounts of material should there be a positive result, that is one of the key features of this product which made us so excited about it. And so, we think that that's a very useful investment for us. The fact that you can execute a pivotal trial such as the one we discussed today and get the results relatively quickly is, I think, very helpful. Keep in mind also that COVID-19 pneumonia's hyperactive immune system is a key focus here. However, if we have good results here, this will allow us to launch subsequent studies in other areas, other pneumonias, treating acute respiratory distress syndrome from sources other than COVID-19, which happens very frequently, and those are a continuing issue in the healthcare system. So it really sets us up very nicely for doing that subsequent study.

Carly Nicole Kenselaar: So it's a pretty exciting opportunity in terms of that, and like I said, we're delighted to be able to launch this trial very shortly. Very helpful. Thanks very much for taking our question. Our next question comes from the line of Eun Yang of Jefferies. Please go ahead with your question. Hi, this is Nalin on behalf of Eun Yang.

The Trinity in terms of it and like I said, we're delighted to be able to most of the trials very shortly.

That's super helpful. Thank you very much for taking our questions.

Eun Kyung Yang: So I just have two questions. Number one is about Tavilis' opportunity in Europe. So Griffo commented this morning that in the first three months of launch, over 90% of the target customers have been contacted by the sales team, but only around 50 patients are currently on Tavilis.

Eun Kyung Yang: So could you please elaborate on the number of target customers? Roughly how many patients, and what percent of the more than 50 patients represents? And what are the key factors preventing patients from starting Tavilis?

Eun Kyung Yang: That's the first question. And the second question is about WEHA. So, an SCRN manufacturer has commented that SCRN may be able to offer a deeper response compared to tabloids. Could you please comment on what criteria would define a deep response in WEHA? And approximately what percent of the 44% of patients who had a response in Phase 2 were deep responders? And would you quantify the depth of response in Phase 3?

Raul R. Rodriguez: Thank you very much. Sure. Thank you, Nalin.

Raul R. Rodriguez: We'll take those in sequence, maybe the first on tablets in Europe. We're delighted with the performance of our partner, Griffles, in Europe and their uptake and the execution of the launch in the UK and Germany. There's still a lot of work to do in Europe. The European market is a very attractive market, maybe second only to the US market in ITP. We're delighted that they've put so much effort and thought into the launch of the product. They've achieved quite a number of targets. They're better positioned to comment on the penetration there since it's really in their area. But we hesitate to say what we know, what they've shared with us, given that they haven't shared more information than that. The market is very attractive, very similar to the US in terms of structure and what products are used. We think that they're off to a very good start, though it's very, very early still. They've only been on the market in those two countries for a short period of time.

And they are uptake and and and the execution of the launch in the U K and Germany, There's still a lot of work to do in Europe European market is a very attractive market, maybe second second only to the U S market M. I T. P. So and we're delighted that they put so much effort and <unk>.

Raul R. Rodriguez: There's still a lot of opportunity left. Maybe I'll ask Dave to make any further comments on that. I think you covered most of it, Raul, but I guess I would just say that those numbers are quite impressive, and it shows their commitment to really getting the word out about Tovles to their clinicians in the EU and, I think, the great success that they're having in terms of receptivity to the messages around Tovles for ITP patients in both Germany and the UK. But as Raul said, I think it's important for them to On your second question, you know, we are very pleased with what Taveli's second edition has been able to show at AIHA.

Raul R. Rodriguez: And we did a phase two trial that showed a very good response, 44, 48 percent response rates, which are very attractive. And based on that, we've launched our phase three efforts. And we're, you know, approaching over 60 percent enrolled, which we're very happy with. And as Wolfgang mentioned, seven patients have enrolled most recently in a month. That's actually a very nice performance in terms of enrollment, so we're very happy about that. It's hard for me to make a comment on other people's products simply because I don't have any data. They haven't generated any data as yet. So when they do, we will be able to do so, and I'm sure others will as well.

And they were you know approaching of over 60% of rolled which we're very happy with an and is Wolfgang mentioned seven patients enrolled most recently the month, that's actually a very nice performance in terms of enrollment. So we're very happy about that it's hard for me to make a comment on other people.

Raul R. Rodriguez: But I can say that we think that there's a tremendously attractive opportunity there and that we are the first with the foremost product in development. We have good phase two trial data already generated that we think is very encouraging, and we're eagerly waiting to finish this trial enrollment and get this product to these patients, because they currently have nothing.

Raul R. Rodriguez: And that represents a tremendous opportunity, and we think that we will be the first product approved for this indication. And that'll give us a tremendous opportunity to really discuss and set the stage for this indication. Keep in mind that we are currently detailing our product to he-monks that treat ITP based on our current indication. There is an almost perfect overlap between the doctors who treat ITP and those who treat AIHA. So all that work that we're doing today to educate doctors about our product, our mechanism, how it works, how you use it, will be completely translatable to AIHA once that's approved because it's the same product, same dose, same name, same dosage. And that's a tremendous advantage.

Raul R. Rodriguez: A lot of the heavy lifting that's required to get the knowledge based on sick inhibition we do today, well ahead of the launch in AIHA. So not only do we have a clinical lead over everybody else, but it's substantial. And I think we've expanded on it this year. But in addition to that, we're building a tremendous installed base of knowledge about our product that will be very helpful once we launch it. So I think we're in pretty good shape for that company. Thank you very much.

Alright, you're all set substantial and I think we've expanded on it this year.

But in addition to that we're building a tremendous installed base of knowledge of our product that will be very helpful. Once you can launch duck. So I think we're in pretty good shape for that competition.

Thank you very much.

Thank you ma'am.

Joseph Pantginis: Thank you, Mel. Thank you. Our next question comes from the line of Joe Pantginis of H.C. Wainwright.

Thank you. Our next question comes from the line the Joe Pat Goodness H C. Wainwright. Please go ahead with your question.

Joseph Pantginis: Please go ahead with your question. Hey, guys, good evening. Thanks for taking the question. So it's nice to see the continually improving commercial profile of Tavalese. But obviously, you continue to mention the COVID-19 headwinds.

Joseph Pantginis: So that's what I wanted to focus on. So when you talk about the mix, or you talk about, you know, getting new patients, as well as improvements in persistency, which is great to see, I guess I wanted to ask about the mix that you're seeing with regard to those two categories. And especially for the new patients, you know, what is driving, you know, obviously, you have the increased virtual touchpoints with Salesforce, but, you know, any anecdotes you can share of what's helping to drive the new patients coming on? Sure, Joe. Could you repeat the first part of your question? I didn't understand the two different groups. Sure, sure. So you talked about, with regard to the commercial profile, you mentioned that you have new patients as well as improvements in persistency of the patients already on the drug. So first, are you able to delineate the mix between those two?

David A. Santos: And then the second part of the question was, you know, for the new patients, what's driving them to get on Tavilon? Great, good question. Now, I'll ask my colleague Dave to comment on that, and then I'll add some further comments. Sure, I'd be happy to comment on that. I think, you know, first of all, what I'd like to do is make sure you know how impressed I am with this team that I have been honored to work with here at Rigel. I mean, the ability for us to look at our data, target our prescribers, and execute against that has been absolutely incredible for me. Because I can tell you I have a very, very committed team to get the word out.

David A. Santos: So both of those things you mentioned are really important to our growth, new patients as well as keeping the patients on that we have already started. And I would say, you know, I'm not going to give specifics right now, but I would say that both have been contributing to our growth over the past year. But we have seen a little more difficulty in kind of getting new patients on, and that's simply because of our reach, which, as I showed you, is continuing to improve even during COVID. So I think one of the big things that will happen is, you know, when we finally open up and can get this message spread, we can get more new physicians prescribing the product because we'll have expanded our reach. And we think that's going to really be an accelerator to getting new patients on the product. But persistency has helped us drive our growth. As you pointed out, you know, we are at 55% on that four-month refill. But recognize that that just represents one point in time.

David A. Santos: And, you know, the earlier we get patients on therapy, the better that can get because those are better prognosis patients; they tend to respond, and that's what keeps them on therapy to the four-month point, and then well beyond that. So both of those things are driving our growth, and we really do believe it's been our ability to, despite COVID, get in front of doctors. But with that said, it could definitely accelerate things if things would open up and we'd be able to see our clinicians in person through those things that normally we're able to do, drop in, go to an exhibit, see a doctor as they come by our exhibit. Those kind of live interactions, which really help reiterate the message, just haven't been happening as much during COVID. That's actually really helpful feedback. Thanks a lot.

David A. Santos: Thank you, Joe. Thank you. Our next question comes from the line of Doe Kim of BMO. Please go ahead with your question. Good afternoon.

Thank you. Our next question comes from the line of do Kim of BMO. Please go ahead with your question.

Doe Kim: Thanks for taking my questions. First, on the European ITP market, I was just wondering if you could share your thoughts on the treatment landscape there. Any differences in how Europe would treat or use tabloids versus how US doctors would?

Doe Kim: Sure, thank you, Dope, for your question. I'll also ask my colleagues to comment as well, Dave and Wolfgang, if helpful. As I mentioned in my response to an earlier question, I don't think there's much difference in the overall treatment landscape in Europe. It resembles the U.S. treatment landscape very closely. That is, patients with ITP are initially put on steroids as the most common form.

Raul R. Rodriguez: IVIG is generally used as a rescue medication there, as it is here in the U.S. Our partner, Ripple, as you may know, is one of the foremost providers of IVIG, and that's why this is a nice fit. That's an acute care use; this is a rescue use; this is a chronic use. After steroids are deployed, then they move on to a second line, and there, the choice is similar to the U.S. Taviliz is available for that line, as well as human agents, as well as Rituxan, though Rituxan is not approved. Different doctors view those agents differently and select them in different orders. Now, there are some differences from country to country.

Our top release is available for that line as well as our people agents as well as reduction, though we're touching is not approved.

Different doctors veal, those agents differently and select dozing different orders and sales.

Some differences country to country I understand that in Germany. For example, there's more people use less with toxin use France the opposite Moreover, toxin.

Raul R. Rodriguez: I understand that in Germany, for example, there's more Tepo use and less Rituxan use. France, the opposite, more Rituxan use and less Tepo use. There are some variances country to country, but in total, they're not that different in terms of what's available to them and what they use. And, much like other areas of our industry, it really is a global market, and that's an important thing to think about: how we position the product here facilitates the positioning of the product there by our partners. So maybe Wolfgang can comment on anything in addition, and maybe Dave can comment as well. Raul, I think you summarized it pretty well.

Use less people use some variances country to country, but in total.

There are not that different in terms of the what's been available to them and what they use and much like other other areas of our industry. It really is a global market and Thats, an important and think about how we position the product here facilitates the positioning of the product. They are by our partner So maybe working income.

Yeah.

Wolfgang Duner: I mean, I don't see any major differences in treatment algorithms for ITP in Europe versus the US, and I think Tavalis or Tavles in Europe should get to good adoption. Dave, do you have any additional comments? Yeah, um, I think, uh, importantly... And this, you know, I've only had one meeting with our Griffith counterparts, but what I saw during that meeting was a tremendous ability to partner, and interact with our commercial medical development team and them. And importantly, what they have that we didn't have at launch is this new earlier line data.

David A. Santos: And so they're out of the gates very quickly with this story that, you know, TAVLESS is an option immediately after steroids with a 78% response rate. And I think that's really important. And obviously, they're learning a lot from us through these interactions, and we're quite pleased with, you know, the things they've adopted and everything they're doing to ensure that the message gets out globally on TAVLESS and TAVALIS. I thought there was a time when splenectomies were a lot more common in Europe than in the U.S. Is that not the case anymore?

Doe Kim: Are they moving more towards therapeutic options ahead of splenectomies? I think doing that is a general trend in the US and Europe, but not so sure about the Japanese market, our Asian market, but I know they are increasingly not favored as patients prefer not to have to undergo a splenectomy given the uncertainty of that. Right, okay. And I would just add, very quickly there, from a treatment standpoint, remember that the International Consensus Guidelines apply there as well as here because that's, you know, an international working group. And so I do think, you know, that's important to note as well. Great, thanks.

I think the door that is.

General and the us and Europe, but not sure so sure about the Japan market, our Asian market, but I know they are increasingly not favorite as patients prefer not to have 200 co splenectomy given the uncertainty of that out.

Right Okay.

Yes, and I would just add.

Very quickly there.

Admin standpoint remember that.

The international consensus guidelines supply there as well as here because that's you know an international working group and so I do think you know that's important to note as well.

David A. Santos: That's very helpful. I just had a question about the phase three study in COVID patients. Could you, could you share with us what your thoughts are on the expectation for the standard of care arm? How you are thinking about what the potential benefit of Fost-Matinib would be in terms of how you power the study and the number of patients you're planning to enroll? Um, Wolfgang, would you like to come?

Wolfgang Duner: Sure. Yeah, so we are very much aware of the changing landscape, but also about the drugs that are being tested and are not successful. So, but clearly, in the U.S., we do expect patients to be on remdesivir and probably more severe patients also be on dexamethasone because it has worked in more severe patients, you know; it has some effect in severe patients. But our patients are more on the milder side, at least in phase three. So that's one thing. And we are stratifying patients by their use of remdesivir and dexamethasone so that we will not end up with an imbalance of patients all on dexamethasone or remdesivir in one arm.

Wolfgang Duner: So we have an insurance policy built in there. Now, I also told you that we are going to places outside of the United States where at least remdesivir will not be as widely available. So we also expect a number of patients who are not on remdesivir but maybe on dexamethasone. Now, both drugs, in my view, have modest treatment effects.

It's in there and I also told you that we are going to places outside of the United States, where we're at least one busy for you will not be is widely available. So we also expect the number of patients who are not on the room disappear, but maybe on <unk>.

So my system now uhm, both drugs in my view has modest treatment effects.

Wolfgang Duner: So, assuming, for example, a 30% progression rate, which we plan to achieve by enriching for some risk factors with some patients with some risk factors, we think we have adequate power to demonstrate statistical significance for post-traumatic over standard of care, regardless of the background therapy. I will pause here and see if you have follow-up questions. I know that that's very helpful. Thank you for taking my questions. Thank you, Joe.

So I'm assuming a.

For example, a 30% proration rates, which we plan to achieve by enriching for some respect us some patience with some respect US we think we have adequate power to demonstrate statistical significance for some ethnic over over standard of care regardless of.

Around therapy.

I haven't posted and see if you have a follow up question.

I don't know that that's very helpful. Thank you for taking my question.

Thank you <unk>.

Wolfgang Duner: Thank you. Our next question comes from the line of Kristen Kluska of Cantor Fitzgerald. Please go ahead with your question. Hi, good afternoon, everybody.

Thank you.

Next question comes from the line of a Christian how close of Cantor Fitzgerald. Please go ahead with your question.

Hi, good afternoon, everybody. Thanks, so much for taking my question [laughter]. So regarding the updates that you had to Canada, Japan in Israel for chronic I T. P. First could you. Please remind us about how you view the market opportunities across these regions and then second do you know if your partners including grasp.

Kristen Brianne Kluska: Thanks so much for taking my questions. Regarding the updates that you have made to Canada, Japan, and Israel for chronic ITP, first, could you please remind us about how you view the market opportunities across these regions? And second, do you know if your partners, including Griffles, intend to collect any data from physicians and users related to the line of usage? I guess it would be interesting to consider, especially in some of these countries outside of the US and Europe, where there might be fewer approved treatment options available. Great. Thank you, Kristen.

<unk> intend to collect any data from the physicians and users related to the line of usage I guess it would be interesting to consider especially in some of these countries outside of the U S and Europe, where there might be less approved treatment options available.

Great. Thanks, Thanks interested I'll come in and that's maybe the update your comment though if any further <unk> for you is market is by far the largest market for I T. P. I think it's about a billion one <unk> as we've said and outside the U S made about 900 million so that would be Europe.

Raul R. Rodriguez: I'll come in and ask Dave to comment, if any, further. You know, the U.S. market is by far the largest market for ITP. I think it's about $1.1 billion, as we've said. And outside the U.S., maybe about $900 million. So Europe would be the lion's share of that $900 million, and a little bit of a guess, $400 million, $500 million.

Is the lion's share of that 900 million and a little bit of a guest Oh, four or 500 million, Canada, Japan, and then Israel are are smaller segments, Sir but attractive segments and obviously in Japan, It's an area, where a partner to say very interested in this indication.

Raul R. Rodriguez: Canada, Japan, and then Israel are smaller segments there, but attractive segments. And obviously, in Japan, it's an area where our partner, Kisei, is very interested in this indication and the subsequent AIHA opportunity as well. And they're doing a study there, Phase 3, as required. I think they'll do very well. The market is attractive in Japan. I would say, aside from Europe and the U.S., probably the largest one of the remaining ones.

And the subsequent yeah, H, a opportunity as well and they're doing a study there appraise three is it required I think that'll do very well the market is attractive in Japan, I would say pulled me aside from Europe and in the U S. Probably the largest one of the remaining ones. So I'm gonna try to.

Raul R. Rodriguez: So an attractive market. Again, similar to the U.S., but I know it a bit less than Europe, so a little bit of a pause there. Canada is a very attractive market simply because it's proximate to the U.S. Again, you know, we've done clinical trials in Canada as part of our ITP and as well as the IHA studies. So an attractive market, obviously, cross-border is useful, and this is a global business overall to cover all of this. It's far smaller than the U.S. The old rule of thumb used to be 10 percent.

Mark against similar to the U S, but I know with a bit less than that Europe. So I've got a bit of Plaza, Canada is a very attractive market simply because it's the approximate to the U S. Again, you know we've done this clinical trials in Canada is part of our I T. P M as well as the Iha's sense, so an attractive market, obviously cross border Uhm.

Is is useful and this is a global business overall to cover all of this is far smaller than the U S. Though overload Tom used to be 10% I think it's less than that in terms of relative to the U S market and Israel was a very attractive market hardly technology technologically advanced and an attractive market, but again.

Raul R. Rodriguez: I think it's less than that in terms of relative to the U.S. market. And Israel is a very attractive market, highly technologically advanced and an attractive market, but again, much smaller given the population sizes of those countries. So I think there are attractive opportunities in those three you mentioned, Japan, the largest, followed by Canada, and then Israel being the smallest. Other places outside the U.S., we beyond Europe, Latin America is an opportunity, as well as some areas in Eastern Asia that are not part of the Kise collaboration. Any other comments on that, Dave, that you'd like to add? Not on the market. Raul, because I think you've covered that pretty well.

A much smaller given the population sizes of those so I think I'll do attractive opportunities of those three you mentioned, Japan the largest uhm followed by Canada, and then Israel being the smallest other places outside the U S. You know, we we beyond Europe, Latin America, as an opportunity as well as some areas and salt.

Eastern Asia that are not part of the QC collaboration.

Any other comments on on that date that you'd like to add.

Not on the market.

But to them cause they think you've covered that pretty pretty well, but I you know on the line of therapy question. You know all I can say Christian is that we at least from what I've seen with a partner cripples are very very interested to learn information and share information.

David A. Santos: But on the line of therapy questions, all I could say, Kristen, is that we, at least from what I've seen with our partner, Griffles, are very interested in learning information and sharing information, and the goal is to continue to gain adoption of fostamatinib worldwide. And so, you know, obviously, we'll continue to work closely with our partners, as we are doing now with medicine, as they are preparing for Canada, the Canadian launch. And I think, you know, if we can get information that helps us with the line of usage, certainly, that, of course, is going to be useful to all of us across partnerships in continuing to move tamales to earlier lines of therapy. And Kristen, the Forte study that Dave described in his presentation is very useful for that because it'll provide us with a very rich data source for use in second-line patients that'll help us really nail down further usage patterns that I think will help us in the discussion of our product with doctors and patients.

So we and the goal is to continue to.

Gain adoption of foster matinee of worldwide into you know obviously will continue to work closely with their partners as we're doing now with medicine S. There I'm preparing for Canada, the Canadian launch and I I think you know if we can get information.

It helps us with the lineup usage certainly you know that of course, he's gonna be useful to all of us across the partnerships in continuing to you didn't move Tahoe Easter earlier light therapy.

It could and put some at the four case study that the date was spot described in this presentation is very useful for that because it'll provide is a very rich data source for Houston second line patience that'll help us really nailed down further further usage patterns that I think will help us in the in the discuss.

<unk> of our product with our doctors and patients.

Great. Thank you so much for that one quick follow up just during this COVID-19 pandemic over the last eight months or so are you seeing or hearing of any shifts in terms of how physicians are now viewing their lines of therapy. So for example, the fact that heavily isn't.

David A. Santos: Great, thank you so much for that. One quick follow-up question: just during this COVID-19 pandemic, over the last eight months or so, are you seeing or hearing of any shifts in terms of how physicians are now viewing their lines of therapy? So, for example, the fact that Tavalese is an oral therapy. Are you noting any changes there? And then also, you know, we've spoken to some doctors where they've pointed out, you know, therapies like Rituximab that may have immunosuppression-related causes. So, you know, that's kind of shifting their mindset.

David A. Santos: So, curious, you know, overall, through this last eight months, whether you're seeing a shift related to therapy options in light of the pandemic. Thank you. Dave, do you want to comment?

David A. Santos: Sure, absolutely. And it's a great question because obviously, you know, patients are concerned and clinicians are concerned about, you know, patients having to spend time with infused products. And so I think you're absolutely right. It has been good to be an oral medication during this time of COVID.

David A. Santos: And I think, you know, that's something that is good for now. And I think it will actually be good for the future as well, because it's more convenient for patients. And it really is something that they can use and becomes a part of, you know, their adaptation to their daily lifestyle, especially with a product like Tomalease. So, anecdotally, clearly, physicians are doing more telehealth visits when possible. And they, you know, I think are very receptive to agents like Tomalease that allow patients to do things on their own at home.

Agents like top of lease that allow patients to do things on their own at home.

David A. Santos: Great. Thank you. Thank you, Kristen.

Great. Thank you.

Thank you Chris.

Thank you if you would like to register for a question. Please press the one for.

Tessa Romero: Thank you. If you would like to register for a question, please press one four. Our next question comes from the line of Tessa Romero of J.P. Morgan. Please go ahead with your question. Good afternoon, guys.

Our next question comes from the line of Tessa Romero of JP Morgan. Please go ahead with your question.

Good afternoon, guys. Thank you for taking the question hope all is well.

Tessa Romero: Thank you for taking the questions. Hope all is well. Just a few from me. So, on the phase 3 Worm AHA trial, are you able to provide any additional granularity on how you are thinking about timelines for full enrollment in the study? Is it a matter of signing the patients? Are there patients in queue that just need to be dosed?

Just a few from me so.

On the sales screen warm and hot trial are you able to provide any additional granularity on how youre thinking about.

Timelines for full enrollment for this study is it a matter of signing the patients are there patients in Q that just need to be dosed.

And then my second question, if I could we noticed a few ash abstract up yesterday for Fostamatinib.

Wolfgang Duner: And then my second question, if I could, we noticed a few abstracts came up yesterday for fostamatinib. Any new analyses or updates we should be monitoring for the conference at the conference next month? Thanks so much, guys. Thank you, Tess. Wolfgang, would you like to address the first of those, the enrollment timelines for Phase 3? I assume you mean autoimmune hemolytic anemia?

And any new analyses are updates we should be monitoring for the conference at the conference next month. Thanks, So much guys.

Thank you.

Well, Greg would you like to address the first was that the enrollment timeline for phase three.

I assume you mean, all the immune hemolytic anemia.

Wolfgang Duner: I'm sorry. Yes. Yeah, yeah. Okay, so as I alluded to in the presentation, I guess the message that I want to send to you is that things are going quite well, right? So before March, we had a very good momentum with about eight to nine patients a month. And then we had a shutdown for several months where nobody got enrolled, and then the sites began to reopen.

Sorry, yes, yes.

Yes, yes.

Okay, So as I eluded to in the in the presentation.

If the message that I want to think two things are going quite well so we'd be before March we had a very good momentum with about eight to nine patients a month.

And then we had a shutdown over several months, where nobody got enrolled in then the sites and began to reopen and.

Wolfgang Duner: And, you know, we got really, really good screening results in September, and they were translated into seven randomizations in October. So seven is only one less than eight, which we had before the shutdown. So, what I want to say is, well, it looks good, and we are optimistic. But then, you know, we also know there's second waves and there are, you know, COVID outbreaks in Europe and in other places. So it's really hard to commit and promise something under the circumstances.

We get like really really good screening results in September and that translated into seven seven randomization in October so saving is only one.

And then eight what we had before the shutdown so what I, what I want to say is well it looks good and we are optimistic.

But then you know we also know that second wave, saying there is a in order to cope with outbreaks in Europe and in other places. So it's really hard to to commit into two promise something under the circumstances Thats why we deliberately.

Wolfgang Duner: That's why we deliberately, you know, didn't specify a date or something like that. But I would say we are optimistic, but we have to respect the pandemic that could, you know, that could interfere with our plans. I hope that's acceptable. Yeah.

You know didn't didn't specify a date or something like that but I would say we are we are optimistic but we have to respect the pandemic that that that cook.

You know there could interfere with our plans.

I hope that's acceptable.

No.

Raul R. Rodriguez: And we'll obviously provide further updates as we progress. And, you know, it's a good place to be at over 60% enrollment in this. And as I said, having as many sites as we have open and available, close to 90 sites, about 90 sites, and we need 30 some patients. So really, about a patient for maybe a third of the sites. That's a pretty good place to be to finish this study, and we're excited about that. Patients are there, and especially once they begin to be confident in terms of the pandemic passing a bit. And the fact that we are in so many different countries, 22 of them, really helps us because I think in some places this is an issue that's come and gone, and in other places at different times it's become an issue and gone. But many of them are screening patients. We see that on a regular basis.

And we'll obviously provide further updates as we progress and it's a good place to be at just over 60% enrollment in this and as I said, having as many sites as we have opened in available posture 90 sites about 90 sites and we need 30 some patients.

So really about a patient for maybe a third of the sites that's a pretty good place to be to finish the study and we're excited about about that patients are there.

And especially once they begin to be confident in terms of the pandemic passing a bit and the fact that we are in so many different countries 22 of them really helps us because I think in some places. This is an issue and this has come and gone and in other places at different times is becoming an issue and come and gone and but.

Many of them are screening patients we are seeing that on a regular basis and we look forward to continued enrollment with the caution that often working just said.

Raul R. Rodriguez: And we look forward to continued enrollment with the caution that Wolfgang just said. On your second question, Anast, we have a few abstracts, as you may have seen, discussing some of the data and some different cuts of the data that I think people will find very useful. So we'll say a little bit more about that in the near future. But I think it should be a very useful series of abstracts and some numbers.

Raul R. Rodriguez: I think we have one, two, three, four. I'm trying to count them as we speak. There were quite a number. At least four of them, talking about AIHA, disorders of platelets.

Raul R. Rodriguez: I know we have some further trials in progress, a description of our phase three program with a little more detail on AIHA, which is useful, as well as another one on the long-term use of Tavalese in long-term ITP patients, which I think should be pretty exciting because that's a key question we frequently get and are very proud of the durability of our ITP data, David said. So really, a good series of posters that we have there, four of them in total, I think. Great Thank you so much for taking my question. Thank you, Tess. There are no further questions at this time. I would like to turn the floor back over to Mr. Raul Rodriguez for questions.

Raul R. Rodriguez: My apologies for closing comments; please go ahead. Thank you so much. I'd like to thank you for your interest in Rigel and your participation in the call. It's an exciting time for Rigel as we wrap up this year. I think we've accomplished a great deal this year and made tremendous progress despite all the difficulties imposed upon us. But even with those difficulties, we saw some opportunities, such as in this COVID area, that I think we're really excited about.

My apologies for closing comments. Please go ahead.

Thank you so much I'd like to thank you for your interest in Rigel and and your participation in the call. It so exciting time for Rigel as we wrap up this year I think weve accomplished a great deal. This year, we made tremendous progress. Despite all the difficulties imposed upon us but were even with those difficulties saw some opportunity.

Such as in this call that area that I think we're really excited about we look forward to sharing with you our plans for next year in.

We look forward to sharing with you our plans for next year on a future call. And with that, I'd like to thank you. Have a good day. This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.

In a future call and with that I'd like to thank you have a good day.

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