Q4 2019 Earnings Call

Only mode. A brief question answer session will follow the formal presentation. If anyone should require operator assistance. During the conference. Please press star zero on your telephone keypad as a reminder, this conference is being recorded.

Operator: A brief question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad.

Operator: 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.

So my pleasure to introduce our first speaker Dolly Vance, who is partials executive Vice President Corporate Affairs and General Counsel. Thank you Ms. Fancy you may begin.

Unknown Executive: Welcome to our fourth quarter and full year 2019 financial results and business update conference call. The financial press release for the fourth 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. A description of these risks can be found in our most recent annual report on Form 10-K, on file with the FCC. 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.

Welcome to our fourth quarter at school year 20, Nike, It's an actual results could differ update conference call.

That's a press release for the fourth quarter issued a short while ago can be viewed along with a company slides for this presentation in the news and events section of our Investor Relations page on our website www dot gradual dot com.

Reminder, during today's call remain make forward looking statements regarding our financial outlook and her plans the timing for regulatory product development.

These statements are subject to risks and uncertainties I may cause actual results could differ from those forecasted.

A description of these risks can be found in our most.

Most recent annual report on form 10-K onboard with assay.

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 like to turn the call over to our C O role Rodriguez.

Raul R. Rodriguez: Thank you, Dolly, and thank you for joining us today on our fourth quarter 2019 financial call. Also joining me today on this call is our Chief Medical Officer, Wolfgang Dummer, who joined Rigel towards the end of 2019, and has already been an excellent addition to the team. Tarek Salam, our Vice President of Marketing, who has been with Rigel for 3 years now, and Dean Schorno, our CFO. I'd like to begin on slide five, looking at Rigel's accomplishments in 2019.

Thank you to always and thank you for joining us today on our fourth quarter 29, Chief financial.

Also joining me today is on this call he's our chief Medical Officer, Wolfgang do or Who's joined Rigel towards the end of 29 cheaper than it already has already been an excellent addition to the team.

Torics Alomar, Vice President marketing I speak with Rigel for three years, no indeed shorten our CFO.

I'd like to begin on slide five.

Looking at why those accomplishments 29 to.

Raul R. Rodriguez: Rigel has four key value drivers, and we're happy with our accomplishments across all of these during 2019, beginning with Tavalisse, the cornerstone of our business. We have continued to grow sales in the U.S. As we announced in January, during the fourth quarter, we generated net product sales of $13.8 million, an increase of 90% from the fourth quarter of 2018. For the full year 2019, we reported a total of $43.8 million in net product sales.

Well, let's four key value drivers, we're happy that our with our accomplishments across all of these 329 to.

Beginning with probably the cornerstone of our business [laughter], we've continued to grow sales in the U.S. as we love to January during the fourth quarter, we generated net product sales up 13.8 million.

Increase up 90%.

From the fourth quarter of 28 cheap.

For the full year 2019, we reported a total of 43.8 million in net product sales.

Raul R. Rodriguez: Along with growing revenues, we're also seeing an increase in how long patients stay on our drug, or the persistency rate for telomeres. The Tavalees label states that patients should remain on the product for three months, and if no benefit is seen, they should stop treatment. The fourth month persistency rate is a percentage of patients who receive that fourth month of treatment and who we believe are seeing a benefit. We have continued to see an uptick in our 4th month persistency rate, which has increased to 54% from 45% previously, suggesting a growing number of patients are receiving a benefit from Tabuli. This is likely due to the increase in use in earlier lines of therapy and the growing physician experience with how to use tablets. There is a substantial opportunity to help patients whose lives are negatively impacted by chronic ITP, and we are pleased with the success of today. Tariq and I will discuss this in a few minutes.

Along with growing revenues were also seeing an increase no long patients stay on <unk>, where the persistency rate fatalities.

The total these label states that patients remain on the product for three months and there's no benefit it seem they should stop treatment.

The fourth month persistency rate is a percentage of patients who receive that fourth month, the treatment and who we believe we're seeing a benefit.

We have continued to see an up tick in our fourth month persistency rate, which is has increased to 54% from 45% previously, suggesting a growing number of patients are receiving a benefit from salaries.

This is likely due to the increase in use in earlier lines of therapy into growing physician experience on how do you stop at least.

There was a substantial opportunity to help patient script, whose lives are negatively impacted by chronic RTP. We are pleased.

With you to success today.

Toric, who will discuss this in a few minutes.

Raul R. Rodriguez: And this is just the beginning of Tablilis in the US ITP market. Along with the U.S., we're also working to expand the availability of our product globally. We have established access to markets in Europe, Japan, and Asia, and Canada and Israel via collaborations with three well-established companies. These agreements were secured over the last 16 months and provide favorable economics to Rigel.

And this is just the beginning of top at least in the U.S. I T P market.

Along with the U.S., we're also working to expand the availability up our product globally.

We have established access to markets in Europe, Japan in Asia in Canada, and Israel via collaborations with three well established companies disagreements were secured over the last six too much it provides favorable economics to rigel.

Raul R. Rodriguez: This demonstrates the attractive opportunity for our product outside of the U.S. In January, our Marketing Authorization Application, or MAA, for Fostomatinib in the Belltronic ITP was approved in Europe, opening the door to the largest global market outside of the U.S. Our partner Grifols is gearing up for a launch, which we expect to initiate in the second quarter. Another important market is Asia, in particular Japan, where our partner Kisei Pharmaceuticals has an ongoing phase 3 trial in Japanese subjects. This is a common regulatory requirement for the approval of a drug developed outside of Japan. We are happy with the progress they are making, and just last week, we were informed that Kisei has received orphan drug designation in Japan for Fostomatinib in ITP. While Medicine will be marketing our product in Canada, Rigel is managing the regulatory approval process, having filed the NDS in Canada. This is the equivalent of an NDA.

This demonstrates the attractive opportunity for our product outside of the U.S.

In January our marketing authorization application <unk> and eight for Fostamatinib in adult chronic heart you'd be was approved in your.

Opening the door to the largest global market outside of the U.S.

Our partner peripherals is gearing up for a launch, which we expect to initiate the second quarter.

Another important market is Asia in particular, Japan.

Where our partner to say pharmaceuticals, as an ongoing phase three trial the Japanese subjects.

This is a comedy regulatory requirement for the approval of a drug developed outside of Japan.

We're happy with the progress they are making and just last week, we weren't form that you see you say has received orphan drug designation in Japan for Fostamatinib in RTP.

Well medicine will be marketing or product in Canada, Rigel is managing the regulatory approval process, having filed the N D. S. In Canada. This is the equivalent of in India.

Raul R. Rodriguez: Based on the length of the regulatory review in Canada, we expect to have approval by early next year. So, as you can see, we're seeing great success globally. We believe that warm autoimmune hemolytic anemia, or AIHA, is an even larger opportunity for Rigel. Warm AIHA is another autoimmune disease, like ITP, where the body produces antibodies against a hematologic cell type. In this case, red blood cells.

Based on the least about regulatory review in Canada, we expect to have approval by early next year.

So as you can see we're seeing great success globally.

[noise], we believe that Werent auto immune hemolytic anemia, or AI itrade isn't even larger opportunity for right now.

For me I. It shows is another autoimmune disease like RTP, where the body produces antibodies against hematologic cell type in this case red blood cells.

Raul R. Rodriguez: We have generated very encouraging data from our Phase II trial of Tavalisse in warm autoimmune hemolytic anemia, giving us the confidence to initiate our Phase III trial. The Phase 3 trial launched in 2019, and we have made excellent progress to date. Wolfgang will add some color to this topic later in his presentation. And finally, we're excited about two key assets in our pipeline, our IRAC1-4 inhibitor and our RIP-1 inhibitor, both of which are in Phase I trials. IRAC and RIP are two of the most attractive immune targets in biopharmaceuticals today, and based on early data, our molecules have demonstrated characteristics that give us a great deal of optimism for their potential. Now I'm turning to slide 6.

We have generated very encouraging data from our phase two trial of top of lease in warm autoimmune hemolytic anemia, giving us the competence.

Phase three trial.

The phase three trial launched in 2019, and we have made excellent progress to date.

Well spend would add some color to this topic later in this presentation.

And finally, we're excited about two key assets in our pipeline, our Iraq, one for inhibitor and our reported inhibitor both of which are in phase one trials.

[noise], Iraq and repairs are two of the most attractive IMMU targets and Biopharmaceuticals today based on early data are much as that demonstrated characteristics, which gives us a great deal of optimism to their potential.

Now turning to slide six.

Raul R. Rodriguez: Our ability to execute on our key value drivers has positioned us well for continued growth in 2020. ICP is a 1.1 billion dollar market and growing. Outside the U.S., the ITP market is about $900 million and also growing, and we think that warm autoimmune hemolytic anemia has the potential to be a billion-dollar market in the U.S., equal to the size of the ITP market. And our pipeline programs continue to offer Rigel tremendous business development opportunities in the near term and in the future. I will now pass the call over to Tarek for a commercial offer. Tarek?

Our ability to execute on our key value drivers has positioned us well for continued growth in 2020.

I see if he is a 1.1 billion dollar market and growing.

Outside the U.S. the I keep the market is about 900 million and also growing.

We think that warm autoimmune hemolytic anemia has the potential to be a billion dollar market in the U.S. equal to the size of the RTP market.

And our pipeline programs continue to offer rigel tremendous business development opportunities in the near term and into future.

I'll now pass the call over <unk> Parekh for a commercial chart.

Tarek Salam: Thank you, Raul. Our current commercial efforts are centered around our first marketed product, Tavalee, which, as you see on slide A, is a kinase inhibitor indicated for the treatment of thrombocytopenia in adult patients with chronic ITP who have had an insufficient response to a previous treatment. On slide 9, you get a sense of what the IPP market in the U.S. looks like. It is sizable, and it continues to grow.

Thank you roll.

Our current commercial efforts are centered around our first marketed product totally.

But you see it which as you see on slide eight and they kinase inhibitor indicated for the treatment of from Oh, excuse me from Kenya, and adult patients with chronic IP, what kind of insufficient response to a previous tree.

On slide nine you get a sense of what the IP marketing U.S. looks like it's sites.

And it continues to grow.

Tarek Salam: As you can see on the left side of the slide, we estimate that there are about 81,000 adult ITP patients in the U.S. Patients with this disease cycle on and off of therapy so that in any given year, there are roughly 21,000 patients in the post-dairy setting, representing our focused market opportunity. Now looking at the right side of the slide, you see how this segment of the market is broken down by lines of therapy, with the vast majority of patients being treated in the second or third line setting. However, the use of tabloids during the initial stages of launch was primarily in the fourth minor wave.

Do you see on the left side of the light we estimate that there were about 81000 adult IC patients in the U.S.

Patients when the disease cycle on an oral therapy, so that in any given year there roughly 21000 patients in the post maritech, representing our focused market opportunity.

Now looking at the right flight you see how that segment of the market is broken down by lines of therapy.

With the vast majority of patients being treated in the second or third line setting.

They used to probably during the initial stages a launch was primarily in the four point earlier.

Tarek Salam: At the time of launch, there was a subset of patients with a high unmet need for a new therapeutic option. These patients had failed multiple therapies or had limited clinical benefit from them, eventually running out of options due to the lack of innovative therapies in the past decade. Over time, we have seen an increase in the utilization of Tavaleet in earlier lines of therapy, and this is being driven by our continued commercial efforts.

At the time of launch there was a subset of patients with a high unmet need for a new therapeutic option.

These patients had failed multiple therapies or limited clinical benefit on them eventually running out of auctions due to the lack of innovative therapy in the past decade.

Overtime, we have seen an increase in the utilization of total lease in the earlier lines of therapy.

Being driven by our continued commercial efforts, most importantly, increasing physician awareness and understanding of Tali.

Tarek Salam: Most importantly, increasing physician awareness and understanding of Tavalli. As physicians gain first-hand experience with the product, they build a level of comfort before utilizing it more broadly among their ITP patients. All of that said, we have delivered substantial quarter-over-quarter growth where we are currently being utilized in the treatment paradigm, and we are excited about the opportunity to increase Tavallis usage in the earlier lines of treatment. Turning to slide 10.

That's positions game first hand experience with the product they built a level of comfort before you lightning it more broadly and I'm underwriting be patient.

All of that said, we have delivered stansell quarter over quarter growth, where we are currently being utilized in the treatment paradigm and we are excited about the opportunity to increase probably of usage in the earlier lines between.

Turning to slide 10.

Tarek Salam: In the past, we have shared data on the fragmented and diverse treatments utilized in the chronic ITP market. It is important to note that after steroids, there is no standard of care for second or third-line therapy. Late last year, the International Working Group on ITP, which consists of a global panel of ITP KOLs, issued its recommended guidelines.

In the past, we've shared data on that fragmented and diverse treatments you'd like from the chronic I came to market.

Important to note that after steroids. There is no standard of care for second or third line therapy.

Late last year, the international working group on IP, which consists of a global panel of IP PK AOL issued its recommended guidelines.

Tarek Salam: These included Tavalese in the same robust evidence category as the Kepomimetics and Rituximab for use after first-line treatment failure. These guidelines highlight the fact that the heterogeneity of the disease results in an unmet need for novel treatment options in order to individualize the treatment strategy. So, alongside the real-world clinical experience of our current prescribers, it is encouraging to have the support of this respected group of thought leaders endorsing Tavalisse as a viable treatment option in the second-line setting. As discussed in the previous slide, there is an unmet need for novel treatments in order to individualize patient care. We believe that we are uniquely positioned in the marketplace to fulfill this unmet need based on our novel and differentiated mechanism of action.

These include it probably in the same robot evidence category as the people memetics and we're talking about for use after first line treatment failure.

These guidelines highlights the fact that heterogeneity of the disease, resulting in an unmet need for novel treatment option in order to individual life the treatment strategy.

So alongside the real World clinical experience of our current prescribers. It is encouraging to have the support of this respected group of thought leaders endorsing tali as a viable treatment option in the second line static.

So, let's turn to slide 11.

As discussed in the previous by there's an unmet need for novel treatment in order to individual life patient care.

We believe that we are poised uniquely in the marketplace to build it unmet need based on our novel and differentiated mechanism of action.

We are the only approved agent that limit immune mediated platelet destruction in a targeted manner.

Tarek Salam: agent that limits immune-mediated platelet destruction in a targeted manner. This Novel Mechanism of Action is the key differentiator for tablolis within the ITP landscape and drives a unique value proposition to support the use of tablolis to be used preferentially in certain patient populations. Slide 12 highlights data presented at the American Society of Hematology conference this past December.

This novel Max <unk> mechanism of action.

The key differentiator for total lease within the IP landscape and drive the unique value proposition to support the use of tableau leave tend to use preferentially and certain patient population.

Slide 12 highlight data presented at the American Society of Hematology Conference the top December.

Tarek Salam: and It is a retrospective.

And is a retrospective analysis the patients in our phase three clinical trial that receive probably at the second line therapy.

Tarek Salam: Medical Trials that received Tavaleet as a second line therapy. Of these patients, 78% achieved a response. This is a similar response rate seen by other agents in the setting.

Oh these patients 78% achieved a response.

This is a similar response rate being by other agents in this setting.

Tarek Salam: The addition of this data supports Tavalese as a viable treatment option in early lines of therapy, which also may result in increased persistency due to the better prognosis of patients in this setting. Up until now, much of our early line usage has been organically driven from early adopters who have seen the benefits of Tavolese in their patients and decided to try it earlier in the early-life aesthetic. We can now provide the broader physician community, including non-prescribers, with both clinical data and guidelines endorsing the utilization of Tavalese in the Early Lines Act. Moving to slide 13.

The addition of that data supports polys as a viable treatment option in early line therapy, which also May result in increased persistency due to the better prognosis for patients and the SEC.

Up until now much of our early line usage has been organically driven from early adopters, who have seen the benefits of probably send their patients and decided to try it earlier.

In the early mindset.

We can now provide the broader physician community, including non prescribers with both clinical data and guidelines endorsing utilization on top of lease and the early line setting.

Moving to slide 13.

Tarek Salam: In general, the ITP market is a highly promotionally sensitive space, and we know that educational measures here have a significant impact on a product's adoption. With the presentation of the second-line data analysis, we believe we have a more compelling story to share with our physicians. I'd like to just add that we just got back from our national sales meeting where we trained our team on new materials that included this data, and the team is extremely excited and ready to go out there and begin introducing this information to their customers. We're also excited to see the impact that they're going to have as they begin their efforts in the field. And so, to capitalize on this, we're increasing our commercial footprint with the expansion of our sales force from 35 to 40 territory business managers.

In general the IP market is a highly promotional defense space.

And we know that educational matters here have a significant impact on a product adoption.

With the presentation on the second line data analysis, we believe we have a more compelling story to share with our position.

I'd like to just that we just got back from our National sales meeting, where we trained our team on new materials that included the data.

And the team is extremely excited and ready to go out there and begin introducing that information to there to their customers.

We're also excited to see the impact that they're going to have actually begin their efforts in the field.

So to capitalize on that we're increasing our commercial footprint with the expansion of our Salesforce.

Five to 42, excuse me 40 territory business managers.

Tarek Salam: This increase will enable us to broaden our reach to our targeted physicians and more effectively deliver the Tavalis method. We are continuing to support these efforts with initiatives focused on driving greater awareness of the value proposition of Tavaleet, such as peer-to-peer educational events and participation at key medical conferences. In addition to the new data analysis, we will continue to support the product by utilizing data beyond our registrational trials, which currently include case-based studies and may include investigator-sponsored trials and an observational trial initiating later this year, which Wolfgang will provide more details on in a moment, all of which will provide further evidence of the product's clinical utility. So, in closing, we are positioned to continue to capitalize on this phenomenal success of the launch thus far. We will leverage the guidelines endorsement and the additional clinical data to continue to build on the momentum from 2019, allowing us to tap into the larger patient pools seen in the earlier lines of therapy. With that, I would like to turn the call over to our Chief Medical Officer, Wolfgang Dummer. Wolfgang?

Increase will enable us to broaden our reach for targeted physicians and more effectively deliver the toppling message.

We're continuing to support these efforts with initiatives focused on driving greater awareness of the value proposition to probably such as peer to peer educational event and participation at key medical conferences.

In addition to the North data analysis, we will continue to support the product by utilizing data beyond our Registrational trials, which currently include Kate <unk> study and May include investigator sponsored trials and an observational trials initiating later this year, which Wolfgang will provide more details on in a moment.

All of which will provide further evidence into the product clinically utility.

So in closing we are positioned to continue to capitalize on this phenomenal success of the launch thus far we will leverage the guidelines endorsement and the additional clinical data to continued to build on the momentum from 2019, allowing us to tap into the larger patient pools scene in the earlier lines of therapy.

With that I'd like to turn the call over to our Chief Medical Officer Wolfgang tumor okay.

Wolfgang Dummer: Thank you, Tariq. And good afternoon, everybody.

Thank you tyreke and good afternoon everybody.

Wolfgang Dummer: As Raul said in his introduction, I just joined Rigel in November 2019. Before coming to Rigel, I spent 11 years at Genentech leading the clinical development of Ocrelizumab in immunology, now an approved drug for multiple sclerosis. I've also led a number of Rituxan immunology programs. In addition, I was a VP of clinical development at Biomarin Pharmaceuticals for five years, which gave me a lot of insight into rare disease drug development at a world-leading company in that space. So, taken together, I'm quite familiar with the space that Rigel is in right now, and it was very clear to me that we should be a great fit for each other moving forward. And I'm very excited about that. So here are a few things summarized that do make me really excited to be here.

It's route since its introduction I'd just joined gradually in November 2019.

Well coming to Rigel I've spent 11 use a genetic leading the clinical development Ocrelizumab hematology now unapproved drugs for multiple sclerosis. I've also made a number off the reduction in immunology programs. In addition, I wasn't VP of clinical development at Biomarin pharma.

Through the codes for five years, which gave me a lot of insight into really the drug development in a world leading company in that space. So taken together I'm quite familiar with the speed Thats rightfully isn't right now and it was very few to me that be should be a great fits for each other moving forward and I'm very excited about that.

Hi, 15.

So here are few things summarize that make me really excited to beat your.

Wolfgang Dummer: Number one is, of course, Tavalis, which is our sick inhibitor with a distinct mechanism of action. This molecule has broad potential for many different indications. As Raul mentioned, this product is the cornerstone of our business, and supporting its commercial success will continue to be a top priority for my team.

Number one is of course.

Good to know Syk inhibitor with a distinct mechanism of action.

This molecule as a broad potentially theoretically many different indications.

As Robert mentioned this product is the cornerstone of our business in supporting its commercial practice, we will continue to be at argue for my team.

Wolfgang Dummer: That includes maximizing existing data and generating new real-world data in ITP that will help to continue to educate the treating physician. Tarek already mentioned the powerful data from phase 3 showing that 78% of ITP patients responded to Talaviz when the drug was used as second-line therapy. Following the presentation of this data at ASH in November, we are working to submit these findings and other findings as manuscripts soon for publication in peer-reviewed journals for broader distribution to reach as many treating physicians as possible. Regarding new real-world data generation in ITP, we're planning to launch an observational study of tabaliz used as second-line therapy later this year to better understand how tabaliz is used in clinical practice and further characterize the clinical benefit in that situation. That would generate data streams on Tavares in ITP starting in 2021.

That includes maximizing existing data and generating new real growth.

Okay.

Moving out to continue to educate the treating physician.

Alright, well already mentioned the powerful data from phase three showing that 78% ATP patients responded to tallies when the drug was used to sticking by therapy.

Following the presentation. These data at Ash in November.

We are working to submit these findings in other findings as manuscripts soon application in peer reviewed journals for broader distribution to reach is many treating physicians as possible.

Regarding new real growth data generation ATP, we're planning to launch an observational study of Cavalese used. This second line therapy. Later this year two beta to better understand how do these is used in clinical practice and further characterize the clinical benefit in that situation.

That would generate.

Data streams on top of using Itps starting in 2021.

Another area rugs three priorities might.

Wolfgang Dummer: Another work stream and a co-priority of my team is to expand Tavalis into new indications beyond ITP. As you heard earlier, we are currently enrolling a phase 3 trial for tablibs in warm autoimmune hemolytic anemia. ARHA is a rare autoantibody-mediated blood disorder in which patients suffer from falling hemoglobin levels and associated fatigue, shortness of breath, all the way down to the risk of heart failure and death. I think this is a great opportunity for Tavalis since we know there is really no FDA-approved therapy for this disease at this point. Enrollment in these rare disease indications is typically extremely difficult, but I've seen that and dealt with these situations And as you will see in a bit, the program is progressing nicely. I'll give you a little bit more detail in a while.

Ben Cavalese into new indications beyond ATP.

As you heard earlier, we are currently enrolling our phase three trials that happened in warm all the immune hemolytic anemia.

He is the Ria all antibody mediated bluff is order in which patients suffer from falling you won't be level in associated teak shortness of breath, although we down to the risk of heart failure in death.

I think this is a great opportunity fatalities we.

We know there's really no FDA approved therapy Proteus disease at this point.

Enrollment in these rare disease indication that typically extremely difficult, but I've seen that in built through the situation is a lot, especially well be environment really wherever you did only trials in rare diseases and I'm very familiar with how to deal with these obstacles.

And as you received a bit the program is progressing nicely I'll give you a little bit more detailed on GAAP NOI.

And why do we are driving to to completion of the phase three trial. My team has also started partnering closely to the commercial team to prepare for the potential commercial launch of Tbilisi D.A. J.

Wolfgang Dummer: And while we are driving to completion of the Phase 3 trial, my team has also started partnering closely with the commercial team to prepare for the potential commercial launch of Tavalisin AIHF. We're also continuing to explore the next indication for tablolis, suitable to expand the label. And while evaluating all the possible disease indications where tablolis may work, it is really super exciting to see how broadly this mechanism of action could benefit patients in so many different areas. Looking a little bit further ahead in the future, we also have two molecules that are scientifically very compelling and will have, in my opinion, huge potential.

We're also continuing to explore the mixed indication for cavalese suitable to expand the label.

And why evaluating all the.

The bone disease indications with half of these may work. It is really to be exciting to see how broadly this mechanism actually benefit patients in so many different areas.

Looking a little bit.

Further hit in the future. We have also two molecules to go scientifically very compelling and we would have been in my opinion huge potential.

Wolfgang Dummer: One is our IRAC1-4 Dual Kinase Inhibitor. We have very nice preclinical data that shows that inflammatory cytokine production can be inhibited more profoundly with IRAC1 for dual targeting over IRAC4 alone inhibition. By targeting these kinases, we interfere with several cytokines that have already been shown to demonstrate efficacy when inhibited with monoclonal antibodies, which tells you there's an enormous opportunity in several large indications but also in some rare diseases. And the other pipeline molecule is a RIP-kinase inhibitor that has shown extremely favorable PK data in healthy volunteers, allowing for very convenient dosing options. Just like IRAC, RIP inhibition could find application in several large and small indications. I'll come back with more details on both molecules later in this presentation, slide 16. Now, let's have a closer look at our ongoing Pivotal Phase III trial with Tavalis in all-immune hemolytic anemia.

One is eirik one for doing the Chinese distributor.

We have.

Very nice preclinical data that shows that inflammatory cytokine production can be attributed more profoundly with eirik one for do it's hard to do well, but eirik for alone issue.

By targeting these cases, we interfere with several cytokines that have already been shown to demonstrate if you can see when you visit monoclonal antibodies.

Rich do there's an enormous opportunity in several large indications.

So in summary, indeed.

Yes.

Accuser repainted inhibitor that has shown extremely favorable PK data in healthy volunteers, allowing for very convenient dosing options.

Just like Iraq inhibition could find application in several large and small indication.

I will come back with more details on both molecules. The later in this presentation.

Slide 16.

Now, let's have a closer look at our ongoing pivotal phase three trial with comedies in autoimmune hemolytic anemia.

Wolfgang Dummer: As a reminder, we plan to randomize 80 patients, 40 per arm, assigned double-blind to either placebo or Tavalis. The blinded study duration is 24 weeks. After that, patients can roll over into an open-label extension period. The primary endpoint is a haemoglobin response defined as a haemoglobin level of greater than 10 and an increase of 2 grams per deciliter from baseline. There's also a durability measure which we will provide once confirmed with the FDA. In our Phase 2 study, we saw 44% of patients achieve such a hemoglobin response.

As a reminder, we plan to randomize ATP suit 40 per arm assigned double blind placebo.

People well it's heavily.

The blinded study of your recent 24 weeks.

After that patient Cana rollover into an open label extension periods.

The primary endpoint is that you hope would be the response defined as the most have been level of greater than 10, and an increase of two grams per deciliter from baseline.

There's also do your ability to measure, which we will provide a one confirmed with the FDA.

In our phase two study.

We saw 44% the patients achieved such that you multi response.

Wolfgang Dummer: We have not formally set a durable endpoint in phase two, but based on post hoc analysis from that study, we are optimistic we can achieve that and see a positive outcome in phase three. If you look at the enrollment numbers in this very difficult-to-enroll patient population, you'll understand why we are extremely pleased. We have 34 patients randomized so far, 29 of them in the last three and a half months.

We have not formally sits a durable endpoint in that phase two but based on post talk analysis from that study. We are optimistic we can achieve that positive outcome in phase three.

If you look at big enrollment numbers into its very difficult to enroll patient population, you'll understand why we're extremely pleased.

We have.

34 patients randomized so far.

29 of them in the last three month after month.

Wolfgang Dummer: And we are also close to having all our sites open. That puts us in a good position to reach completion of enrollment in mid-2020, and that could give us top-line data by mid-2021. We also think we are the most advanced in AIHE development, and that gives us a chance to become the first FDA-approved drug for this disease, which is particularly exciting. And if approved, that indication would be a very nice addition to the ITP indication, because really, the doctors who prescribe Tavalis for ITP are also the ones who prescribe it for AIHA. And that could create obviously nice synergies since doctors and nurses are already familiar with the safety and efficacy profile of this product, and we are already building strong relationships with those healthcare providers via our medical science liaison groups and, Flight 17, As I mentioned earlier, we are continuing to work on identifying a next indication for tablilis. And there are several very compelling indications that we believe could be great opportunities to pursue.

And we also closed to have all our sites open.

That puts us in that good position to reach completion of enrollment in mid 2020 and that could give us topline data by mid 2021.

We also think.

We are the most advanced in Ichi development.

And that gives us a chance to become the first 50 approved drug for this disease, which is a particularly exciting.

And if approved that indication would be a very nice addition to the ATP indication because really the doctors who prescribed have at least for ATP are also the ones who prescribed for AG and that could create.

Obviously, a nice synergies students the doctors and nurses already familiar with a safety and efficacy profile of this product and we are already building strong relationships with those healthcare providers via our medical science liaison groups and our territory business managers.

Slide 17.

As I mentioned earlier, we are continuing to work on identifying a mix indication fatalities.

There are several very compelling indications that we believe could be great opportunities to pursue.

Wolfgang Dummer: We expect to have exclusivity for the molecule out to 2032, and we will certainly take advantage of that as much as possible. Regarding our new molecular entities, our IRAC1-4 inhibitor program is making good progress in the clinic. IREG1 and IV, as you have heard before, probably are kinases downstream from the toll-like receptors in the IL-1 receptor family.

We expect to have exclusive if you put a molecule out to 2032, and we would certainly take advantage of that as much as possible.

Regarding our new molecular entities, our direct one four and give you the program is making good progress into clinic.

Rick one in four did you have heard before probably are tiny leases downstream from the toll like receptors in the Io one resistant family.

Wolfgang Dummer: Our lead molecule, R835, inhibits both IREC1 and IREC4, which enables a more profound inflammatory cytokine inhibition than targeting IREC4 alone, and we believe that could be a substantial competitive advantage. In several preclinical models, we've seen very compelling efficacy data, and given the inhibition of cytokines like TNF-alpha, IL-6, IL-23, and IL-12, it is obvious that the potential for this drug seems huge to me, both in some very large indications as well as in some rare diseases. We've already done one healthy volunteer study in which the drug was generally well-tolerated, and we demonstrated proof of mechanism in that study with successful cytokine inhibition after an LPS challenge. That was a big success in a healthy volunteer study. The other extremely promising molecules are systemic RIP1 inhibitors. RF-552, The RIP pathway is known to be downstream from the TNF receptor and is implicated in necroptosis and the release of damage-associated molecular patterns, the so-called BAMP. That suggests the door should be open to diseases where anti-TNF drugs are effective or where they may play a role.

Our lead molecules are 835 inhibits both eirik, one and our work, which enables more profound inflammatory cytokines distribution been targeting eirik for alone and we believe that could be a substantial competitive advantage.

In Cimarron preclinical models, we've seen very compelling efficacy data.

And given the condition of cytokines like TNF Alpha.

I don't Threethree Io travel.

It is obvious that the potential appointed Dragan seems huge to me both in some very large indication as well as in some rare diseases.

Before we didn't want to healthy volunteer study in which the drug was generally well tolerated and we demonstrated proof of mechanism in that study with a success.

Cytokine inhibition offer an LP is challenge that is a big success in a healthy volunteer study.

The other extremely promising molecule is systemic group one inhibitor.

I have to.

The pathway is known to be downstream from the two units.

If receptor and is implied in the current horses and the release of damage associated molecular patterns, so called Bam.

That's a bit the door should be open to diseases, where anti TNF drugs are effective Walgreens aims may play a role so once again, great potential in several large indications as well is.

Wolfgang Dummer: So once again, great potential in several large indications as well as some rare diseases. We're currently dose escalating in human healthy subjects with this molecule, and so far, the safety is entirely clean. Importantly, we see a very attractive PK profile, with a long half-life of 15 hours, which enables once-a-day dosing.

I'm really diseases.

We're currently dose escalating in human healthy subjects that this molecule in tool for a safety is entirely clean.

Importantly, we see a very attractive PK profile.

With the long half life of 15 hours.

Enable once the dosing and that makes the compound very competitive in the field.

Wolfgang Dummer: And that makes the compound very competitive in the field. We also plan to select a first human disease indication by the end of the year, and that makes me particularly thrilled. We're also working diligently on research on a rib kinase inhibitor that passes the blood-brain barrier and reaches the central nervous system. That would allow studying this pathway in neurodegenerative disorders in the future. So overall, lots of options, lots of opportunity, lots to be excited about. And with that, I'll hand over to Dean for a review of the financials.

We also.

Plan to select a first human disease indication by the end of the year and that makes me, particularly thrilled.

We're also working diligently research on the repainted inhibitor that passes the blood brain barrier in reaches the server central nervous system that would allow studying this pathway in neuro degenerative diseases in the future.

So overall lots of options lots of opportunity looks to be excited about.

And with that I'll hand over to routine for review of the financials. Steve. Thank you. Okay. I'm on slide 19 for the fourth quarter 2019, we shipped 1518 bottles to our specialty distributors, resulting in $16.3 million of gross product sales 1000.

Dean L. Schorno: Thank you, Wolfgang. I'm on slide 19. For the fourth quarter of 2019, we shipped 1,518 bottles to our specialty distributors, resulting in $16.3 million in gross product sales. 1,422 of those bottles were shipped to patients and clinics, while 96 bottles remained in our distribution channels at the end of the quarter. As of December 31st, a total of 596 bottles remained in our distribution channels.

422 of those bottles were shipped to patients Aquadex, while 96 bottles remained our distribution channels that we ended the quarter.

As of December 30, Onest, a total of 596 bottles remained at our distribution channels.

Dean L. Schorno: We reported net product sales from Tavalis of $13.8 million, which was recorded net of estimated discounts, chargebacks, rebates, returns, co-pay assistance, and other allowances of $2.5 million, our gross-to-net adjustment, which is approximately 15.4% of gross product sales. For the full year, our gross-to-net adjustment was approximately 17.5% of gross product sales. Our increase in net product sales was 18% from the previous quarter and 90% from the fourth quarter of 2018. Also notable is the progress we've made to date.

Reported net product sales from top to lease up $13.8 million, which was recorded net of estimated discounts chargebacks rebates returns co pay assistance another allowance as of $2.5 million, our gross to net adjustment, which is approximately 15.4% of gross product sales.

For the full year, our gross to net adjustment was approximately 17.5% across product sales.

Our increase in net product sales of 18% from the previous quarter and 90% from the fourth quarter of 2018.

Also notable as the progress we've made today since launch we have sold 6956 bottles generating $57.7 million and that product sales, which reflects the tremendous growth of our business over the last year and a half.

Dean L. Schorno: Since launch, we've sold 6,956 bottles, generating $57.7 million in net product sales, which reflects the tremendous growth of our business over the last year and a half. Before we move on from net product sales, let me review our expectations for the first quarter of 2020. Similar to last year, we anticipate a moderation in patient demand growth in the first quarter, as patients work through typical first-quarter reimbursement issues, such as the resetting of copays and the Medicare donut hole. As a result, we could see total bottles shipped during the first quarter of 2020 to be in line with total bottles shipped in the fourth quarter of 2019. As we move past the seasonality of the first quarter, we anticipate this sequential growth rate to be higher in the second quarter. Incrementally, we currently expect our growth-to-net adjustment to be approximately 19% in 2020. On to the next slide.

As we move on from that product sales, let me review our expectations for the first quarter 2000 twice.

Similar to last year, we anticipate a moderation in patient demand growth in the first quarter as patients worked through typical first quarter reimbursement issues, such as the reset enough copays and the Medicare Donut hole.

As a result, we could see total bottle ship during the first quarter of 2020 to be in line with total bottles shipped in the fourth quarter of 2019.

As we moved past the seasonality of the first quarter, we anticipate the sequential growth rate to be higher in the second quarter.

Incrementally, we currently expect or gross to net adjustment to be approximately 19% in 2020.

Under the next slide.

In addition to net product sales right just contract revenues from collaboration there was $1.6 million for the three months ended December 30, Onest 2019.

Dean L. Schorno: In addition to net product sales, Rigel's contract revenues from collaborations were $1.6 million for the three months ended December 31st, 2019, which consists of a $1.5 million fee earned pursuant to an amendment of the License and Collaboration Agreement with Eclairs Therapeutics in October of 2019, as well as deferred revenue from our collaboration with GRIPPLES related to the performance of certain research and development services. Moving on to costs and expenses, our cost of product sales was approximately $178,000 in the fourth quarter of 2019. Total cost and expenses were $32.7 million in the fourth quarter of 2019 versus $35.3 million in the fourth quarter of 2018. The decrease in cost was primarily due to decreases in personnel-related expenses and various third-party costs.

Which consist of a 1.5 million dollar fee earner pursuant to an amendment of the license and collaboration agreement with Aclaris Therapeutics in October of 2019, as well as deferred revenue from our collaboration with grip both related to the performance of certain research and development services.

Moving on the cost and expenses our cost of product sales was approximately $178000 for the fourth quarter of 2019.

Total cost and expenses were $32.7 million in the fourth quarter of 2019 versus $35.3 million in the fourth quarter of 2018. The decrease in cost was primarily due to decreases and personnel related expenses and various third party costs.

Dean L. Schorno: As we look towards 2020, we expect our 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. Also, we recently announced that we received European Committee approval of our MAA for fostamatinib for the treatment of chronic ITP in Europe. With this approval, the company received a $20 million payment from Griffles, which is comprised of a $17.5 million milestone payment and a $2.5 million creditable advanced royalty payment. In addition, $25 million of the $30 million upfront payment that we received from Griffles in Q1 of 2019, which had been previously deferred, will no longer be repayable by us to Griffles. Given this information, we expect to recognize approximately $43 million as collaboration revenues in the first quarter of 2020. The remaining deferred amount of $2 million will be recognized as revenue as we complete certain research and development activities mainly related to the conduct of our autoimmune hemolytic anemia phase 3 clinical trials, which we expect over the next 18 months. We ended the quarter with cash and short-term investments of approximately $98.1 million.

As we look towards 2020, we expect our total cost and expenses to increase by approximately 15% to 20% as compared to 2019 as we continue our commercial expansion that further our research and development pipeline.

Also we recently announced that we received European Committee approval of our EMEA for Fostamatinib for the treatment of chronic therapy in Europe.

With this approval the company received a 20 million dollar payment from referrals, which is comprised of a 17.5 million dollar milestone payment at a 2.5 million dollar creditable advance royalty payment.

In addition, $25 million of the 30 million dollar upfront payment we received from griffo as in Q1 of 2019, which had been previously deferred will no longer be repayable biometric referrals. Given this information we expect to recognize approximately $43 million. This collaboration.

Revenues in the first quarter of 2020.

The remaining deferred about a $2 million will be recognized as revenue as we complete certain research and development activities, mainly related to the conduct of our auto immune hemolytic anemia phase three clinical trials, which we expect over the next 18 months, we ended the quarter with cash and short term investments of approximately 98 point.

$1 million with that I'd like to turn the call back over to roll.

Dean L. Schorno: With that, I'd like to turn the call back over to Raul. Thank you, Dean. Moving on to slide 21.

Thank you I'd going on to slide 21.

The growth doing to achieve without at least since launch is just to begin.

Raul R. Rodriguez: The growth we've achieved with Tavalisse since launch is just the beginning. As you heard today, we are well positioned going into 2020 to continue to grow our ITP market share in the U.S., especially in earlier lines of therapy, and with the efforts of our partner, Griffith, to launch Foscomandib in Europe later this year, making our product available to adult Europeans also suffering from chronic ITP. Similarly, in warm autoimmune hemolytic anemia, there is a tremendous opportunity for Tavilis to help patients who currently have no approved treatment option. We would be the first to be approved in this highly synergistic indication. But there's more to Rigel, although Tavalis provides the foundation and the launching point. For what we plan to achieve, we're also continuing to build an incredibly broad development pipeline based on treating immune-mediated diseases, and the opportunities here are immense.

As you heard today, we are well positioned going into 2020 to continue to grow our IACP market share in the us, especially in earlier lines of therapy.

And with the efforts of our partner crystals to launch Fostamatinib in Europe later, this year, making our product available to adult Europeans also suffering from chronic ITD be.

Similarly in more autoimmune hemolytic anemia is a tremendous opportunity, particularly just to help patients who currently have no approved treatment option.

We would be the first to be approved in this highly synergistic indication.

But theres more to ride, although total lease provides the foundation and the launching point.

And for what we plan to achieve we're also continuing to build an incredibly broad development pipeline based on treating immune mediated diseases.

And the opportunities here immense.

Raul R. Rodriguez: We're exploring additional indications for tablilis or sick inhibition, and these are likely to be synergistic add-ons to our Tmall commercial book. We have programs in both RIP and IRAC kinase inhibitions. And as I mentioned, these are two of the most attractive immune targets in the biopharmaceutical industry today. And we have molecules in both of these areas that are near the lead and, we think, potentially the best in class. We believe... and other pharmaceutical companies seem to agree that these compounds have enormous potential. We expect to both partner with and retain substantial positions with these assets to continue to build Rigel into the future. So with that, I'd like to open up the call to your questions.

We're exploring additional indications for capital lease are sick inhibition.

And these are likely to be synergistic add ons to our team all commercial focus.

We have programs in both brick and Iraq kindness inhibitions and as I mentioned these are two of the most attractive immune targets in the biopharmaceutical industry today and we have molecules in both of these areas that are near the lead and we think potentially the best in class.

We believe.

In other pharmaceutical companies seem to agree that these compounds have enormous potential.

We expect to both partner and retained substantial positions with these assets to continue to build rigel into the future.

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

Thank you at this time, we will be conducting a question and answer session. If you would like to ask a question. Please press star one on your telephone keypad. The confirmation from indicate that your line is in the question Q you May Press Star too if you would like to remove your question from the Q for participants using speaker equipment and may be necessary.

Operator: Thank you. At this time, we will be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate that your line is in the question queue. You may press star 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys.

Your handset for pressing the star Keys, one moment, please let me pull for questions.

Operator: One moment, please, while we pull for questions. Thank you. Our first question comes from the line of Chris Raymond with Piper Sandler. Please proceed with your question. Hi, this is Nicole Gabreski on behalf of Chris.

Thank you. Our first question comes from the line of Chris Raymond with Piper Sandler. Please proceed with your question.

Hi, This is Nick will go Brzeski on for Chris Congrats on all the progress and thanks for taking the question.

Nicole Gabreski: Congratulations on all the progress and thanks for taking the question. Just quick on WARM-EHA; it's nice to see the progress on patient enrollment in phase three. I guess just based on physician receptiveness to tabulase and ITP, what gives you confidence that doctors are excited about this mechanism in autoimmune hemolytic anemia? And then could you discuss how you see the overall commercial opportunity in comparison to ITP, particularly with the advancement of other approaches like FCRN and maybe how you see the market evolving as well as the role of tabulase in it? Thanks.

Just quick on warm hi, it's nice to see the progress on patient enrollment in the phase three yes, just based on physician Receptiveness to Talison IBP. What gives you confidence the doctor excited about this mechanism in auto immune hemolytic anemia.

And then can you discuss how you see the overall commercial opportunity in comparison to IBP.

Particularly with advancement of other approaches like CRN you may be how you see the market evolving is wells Rolla capital Ethernet. Thanks.

Thank you Nicole appreciate the questions Hello.

Raul R. Rodriguez: Thank you, Nicole. I appreciate the questions. I'll address the first question. Maybe Wolfgang can tell us his opinion on AIHA as well, and I'll say a few words on the market potential and ask Tariq to comment as well. So the reason we know physicians are excited about AIHA is because they've told us this. We've visited many of the sites already. In fact, many of the sites that are conducting the trial are sites that were previously part of the ITP trial. When we were doing that trial, we went out and visited many of these sites, and they said to us, you know, I'm really excited about fosformatinib in ITP, but there I have a couple options. In AIHA, nothing.

Ill address the first question, maybe working can tell us is opinion on h., as well and and though I'll see if your words on the market potential in as Tarek to comment as well so.

The reason, we know physicians are excited about AI chase because they told us this.

We visited many of the sites already.

In fact, many of the sites that are conducting the trawler sites that were previously part of the RTP trial.

What we're doing that trial, we went out and visited many of these sites and they said to us Im really excited about.

Fostamatinib and ITP.

But there will have a couple options.

NHS nothing so incredibly enthusiastic about the opportunity there to help those patients because I have nothing for those patients. So they were very encouraging then too.

Raul R. Rodriguez: So I'm incredibly enthusiastic about the opportunity there to help those patients, because I have nothing for those patients. So they were very encouraging then to help us launch a new trial in AIHA. And I think that continues to be the case. I think we remain very excited. The clinicians involved remain very excited.

Help us.

Launched a new trial in AI ha and I think that continues to be the case I think.

We remain very excited clinicians involved remain very excited.

Well.

Wolfgang Dummer: Yeah, I can add a few points to that. As Raul has said, there's really nothing approved and no real standard of care for this indication. We are conducting a well-controlled, placebo-controlled trial. We will have a, and we're thinking about this really carefully and using all the experience that we have from ITP, we will have a very proactive data analysis plan that, you know, analyses everything that can be analyzed from this trial from very high-bar endpoints to endpoints that cast a wider net but still demonstrate clinically meaningful results. So, we believe that we can have a very compelling data package right out of the gate at Long. And the other thing is, you know, as I speak with these physicians and as I look into their enrollment in the study, there's really a lot of enthusiasm among those folks, and I think that enthusiasm that we see in the clinical trial can definitely translate into the real world of Long.

I can't wait a few points to that so is wrong as good as we do not being approved in newly expanded appear into syndication.

We are conducting our whaler controlled placebo controlled trial.

We will have.

And we are thinking about this really gift leading use all the excuse that we hear from from ETP. We will have a very proactive data analysis plan.

Yeah.

Annualized EBITDA can be analyzed this trial from very high bar.

8.22 endpoint.

At cast a net wider but do demonstrate meaningful meeting clinically meaningful results.

So so we believe that we can have a very compelling data package right right right out of the gate at long.

And the other thing is a.

Speaking of dispositions and they're looking to the or enrollment in this study is really all of enthusiasm among those books and I think that enthusiasm that we've seen the clinical trial can definitely translate into into the real growth Oklahoma.

Tarek Salam: Hey, Nicole. On your second question, we think the market opportunity here is quite substantial. We think there are somewhere between 40,000 to 45,000 patients with adult warm autoimmune hemolytic anemia in the US, for example, and maybe a quarter, a little more than a quarter of those would be the addressable market using kind of the ITP numbers as kind of a benchmark. So it's a really attractive opportunity.

Hey, Nicole and your second question, we think the the market opportunity here is quite substantial.

We think theres some somewhere between 40 to 45000 patients with adult warm autoimmune hemolytic anemia and to use for example, and maybe a quarter little more than a quarter of those would be the addressable market using kind of the TP numbers as kind of a benchmark. So it's really attractive opportunity currently these pace.

Raul R. Rodriguez: Currently, these patients have steroids, but some use of serotoxin is not approved. And then they have nothing. They have to look at a splenectomy as a possible approach, which many of them would prefer to avoid.

And to have steroids, some use of reduction not approved and then they have nothing they have to look at a split to me as a possible approach, which many of the preferred to avoid so we think it has tremendous opportunity it a little bit smaller in terms of patient size, perhaps the Nike Pete but without the availability of of various other agents I think the.

Raul R. Rodriguez: So we think it has tremendous opportunity. It's a little bit smaller in terms of patient size, perhaps, than ITP. But without the availability of various other agents, I think the market opportunity for Rigel is potentially much larger even than ITP. So I think that's a very exciting market potential.

The market opportunity for Rigel is potentially much larger even the night CP. So I think thats. It thats, a very excited market potential sark, yes. So thank you Raul. So I think also just to add on Nicole I think as we see kind of the story evolving in regards to hemolytic anemia, we believe we're poised to take.

Tarek Salam: Yeah, so thank you, Raul. So I think also just to add on, Nicole, I think as we see kind of the story evolving in regards to hemolytic anemia, we believe we're poised to take advantage of it. And so, as Raul articulated...

Advantage of it and so as well articulated.

Tarek Salam: The desire, as you can imagine, to move away from long-term steroid use or perhaps some of the other agents that are currently used right now in the treatment arsenal are just not ideal in terms of managing this disease, which is a long-term management strategy. And in particular, obviously, this is a pretty symptomatic disease when you have a low hemoglobin. And so, the desire for a therapeutic, quite frankly, with a profile of fostamatinib, of tablilis, is quite high. And so I can tell you, in our initial market research and landscape work, as well as in our advisory board, clinicians really see the profile of tablilis fulfilling this unmet need. So we're extremely excited by the receptivity of this audience.

The desire to view the desire if you can imagine to move away from long term steroid use or perhaps some of the other agents that are currently use right now in the treatment are armamentarium are just not ideal in terms of managing this disease, which has a long term long term management strategy and in particular, obviously this is.

A pretty symptomatic disease, when you have a low hemoglobin levels and so the desire for a therapeutic quite frankly with the profile of Fostamatinib totally is quite high and so I can tell you in our initial market research at landscape work as well as are our advisory board.

Clinicians really see the profile of hobbled lease so filling this unmet needs. So we're extremely excited by the receptivity of this audience.

Raul R. Rodriguez: Thanks, Stark. I wanted to just make a quick comment to fully answer your question, Nicole.

Thanks, Doug I wanted to just make a quick comment to fully answer your question nickel.

Raul R. Rodriguez: You know, there are other molecules that are in development, mostly in earlier stages than ourselves. But we have two really important advantages. Number one, we're the furthest advanced in clinical trials. The only company that is in the middle of a phase three pivotal program for AIHA. That's a tremendous advantage. We'll be the first to have a phase three approved, a phase three filed, and hopefully, a phase three approved by the FDA and then launched. The second substantial advantage we have is a built-in audience in physicians who currently treat patients with warm autoimmune hemolytic anemia who already will have familiarity with our product, Tavalisse, have been using it in a different indication, ITP, who know how to dose regulate, who know how to manage the product well, and that's an advantage that no one else has. So we bring two very distinct and important advantages to this area that I think we'll work to capitalize on.

There are other molecules that are in development, mostly earlier development that ourselves, but we have to really important advantages number one with a little further sit fast in clinical trials. The only company that is in the middle of a phase three pivotal program for ha. That's a tremendous advantage will be the first.

To have a phase three approved the phase three filed and hopefully a phase three.

Approved with it by the FDA led launched the second substantial advantages we have as a built in audience in physicians, who currently treat patients with more moderate hemolytic anemia that already will have familiarity with our product top of lease have been using it in a different indications.

Who know how to dose regulate who know how to manage the product well and that's an advantage that no. One else has so we can bring to very distinct that important advantages to this area that I think I will work to capitalize on.

Nicole Gabreski: Great, that's very helpful. Thank you. Thank you. Our next question comes from the line of Yigal Nochomovitz with Citigroup. I am pleased to see you with your questions. Yeah, hi, good evening. Thanks for taking the question. Are you able to provide at this point some more specifics in terms of the market share that you have in the various lines of therapy? I know you're moving into earlier lines, but I'm just wondering if you have some more specific numbers for the second through the fifth line in ITP.

Great. That's very helpful. Thank you. Thanks.

Thank you. Our next question comes from the line of Yigal Nochomovitz with Citigroup. Please proceed with your question.

Yes, hi, good good evening, thanks for taking the question.

Are you able to provide at this point some more specifics in terms of the market share that you have.

In the various lines of therapy, I know, you're moving into earlier lines, but I'm. Just wondering if you. If you have some more specific numbers there for the second through this this line.

Yigal Dov Nochomovitz: Certainly, so this is hard. I'll start with that question.

Tarek Salam: So, I think at this point, we're not providing any specifics, you know, in terms of market share by line of therapy or overall. Suffice to say that, in 2018, obviously, with our six months in the marketplace, we were primarily being used, as I mentioned, in the later lines of therapy and saw a great uptake there. And as 2019 has evolved, what we've seen is that overall, for the entire post-steroid ITP landscape, our market share actually doubled from the end of 2018.

GP.

Certainly so this is hard ill start with that question. So I think at this point, we're not providing specifics.

In terms of market share by line of therapy, or overall suffice to say that.

In.

2018, obviously with our six months in the marketplace.

We were primarily being used as I mentioned in the later lines of therapy and a great uptake there and as 2019 has has evolved what we've seen is overall for the entire post steroids.

Landscape, our market share doubled actually from the end of 2018. So we've we clearly have a lot of opportunity in terms of penetrating those early line patient pools.

Tarek Salam: Transcripts provided by Transcription Outsourcing, LLC.

We're happy to see the momentum in terms of just the overall share of the landscape that we've been able to accomplish today clearly it's still early and we'll be monitoring it and we're excited about though at 2020 brings.

Okay. Thank you.

Yigal Dov Nochomovitz: Okay, thank you. I'm just wondering if you could comment a little bit more on this persistency rate for the refills. As you noted, it's 64% at month four. I'm curious if you can provide anything in terms of what that persistency rate looks like at months further down the line, you know, months five, six, seven, things like that. And then relatedly, if you can provide the average treatment duration, because the treatment duration commercially is a slightly different statistic.

And just wondering if you could comment a little bit more on this persistency rate for the refills as you've noted 64% at month for I'm curious if you can provide anything in terms of what's that persistency rate looks like at at months.

Further.

Months 567 centers like that and then related Lee if.

If you can provide the the average treatment duration because the treatment duration.

Commercially is slated to slightly different statistics from the persistency rate at month for as I understand.

Yigal Dov Nochomovitz: All of these are statistics from the persistency rate at month four, as I understand it.

Raul R. Rodriguez: Thanks.

Raul R. Rodriguez: Yeah, thanks, Yigal. I think about persistency, that 54% is a really useful metric for us because we wanted to know, and you know, when you do a clinical trial like we did with the Phase III FIT program, and you get certain results out of them, that's fine, but that's quite distinct from what we think clinical practice would be like, and this data verifies that. As you recall, we were at 45% persistency at month four, a little over a year ago, and as the year progressed, last year we went to 50, and now we're at 54, so very good, continual progress in that, and like I said, there are two major reasons for that. One is doctors now using the product in fewer refractory patients and just, frankly, just being better at using it, knowing how to dose regulate, knowing how to manage some AEs as they see those things, and so they're getting better, and in both of those circumstances, we expect the persistency to continue to climb slowly over time.

Thanks, Yeah. Thanks, you go I think on the persistency that 54% is a really useful metric for us because.

We wanted to know and need to what you do a clinical trial like we did with the phase three fit program and you get certain certain results out of then that's fine, but thats quite distinct from what we think clinical practice would be like and the state of verifies that.

As you recall, we were at 45% persistency at month for a little over a year ago and as the year progress last year. We went to 50 and now with 54. So very good continue progress in that and like I said Theres two major reasons for that one is doctors now using the product into less refractory patients.

And just frankly speaking better at using it knowing how to dose regulate.

Knowing how to manage some easy they see those things and so they are getting better and both of those circumstances, we expect the persistency the continue to climb slowly.

Over time that's.

Raul R. Rodriguez: That's certainly going to be the case as we move into earlier lines of therapy, as Tariq shared, as well as doctors continue to use the product. And even though we've been on the market for a little over 18 months now, many doctors still don't have that much experience. There's still a large group of doctors that have not used the product substantially, and they're going to continue to improve how they use it. And so to try to answer your former question, your question is in terms of the longer term.

Certainly going to be the case as we move to into earlier lines of targeted therapy as Tarek show shared as well as doctors continue to use the product and even though we've been on the market for a little over 18 months now.

Many doctors don't have that much experienced still theres still a large group of doctors that have not use the product us substantially and they're going to continue to improve and how they use it.

So to try to answer your former question your customers in terms the longer term.

Raul R. Rodriguez: The patients that have been on the drug for longer, you know, a year or so or more, are very refractory. They're reflective of the initial patient population that we addressed when we launched the product. So they're really not reflective of what we think the end population of these patients would be, that is, a mixture of more, much more, less refractory patients. So it's a little bit unfair.

The patients that had been on drug for longer.

A year or so or more are very refractory their reflective up the initial patient population that we that we addressed when we launched the product so they're really not reflective of what we think the end population of the of of these patients would be that is a mixture more much more less refractory patients.

So it's a little bit on fair I think once we reach some form of stability amount that might be a useful metric to be able to provide.

Yigal Dov Nochomovitz: I think once we reach some form of stability on that, that might be a useful metric to be able to provide. And in terms of your treatment duration question, we should look into that. I don't have that, but let us look into what that might be because it certainly will be dependent on the line of therapy. And we obviously expect patients with earlier lines of therapy to have longer durations as well. But let us come back.

In terms of your treatment duration question, let us look into that I don't have that but let us look into what that might be because it certainly will be dependent on on.

The lines of therapy, and we obviously expect patients with though.

Earlier lines of therapy to have longer durations as well, but let me let us come back.

Okay sure.

Raul R. Rodriguez: Okay, sure. And then my last question is, obviously, there's a heavy overlap between ITP and AIHA in terms of the prescriber base. But I was just curious, are there any key differences between ITP and AIHA that you need to be aware of to launch AIHA successfully?

And then my last question is.

Obviously, there's a heavy overlap between ATP and ha in terms of.

The prescriber base.

But I was just curious are there any key differences between Itps I'd say that you need to be aware of.

To launch.

Yigal Dov Nochomovitz: I'll, you know, in terms of differences, if you mean medically, or do you mean market-wise?

Hey success.

I'll now in terms of differences, if you mean medically or do you mean market market wise, yes.

Yigal Dov Nochomovitz: Yes. Thank you.

Tarek Salam: Just in terms of the market, yeah.

Just in terms of the Mark to Mark Marketwise Yeah.

Tarek Salam: Yeah, so this is Tarek. So I can clarify, at least our current understanding. So obviously, we still have some time from a pre-launch perspective, and as Wolfgang articulated, his organization, as well as the commercial organizations, are putting down the foundational work to ensure that we have a path forward for a successful launch. All of our data thus far, as well as our engagements and research, indicates that the individuals, as articulated, that treat ITP are also carrying patient loads in the community. So this is also still a community-based disease. So much like we've shared statistics in the past, about 90% of the ITP patients being treated in the community, we see that same phenomenon for warm hemolytic anemia. We're not seeing any sort of referral patterns or dynamics that change how we operationalize and execute from a launch strategy perspective. Again, it's really the same prescriber base managing the same, roughly, but proportional, case loads. And so I think there's just a lot of synergies and parallels, quite frankly, to how we've been successful in entering the market in ITP.

Yes. So so this is Tom so I can I clarify at least our current understanding so obviously we're still.

How some time from a pre launch perspective, and as Wolfgang articulated is organization as well as the commercial organizations are putting down the foundational work to ensure that we have a path forward for successful launch all of our data thus far as well as our engagements in research indicates that the individuals as as was articulated.

That treat itps also carrying the patient loads in the community. So this is also still a community treated disease. So much like we've shared statistics in the past about 90% of the ITP patients being treated in the community. We see that same phenomenon for warm humiliated hemolytic anemia, we're not seeing any sort of.

Referral patterns are dynamics that changes, how we operationalize and execute from from a launch strategy perspective.

Again, it's really the same prescriber base, managing the same roughly but proportional Keith loads and so I think theres, just a lot of synergies and parallels quite frankly to to how we've been successful hitting the market IDP hopefully that answers your question.

Yigal Dov Nochomovitz: Yigal, if I could make a comment further to that, in addition, you know, we launched ITP, we're very happy with the performance there, and we're going to do AIHA much better even. We know a lot more now, we're better prepared, we have more of the individual functions within the company here, thinking about how we're going to launch the product, what data we need to be the most effective in the launch of the product, and while we did a great job in ITP, we're going to do a better job in AIHA.

You guys. If I can make a comment further to that in addition.

We launched ITD, we're very happy with the performance there.

And we're going to do you actually much better even.

We know a lot more now were better prepared we have more of the individual functions within the company here thinking about how we're going to launch the product what data we need to be the most effective in the launch of the product and while we did a great job and if you were going to do at a better job in AI Jay.

Okay. Thanks for taking the questions.

Raul R. Rodriguez: Okay, thanks for taking the questions. Sure. Thank you. Our next question comes from a line from Tessa Romero with J.P. Morgan. Please proceed with your question. Hi, guys.

Thank you. Our next question comes from the line of Tessa Romero with Jpmorgan. Please proceed with your question.

Tessa Romero: Thanks for the updates here and for taking our questions. A question from me tonight actually on warm mild immune hemoglobinemia. Are you able to provide a little bit more context around how the primary endpoint for the Phase 3 was chosen, having both a durability and also a hemoglobin component versus what was used in the Phase 2? I suppose I'm getting at how you think about what is clinically meaningful in this patient population. And then I have a follow-up question.

Hello. Thanks.

For taking my questions.

A question for moved from the last warm weather.

Modeling.

I.

Slide a little bit more context around how the primary corn look for the same for you have chosen havin, having both of your ability and also at hemoglobin component.

Versus what was used in the phase two.

Gentlemen, how you're thinking about what is kind of going forward with patient population and then I've a follow up.

Wolfgang Dummer: Great. Thanks, Tess. I'll let Wolfgang know if he would...

Great. Thanks, Dennis I'll, let Wolfgang if he would.

Wolfgang Dummer: Yeah, so I would say the components for end-point selections are relatively straightforward. Obviously, this disease is characterized by a decrease in hemoglobin, so what we need to show is an increase in hemoglobin and some sort of measure of how that increase is sustained, right? And there are various ways to do it. We have, of course, an idea of what we want to do.

So.

With the components for inputs collections are relatively straightforward focus the diseases characterized by decreasing the moment of indeed, so what we need to show is an increase in hemoglobin and some sort of measure how how that increases sustained right and there is.

Various ways to do it's we have to of course.

An idea of.

Fourth we want to do and we have put that into our analysis plan.

Wolfgang Dummer: We will vet this at some point with the FDA. We have time until database lock to provide the final data analysis. We are collecting the data in a way that allows us to depict the data in multiple different ways. So we will practically describe multiple different ways of analyzing the data, and regarding the primary endpoint, we have one pre-specified, and we are confirming it with the FDA.

We will make this in the.

Time with the FDA, we have we have time to.

Onto database lock to provide the final data analysis.

And.

We are collecting the data in a way that allows us to depict the data in multiple different ways. So some we've really practically described multiple different ways of analyzing the data and regarding the primary endpoint. We we have one pre specified and we are confirming is safety.

Tessa Romero: Okay, great. Thank you. And then, I guess, bridging from a prior question, I just wonder, from your research, how many patients have been identified globally? I think you gave a U.S. number, but I was just curious about the global number. And then, kind of, how you're thinking about kagiographies for the disease. Thanks.

Okay.

Okay, great. Thank you.

Okay, great from a prior question.

And your from your research.

How many patients have been identified globally.

You bet you ask number but I was just curious on the global number.

Mhm, how you're thinking about geography.

Thanks.

Raul R. Rodriguez: Sure, I'll try to answer that. Interestingly, in AIHA, what we believe, and others believe, is that the prevalence rate is similar in all countries. So, obviously, Europe would be most likely the second largest market in terms of the size of those patient populations and probably in terms of dollar value as well. Our partner, Grifols, our partner Kisei in Asia, Japan, and our partner, Medicine, all have rights to AIHA as well as ITP. It's all within them.

Sure I'll try to answer that.

Interestingly.

The NIH Jay what we believe others belief is that the prevalence rate is similar in in all countries. So obviously Europe would be most likely the second largest market in terms of all the size of those patient populations and probably in terms of dollar value as well our partner Griffiths our partner he say in Asia.

Japan, and our partner Medicine, all have rights to ha as well as ITD be it's all within them and so the same synergies that we are discussing here in the U.S. between doctors, who treat RTP Sip being the same doctors that treat ha exist in Europe, Canada, Japan et cetera. So it's the same synergy.

Raul R. Rodriguez: And so the same synergies that we're discussing here in the U.S. between doctors who treat ITP being the same doctors that treat AIHA exist in Europe, Canada, Japan, et cetera. And so it's the same synergies. So I think that will help in the launch of the AIHA indication quite substantially. The treatment paradigms are not different in other countries as in the U.S., so all of that is very transferable. In ITP, we think that the market outside the U.S. is a little bit smaller, maybe $900 million relative to a little over a billion in the U.S. for ITP. It's likely that the market in Europe kind of mimics what the market might be in AIHA. There is tremendous opportunity outside the U.S., maybe comparable to the U.S. opportunity. More patients, perhaps lower prices.

So I think that will help being the launch of the ha indication quite substantially the treatment paradigms are not difference in other countries as in the U.S. So all of that is very transferable and CP, we think that the market in in.

Outside the us a little bit smaller maybe 900 million relative to a little over 1 billion in the U.S. for RTP, it's likely that the market in Europe kind of mimic what the market might be an AI ha. So mendis opportunity outside the U.S. may be comparable to the U.S. opportunity.

More patients, perhaps lower prices so.

Thank you will move onto our next question comes from the line of Joseph Pendennis with HC Wainwright. Please proceed with your question.

Raul R. Rodriguez: Thank you. We'll move on to our next question, which comes from the line of Joseph Pantginis with H.C. Wainwright. Please proceed with your question. Hi guys, this is Pasquale Sanzona from the line of Joe.

Hi, guys. This is Phil square. This also from the line of Joe sequential man. So I was wondering.

Joseph Pantginis: A few questions on my end. So, I was wondering, as for the European commercialization plan, can you give us more color on the country-by-country commercialization strategy for Tavalis? Specifically, which geography would make more sense in terms of potential Tavalis adoption?

The European Commission position plan can you give us more color on the country by country theses commercialization strategy fatalities, specifically, which geography would make more sense in terms of potential tulisa adoption.

Tarek Salam: Sure, Pascual. This is Tarek. I'll take that question and then, obviously, ask my colleagues to weigh in. So, in terms of their go-to-market strategy in Europe, we're really not commenting on the exact approach that our partners are taking since they have not publicly shared that. However, as you're well aware, as many are as well, they're looking obviously at some of the bigger, larger markets, such as Germany and the UK, as is commonly seen in the industry, where you can get favorable pricing, have larger patient populations, and then from there, So, you know, we'll defer to our colleagues in gripples to, in more detail, provide explicit country-by-country timing.

Sure. Paul. This is this is Todd ill take that question and then obviously yet my colleagues to weighing in so in terms of their go to market strategy in Europe, we're really not commenting on the exact.

Approach that our partners cripples since they have not publicly shared that however.

As you're well aware as many are as well.

They are looking obviously at some of the big larger markets such as Germany in the UK as is commonly seen in the industry, where you can get favorable pricing how deep the.

Larger patient populations and then from there sequentially have a strategy to some of the other countries in the big pipe markets. So, we'll defer to our colleagues and careful to in more detail provide.

Explicit country by country timing, but that's at a high level. The general approach well yeah. The only thing I'd like to add to that is that now what the attractive while we were sort of track to took referrals as our partner in Europe is that they currently sell IB RG throughout Europe and.

Raul R. Rodriguez: Yeah, the only thing I'd like to add to that is that, you know, what the attractiveness, what we were so attracted to Griffill's as our partner in Europe is that they currently sell IVIG throughout Europe. And IVIG, as you may know, is used as a rescue medication in the treatment of ITP and AIHF. And so they know the physician audiences very well that are the targets for TAVILIS in both of those indications. And so it makes them the ideal partner because of that. They had really fantastic infrastructure in all the large European countries, and that made them a very attractive partner.

As you May know is used as a rescue medication in the treatment of ITD be Andy I checked and and so they know the physician audience is very well that are the targets for tableau lease in both of those indications that meet them the ideal partner because of that they had really fantastic infrastructure in all the large European.

Countries and that means at very attractive a very attractive partner and so and I can honestly say and I am speaking for per Tarek and the rest of our commercial medical affairs team, we've had excellent engagement with them excellent collegiality with our referrals colleagues in making sure we help them as much as we can in getting the.

Wolfgang Dummer: And so, and I can honestly say, and I'm speaking for Tarek and the rest of our commercial medical affairs team, we've had excellent engagement with them, excellent collegiality with our Griffill colleagues in making sure we help them as much as we can in getting the best launch in Europe. And I'm absolutely confident they're going to do a stellar job of it. And you'll hear from them exactly about the details, but we're incredibly confident in their ability to do so and delighted to have them as our partners.

Best launch in Europe, and I'm, absolutely confident they're going to do a stellar job of it and you'll hear from them exactly in the details, but we're incredibly confident and their ability to do so and delighted to ought to have them as our port.

Thank you so much that sale for another question for me so with respect to travel lease label expansion. Besides.

Tarek Salam: Thank you so much. That's very helpful. Another question for me.

Joseph Pantginis: So, with respect to Tavalee's label expansion beyond AHA, can you elaborate a little bit on what indication would make more clinical and market sense, please?

Hey, can you elaborate a little bit what indication would be more clinical at Mccann sense.

Wolfgang Dummer: Yeah, so, as you can imagine, the number of indications where Tavalis might work is actually huge. You know, having worked at Genentech, I think of Tavalis a little bit about the early days of B-cell depletion. And if you look over the last 15 years, where B-cell depletion has expanded to, and I'm not naming the name of a drug, but B-cell depletion...

Yes so.

As you can imagine the number of indications with have a lease might work is actually huge.

Having worked at Amgen and take a.

You guys have at least a little bit about the early days of DCIO depletion and if you. If you look with about 60 news soon where we have you seen depletion has expanded to answer that month.

Naming the name of the drug but because of the please.

[laughter] with our.

So the auctions are enormous now we have worked a lot to narrow this down to a number of indication opted to be done what indications that we can pursue from a resource perspective, we've narrowed it down to about three.

Wolfgang Dummer: So the options are enormous, but we have worked a lot to narrow this down to a number of indications. Obviously, there are more indications that we can pursue from a resource perspective, but we narrowed it down to about three where we believe we have data to suggest that it works. There is already data available in chronic lymphatic leukemia, where we have a paper out of 2010 that has shown pretty compelling efficacy for sick inhibition, and that is one option. The other option that we are considering is chronic graft-versus-host disease. We have an IST going on that has some very interesting preliminary data. And then we are also exploring a few indications that are maybe not as related to hematology as the other two; one of them is, for example, Myasthenia gravis, where we think we have a very good scientific case that the drug...

We believe we have.

Data to suggested Brooks and I'm.

We have.

There is already data available in chronic lymphocytic leukemia, where we have a paper out of 2010 that has shown pretty compelling.

Efficacy for.

Suke inhibition and that is one option.

The option that we are considering is chronic graft versus host disease, we have an ice tea going on that has some very interesting preliminary data and then we also.

Exploring a few.

A few indications that maybe not as related to hematology if the other two of one of them. For example, my senior grab is where we think we have a very good scientific case that the drug might work and so will there be.

We choose use I'm going to be a combination of where we see the biggest opportunity how the how quickly can be fully though what does it cost in however that would fit into the into our portfolio. So so, but we're pretty close to selecting one and want to get this going this year and vessel the of the target I'll just add eight.

Wolfgang Dummer: I'll just add, as Wolfgang was alluding to, clearly there would be a preference to be able to bolt-on to our current commercial and medical infrastructure. We have the boots on the ground and know the customers quite well, but obviously, we're going to select the one that holistically bests the organization. So I think it's exciting, as Wolfgang articulated, to have a wealth of options to entertain.

As Wilkins alluding to clearly there will be a preference to to be able to have a bolt on into our current commercial and medical infrastructure, we out the boots on the ground and know the customers quite well, but obviously, we're going to select from one that holistically besser as the organization. So I think it's exciting as Wolfgang articulated.

To have a wealth of options to entertain.

Tarek Salam: That's very helpful. Thank you so much. Last question on my end. So, thinking about the recent approval of Doppellet in CITP, how would this approval impact Tavalee's market share?

Well that sales thanks, so much less queso length.

So thinking about the recent approval Dr pellets in CTP, how does a pool would impact probably slack a share.

So why don't I take that one on first so this is Tom again, so at least early indications.

Joseph Pantginis: So why don't I take that one on first? So this is Tarek again. So at least early indications of adoption and what we're seeing and hearing from customers is really that the primary strategy of that compound is to cannibalize and quite frankly go after the current market share of L-Traumapac, the other oral tepomimetic. Unknown Executive, Yigal Nochomovitz, Raul Rodriguez, Dean Schorno, Raymond Furey, Richard Miller, Raymond Furey, Unknown Executive, Eun Yang, Nalin Tejavibulya, Rigel Pharmaceuticals Inc. that agent over Tavalisse, because quite frankly, I think, as we've articulated based on a number of factors, we have a very unique value proposition of why a patient or And so I would say, obviously, this could change, but to date, there's been minimal impact on prescribers in terms of their selections for Tavalisse and much more of an impact in the Tipo-Mimetic space.

Of the adoption and what we're seeing and hearing from customers is really the primary strategy of that Tom Challenge is to cannibalize and quite frankly go after the current market share.

Ill trauma pack the other oral people know medical.

In the therapeutic class and so.

There are really a little bit of kind of head to head trying to.

Go after each other in terms of market share capture based on attributes of the product.

We are not seeing is physician selecting that agent over top of leads because quite frankly, I think as we've articulated it's on a number of factors. We have a very unique value proposition of why a patient already physician would want to be on our product and so I would say, obviously this could change but to date.

It's been minimal impact to two prescribers in the terms of their selection or total lease and much more of an impact and the Tivo memetics base.

Tarek Salam: That's it, Allison. Thank you so much for taking my question. Thank you. As a reminder, ladies and gentlemen, if you would like to queue a question, please press star one on your telephone keypad at this time. Our next question comes from the line of Kristen Kluska with Cantor Fitzgerald. Please proceed with your question. Hi, good afternoon, and thank you for taking my questions. The first one is, for chronic ITP, given that Tavalez has this differentiated mechanism than other therapies, have you heard of any combination used in the commercial setting, or do you expect this could become an option as generics may come to play for some of the other therapies?

Yes. Thank you so much for taking my questions.

Thank you as a reminder, ladies and gentlemen, if he would like TQL question. Please press star one on your telephone keypad at this time. Our next question comes from the line of Kristen Wesco with Cantor Fitzgerald. Please proceed with your question.

Hi, Good afternoon. Thank you for taking my questions. The first one is for chronic itps given that tallies has this differentiated.

Mechanism then other therapies have you heard of any combination used in the commercial setting or do you expect this could become an option is generic may come to play for some of the other therapies.

Kristen Brianne Kluska: So there's certainly been a keen interest, and I would say almost an academic and scientific interest in combination therapy, but given that the mainstay of therapeutic approaches in this disease category has been monotherapy, I would say that is really kind of the clinical environment as well as the payer environment in which most of these clinicians operate. And so to answer your question directly, we've seen very little combination therapy that certainly, as for certain patients, particularly those that are in crisis or, frankly, with very low platelet levels, there might be bridging strategies where therapies overlap, which is not unheard of for diseases like ITP. But in terms of overt combination use, we, that's just not something or a phenomenon that we're currently seeing in terms of the commercial usage of the product. I'll defer to others here about, you know, thoughts in the future from an investigative standpoint.

So yes. So what are so there's certainly been a keen interest and I would say almost an academic and scientific interest of combination therapy, but given that the mainstay of therapeutic approach in this disease category has been monotherapy I would say that is really kind of the.

The clinical environment as well pair environment in which most of these these these clinicians operate and so the to answer your question directly we've seen very little combination therapy that were visible to in terms of top Elise certainly as for certain patients, particularly those.

That are in crisis, or frankly, with very low platelet levels, there might be bridging strategies, where therapies overlap which is not.

Unheard of for diseases like IDP, but in terms of overt combination use.

We that's just not upping our phenomenon that we're currently seeing in terms of the commercial usage of the product I'll defer to others here about.

Thoughts in the future from a from an investigational standpoint.

Tarek Salam: I think that we completely agree. I don't think there's a lot of, at this point, interest in exploring that. It's more of an academic thing, and we do get asked that question quite a lot, but the answer is not a lot in actual practice.

So I think that we can be completely agree I don't I don't think theres a lot of at this point interested in exploring that it's more of an academic and we do get asked that question substantially but the answer is not a lot in actual practice.

Okay, great. Thank you and then for for warm and Hey, you discussed the persistency rates in the refill timeline to four months for chronic ITP like given that for warm and Jay there are no approved therapies. What are you going to be looking for in the phase three trial to help with your discussions on this topic in terms.

Kristen Brianne Kluska: Okay, great. Thank you. And then for WARM-AIHA, you discussed the persistency rates and the refill timelines of four months for chronic ITP, but given that for WARM-AIHA, there are no approved therapies, what are you going to be looking for in the Phase 3 trial to help with your discussions on this topic in terms of guiding physicians, should it be approved for this indication as well?

Guiding physicians should it be approved in this indication as well.

Raul R. Rodriguez: Yeah, let me answer that, but I'll ask Wolfgang to also comment. You know, it's very interesting. We have a primary endpoint that's important and useful for approval and for the FDA's evaluation. But in practice, out there in the real world, sometimes you need different and additional metrics beyond that. And so we're making sure that we include those within the analysis plan and the protocol for a Phase III trial to allow us to have exactly that wealth of data to launch the product successfully and provide clinicians with the information that they need on the use of the product in AIHA that will help them understand how best to use it and how best to succeed with it. Wolfgang, do you have any comments on that?

Yeah, let me answer that but I'll ask what's going to also comment it's very interesting.

We have up a primary endpoint, that's important and useful for approval in for the FDA devaluation, but in.

In practice out there in the were real world. It's sometimes you need different in additional metrics beyond that and so we're making sure that we include those within the analysis plan and the protocol for for the Phase three trial to allow us to have exactly that wealth of data to launch the product successfully and provide clinicians.

The information that they need on the use of the product in AI ha that will help them understand how best to use it in and how best to succeed with it.

What's going to any comments on it.

Wolfgang Dummer: Yeah, I mean, it's always the best guidance to have data to prove what you want physicians to do. I guess the objectives in a disease like AIH are, first of all, to increase hemoglobin levels from where they are too low, then make sure you maintain those increased hemoglobin levels. But there's also, we're also looking at how many patients we prevent hemoglobin decrease. So it's very conceivable to believe that a patient stays stable, and that is a treatment effect of Cavalese, while a placebo patient may drop down. So then that would lead us to say, look, the natural history in AIH is such that hemoglobin goes down over time, but we show you data that shows that hemoglobin stays stable or stays up.

Yes, I mean, it's always it's always the vast guidance to have data.

To prove what you want physicians to do I guess the objectives in the disease like HP. All first of all increase hemoglobin levels from from where they are too low and make sure you maintain those increased.

In levels, but there's also we also looping its.

How many patients to be prevent a hemo.

Hey motive in decrease so three via conceivable due to believes that the patient stayed stable and it is a treatment effect will cover these wireless placebo patients may drop downs. So then you would so that's something that would lead us to say look.

The natural history in ha, such that the emotional being goes down overtime, but we should be data that hemoglobin stay stable oil stays up and then another thing would be for example can be shows at.

Wolfgang Dummer: And then another thing would be, for example, can we show that physicians can spare some steroids, you know, use lower steroids at some point, and that would also be a very valuable outcome if you could say the patient stays stable on Cavalese and at a tolerable steroid dose of, let's say, less than 10 milligrams per day or less than 5 even. So all of these things together would determine how we tell physicians to use this drug.

That physicians can spasm steroids and no use the lowest Detroit.

At some point and that would also be a very valuable outcome. If you could see the patient base stable on top of these and in the tolerable steroid dose of Lixilan listened in milligrams to put the or this insight you can so all of these things together boots determined to book.

Heading to physicians how to use this drug.

Raul R. Rodriguez: The only thing I would add to that, as well, is just to remind you that the 80-person Phase 3 study really hurt Julian. No one has ever attempted that before us, and we're well on our way to getting that completed.

The only thing I would add to that is as well as just to remind you.

The 80 person.

Phase three study really herculean nobody has ever attempted that before before us and we're well on our way to getting that completed but in addition to that we also have the long term extension study and what we hope to do out of that study is to follow as many of these 80 patients on over the long term at this point all on foster amended lease and be able to.

Raul R. Rodriguez: But in addition to that, we also have the long-term extension study. And what we hope to do out of that study is to follow as many of these 80 patients on over the long term, at this point, all on FOSDMA, at the very least, and be able to understand how best to continue to use that treatment and provide that data over the longer term to our customers, so that they understand the benefit of the product. That's something that, you know, is very valuable. Much like with ITP, we'll have that data; we'll continuously publish on that data and provide updates. So it really provides a wealth of information. Now that we've built this 80-person clinical trial, we want to make sure we continue to follow and derive as much value out of it as possible.

Understand how best to continue to have that used and provide that data over the longer term to our customers. So that they understand the benefit of the product. That's something that you know is very valuable much like with HCP will have that data will continuously published on that data and provide updates. So really provides a wealth of information now that we've built this.

Any person.

Clinical trial, we want to we want to make sure. We continue to follow in derive as much value out of it as possible.

Okay, great. Thank you for taking my questions.

Kristen Brianne Kluska: Okay, great. Thank you for taking my questions. Thank you. There are no further questions at this time, so I'd like to turn the floor back over to Mr. Raul Rodriguez for closing comments.

Thank you there are no further questions at this time, so I'd like to turn the floor back over to Mr. Raul Rodriguez for closing comments.

Raul R. Rodriguez: Well, thank you. I appreciate your questions.

Well. Thank you I. Appreciate your questions 2019 was a fantastic year for US we really did all the things that we set out to do early in the year across the board increase Oh, the availability of top at least to our to our audience our patients.

Raul R. Rodriguez: You know, 2019 was a fantastic year for us. We really did all the things that we set out to do early in the year, across the board. Increase the availability of Tavalisse to our audience, our patients, and expand it overseas with great partners. Launch a very difficult, challenging trial and now execute well on that in AIHA. And then build a pipeline with two additional molecules that really are just fantastic additions to the pipeline.

Expanded overseas with Great partners launched a very difficult challenging trial and now executing well on that in AI ha and then build the pipeline with two additional molecules that really are just fantastic additions to the pipeline. It was a fantastic year in 2019 and in 2020 I we have equally.

Raul R. Rodriguez: It was a fantastic year in 2019, and in 2020, we have equally high and aggressive challenges for us to achieve. And I'm absolutely confident across all these areas that we'll do really well. And thank you for your help in helping us do that.

Equally chart, a high in aggressive challenges for us to achieve and I'm absolutely confident across all these areas that will execute really well and thank you for your help and helping us do that.

Operator: Ladies and gentlemen, this concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.

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

Yes.