Q3 2021 Rigel Pharmaceuticals Inc Earnings Call

Greetings and welcome to Rigel Pharmaceuticals Financial conference call for the third quarter of 2021.

Operator: Rigel Pharmaceuticals financial conference call for the third quarter of 2021. At this time, all participants are in a listen-only mode.

At this time all participants are in a listen only mode. A brief question and answer session will follow the formal presentation. If anyone should require operator assistance. During the conference. Please press star zero on your telephone keypad.

Operator: A brief question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please star zero on your telephone. 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. Thank you, Ms. Vance. You may...

As a reminder, this conference is being recorded.

It is now my pleasure to introduce our first speaker Dolly Vance, who is rigel as executive Vice President Corporate Affairs and General Counsel. Thank you Ms. Vance you may begin.

Welcome to our third quarter 2021 financial results and business update conference call. The financial press release for the third quarter. It was issued a short while ago and can be viewed along with the accompanying slides for this presentation and the news and events section of our Investor Relations page on our website www.

Dolly Vance: Welcome to our third quarter 2021 financial results and business update conference call. The financial press release for the third quarter was issued a short while ago and can be viewed along with the accompanying slides for this presentation in the news and events section of our investor relations page on our website, www.rigel.com. As a reminder, during today's call, we may make forward-looking statements regarding our financial outlook and our plans and timing for regulatory and product development. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted.

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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.

Dolly Vance: A description of these risks can be found in our most recent annual report on Form 10-K for the year ended December 31, 2020, and subsequent filings with the SEC, including our Q3 quarterly report on Form 10-Q on file with the SEC. Many forward-looking statements are made only as of today, and we undertake no obligation to update these forward-looking statements to reflect subsequent events or circumstances. At this time, I would like to turn the call over to our CEO, Raul Rodriguez. Thank you, everyone. Thank you, Dolly.

Christian about these risks can be found in our most recent annual report on Form 10-K for the year ended December 31, 2020, and subsequent filings with the SEC, including our Q3 quarterly report on Form 10-Q on file with the SEC.

Any forward looking statements are made only as of today's date and we undertake no obligation to update these forward looking statements to reflect subsequent events or circumstances.

At this time I would like to turn the call over to our CEO Raul Rodriguez.

Thank you Mary Thank you Dolly and thank you everyone for joining our third quarter 'twenty 'twenty. One conference call also with me today are Wolfcamp dermer, our chief Medical Officer.

Raul R. Rodriguez: And thank you, everyone, for joining our third quarter 2021 conference call. Also with me today are Wolfgang Dummer, our Chief Medical Officer; Dave Santos, our Chief Commercial Officer; and Dean Schorno, our CFO.

Santos, our chief commercial officer.

And Dean <unk> our CFO.

Raul R. Rodriguez: Now beginning on slide five, we made significant progress that sets us up for success in each of our key value drivers now and into 2022. On this call, we'll tell you about growing ITP sales and advancing our clinical program in autoimmune hemolytic anemia.

Now beginning on slide five.

During the third quarter, we made significant progress that sets us up for success in each of our key value drivers now I need to 2022.

On this call, we'll tell you about growing our T P sales.

Advancing our clinical program in autoimmune hemolytic anemia.

Raul R. Rodriguez: Treating Hospitalized COVID-19 Patients, as well as preparing our earlier stage pipeline programs for mid-stage clinical trials. Today, let me start with our second key value driver, warm autoimmune hemolytic anemia, or WARM-AIHA. WARM-AIHA In WARM-AIHA, we achieved an important milestone this quarter. I'm happy to announce that the Pivotal Phase III Forward Trial is now fully enrolled. This brings us closer to delivering robust evidence for tablilis as a potentially new first-in-class medicine for the treatment of patients with form AIHA.

Treating hospitalized COVID-19 patients as well as preparing our earlier stage pipeline programs for mid stage clinical trials.

Today, let me start with our second key value driver warm autoimmune hemolytic anemia, or warm AIA tree wore me out he chi and wouldn't be where we achieved an important milestone this quarter I'm happy to announce that the pivotal phase III forward trial is now fully enrolled.

This brings us closer to delivering robust evidence for top of lease that's a potentially new first in class medicine for the treatment of patients with warm AIA trick.

Raul R. Rodriguez: Dave will provide an overview of the opportunity in warm AIHA, and Wolfgang will discuss what we expect to see from the FORWARD trial and provide insights into why this is an important step forward for patients suffering from this disease. In the past quarter, we completed the expansion of our He-Monk commercial organization. We added 16 new sales reps who are now fully trained, out in the field, and are looking to make an impact starting this quarter.

Dave will provide an overview of the opportunity and wore me I a tree and Wolfgang will discuss what we expect to see from before trial and provide insights into why this is an important step forward for patients suffering from this disease.

In the past quarter, we completed the expansion of our hemo commercial organization.

We added 16, new sales reps, who are now fully trained out in the field and they're looking to make an impact starting in this quarter.

Raul R. Rodriguez: We have an incredibly capable and experienced organization, and now one with even greater reach. Dave will speak about the caliber of this team he's assembled and how this positions us to drive further awareness of Tavalisin ITP and prepares us for a potential opportunity in warm autoimmune hemolytic anemia. In ITP, we continue to see growth in demand this year, but we're also encouraged by some key metrics that mark the potential for future growth, specifically new patient starts, which are the strongest we've seen since 2019, when the pandemic started.

We have an incredibly capable and experienced organization and no one with even greater reach.

Dave will speak about the caliber of this team he's assembled and how this positions us to drive further awareness of the tower leasing like T P and prepare for a potential opportunity and warm.

Autoimmune hemolytic anemia.

And I T. P. We continue to see growth in demand this year.

But we're also encouraged by some key metrics that mark the potential for future growth, specifically, new patient starts which are the strongest we've seen since 2019 when the pandemic started.

Raul R. Rodriguez: Dave and Dean will describe the sale trend in a little bit more detail during this call. On our COVID-19 program, we continue to move forward with 210 patients now enrolled in our Phase 3 study. In early September, results from the Phase II study conducted by the NIH were published in the journal Clinical Infectious Disease. This publication provides important clinical data on the use of foster magnum in patients hospitalized with COVID-19.

They even dean will describe the scale trend in a little bit more detail during this call.

On our COVID-19 program, we continue to move forward with 210 patients now enrolled in our phase III study.

In early September results from the Phase two study conducted by the NIH were published in the journal clinical infectious disease.

This publication provides important clinical data on the use of post imatinib in patients hospitalized with COVID-19.

Raul R. Rodriguez: Wolfgang will discuss our progress in this program. Regarding our earlier pipeline programs, our IRAC 1.4 program is moving forward with preparations for a Phase 1B-2 study in low-risk MDS. This is an area where there's high unmet need, and we think that our IRAC1N4 molecule, R289, is ideally suited to address that.

Wolfgang will discuss our progress in this program.

Regarding our earlier pipeline programs, our Iraq, one four program is moving forward with preparations of our phase one b slash two study in low risk Mds.

This is an area, where there is high unmet need and we think that our Iraq. One in four molecules are two eight is ideally suited to address this.

Raul R. Rodriguez: Our RIP-1 inhibitor program, partnered with Eli Lilly, includes a systemic molecule, R552, which is targeting autoimmune diseases, and we are jointly working on starting a Phase II trial in 2022. The program also includes a molecule that can penetrate the blood-brain barrier for applications in CNS diseases such as Alzheimer's and ALS. We made progress across all our value drivers this quarter and set the stage for a transformative year for the company in 2022. To tell you more about this, we'll start with Dave's discussion on our commercial progress and expansion, followed by Werfgang's update on our clinical programs, and then Dean's financial update. It's over to you, Dave.

Ah Rip one inhibitor program partnered with Eli Lilly includes a systemic molecule are 552, which is targeting autoimmune diseases and we are jointly working on starting the phase III trial in 2022.

The program also includes a molecule that can penetrate the blood brain barrier for applications in CNS diseases, such as Alzheimer's and ALS.

We made progress across all our value drivers this quarter and setting the stage for a transformative year for the company in 2022.

To tell you more about this we'll start with Dave's discussion of our commercial progress and expansion followed by worth gangs update on our clinical programs and then deemed financial update.

Over to you Dave.

David A. Santos: Thanks very much, Raul. I'd like to now move to slide seven, where you'll see our FDA-approved indication, which is for adult patients with chronic immune thrombocytopenia, or CITP, who've had an insufficient response to a previous. Moving to slide eight, we continued to grow demand for Tavalese in Q2, again reaching over 1,700 total bottles shipped to patients. This represented 5% growth over our demand volume during Q3 of 2020. We were encouraged by the new patients starting therapy in Q3 and believe that will translate into higher demand volume as we move through. However, despite growing demand, our total bottle volume decreased.

Thanks, very much Raul.

Like to now move to slide seven.

Where you'll see our FDA approved indication, which is for adult patients with chronic immune thrombocytopenia or <unk>, who had an insufficient response to a previous treatment.

Moving to slide eight we continue to grow demand for <unk> in Q3 again, reaching over 1700 total bottles shipped to patients and clinics.

This represented 5% growth over our demand volume during Q3 of 2020.

We were encouraged by the new patients starting therapy in Q3, and believe that will translate into higher demand volume as we move through this quarter.

Despite growing demand our total bottle volume decreased resulting in net sales of $16 million for Q3.

David A. Santos: Resulting in net sales of $16 million. The reason for this volume decline is seen on slide 9. As you can see, our demand grew by 5% to 1,710 bottles, while total bottles decreased by 4% to 1,657.

The reason for this volume decline is seen on slide nine.

As you can see our demand grew by 5% to 1700 10 bottles, while total bottles decreased by 4% to <unk> hundred 57 bottles.

David A. Santos: This decline was due to the impact of inventory, are bottles remaining in the distribution. Last year, we built up 102 bottles, and this year, we declined by 53. While inventory impacted our total number of bottles and net sales.

This decline was due to the impact of inventory our bottles remaining in the distribution channel.

Last year, we built up a 102 bottles and this year, we declined by 53 bottles.

While inventory impacted our total bottles and net sales we remain confident that we can continue to grow demand through accelerating our awareness among prescribers.

David A. Santos: We remain confident that we can continue to grow demand through accelerating our awareness among prescribers, continuing to increase the number of new patients starting on top, and maximizing the benefits to those patients by ensuring they get timely. To achieve those growth objectives, we continue to focus on expanding our research. Moving to slide 10, we are pleased to see that interactions with cu continued a strong growth trend during even though there were persistent COVID challenges relative to Q2 based on the Delta.

<unk> increased the number of new patients starting on <unk> and.

And maximizing the benefits to those patients by ensuring they get timely refills.

To achieve those growth objectives, we continue to focus on expanding our reach to customers.

Moving to slide 10, we are pleased to report that our interactions with customers continued a strong growth trend during Q3.

Even though there were persisting COVID-19 challenges relative to Q2 based on the Delta search.

David A. Santos: We saw more than a 30% increase in in-person interactions versus Q2, and virtual interactions still represented 40% of our calls. This was solid productivity in a transition quarter, given that it was a period where we were focused on recruiting and training to complete our task. Overall, we're getting more opportunity to get in front of customers.

We saw more than a 30% increase in in person interactions versus Q2.

And virtual interactions still represented 40% of our calls.

This was solid productivity in a transition quarter given that it was a period, where we were focused on recruiting and training to complete our expansion.

Overall, we're getting more opportunity to get in front of customers and spread the efficacy messages of Halloween.

On Slide 11, you will see why we are so confident that the strong interaction trend should continue to accelerate in Q4 and beyond.

David A. Santos: On slide 11, you will see why we are so confident that this strong interaction trend should continue to accelerate in Q4. We completed our expansion to 55 territories on schedule in Q3. We fully trained our new team members, and that expanded team is now in place calling on customers. We were able to attract and recruit highly experienced salespeople, and as you see on the right, they not only know the hemoglobin... They have, on average, nearly a decade of experience in their field.

We completed our expansion to 55 territories on schedule in Q3.

Fully trained our new team members and that expanded team is now in place calling on customers.

We were able to attract and recruit highly experienced salespeople to join our expanded team and.

And as you see on the right.

Not only know the hemo space they have on average nearly a decade of experience in their geography. So they are familiar with our customers.

David A. Santos: So they're familiar with our customers. While it will take some time to realize the full benefit of, we do expect the team will have an accelerated impact on prescribers and new patients in their territory. Additionally, on slide 12, we're excited to be preparing for the first live ASH meeting since 2008. We are planning to connect and reconnect with many customers in Atlanta.

While it will take some time to realize the full benefit of this expansion. We do expect the team will have an accelerated impact on prescribers and new patient.

Because of their depth of knowledge and relationships in their territories.

Additionally, on slide 12, we're excited to be preparing for the first live ash meeting since 2019.

We are planning to connect and reconnect with many customers in Atlanta, even through our exhibit booth, which has a sizable footprint near one of the entrances to the exhibit hall.

David A. Santos: Unknown Executive, Eun Yang, Nalin Tejavibulya, Richard Miller, Raymond Furey, Raymond Pharmaceuticals Inc., or other key customer activities we have. My thanks to the entire U.S. commercial team for all their efforts to continue to impact more customers with our expanded and ultimately grow our impact. Moving to slide 13, outside the US, our partners are making steady progress to extend our reach. In September, our partner Griffels announced the continuation of the commercial rollout of Tablets in Europe, with launches in France, Italy, and Spain. In the U.K. and Germany, Topless is now available in the top five markets.

Or other key customer activities, we have planned at the meeting.

My thanks to the entire U S commercial team for all their efforts to continue to impact more customers with our expanded team and ultimately grow our impact on patients.

Moving to slide 13 outside the U S. Our partners are making steady progress to extend our reach globally.

In September our partner <unk> announced the continuation of the commercial rollout of top left in Europe with launches in France, Italy and Spain.

With UK and Germany top left is now available in the top five markets in Europe.

David A. Santos: The phased rollout across the rest of Europe planned over the coming years will include the Czech Republic, Denmark, Finland, and Norway. So in summary, we are looking forward to continued progress as we move through Q4 and into 2022. We believe we have the tools and team in place. Accelerate our growth across a broad group of prescribers. Moving to slide 14, we are also extremely excited that we have another potential opportunity ahead with warm autoimmune disease.

The phased rollout across the rest of Europe planned over the coming months will include the Czech Republic, Denmark, Finland, Norway and Sweden.

So in summary, we are looking forward to continued progress in I T E. As we move through Q4 and into <unk>.

2022.

We believe we have the tools and team in place to accelerate our growth across a broad group of prescribers.

Moving to slide 14, we are also extremely excited that we have another potential opportunity ahead with warm autoimmune hemolytic anemia.

On slide 15.

David A. Santos: Warm AIHA is an indication that has a highly synergistic customer base and the same set of established treatments for steroids and rituximab but lacks an approved agent to use post-steroid. We believe we are uniquely positioned to leverage our knowledge and experience in ITP to fully capitalize on our potential first-mover advantage and significantly build the Tavalese franchise upon FDA approval and launch. I look forward to talking with you more on future calls about our, Thanks for your attention. And I will now turn the call over to Wolfgang to further discuss this exciting new research in warm autoimmune hemolytic, Workday. Thank you, Dave.

Warm AIA Jay is an indication, which has a highly synergistic customer base and the same set of established treatment steroids and rituximab, but lacked an approved agent to use post steroid.

We believe we are uniquely positioned to leverage our knowledge and experience in IPP to fully capitalize on our potential first mover advantage and significantly build the <unk> franchise upon FDA approval and launch.

I look forward to talking with you more on future calls about our plan.

Thanks for your attention and I will now turn the call over to Wolfgang to further discuss this exciting opportunity in warm autoimmune hemolytic anemia Wolfgang.

Yeah.

Thank you Dave.

Wolfgang Dummer: As mentioned, enrollment for our Phase 3 AIHA trial has been completed, so I'd like to take a moment to reorient everyone to the program and make clear why we are excited about the opportunity. Warm autoimmune hemolytic anemia is a serious, rare disorder with approximately 10 to 13,000 patients in the U.S. who are not responding adequately to steroids and need additional lines of therapy. Currently, there are no drugs approved by the FDA to treat this disease.

As mentioned enrollment for our phase III.

Trial has been completed.

Like to take a moment to reorient, everyone with the program and make clear why we are excited about the opportunity continuing with slide 15.

Warm autoimmune hemolytic anemia is a serious rare disorder.

With approximately 10 to 13000 patients in the U S, who are not responding adequately to steroids and need additional lines of therapy.

Currently there are no drugs approved by FDA to treat this disease.

Wolfgang Dummer: Right now, rituximab is often used off-label as second-line treatment, but profound B-cell depletion for long periods of time is an issue and excludes the drug as a long-term disease management option. Splenectomy, another common treatment measure, is an invasive procedure and irreversibly removes the spleen from patients with unknown long-term consequences for those patients.

Right now Rituximab is used off label.

And blind treatment, but profound b cell depletion prolonged periods of time is an issue and include excludes the drug as a long term disease management options.

Splenectomy.

Another common treatment measure is an invasive procedure and irreversibly removes the spleen from patients with unknown long term consequences for those patients.

Wolfgang Dummer: Hence, an effective, well-tolerated immune modulator with long-term safety data that is approved and can be easily prescribed is clearly an unmet medical need. An indication for Tavalis for AIHA would be very synergistic to the already existing approval for ITP because the same position to prescribe for ITP also treats AIHA. That means they are already familiar with Tavalis and aware of the Taste and Efficacy Program. The mechanism of action of TAVALIS in warm AIHA is very similar to the MOA in ITP, and there's a strong rationale that TAVALIS should work in warm AIHA as well.

I mean, 50, well tolerated immune modulator with long term safety data that is approved and can be easily prescribed is clearly an unmet.

Medical need.

An indication of penalties for E. I H E would be very synergistic to the already existing approvals for ATP, because the same physicians, who prescribed by ATP also treating aging.

That means they are already familiar with families and the weird.

Because he proclaims.

The mechanism of external catalyst in warm.

He is very similar to the moh in ATP and if there's a strong rationale that pebble. This should work in warm AIG as well.

Wolfgang Dummer: Moreover, we do have encouraging phase 2 data from a previous study that make us even more optimistic for a positive phase 3 trial readout. Slide 16. This Phase II open-label study included adults with warm AIHA who had hemoglobin levels of less than 10 grams per deciliter and who had failed at least one prior treatment. The primary endpoint was hemoglobin greater than 10 grams per deciliter with an increase of greater or equal to 2 grams per deciliter from baseline by week 24 without rescue therapy or red blood cell transfusion. 11 of 25 patients, 44%, achieved that goal. If you included a late responder around week 30, the percentage would be 48%.

But we do have encouraging phase two data from a previous study that make us even more optimistic for a positive phase III trial readout.

Okay.

Slide 16.

This phase two open label study included adults with a warm AI H E, who heads haemoglobin levels of less than 10 grams per deciliter, and who had failed at least one prior treatment.

Main point was haemoglobin <unk> greater than 10 grams per deciliter, with an increase of greater or equal than two grams.

Neither from baseline by week 24, without the risk of therapy.

Sure.

11 of 25 patients, 44% achieved that goal.

If you included a late response around to be clearly the percentage would be 48%.

Wolfgang Dummer: There were also nice increases in median hemoglobin levels detected as early as week two and sustained over time. The safety profile was favorable and similar to the experience in previous ITP and RA trials. Now, as you know, we have reached agreement with FDA on a primary endpoint for our phase 3 trial, considering a durability measure as well as the challenges of the COVID-19 pandemic. So we landed on the endpoint of three consecutive available time points with a hemoglobin of greater or equal to 10 and a change from baseline of greater or equal to plus two.

There were also a nice increases in medium haemoglobin levels detected as early as week two and so.

And over time.

Safety profile was favorable and similar to the experience in previous ATP in the OA trials.

No as you know we have reached agreement with FDA on the primary endpoint for a phase III trial, considering a durability measure Israel is the challenges of the COVID-19 pandemic.

So we landed on the endpoint of three consecutive available time points with a hemoglobin of greater or equal than pin and a change from baseline of greater what you call It plus two.

If we apply that very high bar with respectively to our phase III data about 27% or a.

Wolfgang Dummer: If we applied that very high bar retrospectively to our phase 2 data, about 27% of patients on foster math met those criteria. Since this is indeed such a high bar, very few placebo patients should meet that goal. Therefore, with mainly patients, we are adequately powered to demonstrate statistical significance in the ongoing phase three study. Slide 17.

Patients on post Imatinib met those criteria.

This is indeed set a high bar very few placebo patients should meet that cool.

Therefore, with 90 patients we are adequately powered to demonstrate statistical significance in the ongoing phase III study.

Yeah.

Slide 17.

Wolfgang Dummer: This is our Pivotal Phase III study, which has now completed enrollment. Patients were randomized one-to-one to either fostamatinib or placebo arm and were treated for 24 weeks. So we can expect the last patient to have their last visit in about six months. After week 24, patients have the option to roll over into an open-label extension study, which most patients choose to do from what we can tell at this point. I mentioned a very high bar for the primary endpoint.

It is our people do a phase III study, which is now completed enrollment.

Patients were randomized one to one to be the post imatinib or a placebo arm and treated for 24 weeks. So we can expect the last patient to have the last visit in about six months.

After week 24 patients have the option to roll over into an open label extension study, which most patients choose to do from what we can tell at this point.

I mentioned at the very high bar for the primary end point let.

Wolfgang Dummer: Let me emphasize that the patients who meet this goal are not all the patients who derive meaningful clinical benefits. There are other clinically meaningful degrees of hemoglobin benefits, and there are other clinically important benefits, such as use of rescue therapy, spirit-bearing potential, or quality of life improvement.

Let me emphasize that the patients who meet this school are not all the patients who derive meaningful clinical benefit.

There are other clinically meaningful degrees of haemoglobin benefit and there are other clinically important benefits such as use of rescue therapy steroid sparing potential well quality of life improvement.

Wolfgang Dummer: These benefits will be captured through pre-specified secondary and tertiary endpoints in the protocol. Taking these additional endpoints into account, the percentage of patients with tangible clinically meaningful benefits beyond the primary endpoint should be clearly higher than 27 percent. That totality of the data should provide a comprehensive data package right around unblinding and time of topline results. I told you my last patient's last visit was in about six months. That will be early May, and then top-line data can be expected in mid-2022. Moving to COVID-19. Slide 19.

These benefits will be captured through pre specified secondary and tertiary endpoints in the protocol.

These additional endpoints into account the percentage of patients with tangible clinically meaningful benefits beyond the primary endpoint should be clearly higher than 27%.

That's a plurality of the data should provide a comprehensive data package right around on blinding and time of topline results.

I told you last patient last visit in about a six months. It would be early may and then topline data can be expected in mid 2022.

Yeah.

Moving to COVID-19.

Slide 19.

Wolfgang Dummer: We've taken you a few times through the very compelling scientific rationale for Tavallis in COVID-19 disease, which has been supported by several pieces of external research at independent institutions. That scientific rationale was confirmed by very positive clinical data from NIH, which was published in September in the journal Clinical Infectious Diseases. There are additional studies ongoing, including our Rigel-sponsored and Department of Defense-supported Phase III trial, which we believe will generate a data package sufficient for approval of Tavalis in this indication.

We've taken you a few times through the very compelling scientific rationale for tablets in COVID-19 disease.

Which had been supported by several pieces of external research independent institutions.

Scientific rationale was confirmed by very positive clinical data from NIH, which was published in September in the journal clinical infectious diseases.

There are additional studies ongoing including a rigel sponsored and department of defense supportive Phase III trial, which we believe will generate a data package sufficient for approval in this indication.

Wolfgang Dummer: As you can hear in the news, full vaccination of the entire population is difficult to achieve, and COVID cases and deaths continue to persist. So there remains a need for effective treatment options for hospitalized patients. If and when approved, Tavalis can be available for immediate use. Slide 20.

As you can hear in the news flu vaccination of the entire population.

Difficult to achieve in Covid cases, and deaths continue to persist.

So there remains a need for effective treatment options for hospitalized patients.

If and when approved companies can be available for immediate use.

Okay.

<unk>.

Wolfgang Dummer: This gives you some more details on all ongoing COVID-19 trials using TAVALIS. I won't go through all those details, but some takeaways are that there are additional shots on goal with our phase 3 trial certainly being the next big milestone, but then also the large ACTIV-4 NIH trial that is progressing well as we speak. All these studies are looking at hospitalized patient populations, spanning most disease severities. Slide 21, reminds you of our Rigel-led Phase III study design. The study includes hospitalized patients with mild disease who have risk factors for developing more severe disease and evaluates if progression to severe disease can be prevented.

This gives you some more details on all ongoing COVID-19 trials using type of lease.

I won't go through all those details, but some takeaways or.

There are additional shots on goal with our phase III trial, and certainly being the next big milestone, but then also the large exit for each trial that is progressing well as we speak.

All these studies are looking at hospitalized patient population spanning most of disease severity.

Slide 21.

Remind you of our Rachel late Phase III study design.

They include hospitalized patients with mild disease, who have risk factors for developing more severe disease and evaluate if progression to severe disease can be prevented.

Wolfgang Dummer: In our discussions with the FDA, if positive, this trial could be the basis for a potential label extension for fostamatinib to treat patients with COVID-19. The study has enrolled 210 patients to date. The pace of enrollment has slowed in the past two months, mostly due to geographic variability in case numbers. Many of the sites in South America and Brazil and Argentina were enrolling swiftly in June, July, and August, which are their winter months.

Crowd discussions with FDA if positive this trial could be the basis for a potential label extension proposed them to.

To treat patients with COVID-19.

Study has enrolled 210 patients to beep.

The pace of enrollment has slowed in the past two months, mostly due to geographic variability of case numbers.

Many of the sites in South America, and Brazil, and Argentina were enrolling swiftly in June July and August which are the winter months.

Wolfgang Dummer: And we have now seen cases slowing there as they go into spring and pandemic conditions ease a bit. To counter the enrollment flow in Brazil and Argentina, we have opened additional sites in different regions, such as in Mexico and the United States, where we expect there could be an uptake. So while we hoped we would complete enrollment in the study by year end, we cannot predict with certainty when it will be complete.

We have now seen cases slowing there if they go into spring and Hyundai.

They make conditions ease a bit.

To counter the enrollment flow in Brazil, and Argentina, we have opened additional sites in different regions, such as in Mexico, and the United States, where we expect there could be an uptick.

So why are we hoped we would complete enrollment of the study by year end, we cannot predict with certainty when it will be complete.

Wolfgang Dummer: At this point, we think it may be closer to the end of Q1, and we will provide another update on our progress in January. Now, let's turn to our pipeline programs, IREG 1.4 and RIP-1, starting on slide 23. Our IRAC inhibitor, R289, and its active metabolite, R835, is a dual inhibitor of both IRAC1 and 4, which in preclinical studies showed more complete suppression of inflammation compared to a selected inhibitor of IRAC4 only.

At this point, we think it may be closer to the end of Q1, and we will provide another update on our progress in January.

Yeah.

Now, let's turn to our pipeline programs, Iraq, one four and group one.

Starting on slide 23.

Oh, Iraq inhibitor, two or 289, and its active metabolite or 835.

He is a dual inhibitor of both Iraq, one four which in preclinical studies showed more complete suppression of inflammation compared to selective.

He'd be the Iraq War on me.

Wolfgang Dummer: As discussed previously, we believe the IRAC1-4 pathways are ideal targets for treatment of low-risk MDS, which is caused by inflammation in the bone marrow that leads to bone marrow deficiency and cytopenia. Preparations are now underway for a Phase 1b-2 study in low-risk MDS patients, which we plan to start in Q1 2022. We look forward to sharing more details on the trial design once we are close to the beginning of the study. We also continue to explore indications in rare autoimmune diseases, such as palmoplantar pustulosis, hydradenitis superlativa, and others, where we see great potential for IRAC inhibition as well. Slide 24.

As discussed previously we believe the Iraq, one four pathways are ideal targets for treatment of low risk Mds, which is caused by inflammation in the bone marrow that leads to bone marrow with efficiency and type of opinion.

Preparations are now underway for a phase one b slash two study in low risk Mds patients, which we plan to start in Q1 2022.

We look forward to sharing more details on the trial design once we are closer to beginning the study.

We also continue to explore indications in the ria or the immune diseases, such as part of Muslims her put colossus.

Hidradenitis, Suppurativa and others, where we see great potential for Iraq inhibition as well.

Slide 24.

Wolfgang Dummer: I'll conclude with the other very important value driver for Rigel, our RIP1 inhibitor program that we have partnered with Eli Lilly. The first candidate, R552, is an oral systemic RIP inhibitor for inflammatory conditions. We're working closely with Lilly on initiating the first Phase 2 study in an autoimmune indication. We're very excited about the broad potential for RIP1 inhibitors in numerous large indications. In addition, here at Rigel, we are currently working on selecting a RIP1 inhibitor candidate that can cross the blood-brain barrier.

I'll conclude with the other very important value driver for Rachel or <unk>, one inhibitor program that we've partnered with Eli Lilly.

The first candidate or if I try to is an oral systemic rip inhibitor for inflammatory conditions.

We're working closely with Lilly on initiating the first phase two study and then all the immune indications.

We're very excited about the broad potential for rip one inhibitors in numerous large indications.

In addition here at Rigel, we are currently working on collecting a rip one inhibitor candidate they can cross the blood brain barrier.

Wolfgang Dummer: Lilly will then lead the clinical development of the brain-penetrating RIT1 inhibitors in CNS diseases. With their huge expertise in developing therapies for autoimmune and TNS diseases, Lilly is the ideal partner to collaborate on these very exciting opportunities. With that, I'd like to turn to Dean for a finance update.

Mindy will then lead to the clinical development of the brain penetrating route one inhibitors.

N S diseases.

With a huge expertise in developing therapies for autoimmune and CNS diseases.

He is the ideal partner to collaborate on these very exciting opportunities.

With that I'd like to turn to Dean for finance update.

Dean L. Schorno: Thank you, Wolfgang. I'm on slide 26. For the third quarter of 2021, we shipped 1000 units.

Thank you Wolfgang I'm on slide 26 for the third quarter of 2021, we shipped 1657 bottles to our specialty distributors, resulting in $25 million of gross product sales 1710 of those bottles were shipped to patients and clinics while.

Dean L. Schorno: 657 bottles.

Dean L. Schorno: Specialty Distributors, resulting in $20.5 million in gross product sales. 1,710 of those bottles were shipped to patients and clinics, while 908 bottles remained in our distribution channels at the end of the quarter.

908 bottles remained in our distribution channels at the end of the quarter we.

Dean L. Schorno: We reported net product sales and top lease of $16 million, a 2% decrease compared to the third quarter of 2020. Our net product sales from Tavalis were recorded net of estimated discounts, chargebacks, rebates, returns, co-pay assistance, and other allowances of $4.5 million. Our gross to net adjustment was approximately 22.1% of gross product sales. Let me briefly provide a bit more color around this year-over-year decrease in our net product sales. While we expect our channel inventory to generally track our sales growth, there are numerous factors...

We reported net product sales from <unk> of $16 million, a 2% decrease compared to the third quarter of 2020.

Our net product sales from <unk> were recorded net of estimated discounts charge backs rebates returns co pay assistance and other allowances of $4 $5 million. Our gross to net adjustment was approximately 22, 1% of gross product sales let.

Let me briefly provide a bit more color around this year over year decrease in our net product sales, we expect our channel inventory to generally track our sales growth. There are numerous factors that will create fluctuations we're likely to see from time to time and we saw this quarter.

Dean L. Schorno: Unknown Executive, Yigal Nochomovitz, Raul Rodriguez, Dean Schorno, Raul Rodriguez, Dean Before we move on from net product sales, let me review our expectations for the fourth quarter. With our Salesforce expansion now complete, we expect to see growth in bottle shipment to patients and clinics in the fourth quarter. Incrementally, we expect our gross to net adjustment to be approximately 23 to 24% in the fourth quarter of 2021. Moving on to slide

<unk> pointed out we saw 5% year over year increase during the quarter and bottles shipped to patients and clinics, while we saw a sequential decrease in our channel inventory.

If you were to remove the effects of channel inventory fluctuation, we would've seen year over year net product sales growth of approximately 8%. This net revenue growth rate is higher than the demand growth rate as a result of net price increases.

Before I move on from net product sales, let me review our expectations for the fourth quarter, which our sales force expansion now complete we expect to see growth in bottles shipped to patients at clinics in the fourth quarter.

For mentally we expect our gross to net adjustment to be approximately 23% to 24% in the fourth quarter of 2021.

Moving on to Slide 27. In addition to net product sales by just contract revenues from collaborations were $4 $5 million for the three months ended September 32021, which consisted of revenues recognized from our deferred revenues of $2.4 million from our license agreement with Lilly one.

Dean L. Schorno: In addition to net product sales, Rigel's contract revenues from collaborations were $4.5 million for the three months ended September 30, 2021, which consisted of revenues recognized from our deferred revenues of $2.4 million from our license agreement with Lilly, $1.8 million for the achievement of a Daiichi milestone, $225,000 related to the performance of certain research and development services pursuant to our Rigel collaboration with Grifols, and a $75,000 Government contract revenue of $1 million was related to income we recognize pursuant to our agreement with the U.S. Department of Defense for our ongoing phase three clinical trial of fostamatinib in COVID-19.

$8 million for the achievement of a daiichi milestone.

$25000 related to the performance of certain research and development services pursuant to a rigel collaboration with referrals and a $75000 milestone payments from bat aside.

Government contract revenue of $1 million was related to income we recognized pursuant to our agreement with the U S Department of defense for our ongoing phase III clinical trial of fast Imatinib and COVID-19 moving.

Dean L. Schorno: Moving on to cost and expenses, our cost of product sales was approximately $151,000 for the third quarter of 2021. Total costs and expenses were $41.3 million in the third quarter of 2021 versus $32.2 million in the third quarter of 2020.

Moving on to costs and expenses our cost of product sales was approximately $151000 for the third quarter of 2021.

Total costs and expenses were $41 $3 million in the third quarter of 2021 versus $32 $2 million in the third quarter of 2020.

Dean L. Schorno: The net increase in cost and expenses was primarily due to research and development costs related to our ongoing phase 3 clinical trial of fostamatinib for the treatment of hospitalized patients with COVID-19, as well as increased commercial activities, including the recent Salesforce expansion.

That increase in cost and expenses was primarily due to research and development costs related to our ongoing phase III clinical trial of Foster mountain nib for the treatment of hospitalized patients with COVID-19, as well as increased commercial activities, including the recent sales force expansion.

Dean L. Schorno: Finally, we ended the quarter with cash, cash equivalents, and short-term investments of $143 million.

Finally, we ended the quarter with cash cash equivalents and short term investments of 143 quite $1 million with that I'd like to turn the call back over to Ralph.

Dean L. Schorno: $143.1 million

Uh huh.

Thank you D.

Dean L. Schorno: In 2021, we set ourselves up for a number of exciting catalysts, and we believe 2022 will be a transformative year for the company. I'm now on slide 28.

In 2021, we set ourselves up for a number of exciting catalyst and we believe.

2022 will be a transformative year for the company.

I'm now on slide 28.

Dean L. Schorno: Despite the challenges of the pandemic, we are regaining a good trajectory in growing ITP sales as access to physicians improves for both patients and our newly expanded field organization. Our enrollment in Phase 3 with warm autoimmune hemolytic anemia sets us up for data in mid-2022. If the data is positive, we will file for a new indication for TAVILIS, a potentially new first-in-class medicine for the treatment of patients with warm autoimmune hemolytic anemia. At COVID-19, we made important steps forward this year that provided us with clinical data that illustrates the potential of Tavalese in treating hospitalized COVID patients.

Despite the challenges of the pandemic, we are getting a good trajectory and growing our T. P sales as access to physicians improves for both patients and our newly expanded field organization.

Our enrollment in phase III are with warm autoimmune hemolytic anemia sets us up for data in mid 'twenty to 'twenty two.

If the data is positive we will file for a new indication for top of lease a potentially new first in class medicine for the treatment of patients with warm autoimmune hemolytic anemia.

And COVID-19, we made important steps forward. This year that provided us with clinical data that illustrates the potential of <unk> in treating hospitalized COVID-19 patients.

Dean L. Schorno: We expect pivotal data in 2022 from our Phase 3 trial, and we will file an EUA if the data is positive. Additionally, we are advancing two of our pipeline candidates into mid-stage trials. We are initiating a Phase 1B-2 study with our wholly-owned IRAC1-4 molecule, R289, in low-risk MDS. We'll also be starting a Phase 2 study in an autoimmune indication with our RIP-1 inhibitor, with our partner Lilly. As we look forward to 2022, we are very excited about these significant clinical milestones and the potential they have for transforming our business.

We expect pivotal data in 2022 from a phase III trial, we will file an EUA if the data is positive.

And lastly, we are advancing two of our pipeline candidates into mid stage trials.

We are initiating a phase one b slash two study with our wholly owned Iraq, one four molecules are to ignite and low risk Mds.

We will also be starting a phase two study in auto and then autoimmune indication with a rip one inhibitor with our partner Lilly.

As we look forward to 2022, we're very excited about these significant clinical milestones and the potential they have for transforming our business.

Dean L. Schorno: Thank you again for your interest in our progress in this quarter. And we will now turn the call over to your questions. Thank you. If you would like to register a question, please press the one key followed by. I'm sorry, please press the star key followed by the number one key on your telephone. A confirmation tone will indicate that your line is in a question queue.

Thank you again for your interest in our progress in this quarter and we will now turn the call over to your questions.

Thank you.

If you would like to register a question. Please press.

The one key followed by.

I'm sorry, please pass the stocky followed by the number one key on your telephone keypad.

A confirmation tone will indicate that your line is in the question queue.

Operator: To withdraw your question, please press star 2 on your telephone. Our first question comes from Yigal Nochomovitz. Hi, this is Carly on behalf of Yigal. Thanks so much for taking our questions. We had two questions about AIHA. First, can you talk about the bar you need to meet?

To withdraw your question. Please press star two on your telephone keypad.

Our first question comes from Yigal <unk> with Citi. Please state your question.

Hi, This is carly on for Yigal. Thanks, so much for taking our question.

Two questions on AI H H.

First can you talk about the bar you need to meet on the primary endpoint of Turbo hemoglobin response rate compared to placebo for the phase III trial to be positive and then second is there any reason to expect differences in patient baseline characteristics between the phase two study and the phase III.

Operator: on the primary endpoint of durable hemoglobin response.

Operator: for the Phase 3 trial to be positive. And then second, is there any reason to expect differences in patient baseline characteristics between the phase two study and the, Thank you, Carly. Wolfgang, would you like to take those? First question on the bar.

Thank you currently Wolfgang but you'd like to take those.

First question at the bar.

Wolfgang Dummer: Yeah, so, we looked at the phase two data, and I told you that if you applied the primary endpoint criteria, then we would have met that in 27% of patients. So we modeled according to that, and with 90 patients, we are in a position where the trial is still statistically significant if there were three placebo patients who meet that bar. Now, that is... As I told you, quite unlikely because the goal is extremely high, so this very high bar of the primary endpoint helps us in that respect because the placebo response rate is expected to be very low. In particular, the plus two criterion, as KOLs will tell you, is extremely unlikely to be met by a placebo patient. So I do think we are adequately powered to demonstrate that effect.

Yeah. So so we looked at the phase II data and I told you that if you apply at the primary endpoint criteria be.

We would have met that and 27% of patients. So we modeled according to bet and with 90 patients we are in a position where the trial soon.

Statistically significant if there were three placebo patients who meet that bar.

Now that is as I told you quite unlikely because the.

The goal is extremely high so it is very high both the primary end point helps us in that respect because the placebo response rate is expected to be very low in particular.

Plus two criterion as Kols will tell you is.

Extremely unlikely to be made by placebo patients. So I do think we are adequately powered to demonstrate steady picked also you were asking how how does this maybe compared to how does the phase III population compared to the phase II population.

Wolfgang Dummer: So you are asking, how does the phase three population compare to the phase two population? I think it gives reason for additional optimism because the Phase II population was recruited in the United States only. They were very severe patients, so on average, they had AIHA for about six years, and most of the patients had had more than one previous treatment, so they were very treatment-experienced. Now our Phase III trial is global in several countries where, for example, access to rituximab may not be as easy as it is in the U.S., so we might get somewhat earlier patients than we had in Phase II, so I think the Phase III population might look even a little bit more promising than the Phase II data set.

I think it gives us a reason to additional optimism because the phase II population was recruited into United States only if a very severe patients. So so on average they had a a G for about six years.

And most of the patients had greater than one previous treatment. So so I think they're very treatment experience now of our phase III trial is global.

In several countries where for example, the excess to Rituxan may or may not be as easy as have you seen in the U S. So we might get.

Somewhat earlier patients than we had in phase two so so.

I think the phase III population.

Look even a little bit more promising than the phase two data stake.

Wolfgang Dummer: Great, that's very helpful. And then we just had one on ITP. I guess putting aside sort of the negative impact from the inventory drawdown this quarter, it seemed like the growth in bottle ship was a bit lighter than your prior expectations for a number closer to what was reported in the second quarter.

Great. That's very helpful. And then we just had one on the I T. P. I guess, putting aside sort of negative impact from the inventory draw down this quarter. It seemed like the growth in bottles shipped to patients and clinics was a bit lighter than your prior expectations for a number closer to what was reported in the second quarter. So just curious if you could.

Wolfgang Dummer: Just curious if you could provide any sort of additional perspective on what drove a bit of a deceleration there. Yeah, I think I'll ask Dave to answer that. I think the bottles showed slight growth in demand this quarter over last quarter. But Dave, maybe you can comment.

Provide any sort of additional perspective on what drove the deceleration there.

Yeah, I think I'll ask Dave to answer that I think the bottles with slight growth in demand this quarter over last quarter, but Dave maybe you can comment.

David A. Santos: Yeah, thanks very much, Carly, for the question. And, you know, as we move through Q3, we saw a nice positive trend in not only those demand bottles but in new patient starts on Tamalese. And as Raul said, they were among the highest levels we've seen since the pandemic began, which includes last quarter. And, you know, we believe truly that our increased ability to engage customers this quarter contributed to that. And that's why we are so encouraged by the new patients we saw last quarter.

Yes, thanks very much currently for the question and you know as we move through Q3, we saw a nice positive trend and not only does.

Demand bottles, but in new patient starts on totally soon as Raul said they were among the highest levels. We've seen since the pandemic began which includes last quarter.

And.

We believe.

Really that our increased ability to engage customers. This quarter contributed to that and that's why we are so encouraged by.

The new patient last quarter, and remember when patient start in a quarter, you're only going to get.

So many bottles out of them depending on when they start, particularly those that start in the back half of the quarter. So again you know it's.

David A. Santos: And remember, when patients start in a quarter, you're only going to get so many bottles out of them, depending on when they start, particularly those that start in the back half of the quarter. So we do expect that as we move forward and those patients stay on therapy, demand should grow, and net sales should follow that.

It's hard because.

I of course, just like everyone else would love to see more increased demand than we had over the 5% to asymmetric.

Asymmetric watching is how many patients are starting on top of lease and that's a metric that tab.

At least for us during the pandemic this.

This is a positive quarters so.

We do expect that as we move forward and those patients stay on therapy demand should grow in net sales should follow that.

Raul R. Rodriguez: If I could add something as well to that, you know, we expanded the size of the organization, and the sales of organizations substantially this past quarter, adding 16, a 40% increase in the number. And really, like we said, really fantastic people joining the company. And really, what we find is that this is a promotion-sensitive category, that you really need to have a cadence and a volume of your message, and having these new reps on board and, frankly, more opening up, really will allow us to tell that story very effectively. So we're excited about that as well. That makes sense. Thank you.

I hope that helps.

If I could add something if I could add something as well too that you know we expanded the size of the organization of the sales organization substantially this past quarter, adding 16, 40% increase in the number and really like as you said really fantastic people joining the company and really what we find is that this is a promotion sensitive.

Category that you really need to have a cadence and a volume of your message and having these are new reps on board and frankly more opening up really will allow us to tell that story very effectively. So we're we're excited about that as well.

That makes sense. Thank you so much thank you Ken.

Operator: That makes sense. Thank you so much. Thank you, Carly.

Thank you. Your next question comes from Gary Nachman with BMO capital markets. Please state your question.

Operator: Thank you. Our next question comes from Gary Nachman with BMO Capital Markets. Please state your name.

Gary Nachman: Hi, good afternoon, guys. First on Tevalise for ICP. So have the inventory levels normalized after the first three quarters here so that sales should reflect the increased demand that you guys are expecting in the fourth quarter. I think you said you expected higher bottle shift. I just want to make sure that you don't think, you know, that this means that inventory should be moving in the right direction for you into the next quarter.

Hi, good afternoon guys.

Town's heavily for ICP, so have the inventory levels normalize after the first three quarters here. So that sales should reflect the increased demand that you guys are expecting in the fourth quarter. I think you said you expect higher bottles shipped I just wanted to make sure that you don't think that you know so that means that inventory should be moving in the right direction.

For you into the next quarter.

Gary Nachman: And then maybe just talk about the new sales force and what sort of promotional efforts they're going to be doing. You know, are they going to be talking about the five-year platelet data? At what point do you think that might be responding with physicians? When should we really see an inflection in the volumes from that?

And then maybe.

Maybe just talk about the new sales force and what sort of promotional effort.

They're gonna be doing you know, where they're going to be talking about the five year play it with data at what point, you think that might be resonating with physicians when should we really see an inflection in the volumes from that and for warm IHA. Since there's a lot of overlap in synergies would you expect to increase the size of the sales.

David A. Santos: And for warm AIHA, since there's a lot of overlap and synergies, would you expect to increase the size of the sales force for that indication, or do you think with this newly increased sales force that would be sufficient? Thank you.

Force for that indication or do you think with this newly increased sales force that would be sufficient.

Great. Thank you. Thank you Gary I'll ask my colleague Dave to comment on those in sequence I T. P normalize inventory next quarter.

David A. Santos: Thank you. Thank you, Gary. I'll ask my colleague Dave to comment on those in order. ITP will normalize inventory next quarter. The new sales force, what are they focusing on, and when we'll see an inflection? And for me, autoimmune hemolytic anemia, do we expect an increase in sales force for that? Sure.

The new sales force what are they focused on and what.

We will see an inflection and wore me out at immune hemolytic anemia, do we expect an increase in sales force for that.

Sure. Thanks, Thanks for the question Gary.

David A. Santos: Thanks for the questions, Gary. I guess, first of all, on the inventory, I'd just like to remind everyone that, you know, if you look at our distribution channel, we hold inventory at both our distributors and at the specialty pharmacy. And you have to think of it as each of those entities maintaining dynamic inventory levels based on what they're shipping to patients and clinics. So where we end a quarter is a point in time that could change up or down based on their inventories, and in Q4 and Q2, it was up, and in Q1 and Q3, it was down relative to demand.

I guess first of all on the inventory I, just like to remind everyone that if you look at our distribution channel.

Old inventory at both our distributors and at the specialty pharmacies.

And you have to think of it as each of those entities.

Entities, maintaining dynamic inventory levels based on what their shipping to patients and clinics.

So where we end the quarter is a point in time that could change up or down based on their.

Their inventories and in Q4, and Q2 was up and in Q1 and Q3 it was down relative to demand. So that's why we tend to focus on demand more we believe that if we continue to grow new prescribers, new patients and are successful at keeping them on therapy or demand will grow.

David A. Santos: So that's why we tend to focus on demand more. We believe that if we continue to grow new prescribers, new patients, and are successful at keeping them on therapy, our demand will grow, and corresponding inventory throughout the channel will grow to supply that demand, ultimately growing our total bottles and our net sales. So, you know, that's kind of, in a nutshell, what happened.

And corresponding inventory throughout the channel will grow to supply that demand ultimately growing our total dork bottles and our net sales.

So you know that's kind of in a nutshell what happened at that point in time it went down this quarter.

David A. Santos: It's the point in time; it went down this quarter, but, of course, if we can continue to increase demand, we expect inventory levels to fall. Your second question on the new sales force, I guess I'd first like to say that we were tremendously pleased at the job our sales management team did in recruiting outstanding HEMOC experience and sales talent to the team. And as I said, they not only know HEM, but they know the customers in their territory.

But yes of course, if we can continue to increase demand, we expect inventory levels to follow.

Your second question on the New sales force I guess I'd first like to say that we were tremendously pleased at the job our sales management team did in recruiting outstanding he mark experienced sales talent to the team and as I said, they not only know him they know their customers.

In their territory. So we do think we'll continue to grow interactions in Q4 and increase our reach to more prescribers as we move into 'twenty two.

David A. Santos: So we do think we'll continue to grow interactions in Q4 and increase our reach to more prescribers as we move into 22, but it'll take some time to leverage those opportunities fully into what we ultimately want, right, new prescribers, new patients, and ultimately accelerated demand growth. And I think there are lots of different factors that influence how quickly the sales grow, but I can tell you one thing, I have tremendous confidence in the team and the passion and energy they bring to every single interaction they have with customers to create that awareness of Tavalis and keep it top of mind so when the clinician is ready to switch or start a new patient after steroids it can happen and so I really do believe our interactions will grow, new prescribers will grow, and new patients will grow as we move forward and that's what it's all about.

It'll take some time to leverage those opportunities fully into what we ultimately want bright new prescribers do patient ultimately accelerated demand growth.

And I think there are lots of different factors that influence how quickly the sales grow but I can't tell you one thing I have tremendous confidence in the team and the passion and energy they bring to.

Every single interaction they have with customers to.

To create that awareness of <unk> and keep it top of mind as to when the clinician is ready to switch or start a new patient.

After steroids it can happen and.

So I really do believe our interactions will grow new prescribers will get grow and new patients will grow as we move forward and.

And that's what it's all about and your last question on warm autoimmune hemolytic anemia as I mentioned in my opening comments.

David A. Santos: And your last question on warm autoimmune hemolytic anemia, as I mentioned in my opening comments, incredibly synergistic, right? We're scaled up now to call on a diffuse group of treaters in ITP, and it's pretty much the same group of treaters in warm autoimmune hemolytic anemia, so that's why we're so excited about this opportunity. Again, we're talking about post-steroids, post-rituximab, or why people would want to use Tavalis instead of rituximab, and I think that to answer your question, we've got the team in place that can do that, so we don't foresee any need to continue expanding to tap into that market. Hope that helps. Yeah, no, that was great.

Incredibly synergistic right.

We're we're scaled up now to call on a diffuse creep of treaters in it.

Pretty much the same treaters in warm autoimmune hemolytic anemia. So that's why we're so excited about this opportunity again, we're talking about post steroids post rituxan map.

Or why people would want to use.

<unk> lease instead of Rituximab.

And I think that to answer to your question. We're perfectly we've got the team in place that can do that so we don't foresee any need to continue expanding.

To tap into that market, it's very synergistic hope that helps.

Yeah, no that was great. Thank you very much.

David A. Santos: Thank you very much. Our next question comes from Joe Pantginis with HC Wainwright. Hey, everybody. Good afternoon.

Thank you.

Our next question comes from Joe <unk> with H C. Wainwright. Please state your question.

Hey, everybody. Good afternoon. Thanks for taking the question a couple of questions I guess I'd like to focus first on a.

Joseph Pantginis: Thanks for taking the question. A couple questions. I guess I'd like to focus first on a mechanistic question for Tavalis.

Mechanistic question for Teva lease during a Wolfgang prepared comments, obviously mentioned a a late responder in the way how our phase two study that could have increased the.

Joseph Pantginis: During Wolfgang's prepared comments, he obviously mentioned a late responder in the Weiha Phase II study that could have increased the... Response Rate, and I think also if you look at the ITP data in the past, there were also some potential late responders, so I'm just curious if you can just remind us or discuss a little bit of the underlying MOA that could lead to some of these late responders. Dr. Yang, would you like to take this?

Response rate and I think also if you look at the ITT data in the past there were also some potential late responders. So I'm. Just curious if you can just remind us or discuss a little bit of the underlying M. A way that could lead to some of these late responders.

Okay would you like to take it.

Wolfgang Dummer: Sure, sure. Thank you for your question. I personally don't really think that the underlying MOA would be responsible for a late responder. I can tell you that there are some patients who get better from baseline, say they start at a 7.5 or 8, and then they do improve but bounce around at like 9.5 and 9.7. And that is already an improvement. They just haven't met that one threshold yet.

Sure sure. Thank you for your Christian I will say aye.

I personally don't really think that the underlying E woods would be responsible for late responders I can't tell you that there are some patients who get better from baseline to say they've started a seven and a half or eight and then they do improve bounce around it like.

19, behalf, and 97 and and embed that he's.

He is already an improvement there.

Just haven't makes that's one threshold yet.

Wolfgang Dummer: And some of the patients still have a chance to meet that threshold, that sort of arbitrary threshold, a little bit later. So I think that's the key reason why there might be some patients who respond later. It's not that they have some sort of different underlying mechanism of disease or something like that.

And some of the patients still have a chance to meet the thresholds.

So the arbitrary threshold a little bit later, so so I think that's the key the key reason why there might be some patients who respond later, it's not that they they have some sort of a different underlying mechanism of disease or something like that it just takes a little longer for them to respond.

Wolfgang Dummer: It just takes a little longer for them to respond. But no, very, very helpful. Thank you. And I guess I don't want to belabor the questions on the, you know, decrease in bottles and inventory. So I'm just curious, I'm going to approach it from this standpoint, either for the bottles or your overall business at Rigel. Number one, have any of the issues with regard to global supply chain issues impacted, even, you know, the shipping of the bottles or what have you?

I don't.

No very very helpful. Thank you and I guess I don't want to belabor the questions on the the decrease in bottles and inventory. So I'm just curious I'm going to approach it from this standpoint.

Either for the bottles of your overall business at Rigel number one.

Has any have any of the issues with regard to our global supply chain issues impacted even you know the shipping of the bottles or what have you and secondly, I know during Dave's prepared comments I just wanted to see if there was any further color on one of the comments with regard to wanting.

Joseph Pantginis: And secondly, during Dave's prepared comments, I just wanted to see if there was any further color on one of the comments with regard to wanting to continue timely refills and if that has any impact with regard to, you know, supply chains or any of the, you know, bottles and inventory. Thank you, Joe. Dave, do you want to comment on that? Yeah, Raul, from my standpoint, you know, on the persistency piece that you're asking about, I'll take the second question first.

To continue timely refills and if that.

Has any impact with regard to supply chain or any of the you know our bottles in inventory. Thanks.

Thank you Joe Dave do you want to comment on that.

Yeah.

Yeah well.

From my standpoint, you know on the persistency piece.

Asking about I'll take the second question first.

Joseph Pantginis: You know, throughout the pandemic, we've been able to maintain that four-month persistency in the mid-50s. So I do think that, you know, that's what we're talking about. We want to make sure that patients get their refills on time and that they stay on the product and get benefits as long as possible. So that's to your second question, but there have been absolutely no issues with supply, and that's not a driver of inventory issues in the third quarter. This is simply how, again, you're talking about specialty pharmacies, and you're talking about our distributors, who all maintain dynamic inventory levels based on how much product they're shipping out.

Throughout the pandemic, we've been able to maintain that four months persistency.

In the mid fifties, so I do think that.

That's what we're talking about we want to make sure that patients get their refills on time and they stay on the product and get benefit as long as possible.

So that's to your second question, but there has been absolutely no issues with supply and that's not a driver of.

Inventory issues.

In the third quarter this is simply.

How again youre talking about specialty.

Specialty pharmacies, and you're talking about our distributors at all maintain dynamic inventory levels based on how.

How much product, they're shipping out to you.

David A. Santos: So, you know, and frankly, kind of where are we in that? Got it. Nice to hear, and thanks for the color.

And it and frankly kind of where we ended the quarter.

Got it and just your and thanks for the color Oh, Sorry go ahead rural no I've just covered we have ample inventories in house of our product and in the U S. So we don't think that the global supply chain issues that you read about we will have any meaningful impact on on those levels in the U S for quite some time.

Raul R. Rodriguez: Oh, sorry. Go ahead, Raul. No, just a comment. We have ample inventories of our product in-house and in the U.S., so we don't think that the global supply chain issues that you read about will have any meaningful impact on those levels in the U.S. for quite some time.

Raul R. Rodriguez: Great. Thank you. Thank you, Joe. Our next question comes from Kristen Kluska with Cantor Fitzgerald. Please state your question. Kristen, one moment. Kristen Kluska, your line is open, please go ahead.

Great. Thank you.

Thank you Joe.

Yeah.

Our next question comes from Kristen <unk> with Cantor Fitzgerald. Please state your question.

[noise], especially one moment please.

Christian Your line is open. Please go ahead.

Kristen Brianne Kluska: Hi, thanks for taking the question. Just a comment on ASH. This is really one of the first big conferences that you'll be attending since you first presented some of these post hoc analysis data two years ago at this conference. So just wondering how this format change might help you in terms of your conversations and helping to further get the message out.

Hi, Thanks for taking the question just to comment on the Ash. This is really one of the first banks conferences that you'll be attending since you first presented some of these post hoc analyses data at two years ago at the conference. So just wondering how this format change might help you in terms of your conversations.

And helping to further got the message out.

David A. Santos: Thank you, Kristen. Good question. Dave?

Thank you Crystal good question Dave.

David A. Santos: Sure. Thanks for the question, Kristen. And that's why we are really doing a lot of preparation for ASH and investing in the resources to have a really nice booth there close to the entrance to ensure that, you know, the customers that are there, we're able to engage them and tell them exactly that story, both about our post-hoc analysis and the high response rates and earlier lines. And secondly, that you not only have a chance of a response, particularly in earlier stage patients, but it will be a durable response.

Sure. Thanks for the question Kristen and Thats why we are really doing a lot of preparation for ash and invested.

For us is to have a really nice fit there close to the entrance.

To ensure that the customers that are there, we're able to engage them and tell them exactly that story are both about our post hoc analysis and the high response rates in earlier lines and secondly that you not only have a chance to ask for a response, particularly in earlier line patients, but it will be a durable response.

David A. Santos: And so we will be out there talking about that message at the booth, and certainly we've got a lot of engagements planned with folks that we've already confirmed are going to be on site. And, you know, we know it's likely not going to be where it was in 2019, but we're going to make every effort to get the messages that we have out there. And we really will be talking about that five-year data, the BGAH article, and the line of therapy responses, as well as the numerous case studies that we have. All of those panels have been built at our booth, and our team is going to be prepared to drive that message.

And so we will be out there talking about that message in the booth and certainly we've got a lot of them.

Engagement plan with folks that we've already confirmed are gonna be onsite. So we'll be attacking it from many different angles and again, we do look at it as a great sign.

That is.

The largest hematology conference.

And it is being held live in Atlanta, So we are.

Investing the time, the resources and the people to.

To make sure. It's worked carefully and you know we know it's likely not going to be where it was in 2019, but we're gonna be every effort to get the messages.

That we have out there.

And we.

We are we really are we'll be talking about that five year data.

David A. Santos: Okay, thank you for that. And as you begin to move the expanded sales force for Tavalese into the field, are you encountering any specific geographic regions where it's easier to get face-to-face interactions with prescribers due to COVID-19? And then, you know, going forward, how do you anticipate the ongoing case numbers might affect this strategy?

Bgh article in the line of therapy responses as well as numerous case studies that we have all of those panels have been built in our booth and our team is going to be prepared to.

To drive that message.

Okay. Thank you for that and as you begin to move the expanded sales force for Cavalese into the field are you encountering any specific geographic regions, where it's easier to get face to face interactions with prescribers are due to COVID-19, and then you know going forward how do you.

David A. Santos: Transcription by Trans-Expert at Fiverr.com I appreciate the question, and there certainly are regional differences. I mean, we, you know, and it changes based on surges, and it can change rapidly in one direction or the other. So we don't, we can't control that, but we, again, that's why I think it's important for me to have shown you that not only are our in-person interactions going up, but our virtual interactions are remaining at about 40% of our total interactions.

The ongoing case numbers might affect the strategy.

I appreciate the question and there certainly are regional differences I mean, we you know.

It changes based on searches.

And it can change rapidly in one direction or the other so we don't we can't control that but we again, that's why I think it's important for me to have shown you that not only are our in person interactions are going up but our virtual interactions are remaining at about 40% of our total.

David A. Santos: So just like ASH, whether it's virtual or whether it's live, we're going to do our best to send a message, but the more live, the better. And obviously, that's why we expanded. We do see that, you know, regardless of the pandemic, we're going to see more patients treated, and I think that's what we're seeing now, and we need to get the message out there.

Actions, so just like cash whether it's virtual or whether it's live we're going to do our best to send a message, but the more lives better and obviously, that's why we expanded we do see that.

Regardless of the pandemic, we're going to see more patients treated and I think that's what we're seeing now and we need to get the message out there. So I think our strategy is good both.

Kristen Brianne Kluska: Okay, thank you for taking my questions.

In the near term and the longer term for sure as I mentioned before about potentially having a launch with warm autoimmune hemolytic anemia in the future.

Operator: Thank you. Just a reminder to ask a question, press star 1 on your telephone keypad. Our next question comes from Eun Yang with Jefferies. Please state your question.

Okay. Thank you for taking my questions.

Thank you Chris.

Thank you just a reminder to ask a question press star one on your telephone keypad.

Our next question comes from young young with Jefferies. Please state your question.

Eun Kyung Yang: Hi, this is Nalin speaking on behalf of you, and thank you very much for taking the questions. I have two questions, please. Number one, could you please comment on any off-label use of Tavalese in COVID-19? And number two, aside from the COVID impacts, why did enrollment take so long for Phase 3 for WEHA, given that there is no approved therapy out there? Does it have anything to do with the entry criteria? Thank you very much.

Hi, This is Neil Lane on for you and thank you very much for taking the questions I have two questions. Please number one could you. Please comment on any off label use of <unk> in COVID-19.

And number two aside from the Covid impacts.

Why why is it enrollment takes so long for phase III for <unk> given that there is no approved therapy out there does it have anything to do with the entry criteria. Thank you very much.

So Steve maybe you want to comment on the first one and then Wolfgang and I can comment on the second one.

David A. Santos: Dave, maybe you want to comment on the first one, and then Wolfgang and I can comment on the second. Yes, Raul.

Yes Raul.

David A. Santos: And I appreciate the question. Obviously, with COVID-19, we do not have any approval or an EUA. And so there is little awareness, except those who are intimately familiar and have read the publication.

I appreciate the question, obviously with COVID-19, we do not have any.

Any approval or an EUA and so there is little awareness.

Except those who are intimately familiar and have spread the publication. So we've got very.

Raul R. Rodriguez: So we've got very, submitted the use of Tamalese or Fosmatinib in COVID. That's what I can share. Just to add to that, you know, the publication was available this quarter, which is very good. And obviously, but we're very restrictive in terms of what we can do based on it. And on the second question, maybe Wolfgang, aside from COVID-19, why did it take so long to enroll the phase three study? and A.I.

Limited use of.

Total lease or fast madness in a COVID-19, that's what I can share for now.

Just to add to that you know its the publication was available.

Available this quarter, which is very good and obviously, but were very restrictive in terms of what we can do based on based on that.

And then the second question maybe Wolfgang.

Aside from COVID-19, why did it take so long to enroll the phase III study.

Uh huh.

Wolfgang Dummer: Yeah, sure, sure. Well, first of all, we're very happy to announce that we're done with enrollment. So that's good news for today. I understand your question, "Why did it take so long?" Well, you have to really, you know, account for several factors. Initially, of course, you have the need to get the numbers of sites up.

Yeah sure sure well first of all again.

Happy to.

To announce it but done with enrollment so so so that's that's good he was supposed to be I understand for sure. Your Christian why did it take so long well you have to really.

Accounts of several Texas initially of course.

The need to get to the numbers of sites up but then most importantly last year during the height of the pandemic. There was almost no study that's not oncology related or COVID-19 related that could be enrolled on the irregular pace and it has to do with you know.

Wolfgang Dummer: But then, most importantly, last year, during the height of the pandemic, there was almost no study that's not oncology related or COVID-19 related that could be enrolled at a regular pace. And that has to do with, you know, distance rules and private practices, and then patients are being scared. Why would I, maybe I can wait, maybe I should stay on steroids a little bit longer until I can get safely to the doctor's office?

This thing through good private practices and then patients are being scared why would a maybe I can wait maybe I'll stay on steroids, a little bit longer until they can get safely to the to the to the Doctor's office.

Wolfgang Dummer: I think that that is really the key reason why it was just sluggish to find all these patients. I am personally glad that we came out of this crisis, and we got it over the finish line. And I'm looking forward to, you know, unblinding and getting meaningfully three data. But that's, I think that's my most likely explanation.

I think that that is really the key reason why why it was just sluggish to find all these patients.

I am personally glad that became out of this crisis and we got it over the finish line and I'm looking forward to you know.

Blinding and get meaningful phase III data.

But that's I think that's my most most likely explanation.

I think it was a this was a is a very important indication for us. We just a note to enroll 90 patients. We opened about 90 sites across the world. That's how important it was for US and we were very fortunate that many of our competitors put their trials on hold or stop them entirely during this period and we weren't.

Raul R. Rodriguez: I think this is a very important indication for us. We, just to note, to enroll 90 patients, we opened about 90 sites across the world. That's how important it was for us, and we are very fortunate. Many of our competitors put their trials on hold or stopped them entirely during this period, and we were able to enroll, albeit for some months, very few patients, but we continue to make progress and are the first to have a Phase III trial in warm autoimmune hemoglobinemia fully enrolled. We're, in fact, the only trial that has some Phase II data that we think is really compelling.

Able to enrol up be it so much with very few patients, but we continue to make progress in and are the first to have a phase III trial in warm autoimmune hemolytic anemia fully enrolled for refract. The only trial that has.

Some phase two data that we think is really really compelling. So it really is a was a herculean effort to get it done during these during these times and it will be a tribute to the determination because there are patients out there and we know that they've me out during COVID-19 not be seeking new treatments, but they are out there and once COVID-19 subsides.

Raul R. Rodriguez: So it really was a Herculean effort to get it done during these times, and it will be a tribute to the determination because there are patients out there, and we know that they may, during COVID, not be seeking new treatments, but they are out there, and once COVID subsides, they will be in need of new treatments, and I think we will have one for them, now with approval from the FDA, hopefully. I got it. Thank you very much. Thank you. Thank you. There are no further questions at this time. I would like to turn the floor back over to Mr. Raul Rodriguez for a closing comment.

They will be in need of new patient new treatments with I think we will have one for them now with an approval from the FDA hopefully.

Got it thank you very much.

Thank you Holly.

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

Raul R. Rodriguez: Thank you so much. I appreciate that. In closing, I'd like to thank everyone for joining us on this call and your continued interest in Rigel. I'd also like to thank our employees for their commitment to improving the lives of patients, a commitment that now stretches beyond he-monk conditions and rare immune conditions but also includes COVID-19. We look forward to updating you on our progress on all these programs in future calls and in other press releases throughout the next year. And thank you so much for your participation. Have a great day. Thank you. This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.

Thank you so much I appreciate that.

Of course, we would like to thank everyone for joining us on the call and your continued interest in Rigel I'd also like to thank our employees for their commitment to improving the lives of patients a commitment that no stretches beyond he monk conditions in rare immune conditions, but also now includes COVID-19, we look forward to updating you on our <unk>.

Progress on all of these programs in future calls and then the other press releases throughout the next year.

Thank you so much for your participation and have a great day.

Thank you.

This concludes today's conference.

You may disconnect your lines at this time, thank you for your participation.