Q1 2022 Rigel Pharmaceuticals Inc Earnings Call

May 3, 2022

Greetings and welcome to Rigel Pharmaceuticals Financial conference call for the first quarter 2022.

Greetings.

Welcome to Rigel Pharmaceuticals financial conference call for the first quarter 2022. At this time, all participants are in listen-only mode.

A brief question and answer session will follow the formal presentation.

At this time, all participants are in listen only mode a.

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.

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.

It is now my pleasure to introduce our first speaker Dolly Vance, who is Rachel's executive Vice President Corporate Affairs and General Counsel.

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 now begin.

Thank you.

Welcome to our first quarter 2020, and hassles yourself.

Thank you, Ms. Vance.

This conference call is there a natural press release for the first quarter was issued a short while ago and can be viewed along with your company sponsored presentation in the news section of our Investor Relations site Www Dot graduate dotcom.

You may now begin.

As a reminder, during today's call we may make forward looking statements regarding our financial outlook and the plans and timing for regulatory and product development.

These statements are subject to risks and uncertainties that may cause actual results to differ.

As forecasted and.

A description of each can be found in our most recent annual report on Form 10-K for the year ended December 31st 2021, and subsequent filings with the SEC.

Including our Q1 quarterly report on Form 10-Q on file with the S E T.

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 President and CEO Raul Rodriguez Roe.

Thank you.

Thank you Kelly and thank you everyone for joining today also.

Welcome to our first quarter 2022 financial results and business update conference call.

Also with me today are Dave Santos, our Chief commercial officer, Dr. Wolfgang tumor our chief medical.

Officer, and Dean <unk>, our Chief Financial Officer.

Moving on to slide five we are also thrilled to introduce you to Caroline.

M D who is joining us on the call today, Dr. Biotech is associate professor of clinical medicine at the chain and the division of Hematology at Usc's Keck School of Medicine.

She has deep expertise in <unk> and warm autoimmune hemolytic anemia or warm AIA chip.

She's also an investigator on the forward trial Rogers phase III clinical trial in warm AIA J D.

During this call Dr. Biotech Hi, Eric will discuss the disease state treatment landscape and patient journey and for me I am sure.

She will also provide clinical insights into how she treats warm IHA patients and their experience treating patients with ITT with top elites.

Lastly, she will discuss our she views the opportunity per tower leasing warn me I am sorry.

I'd like to thank Dr. Patrick for joining us today and look forward to her perspectives.

Beginning on slide six.

The financial press release for the first 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 site on www.rigel.com.

We have made significant progress growing our commercial hematology oncology organization, while executing.

Several near term value drivers and our late and mid stage pipeline.

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, and may cause actual results to differ from those forecasted.

Starting with the first value driver growing IGT shifts during the fourth quarter, we began to see momentum build for top Alicia sales in our G. P with the highest quarterly demand since launch.

We believe this is a direct results of our commercial initiatives as you may recall last year, we undertook a sales force expansion.

A description of these risks can be found in our most recent annual report, on Form 10-K for the year ended December 31, 2021, and subsequent filings with the SEC, including our Q1 quarterly report on Form 10-Q on file with the SEC.

Jordan, our reach improve efficiency and increase in person interactions.

We also secured preferred status on three major national Formularies.

We are pleased to see that these initiatives have translated into a positive growth trend in both bottle demand and new patient starts fotopoulos.

We believe that we have built a foundation that will enable continued growth and also positions us favorably for a potential launch all of these and more may IHA.

Yeah.

In global New ITT news, our collaboration partner Chiesi has submitted their NDA in Japan for Pos demand up in our G. P.

Look forward to news on the approval a Q1 'twenty 'twenty three.

We're also on track for top line data from our pivotal phase III <unk> trial in war May IHA in mid 2022.

If the data is positive we expect to move forward with regulatory filings and commercial launch preparations.

With no currently approved therapy in this indication we believe there's a tremendous opportunity for Todd the leash to improve the outcomes of patients with this disease.

Importantly, an approved indication for warm IHA would be synergistic with our current tower lease commercial efforts, providing another treatment to market with our to our current physician segment.

In just a moment, Dave will provide perspective on the market opportunity for top Alicia wore me IHA.

Followed by Wolfgang who will provide a brief overview of the previous phase II results and the current phase III study.

Doctor Biotic will then share her experience and insight treating patients with poor AIA.

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.

And COVID-19, our pivotal phase III trial continues to progress as you May know Covid hospitalizations have slowed and we now anticipate completing and completing enrollment and reporting topline data by year end for.

Plus Amanda.

Also being evaluated in a phase III trial sponsored by NIH NHL B O S.

The potential of it as a potential treatment for high risk patients with hospitalized with COVID-19. These trials have the potential to show the benefit of past as a potential treatment for patients.

It's severe COVID-19.

Wolfgang will discuss our COVID-19 program later on the call.

Lastly.

Turning to our earlier stage pipeline programs start up activities for a phase one b trial evaluating our 289 or Iraq, one <unk> inhibitor in low risk Mds patients are ongoing or tweak knowing it has the potential to provide a better suppression of the pro inflammatory environment that causes low risk.

B S. We look forward to keeping you updated as this trial progresses.

We're also excited about the advancement of our <unk>, one inhibitor being developed in collaboration with our partner Eli Lilly into Phase III development why Wolfgang will also provide an update on this program.

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

Now I would like to turn the call over to Dave to discuss our commercial progress in I T P and opportunities and more may IHS data.

Raul?

Thank you.

Thank you, Dolly, and thank you, everyone, for joining today.

On slide eight you'll see our FDA approved indication.

Also with me today are Dave Santos, our Chief Commercial Officer, Dr. Wolfgang Dummer, our Chief Medical Officer, and Dean Shornow, our Chief Financial Officer.

As for adult patients with chronic immune thrombocytopenia or Ti T. P, who had an insufficient response to a previous treatment.

Moving on to slide five, we are also thrilled to introduce you to Caroline Piotek, MD, who is joining us on the call today.

Dr. Piotek is Associate Professor of Clinical Medicine at the Jane and Noel Division of Hematology, at USC's Keck School of Medicine. She has deep expertise in ITP and warm autoimmune hemolytic anemia, or WARM-AIHA. She's also an investigator on the FORWARD trial, RIGEL's Phase III clinical trial in WARM-AIHA.

Moving to slide nine.

Q1 was the second quarter in a row that we achieved a new high in bottles shipped to patients and clinics.

Achieving this new high during a quarter when we have declined over the past few years was particularly good to see especially given the typical Q1 of the challenges associated with reimbursement and access limitations due to COVID-19.

We view this as a highly positive side, yes, we are back on a growth trajectory.

<unk> <unk> hundred 36 bottles shipped to patients and clinics, representing 15% growth over Q1 last year and were driven by both new patient starts in any other quarter during COVID-19.

Particularly as we move into the latter part of the quarter.

We achieved net sales of $16 $2 million at 31% increase over the same quarter last year.

Although the increase compared to a year ago was partially driven by the absence of an inventory drawdown. We are pleased with the positive momentum we're seeing sales.

Sales.

On slide 10, you see how our customer interactions continues to grow above where they were in Q4.

Starting the quarter with major access challenges.

Yeah.

Our team accelerated in person customer interactions in Q1 to more than five times the number of in person interactions that we did a year earlier.

As Omar Crown faded and we moved into March we were able to have more in person interaction than ever.

Two years exceeding our previous high in November by more than 25%.

Moving forward, we expect to see a continued increase in person interactions, creating even more opportunities for us to positively impact our customers. We believe that these increased interactions were a major driver.

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Okay.

Thanks.

Okay.

Yes.

Okay.

Yes.

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Yeah.

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Okay.

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Thank you apologies for we were disconnected there momentarily I'll ask Dave to continue and begin on slide 10.

Great. Thank you Pavel.

So on slide 10, you'll see how our customer interaction continues to grow above where they were in Q4, despite starting the quarter with major access challenges on the crop.

Our team accelerated our in person customer interactions in Q1 to more than five times, the number of inquiries and interaction that we get a year earlier.

As <unk> stated and we moved into March we were able to have more in person interactions than ever during the past two years exceeding our previous high in November by more than 25%.

So moving forward, we expect to see it continue to increase it in person interactions, creating more opportunities for us to positively impact our customers.

We believe these increased interactions were a major driver of our growing new patient starts in the latter part of Q1, and we are optimistic that the trend will continue to grow as we move through Q2.

Additionally, our in persons eager program said continues to be an important part of spreading probably's awareness and education and we executed significantly more programs in Q1 of this year than we did in Q1 of last year.

And lastly on slide 11, we have several additional initiatives to expand awareness of our beliefs and access for patients. This quarter in June we will attend our first live Astro meeting in 2019, we.

We will have solid commercial and medical affairs presence there just as we did at Ash in December and we are planning many activity in.

Our act with customers throughout the meeting.

Additionally, in our efforts to expand our patient access globally, our partner Keith a recently submitted an NDA for cost Matt needed in ITT to Japan's P. M B a.

And lastly in the first quarter, we continued to improve access for commercial patients in the U S cotton.

<unk> is now preferred on the national formulary of three Etfs, continuing to improve our broad coverage of commercial lives.

We're extremely proud of these achievements and our ability to provide broader patient access the tallies with easier reimbursement processes for clinicians.

We are quickly spreading the needs of preferred formulary status via our sales force and other non personal tactics and customer feedback continues to be part of it.

Overall, we continue to leverage our expanded commercial team to grow awareness and probably see ITT among our customers as the reopening continue.

We are pleased that we are increasing our in person interaction and look forward to continued growth of new patients as demand is we'd be at <unk>.

Now I'd like to provide a brief overview of the car shall opportunity in warm autoimmune hemolytic anemia.

During this call, Dr. Piotek will discuss the disease state, treatment landscape, and patient journey in WARM-AIHA.

She will also provide clinical insights into how she treats WARM-AIHA patients, and her experience in treating patients with ITP with TAVALYS.

Moving to slide 13, we believed that <unk> is a very attractive market opportunity for colleagues are qualitative and quantitative research found that a 45000 adults with autoimmune hemolytic anemia, 20% of them have cold agglutinin disease, leading 36000.

Lastly, she will discuss how she views the opportunity for TAVALYS in WARM-AIHA.

I'd like to thank Dr. Piotek for joining us today and look forward to her perspectives.

Beginning on slide six, we have made significant progress growing our commercial hematology, Starting with the first value driver, growing ITP sales. During the first quarter, we began to see momentum build for Tavalisa's sales in ITP, with the highest quarterly demand since launch. We believe this is a direct result of our commercial initiatives. As you may recall, last year, we undertook a Salesforce expansion to broaden our reach, improve efficiency, and increase in-person interactions. We also secured preferred status on three major national formularies. We are pleased to see that these initiatives have translated into a positive growth trend in both bottle demand and new patient starts for Tavalisa.

We believe that we have built a foundation that will enable continued growth and also positions us favorably for a potential launch of Tavalisa in warm AIHA.

Patients with warm autoimmune hemolytic anemia.

If the data is positive, we expect to move forward with regulatory filings and commercial launch preparations. With no currently approved therapy in this indication, we believe there's a tremendous opportunity for Tavalisa to improve the outcomes of patients with this disease. Importantly, an approved indication for warm AIHA would be synergistic with our current Tavalisa commercial efforts, providing another treatment to market to our current physician segment.

In our quantitative research last year, we found that approximately 65% of those patients or about 23000 are treated each year and have been about 9000 are treated with first line therapy, which overwhelmingly include steroids.

In just a moment, Dave will provide perspective on the market opportunity for Tavalisa in warm AIHA, followed by Wolfgang, who will provide a brief overview of the previous Phase II results and the current Phase III study.

Dr. Piatek will then share her experience and insight treating patients with warm AIHA.

In COVID-19, our Pivotal Phase III trial continues to progress. As you may know, COVID hospitalizations have slowed, and we now anticipate completing enrollment and reporting top-line data by year-end.

Fostamadam is also being evaluated in a Phase III trial sponsored by NIH and NHLBI as a potential treatment for high-risk patients hospitalized with COVID-19. These trials have the potential to show the benefit of Fostamadam as a potential treatment for patients with severe COVID-19.

That leaves a significant patient population about the 14000 patients each year, who are looking for additional options and that represents an exciting opportunity for trolleys.

On slide 14, the results of our latest quantitative research last year shell have W. A R. J agent in each line of therapy are currently treated and further highlight the complexities surrounding current prescribing landscape.

In conducting this research we have 100 inclination to think about there W. A R. J P. In each line of therapy, and then a silent percentage for the treatments they utilized in those patients.

As previously discussed there is no currently approved targeted therapy for the treatment of W. Ay Ay, Jay and treating patients using existing therapies can be challenging.

This often results in a mix and match approach.

Taken by physicians as illustrated by the bars in each line of therapy, adding up to more than 100%.

Furniture confounding prescribing landscape, our variety of treatment approaches from chronic intermittent use of these therapies.

Also as you look at the Gray dark blue portions of the bar you see that splenectomy and other cytotoxic Immunosuppressant cyclophosphamide.

Cyclophosphamide in Asia accurate make up a significant portion to second line third line and fourth line and later therapies.

Given the burdensome effects of these treatments it is important to consider patient characteristics such as pre existing conditions when analyzing therapy.

Our recent shares they are determining of patients lineup therapy and choice of therapy can be complex. However, we view this data as showing multiple entry points for top of lease NWA IHA, especially because the heterogeneity treatment beyond the first slide.

Particularly we've used <unk> has the potential to significantly change the treatment landscape with its well established side effect profile and significantly reduced treatment burden on patients associated with current therapies.

On Slide 15, you see this lines up very well with half the patients perceive a need for a new approved therapy in warm autoimmune hemolytic age they perceive a very high unmet need in third line and later or they do resort decided toxic immediate suppress symptoms.

We believe adoption of <unk> will be faster in patients who are third line and later because of his perception and it'll be our goal at launch to quickly drive awareness in appropriate patient selection. So we can become the standard of care here to satisfy that high unmet need.

The real opportunity will be to elevate the value of our first approved targeted agent used chronically instead of say quickly and move earlier in treatment being first to market will be a great advantage for us to differentiate <unk> from other agents.

That said changing perceptions for deeply cyclical therapies in this disease to using a chronic one will be a challenge to overcome.

And we're continuing to understand the W. A IHA treatment journey through claims analysis and market research with W. E. T treat treaters that we are currently conducting.

And early finding it back claims analysis show, an approximately 56% of W. A R. J patients received multiple therapies in the first six months following diagnosis.

We've also seen an early market research abuse than physicians appear to be receptive to using chronic therapies as many have acknowledged the need for a long term tolerable treatment option for <unk> patients, who are refractory to or unsatisfied with steroids.

And our claims and Alan since revealed that treatment duration can last multiple years, so Tom Elise could really fulfill the needs of both.

Patients and patients.

I am confident that our continuing efforts to gain further waa Iga treatment insights this year will enable us to leverage the many opportunities ahead and address any challenges of rapid cavalese adoption in treating W. P.

Patients now.

Now I'll turn the call over to Wolfgang to talk about the Wi H T trial results and phase III trial design Wolfgang.

Wolfgang will discuss our COVID-19 program later on the call.

Thank you for that overview Dave.

Lastly, turning to our earlier stage pipeline programs, start-up activities for our Phase I-B trial evaluating R289, our IRAC1 and IV inhibitor, in low-risk MDS patients are ongoing. R289 has the potential to provide a better suppression of the pro-inflammatory environment that causes low-risk MDS.

Like to reiterate our excitement as we are getting close to topline results from our pivotal phase III <unk> trial.

We look forward to keeping you updated as this trial progresses.

We're also excited about the advancement of our RIP-1 inhibitor being developed in collaboration with our partner, Eli Lilly, into Phase II development.

Our lease in the a G I.

I remind you of tower leases targeted mechanism of action a phase II clinical trial results and the design of the former trial on the next few slides.

Slide 17 pretty much explains how and why to have a least should work in the AG.

Very similar to ATP in H E. A human body begins to produce ultra antibodies that bind to components of the red blood cells.

The constant region of those antibodies for the FC region, then binds to serve that carry FC receptors for example, macrophages.

The intracellular signaling downstream from the X series, Sip Sip dependent and leads to phagocytosis and construction of the antibody bearing red blood cells.

Some of the Detroit Red blood cell antigens are presented to TD for positive T helper cells, which in turn again, probably more b cells to make even more antibodies.

<unk> for that.

This b cell activation and differentiation process also immediately basic and inhibited by costs.

Taken together there is compelling scientific rationale.

The post Imatinib Burps in H E N should not lead to broad immunosuppression as immunosuppression is northern issue in the large safety database of almost 5000 patients treated discoveries.

Slide 18.

In this first clinical dataset reevaluated cover these in adult patients with warm AIG in the phase II study.

11 of 24 patients 46%.

If the haemoglobin level greater than 10, and an increase from baseline of greater than plus two grams per deciliter by week 24.

We saw substantial increases in median haemoglobin levels effective as early as week, two and sustained over time.

The safety profile was favorable and consistent with the experience in previous ATP and rheumatoid arthritis trial.

This data was recently published in the American Journal of Hematology.

When we looked at this phase two data to see how many subjects would have met the FDA agreed approvable primary endpoint, we cant greater or equal than 10 in greater equal them plus two from baseline on three consecutive available time points, we feel good about 29% of patients on both of them.

Meet those criteria.

This endpoint is quite a high bar. So we expect very few placebo patients to meet that goal and believe his 90 patients. We are adequately powered to demonstrate statistically significant in phase III.

Moving to slide 19.

As you know our pivotal phase III study has completed enrollment.

<unk> are treated with active or placebo for 24 weeks. After a week 24 patients have the option to roll over into an open label extension study.

The vast majority of patients who reached 24, indeed took the option of continuing in the open label extension.

Some patients have been treated now between the half years.

As I mentioned on the previous slide the primary endpoint is a high bar to meet.

But let me emphasize that this primary endpoint alone does not capture the entire clinical benefits. There are other important benefits for patients such as reduced use of rescue therapy, steroid sparing potential or quality of life improvements.

These benefits are captured through pre specified secondary endpoints in the protocol.

Taking these additional endpoints into account in the totality of the data that we believe Teva lease can provide clinically meaningful benefit to a substantial percentage of patients.

We're looking forward to reporting data from this trial around mid year.

With that I now hand, the call over to my colleague and our clinical experts Dr. Caroline.

Nick.

To discuss her experience and insights treating V H eight patients.

Wolfgang will also provide an update on this program.

To kick things off I'm interested to hear your thoughts on these endpoints in our clinical how clinicians might use them to determine we took their patients may benefit from this therapy.

Okay.

Now, I'd like to turn the call over to Dave to discuss our commercial progress in ITP, and opportunities in warm AIHF.

Yeah.

Thank you.

I've mentioned that while achieving.

So designates with the pilot.

And playing to the regulatory bar for success, it's really the totality of the data that will provide physicians with a full picture of which patients will drive meaningful benefits from the ERP I would like to point out the significance of the secondary endpoints and improvement in hemoglobin defined and the secondary end point and no need for rescue therapy as a clinical meeting.

Paul improves hemoglobin values.

Feel better.

Monitoring less use of rescue medications are transfusion and less frequent hospitalization.

Next slide.

Okay. So let's talk some more about job here.

Dave?

There are approximately 36000 adults with W. A 8-K in the U S with approximately 9000, receiving first line treatment thereabout.

14300 patients requiring second or later lines of treatment similar to ATP patients are cycling on and off of treatment.

And we will discuss more about this in a few moments.

W. AIA.

Thank you, Raul.

On slide 8, you will see our FDA-approved indication, which is for adult patients with, chronic pneumothorombocytopenia, or CITP, who've had an insufficient response to a previous treatment.

Immune disorder characterized by low hemoglobin level and laboratory evidence of hemolysis.

Moving to slide 9, Q1 was the second quarter in a row that we achieved a new high in models, shipped to patients at clinics.

The severity of symptoms is related to the degree of anemia and includes fatigue severe weakness get snia challenges magli palpitations and other cardiovascular complications.

There is an increased risk of thromboembolic events with an incidence of T E highest early after diagnosis and more common in patients with severe <unk>.

The mortality rate.

Great is reported at 8% to 11%, which is related to capex together events, including pulmonary embolism myocardial infarction stroke as well as the infection are successful they did had W. Treatments.

Thomas description you can see that these are sick patients.

For a T P. We often manage relapses in the outpatient putting however, W. A H a patients often require hospitalization diagnosis as far as relapsed and it can take days potentially several weeks to get some of these patients.

Achieving this new high during a quarter when we have declined over the past two years was, particularly good to see, especially given the typical Q1 challenges associated with reimbursement and access for the patients due to COVID.

We view this as a highly positive sign that we are back on a growth trajectory. Our 1,836 bottles shipped to patients at clinics represented 15% growth over Q1 last year and, were driven by more new patient starts than any other quarter during COVID, particularly as we move into the latter part of the quarter.

We achieved net sales of $16.2 million, a 31% increase over the same quarter last year. Although the increase compared to a year ago was partially driven by the absence of an, inventory drawdown, we are pleased with the positive momentum we're seeing in ITP sales.

To achieve a stable improvement in hemoglobin with rescue medications and transfusions.

That's fine.

On slide 10, you see how our customer interactions continued to grow above where they were in, Q4, despite starting the quarter with major access challenges due to Omicron.

Our team accelerated our in-person customer interactions in Q1 to more than five times, the number of in-person interactions that we did a year earlier. As Omicron faded and we moved into March, we were able to have more in-person interactions, than ever during the past two years, exceeding our previous high in November by more than 25%. Moving forward, we expect to see a continued increase in in-person interactions, creating, even more opportunities for us to positively impact our customers.

We believe that these increased interactions were a major driver.

Ladies and gentlemen, please stand by.

W. AAJ is a chronic heterogeneous.

We are experiencing technical difficulties.

Several immunologic mechanisms involved in its pathogen, making it challenging to treat is.

It is thought to be mediated by accelerated clearance of circulating agg codec red blood cells by immune globulin FC receptor binding macrophages in the spleen and liver, which is the pathway targeted by <unk>.

The type and extent of immune dysregulation may be different in each patient and may change over time, often resulting in an unpredictable clinical course. There are currently no approved treatments for <unk>. There are new therapies under active development, which will offer increase therapeutic opportunities to treat this disease.

We will resume momentarily.

Thank you for staying online.

That's fine.

As we talk about the current treatment landscape for W. A H N I will again mention that there are no approved treatments for this therapy.

Available therapies are limited by waning efficacy overtime as volatile or side effect profiles, which add to the patient symptom burden.

As Dave pointed out earlier in his presentation. The lines of therapy are clearly defined and various therapies can be used in combination.

Steroids are the standard first line therapy for newly diagnosed patients they work by reducing antibody production, which results in decrease red blood cell destruction.

While the initial response rates are high most patients relapsed upon discontinuation.

Currently there are a number of short and long term adverse events, which limit their tolerability.

Steroids are also often used as rescue therapy at times, a relapse to raise the hemoglobin and to allow time to French turned up therapy.

But <unk> has long been used as an off label treatment for W.

It's a monoclonal anti CD 20 antibody that works by depleting b cells among.

Among its side effect profile it notably is associated with an increased risk of infection. Additionally, and in Paris vaccine response for at least six months, which has become which have come into particular focus during the Covid era.

While the initial response rates are high and it.

It often takes time to see the response to Rituxan unhappy with responses noted out too.

Far out of 16 weeks Rituxan Mab is typically used in the second line setting, but it can also be used in combination with steroids.

In the frontline setting as well.

And it changes.

Now, let's talk about some alchemy.

We will resume momentarily.

This explains the major side of Red blood cell destruction, removing the spleen can be an effective treatment for W. AIA, China. However, the complete response rate is around 40 question.

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There are also risks of surgical complications patients may have prolonged recovery. There's also a long term increased risk of thromboembolic events as well as serious infection with this in mind splenectomy may not be tolerated and those who are older with significant comorbidities or those who are otherwise he condition.

So and that can be remains an option following rituximab therapy in practice splenectomy is often deferred because of it just because of the short and long term.

<unk>.

Other immunosuppressive and cytotoxic medications can be used with limited data regarding their efficacy and notably immunosuppressive therapies carrying at risk of infection again patients are cycling on and off of treatment and in between treatments. During the course of their disease lines of therapy or not.

Clearly defined and therapies may be used in combination.

Next slide.

The severity of anemia initial presentation of W. W. AIA, China strong protection.

The patient then can vary and depend on the rate of onset generally of hemolysis as well as underlying disorders quality of life me being negatively impacted by the symptoms of the disease as well as the side effects associated with current therapies about 50% of cases relapse. After first line therapy.

Well my usual approaches to use steroids often in combination with rituximab in the frontline setting trusted where cases in the past some of that heavier cases treated at our center.

Have also.

Had the addition of cyclophosphamide into the ration as you'll see in a moment.

The approach following Rihanna pink fields repeating prior therapy, depending on the duration of prior response or yourself alternative immuno suppressant qualities.

Next slide.

With that setup I'm going she got a few cases with you from my clinical practice. The first case illustrates the cycling through various treatments that we've touched on a few times now and highlights the long clinical journey experience by some patients with it.

We will resume momentarily.

So this is a 45 year old woman with a history of Grace's fees previously treated with radioactive iodine ablation in 2013.

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2013. She was also diagnosed with Alessandro which is the combination of ATP and W. A H N at the time of presentation. She had both ETP and WHI. She was treated with steroids and because of disease severity with escalated to combination therapy with Rituximab HOKA bottom line.

Excellent.

This was effective for her W. A IHA her ATP was still not controlled and that's was treated with prednisone a platform and eventually stumped me. She did well for several years until 2017, when she presented with relapsed W. A H J.

That time, she was retreated with combination therapy.

Of Rituximab.

Cyclophosphamide and dexamethasone given that the duration of a prior response, which was followed by a prednisone.

She did well for several years again and cashew relapses past year. She was given a pulse of dexamethasone to control small pets and so as we look at this case U I would point out that there's a couple of times. During this patient's journey, where soft imatinib could've been a reasonable option Boston that and it certainly could have been an option for the management of our I T.

T. In 2014. Additionally, it would've been an option for a W. A H Shang admirably last for 2017 and her most recent relapse.

The second case is part of that 33 year old woman with primary W. E K diagnosed in 2019.

Your conference will resume momentarily.

And initial presentation, she was treated with steroids and rituxan.

Please stand by.

However, following the steroid taper she continued to have ongoing hemolysis.

And if a firepower with initially.

It's led to some stabilization of the hemoglobin.

But still with some ongoing smaller Seth on.

Eventually her hemoglobin met the threshold for treatment change.

Thank you for joining us today.

We review this case, there's also several time points for this patient excuse me, we're fast imatinib could have been used for this patient it with an option instead of azathioprine as well off after either.

Pete.

So both cases demonstrate that the currently available therapies.

<unk> in treating patients with this disease, even when used in combination.

Emphasizing the need for additional therapies such as Boston.

Please stand by.

Mccoy.

Macquarie.

Now, let's turn to talk about Fox you might know that the potential treatments for W. AIA.

In contrast to malignant hematology, where response rates are the primary driver of treatment selection W. A H a is considered a chronic benign disease that requires treatment over years.

So it's a greater importance sure to have a therapy that will manage the disease consistently with a favorable long term safety profile.

The fast Imatinib is approved for this indication it will follow it would offer the following potential advantages <unk> has a unique mechanism of action targeting the underlying pathophysiology of the disease is an oral therapy, which is not immunosuppressive, which which has come into particular focus.

During the Covid era.

Safety profile is well characterized it has a rapid response, which is durable from the clinical perspective, a rapid and durable response results in less use of rescue medications and decrease the need for hospitalization.

Additionally, since it is a true for ATP physicians already have experience using the therapy and having another indication will likely reinforced the cheese and ITT.

I will finish by saying that from my years in clinical practice treating W. A IHA and other serious blood disorders, I know firsthand that the available treatments for W. A H are insufficient and there's a clear unmet need for new therapies in this disease.

Thank you.

Our teleconference will resume momentarily. Please remain on the line.

Thank you.

Thank you Doug hepatic shifting gears now to a quick update on <unk>.

Thank you for joining us today.

Jim.

Moving to slide 28.

We continue to believe the post imatinib can provide therapeutic benefit in COVID-19.

Please stand by.

Our teleconference will resume momentarily.

There are several scientific pieces of external research and independent institutions. Most importantly last year, we reported positive clinical data from the NIH and H N V. I a phase II study in hospitalized patients with severe COVID-19.

That data was published last fall.

Additional data will be presented by our collaborators at this year's <unk> conference in May.

Given persistent resistance to vaccination in some places and the possibility of new virus variants, we believe our need for effective treatment options for severely <unk> patients remained well.

We have two ongoing phase III studies that will provide us with the pivotal data and if approved in this indication tablets would be available for immediate use for these patients.

Slide 29.

Thank you again for joining us and our conference will resume momentarily.

Before I discuss our pivotal phase III study I would like to provide an update on two other trials from collaborators.

We are currently experiencing technical difficulties.

Thank you.

<unk> phase II study, if the Imperial College of London, and the exited four caused tissue phase III study from an H.

Regarding met is an independent data review board recommended not to continue post imatinib into the second phase of the trial.

Lets recommendation was not due to any safety concern.

The focus of this study was the prevention of progression of mild to severe disease.

Regarding the NIH exit cost study and interim analysis was run on two of the three experimental drug arms of the study and enrollment was discontinued for board.

So first Imatinib is now the only remaining active arm of the study and continues to enroll patients.

Right. So its own amended phase III trial is also continuing.

As mentioned earlier this year, we updated the inclusion criteria for the trial to focus on more severe patients and change the primary endpoint two days on oxygen for a more sensitive measure and better comparison to the NIH exits trials.

One study is now focused on post imatinib as a treatment for COVID-19, rather than a preventative agents.

As Robert mentioned earlier due to the recent decline in COVID-19, hospitalizations enrollment has been slower than anticipated.

To date, we have 268 patients.

Nearly 90% of our targeted enrollment.

We are reviewing strategies to complete enrollment and report top line results by year end, including potentially completing the trial with fewer patients than the initially targeted targeted 308.

Now, let's turn to our pipeline programs <unk>, one or in groups.

Thank you for standing by.

One inhibitor starting on slide 31.

We have shared with you before we are evaluating <unk> hundred eight nine or Iraq, one aric for dual inhibitor initially in low risk Mds.

We believe our 289 has the potential to provide effective suppression of the pro inflammatory environment that causes low risk Mds.

Slide 32 shows a phase one b trial for patients with low risk Mds study has two parts part one is a dose escalation phase with a commonly used three by three approach.

Toward those levels are being supported by our favorable safety data from already completed studies in healthy volunteers after.

After dose escalation and thorough evaluation of all safety clinical activity PK in biomarker data, we will take those into an extension phase to obtain more longer term safety and preliminary efficacy data to support a larger a registrational study.

Study start up activities are currently ongoing and we are targeting the second quarter of the year to achieve study initiation.

Moving to slide 33, or <unk>, one inhibitor program developed together with our partner Eli Lilly is another important value driver for Rigel.

We see a mechanistic and clinical and scientific rationale for <unk> <unk> two in favor of large indications and we continue to prepare for a phase II clinical trial in an immunologic disease indications.

As we noted in our press release the initial phase II study is now anticipated to start in Q1 2023.

As is common in drug development, we encountered opportunities for formulation optimization that we plan to leverage and take forward into the program.

The results being a delay in the timing for the first indications, which mainly we'll disclose closer to the initiation of the study.

Additionally, we are advancing our work to select a rip one inhibitor candidate that can cross the blood brain barrier for the treatment of central nervous system diseases.

We will then.

Lead the clinical development of these brain penetrating rip one inhibitors.

We're pleased to collaborate with Lilly on those very exciting opportunities moving their deep expertise in the CNS therapeutic areas.

That concludes my development summary, and I will now turn the call over to Dean Dean.

Our conference will resume.

Thank you Wolfgang I'm on slide 36 for the first quarter of 2022, we shipped 1824 bottles to our specialty distributors, resulting in $22 $6 million of gross product sales 1836 of those bottles were shipped to patients and clinics while 900.

Thank you.

Apologies for we were disconnected there momentarily.

25 bottles remained in our distribution channels at the end of the quarter, we reported net product sales from <unk> of $16 2 million.

I'll ask Dave to continue and begin on slide 10, please.

A 31% increase compared to the same period in 2021.

Great.

Net product sales from probably useful recorded net of estimated discounts charge backs rebates returns co pay assistance and other allowances of $6 $4 million a gross to net adjustment was approximately 28, 4% of gross product sales for the first quarter of 2022.

Thank you, Raul.

Before we move off net product sales, let me review our expectations for the second quarter of 2022, we are pleased with the strength of our bottles shipped to patients of credits at the end of the first quarter that Dave described and expect growth to continue as access to physicians in new patient starts continues to expand.

So on slide 10, you'll see how our customer interactions continue to grow above where they were in Q4, despite starting the quarter with major access challenges due to Omicron.

Our team accelerated our in-person customer interactions in Q1 to more than five times the number of in-person interactions that we did a year earlier. As Omicron faded and we moved into March, we were able to have more in-person interactions than ever during the past two years, exceeding our previous high in November by more than 25%. So moving forward, we expect to see a continued increase in in-person interactions, creating more opportunities for us to positively impact our customers. We believe these increased interactions were a major driver of our growing new patient starts in the latter part of Q1, and we are optimistic that the trend will continue to grow as we move through Q2.

Additionally, our in-person speaker programs have continued to be an important part of spreading Tavalease awareness and education, and we executed significantly more programs in Q1 of this year than we did in Q1 of last year.

And lastly, on slide 11, we have several additional initiatives to expand awareness of Tavalease and access for patients this quarter.

In June, we'll attend our first live ASCA meeting since 2019.

We will have solid commercial and medical affairs presence there, just as we did at ASH in December, and we are planning many activities to interact with customers throughout the meeting.

Incrementally we currently expect our gross to net adjustment to be approximately 30% in the second quarter of 2022.

Well, we don't typically comment on potential collaboration milestone payments due to payment variability and uncertainty we wanted to provide a brief financial update as it relates to key saves NDA filing in Japan that Raul highlighted with this filing we expect to receive a 5 million dollar milestone in the current quarter. If approved we would expect.

Additionally, in our efforts to expand our patient access globally, our partner Kise recently submitted an MBA for phosphomatin in ITP to Japan's PMBA.

Steve an incremental 20 million dollar milestone in the first quarter of 2020, we will continue to provide updates on key says progress Chris importance hiring.

And in the next slide in addition to net product sales <unk> contract revenues from collaborations were $500000 stood at three months ended March 31, 2022, which consisted of $200000 from our license agreement with Lilly and $300000 Smart collaboration agreement bristles.

And lastly, in the first quarter, we continue to improve access for commercial patients in the U.S. Tavalease is now preferred on the national formularies of three key PBMs.

On the cost and expenses our cost of product sales was approximately $121000 for the first quarter of 2022.

Total cost and expenses were $43 million in the first quarter of 2022 versus $39 $3 million in the first quarter of 2021.

The increase in cost and expenses was primarily due to increased commercial activities related to the sales force expansion in late 2021 increased research and development costs for the development of Rogers Iraq, One four inhibitor program and increased personnel related costs and stock based compensation expense.

We offset by decreased research and development costs related to our phase III clinical trial cost imatinib for warm autoimmune hemolytic anemia, and our ongoing phase III clinical trial of <unk> in hospitalized patients with COVID-19.

Finally, we ended the quarter with cash cash equivalents and short term investments of $107 $5 million with that I'd like to turn the call back over to Ralph.

We are extremely proud of these achievements and our ability to provide broader patient, access to Catalyst with easier reimbursement processes for clinicians.

Thank you Dean.

<unk> performance in the first quarter has given us a strong start to the year.

We are quickly spreading the news of preferred formulary status via our Salesforce and other, non-personal packets, and customer feedback continues to be positive.

We'll continue to execute on our strategic priorities as you see here.

Overall, we continue to leverage our expanded commercial team to grow awareness of Pavlis, and CITP among our customers as the reopening continues.

We are pleased that we are increasing our in-person interaction and look forward to, continued growth of new patients in demand as we move through Q2.

Looking forward, we expect our momentum that we were seeing in the commercial print to continue into the coming quarters, facilitating ITB sales growth.

Most importantly is our upcoming phase III trial readout at warm IHA.

Now, I'd like to provide a brief overview of the commercial opportunity in warm autoimmune, hemolytic anemia.

We're excited about this readout because it is a key step in building our hemo portfolio.

War May IHA is complementary to our current commercial focus and so it will be highly synergistic and accretive it.

It'll be great to be able to deliver a new and helpful Medicine for the first time to patients suffering from more AIA.

Moving to slide 13, we believe that WAIK is a very attractive market opportunity for Catalyst.

And to do so as early as 2023.

Now, let's open the call to your questions and given that that Dr. Piatt periodic as witness, let's prioritize prioritize more may IHA related questions.

Our qualitative and quantitative research found that of 45,000 adults with autoimmune, hemolytic anemia, 20% of them have cold and gluten disease, leaving 36,000 patients with warm autoimmune hemolytic anemia. In our quantitative research last year, we found that approximately 65% of those patients, or about 23,000, are treated each year, and of those, about 9,000 are treated with first-line therapy, which overwhelmingly includes steroids.

Operator.

Thank you.

I'd like to ask a question. Please press star one from your telephone keypad and a confirmation tone indicate your line is in the question queue.

That leaves a significant patient population of up to 14,000 patients each year who are, looking for additional options, and that represents an exciting opportunity for Catalyst.

On slide 14, the results of our latest quantitative research from last year show how WAIK patients, in each line of therapy are currently treated and further highlight the complexities around the current prescribing landscape. In conducting this research, we asked 150 clinicians to think about their WAIK patients, in each line of therapy and then assign a percentage for the treatments they utilize in those patients.

As previously discussed, there is no currently approved targeted therapy for the treatment, of WAIK, and treating patients using the existing therapies can be challenging.

Start to if you like to remove your question from the queue.

For participants using speaker equipment may be necessary to pick up your handset before pressing the star keys.

This often results in a mix-and-match approach taken by physicians, as illustrated by the, bars in each line of therapy adding up to more than 100%.

Further confounding prescribing landscape are a variety of treatment approaches from, chronic to intermittent use of these therapies.

One moment, please we poll for questions.

Also, as you look at the gray and dark blue portions of the bar, you see that splenectomy, and other cytotoxics and immunosuppressants, like cyclophosphamide and azathioprine, make up significant portions of second-line, third-line, and fourth-line and later therapies.

Thank you.

Our first question is from the line of Union Yang with Jefferies. Please proceed with your question.

Given the burdensome effect of these treatments, it is important to consider patient characteristics, such as pre-existing conditions when analyzing lines of therapy.

Our research shows that determining a patient's line of therapy and choice of therapy can, be complex. However, we view this data as showing multiple entry points for TAVILIS in WAIHA, especially, because the heterogeneity of treatment beyond the...

Particularly, we view Tavalese as the potential to significantly change the treatment landscape, with its well-established side effect profile and significantly reduce the treatment burden on patients associated with the current therapies.

Thank you I have one question to Dr. A poetic.

On slide 15, you see this lines up very well with how physicians perceive a need for a, new approved therapy in warm autoimmune hemolytic anemia.

They perceive a very high unmet need in third line and later, or they do resort to cytotoxics, and immunosuppressants and splenectomy.

So in phases, three and four the trial.

If I remember it correctly.

Patients have actively hemolysis.

So they are on.

Some background therapy so.

D and truck and she criteria what do you expect the placebo response to be according to phase three primary endpoint.

Thank you Victor Panic.

Yeah.

I like Wolfgang and put on this as well, but I would anticipate there would be a low response rate for a whole bal.

Coral let's hear.

All that and the whole <unk> non responders could not achieve hemoglobin response are callable now.

Sure we would anticipate.

Alot response rate.

Great.

Yes, I would agree with that.

We do not we do not see patients generally just bounce.

Inbound two units.

It's a pretty large jump up from from any baseline and to stay up there for three consecutive visits would be very surprising.

Patient is on an effective therapy.

Okay.

Okay, and I have a question to the company so in phase two.

I think of about 38% of our patients who are in second line and the remainder of the patients who are third or fourth line level line of therapies and although the overall response rate was over 40 around 45% I think that there is a higher <unk>.

We believe adoption of Tavalese will be faster in patients who are third line and later because, of this perception, and it will be our goal at launch to quickly drive awareness and appropriate patient selection so we can become the standard of care here to satisfy that high unmet need.

The real opportunity will be to elevate the value of a first approved targeted agent used, chronically instead of cyclically and move earlier in treatment.

Being first to market will be a great advantage for us to differentiate Tavalese from other, agents.

That said, changing perceptions from using cyclical therapies in this disease to using, a chronic one will be a challenge to overcome.

And we're continuing to understand the WAIEK treatment journey through claims analysis, and market research with WAIEK treaters that we are currently conducting. An early finding of that claims analysis showed that approximately 56% of WAIEK patients received, multiple therapies in the first six months following diagnosis.

We have also seen in early market research interviews that physicians appear to be receptive, to using chronic therapies as many have acknowledged the need for a long-term tolerable treatment option for WAIEK patients who are refractory to or unsatisfied with steroids. And our claims analysis revealed that treatment duration can last multiple years, so Tavalese, could really fulfill the needs of both physicians and patients.

I am confident that our continuing efforts to gain further WAIEK treatment insights this, year will enable us to leverage the many opportunities ahead and address any challenges to rapid, Tavalese adoption in treating WAIEK patients.

Now I'll turn the call over to Wolfgang to talk about the WAIEK Phase 2 trial results, and Phase 3 trial design.

Response in second line patients. So my question to the company is that in terms of baseline patient characteristics for by the line of therapy in phase three is that kind of a similar to our.

Wolfgang?

Thank you for that overview, Dave.

Page 10.

I'd like to reiterate our excitement as we are getting close to top-line results from, our Pivotal Phase 3 forward trial with Tavalese in AIHA. I remind you of Tavalese's targeted mechanism of action, our Phase 2 clinical trial results, and the design of the forward trial on the next few slides.

Slide 17 pretty much explains how and why Tavalese should work in AIHA. Very similar to ITP, in AIHA the human body begins to produce autoantibodies that bind, to components of the red blood cells. The constant region of those antibodies for the FC region then binds to cells that carry, FC receptors, for example macrophages. The intracellular signaling downstream from the Fc receptor is sick-dependent and leads, to phagocytosis and destruction of the antibody-bearing red blood cells.

I'll ask Wolfgang to comment.

Yes, so in general I would say, we've had probably somewhat more patients in earlier lines because as you. All aware we are conducting this trial in the United States, but also in a number of countries in Europe , including Eastern Europe , where compounds, such as Rituxan break sample or a little bit less used oil avail.

Some of the destroyed red blood cell antigens are presented to CD4-positive T helper cells, which in turn again prime more B cells to make even more antibodies, thus perpetuating the disease further.

This B-cell activation and differentiation process is also mediated by Zik and inhibited, by prostamatinib.

Taken together, there is compelling scientific rationale to expect that prostamatinib works, in AIHA and should not lead to broad immunosuppression, as immunosuppression is not an issue in the large safety database of almost 5,000 patients treated with Pavlis.

In 2018, in this first clinical data set, we evaluated Pavlis in adult patients with, warm AIHA in a phase 2 study. Eleven of 24 patients, 46%, achieved a hemoglobin level greater than 10 and an increase from, baseline of greater than plus 2 grams per deciliter by week 24. We saw substantial increases in median hemoglobin levels detected as early as week 2 and sustained, over time.

The safety profile was favorable and consistent with the experience in previous ITP and rheumatoid, arthritis trials. This data was recently published in the American Journal of Hematology.

When we looked at this phase 2 data to see how many subjects would have met the FDA-agreed, approvable primary endpoints, which is greater or equal than 10 and greater or equal than plus 2 from baseline on three consecutive available time points, we see that about 29% of patients on post-traumatic did meet those criteria.

So in general.

This endpoint is quite a high bar, so we expect very few placebo patients to meet that goal, and believe with 90 patients, we are adequately powered to demonstrate statistically significant in phase 3.

Yeah.

Most like a similar patient population, but maybe somewhat earlier line and.

We do expect certainly comparable or even slightly better.

Data from phase III than what we had seen in phase II.

Thank you.

Moving to slide 19, as you know, our pivotal phase 3 study has completed enrollment. Patients are treated with active or placebo for 24 weeks. After week 24, patients have the option to roll over into an open-label extension study. The vast majority of patients who reached week 24 indeed took the option of continuing, in the open-label extension. Some patients have been treated now for two and a half years.

Our next question is from the line of Yigal <unk> with Citi. Please proceed with your questions.

As I mentioned on the previous slide, the primary endpoint is a high bar to meet, but, let me emphasize that this primary endpoint alone does not capture the entire clinical benefits. There are other important benefits for patients, such as reduced use of rescue therapy, steroids, bearing potential, or quality of life improvements. These benefits are captured through pre-specified secondary endpoints in the protocol. Taking these additional endpoints into account in the totality of the data set, we believe, TAVALIS can provide clinically meaningful benefits to a substantial percentage of patients.

Hi, This is carly on for Yigal, Thanks for taking our questions. We have one for doctor periodic.

We're looking forward to reporting data from this trial around mid-year.

With that, I now hand the call over to my colleague and clinical expert, Dr. Caroline, To kick things off, I'm interested to hear your thoughts on these endpoints and how clinicians might use them to determine which of their patients may benefit from this therapy.

Wondering how that a 46% response rate and the 29% durable responder rate.

And in the phase two study compared to experience with Rituximab and other therapies currently used.

Alright.

If the phase III data are largely replicated in the phase III could you go into a bit more detail on how you would think about using tableau is in your practice in terms of line of therapy. Thank you.

Thank you Carla.

Dr. Payadek?

Thanks, Patrick.

Thank you.

Yeah.

So I mean I think it was.

If <unk> is approved it would be the only approved medication for this indication in the third line setting there's a clear role.

And the second line setting it would also be a reasonable choice and I would like to see.

With in the baseline demographics for the phase three we see a lot of patients who had not received prior rituximab.

So it would be beneficial to ask at the data there to see how these patients benefit but our anticipation is similar to the ITT data is at the earlier on.

Tackle these are the higher that efficacy would be.

Suggesting.

Our role in the second line setting.

And.

So Ed Wolfgang with Kevin Yeah, I would just add to that in the sort of elaborated a little bit on this.

I would mention that while achieving a statistical significance with a primary endpoint is a, regulatory bar for success, it's really the totality of the data that will provide physicians with the full picture of which patients will derive meaningful benefit from the therapy. I would like to point out the significance of the secondary endpoint. An improvement in hemoglobin defined in the secondary endpoint and no need for rescue, therapies are clinically meaningful. Improved hemoglobin values in this disease mean our patients feel better, need less frequent, monitoring, less use of rescue medications or transfusions, and less frequent hospitalization.

Primary endpoint that you.

No.

Quiet by regulatory agencies as a very high bar.

Next slide.

Okay.

But we have a number of secondary endpoints that also kept a clinical benefit. So so we really think there is a substantial percentage of patients that can have a clinical benefit and it's gonna be a totality of the data in both the practically confirmed.

So, let's talk some more about WAIHA.

There are approximately 36,000 adults with WAIHA in the U.S., with approximately 9,000, receiving first-line treatment.

The totality of the data that will make.

Make a treatment decision and also in collaborations with a patient when a patient might want to have an oral drug all the open infusion.

Vice versa. So I think we are well positioned to play an important role there the last comment that I want to make it.

When you referred to other compounds such as Rituxan, if you want to make comparisons be free to do so but do we need to be very very stringent in in really understanding what the endpoints and how it's not apples to apples. When you talk about overall response rates visits our primary endpoint.

Comparable so so I believe we can certainly.

<unk> come out in a similar ballpark.

Okay got it that's really helpful. And then just one sort of housekeeping question for the company.

Are you able to refine the timing guidance at all for the forward data from mid year to maybe around which month. This summer we could expect to see the data.

Thanks, so much again.

I can I can clarify that I think.

We could tell you that it's going to be in June to be more specific not more specific than that though.

Okay.

Coming months.

Our next question comes from the line of Gary Nachman with BMO capital markets. Please proceed with your questions.

Hi.

Your Doctor Paddock first.

When you see heavily fitting into the treatment paradigm for warm AIA, Jay will that'd be a lot of combination use with this product and do you envision any challenges in terms of access with that and what would it take for the product could potentially be a first line drug is that even a possibility.

<unk> overtime.

Alright. Thank you I'll ask Dr. Bhatt, if you'd comment, but also Dave come because we've done some market research in that area.

Go ahead sorry.

Yeah. So we don't have any data to.

10 form on combination use.

You know the clinical trials do have washout period, then and 10.

Time for stability on steroids. So the potential is that it would be overlaps more closely with steroids with the effort for it to be a steroid sparing agent.

We do not have any data in the first line setting there is a role for steroids.

W. A HHS as ATP, so I, it's hard to go beyond that.

Thank you.

Gerry one thing I would like to mention here is that you know it depends on where patients are.

Ah relapsing.

They are an acute setting in the hospital, sometimes it's very difficult as we learned from recent market research for clinicians to prescribe rituxan and administered in the inpatient setting and so they have to wait for the patient to be discharged and use it in the outpatient setting it's not everywhere, but certainly in the community that that is happening in <unk>.

Do you think about a drug like box, Matt Knabe, which could be used starting in the inpatient setting patient takes it and move it.

Into the outpatient setting and then because of its potentially rapid rates response. The ability then to taper steroids that appears to be very interesting to clinicians as we talk to them and you saw in the slide that they provided earlier theres substantial mixing and matching including in first line therapies.

I would say, it's a little bit different than 19 P in that regard.

There are about 14,300 patients requiring second or later lines of treatment.

Yes, Okay. That's helpful. And then I guess for both Doctor play out I got in the company for the 14.3 thousand addressable patients in second line plus how many of these are easy to tap into.

Will there be challenges getting to any of these patients to get treated in the later lines, where they readily available for the most part.

Similar to ITP, patients are cycling on and off of treatment, and we'll discuss more about, this in a few moments.

WAIHA is an autoimmune disorder characterized by low hemoglobin levels and laboratory evidence, of hemolysis. The severity of symptoms is related to the degree of anemia and includes fatigue, severe, weakness, dyspnea, jaundice, spondylomegaly, palpitations, and other cardiovascular complications. There's an increased risk of thromboembolic events with an incidence of TEE, highest early, after diagnosis, and more common in patients with severe hemolysis.

The mortality rate is reported at 8 to 11 percent, which is related to vascular events, including pulmonary embolism, myocardial infarction, stroke, as well as infection or sepsis related to WAIHA treatments.

I'm curious how much of an effort is required to increase the awareness for W. A IHA or is it well now and then the clinicians are treating most of these patients already.

Based on this description, you can see that these are sick patients.

Hey, Gary I'll, let state carbon first men.

Dr. Badylak, if you would.

Two as well.

So what I would say Gary.

For ITP, we often manage relapses in the outpatient setting.

It is.

It is 14000 patients out there who are actively undergoing treatment every year, but it will require.

However, WAIHA patients often require hospitalization and diagnosis as well as relapse, and it can, take days to potentially several weeks to get some of these patients to achieve a stable improvement in hemoglobin with rescue medications and transfusions.

<unk> to reach a broad number of physicians, because particularly in the community.

Pretty evident that clinicians see a handful of these patients over time and they manage them in and we'll be on treatment and some well. So I think they are aware of patients that are out there they know that.

They do relapse.

They're going to need to treat them, but we will have to reach a large number of prescribers in order to get that awareness out there.

Next slide.

Keep in mind on that point before he has talked biotic to combat ulcers is that its not unlike RTP, where it's a rare disease.

WAIHA is a chronic heterogeneous disease with several immunologic mechanisms involved in, its pathogenesis, making it challenging to treat.

It's thought to be mediated by accelerated clearance of circulating IgG-coded red blood, cells by immune globulin FC receptor-bearing macrophages in the spleen and liver, which is the pathway that's targeted by Fostamatinib.

The type and extent of immune dysregulation may be different in each patient and may change, over time, often resulting in an unpredictable clinical course.

There are currently no approved treatments for WAIHA. There are new therapies under active development, which will offer increased therapeutic opportunities, to treat this disease.

Hematology benign hematology and these docs to see a small number of these patients when you add these two indications together it becomes a much more substantial patient population within that Doctor Dr.

Doctor visit.

As we talk about the current treatment landscape for WAIJ, I will again mention that there, are no approved treatments for this disease. The available therapies are limited by waning efficacy over time, as well as their side-effect, profiles, which add to the patient's symptom burden.

As I said substantial almost complete overlap in the doctors treat both of these indications. So it's something that we are knowledgeable and experienced it handle it.

As Dave pointed out earlier in his presentation, the lines of therapy are not clearly defined, and various therapies can be used in combination.

But the biotic any anything to add beyond that.

Steroids are the standard first-line therapy for newly diagnosed patients.

They work by reducing antibody production, which results in decreased red blood cell, destruction.

Okay.

I think that was fairly covered everything I would have thought I would just add that the multiply refractory patients often get referred to an academic center.

And in that setting.

<unk>, probably have a higher awareness.

Okay. That's great. Thank you.

The next question is coming from the line of do Kim with Piper Sandler. Please proceed with your questions.

Hi, everyone. This is Kate on for dough. Thanks for taking the question and congrats on the continued progress.

Doctor Biotic, so quick one on <unk>.

I missed it but if you can speak on.

Year is your belief of the receptivity.

Your colleagues yourself of a total lease.

N warm as I say, given the current dynamics of how you're treating patients and.

The relapse rate.

There is a.

Entrenchment of sorts with their current therapies and your colleagues are looking for something novel or you know just your brief thoughts on it would be helpful for us.

Yeah.

Sure.

No.

Okay.

So I would say that.

While the initial response rates are high, most patients relapse upon discontinuation. Additionally, there are a number of short- and long-term adverse events, which limit, their tolerability in use.

Steroids are also often used as rescue therapy at times of relapse to raise the hemoglobin, and to allow time to bridge to another therapy.

There is definitely a clinical need for targeted therapies. In this disease you can see from some of the cases, we discussed that the especially nice multiply refractory patients with really just don't know how to treat these patients and it leads to that cycling through therapies with unclear ethics fee.

Rituximab has long been used as an off-label treatment for WAIJ. It's a monoclonal anti-CD20 antibody that works by depleting B cells. Among its side-effect profile, it notably is associated with an increased risk of infection. Additionally, it impairs vaccine response for at least six months, which have come into, particular focus during the COVID era.

While the initial response rates are high in WAIJ, it often takes time to see the response, to rituximab therapy, with responses noted out to as far out as 16 weeks.

Rituximab is typically used in the second-line setting, but it can also be used in combination, with steroids in the front-line setting as well, and at times of relapse.

Now let's talk about splenectomy. Since the spleen is the major site of red blood cell destruction, removing the spleen, can be an effective treatment for WAIJ. However, the complete response rate is around 40%. There are also risks of surgical complications. Patients may have prolonged recovery. There's also a long-term increased risk of thromboembolic events as well as serious infection. With this in mind, splenectomy may not be tolerated in those who are older, with significant, comorbidities, or those who are otherwise deconditioned.

Splenectomy remains an option following rituximab therapy. In practice, splenectomy is often deferred because of the short- and long-term risks, associated with it.

Other immunosuppressive and cytotoxic medications can be used with limited data regarding their, efficacy, and notably, immunosuppressive therapies carry a risk of infection.

Again, patients are cycling on and off of treatment and in between treatments through, the course of their disease. Lines of therapy are not clearly defined, and therapies may be used in combination.

So it kind of is.

It's challenging for the patients as well as the professions saturate these types of patients.

During the Covid times.

Next slide.

The severity of anemia initial presentation of WAIJ is a strong predictor of outcome. The patient's symptoms vary and depend on the rate of onset, degree of hemolysis, as, well as underlying disorders.

Quality of life may be negatively impacted by the symptoms of the disease, as well as, the side effects associated with current therapies. About 50% of cases relapse after first-line therapy.

And that a preference towards oral therapies and keeping our patients out of the infusion centers when possible and a patient preference.

Well, my usual approach is to use steroids often in combination with rituximab in the, front-line setting for severe cases. In the past, some of the severe cases treated at our center have also had the addition of, cyclophosphamide into the regimen, as you'll see in a moment.

The approach following relapse includes repeating prior therapy, depending on the duration of, prior response or use of alternative immunosuppressants, such as azathioprine.

Next slide.

Our oral treatment.

So I think there definitely is a need and a targeted mechanism of action is compelling.

Is of interest to trailing commissions.

Yeah.

Okay great.

Right.

Well it's somewhat.

Alright.

So just a quick follow up on.

On the available treatments or emerging treatment I don't know if you have any experience with some of the different therapies are coming down the pipe such F. F. C. R N antagonist.

If you are.

Kind of speak to.

What you think about the.

Mechanisms of action for those therapies compared to <unk>.

Yeah.

Okay.

With that setup, I'm going to go through a few cases with you from my clinical practice. The first case illustrates the cycling through various treatments that we've touched on a, few times now and highlights the long clinical journey experienced by some patients with this disease.

Okay.

Bye.

Sure.

What we're seeing is that this is a heterogeneous disease and some patients may respond to pump therapy versus another I think it's clear that we're moving to an era of targeted therapy in this disease, but to really comp to contrast, the different mechanisms.

So this is a 45-year-old woman with a history of grave disease, previously treated with, radioactive iodine ablation in 2013.

In 2013, she was also diagnosed with Ehlmann syndrome, which is a combination of ITP and, WAIHA. At the time of presentation, she had both ITP and WHA.

She was treated with steroids, and because of disease severity, was escalated to combination, therapy with rituximab, cyclophosphamide, and dexamethasone.

Fostamatinib certainly could have been an option for the management of her ITP in 2014.

While this was effective for her WAIHA, her ITP was still not controlled, and thus was, treated with prednisone, ronoplastin, and eventually splenectomy. She did well for several years until 2017, when she presented with relapsed WAIHA. At that time, she was retreated with combination therapy of rituximab, cyclophosphamide, and, dexamethasone, given the duration of her prior response, which was followed by a prednisone tape in. She did well for several years again, until she relapsed this past year.

Additionally, it would have been an option for her WAIHA at her relapse in 2017 and her, most recent relapse.

She was given a pulse of dexamethasone to control hemolysis, and so as we look at this, case, I would point out that there's a couple times during this patient's journey where fostamatinib could have been a reasonable option.

The second case is that of a 33-year-old woman with primary WAIHA, diagnosed in 2019. At initial presentation, she was treated with steroids and rituximab. However, following the steroid taper, she continued to have ongoing hemolysis, and isothioprine, was initiated. This led to some stabilization of the hemoglobin, but still with some ongoing hemolysis on lapse.

Eventually, her hemoglobin met the threshold for treatment change.

So, as we review this case, there's also several time points where this patient, excuse me, where fostamatinib could have been used for this patient. It was an option instead of isothioprine, as well as after isothioprine therapy.

But both cases demonstrate that the currently available therapies are not sufficient in, treating patients with this disease, even when used in combination, emphasizing the need for additional therapies, such as fostamatinib for WAIHA.

Now, let's turn to talk about fostomotinib as a potential treatment for WAIHA.

In contrast to malignant hematology, where response rates are the primary driver of treatment, selection, WAIHA is considered a chronic, benign disease that requires treatment over years. So, it's of greater importance here to have a therapy that will manage the disease consistently, with a favorable long-term safety profile. If fostomotinib is approved for this indication, it would offer the following potential advantages.

Fostomotinib has a unique mechanism of action targeting the underlying pathophysiology of, the disease.

And so a little bit beyond that that data that we have right now.

Thank you Adam.

Okay.

Is that many of these doctors and the objective for US is to have the doctors that are already using Java lease.

It's an oral therapy, which is not immunosuppressive, which has come into particular focus during, the COVID era. The safety profile is well-characterized. It has a rapid response, which is durable. From the clinical perspective, a rapid and durable response results in less use of rescue, medications and decreased need for hospitalization.

For ITT, so they already know the product stability mechanism they have some experience with it.

Additionally, since it is approved for ITP, physicians already have experience using the, therapy, and having another indication will likely reinforce its use in ITP.

I will finish by saying that, from my years in clinical practice treating WAIHA and other, blood disorders, I know first-hand that the available treatments for WAIHA are insufficient, and there's a clear unmet need for new therapies in this disease.

Thank you.

And I think that'll help the receptivity for new indication AIA.

Where there's even less available treatments.

For that indication so I think that should help in terms of the rest of activity in part. The reason we expanded the commercial organization last year is to raise that awareness for tower leasing ITB. So as to facilitate the rest activity for AIA.

Thank you, Dr. Paratic.

Shifting gears now to a quick update on our COVID-19 program, moving to slide 28, we continue, to believe that fostomatinib can provide therapeutic benefit in COVID-19. There are several scientific pieces of external research at independent institutions. Most importantly, last year we reported positive clinical data from the NIH-NHLBI Phase 2 study, in hospitalized patients with severe COVID. That data was published last fall.

Okay, great. Thanks for that Roy was just one last question.

For Dean.

Can you tell us what happened with the non recognition of the government revenues.

I believe it was $6 million this left within those contracts and Dennis.

We didn't see anything in the queue.

Its very.

Correlation with the timelines of the current Covid sponsor trial or is it completely distinct.

Distinct from that.

Yeah. Thanks, Vijay for the question. So just to remind everyone. We have a $16 $5 million overall grant from the D. O D, which is supportive of our phase III study in Covid.

Additional data will be presented by collaborators at this year's ATS conference in May.

Given persistent resistance to vaccination in some places, and the possibility of new, virus variants, we believe a need for effective treatment options for severely ill patients remains. We have two ongoing Phase 3 studies that will provide us with pivotal data, and if approved, in this indication, tablis would be available for immediate use for these patients.

Which largely pays for the cost our external cost of that study to date, we've recognized $10 million of revenue.

Slide 29.

Collected $10 million of cash that contract specifies that over the course of the study there are certain milestones that we get paid for and therefore.

Before I discuss our pivotal Phase 3 study, I would like to provide an update on two other, trials from collaborators.

So, MADIS Phase 2 study at the Imperial College of London, and the ACTIV-4 host tissue Phase, 3 study from NIH.

Regarding MADIS, an independent data review board recommended not to continue fostamatinib, into the second phase of the trial. That recommendation was not due to any safety concern. The focus of this study was the prevention of progression of mild to severe disease.

In the NIH ACTIV-4 study, an interim analysis was run on two of the three experimental drug, arms of the study, and enrollment was discontinued for both. So, fostamatinib is now the only remaining active arm on the study and continues to enroll, patients.

Rigel's own amended Phase III trial is also continuing. As mentioned earlier this year, we updated the inclusion criteria for the trial to focus, on more severe patients and changed the primary endpoint to days on oxygen for a more sensitive measure and better comparison to the NIH active trials.

Now let's turn to our pipeline programs, IRAC1.4 and GRIP1 inhibitor, starting on slide 31.

Both studies now focus on fostamatinib as a treatment for COVID rather than a preventive, agent.

As Raul mentioned earlier, due to the recent decline in COVID-19 hospitalizations, enrollment, has been slower than anticipated. To date, we have 268 patients, nearly 90% of our targeted enrollments. We are reviewing strategies to complete enrollment and report top-line results by year end, including, potentially completing the trial with fewer patients than the initially targeted 308.

As you point out of U K, we've got $6 $5 $6 million remaining of that $16 5 million will incur during the future of the study.

And is the revenue and collect the cash over the course of.

The remainder of the study so stay tuned that will come out in future quarters, but there was no recognition no milestone in Q1 as you highlight.

We have shared with you before we are evaluating R289, our IRAC1 and IRAC4 dual inhibitor, initially in low-risk MDS. We believe R289 has the potential to provide effective suppression of the pro-inflammatory, environment that causes low-risk MDS.

All right sounds good thanks to everyone.

Thank you.

Our next question is coming from the line of <unk> Patel with B Riley. Please proceed with your questions.

Slide 32 shows our Phase 1b trial for patients with low-risk MDS.

Yes, hi, thanks for taking my questions I'll start with Doctor Pi attic.

The study has two parts. Part one is a dose escalation phase with a commonly used three-by-three approach. The four dose levels are being supported by our favorable safety data from already completed, studies in healthy volunteers.

Sure.

For the phase III trial, what is the delta that you're looking for between the active arm and the placebo arm that would be clinically meaningful in your view I mean is there a percentage like 20% 30%.

After dose escalation and thorough evaluation of all safety, clinical activity, PK, and, biomarker data, we will take a dose into an extension phase to obtain more longer-term safety and preliminary efficacy data to support a larger registration of study.

Study startup activities are currently ongoing, and we are targeting the second quarter of, the year to achieve study initiation.

Moving to slide 33, our RIP1 inhibitor program developed together with our partner Eli Lilly, is another important value driver for RIGEL. We see a mechanistic and clinical scientific rationale for R552 in several large indications, and we continue to prepare for a Phase 2 clinical trial in an immunologic disease indication.

That that you would view as impressive.

As we noted in our press release, the initial Phase 2 study is now anticipated to start, in Q1 2023. As is common in drug development, we encountered opportunities for formulation optimization, that we plan to leverage and take forward into the program.

The result being a delay in the timing for the first indication, which Lilly will disclose, closer to the initiation of the study.

Additionally, we are advancing our work to select a RIP1 inhibitor candidate that can, cross the blood-brain barrier for the treatment of central nervous system diseases. Lilly will then lead the clinical development of these brain-penetrating RIP1 inhibitors.

We are pleased to collaborate with Lilly on those very exciting opportunities, knowing, their deep expertise in these DNS therapeutic areas.

In addition to hitting stat Sig.

And then I have a follow up.

Yeah.

Okay.

Thank you Patrick do you have a comment.

There isn't a specific skill set that I'm looking for in the phase three what I'm interested in is.

Is seeing that there's a clear group of responders with durable responses.

And and trying to parse out you know which patients are.

Derive benefit from from faster.

And kind of sorting out those characteristics.

And again kind of highlighting that the secondary endpoints a number of them are clinically meaningful in clinical practice.

Okay fair enough.

And then I know the protocol allows the use of rescue therapies, but the patients that received the rescue therapies. They won't be counted as a responder. If it's received within a certain time period. So I guess my question for you Doctor is that if you were to receive an RBC transfusion how long is that.

Improvement good for in the real World.

Yeah.

So the red blood cells that these patients are transfused are also hemolyze.

So it would it varies a little bit but it could be you can see no response to maybe a response that lasts for several days, but it does not last the same duration as somebody who.

Is transfused for another reason.

Without hemolysis.

Okay Fair kitchen, and then remind you I'm sorry.

Just wanted to remind you that you have to be off of that rescue therapy for at least four weeks updated sculpsit before you can start counting as a response.

If that's clear.

So like a response after for a few days or even a couple of weeks of the transfusion is very unlikely, making a durable responder also.

Okay and then one question for the company.

Now that you have three years of experience launching Teva lease.

Do you have any metrics on the median duration of.

Treatment with real real World patients and then if you can also breakdown.

The new starts versus continued treatment in your in your sales metrics for the latest quarter that would be useful.

Okay.

Thanks to all our stake to cause I'm not sure that we provided the ladder as yet.

So maybe you can comment on the first how long the longevity perhaps.

Patients on ITC, yes. So currently we have in the mid fifties as our persistency rate, which we've maintained for Cui.

Oh Wow.

For patients at four months of therapy. So generally about five bottles as what you would say that most patients would get on therapy.

If you averaged it out over all of the patients and all I would say as you know.

When we saw this growth in Q1 it was clearly.

That we were putting more patients in the top of the funnel then we were actually there.

Patients were going out at the bottom of the funnel I'd say, we're coming off drug.

So I, although we're not telling you the percent of our business that is new patients right now its a growing percentage.

You saw this helpful. As you saw good good increase in new patient starts, which I think bodes really well for future quarters as we see that entry. So we're excited about having achieved that in Q1, which is really a good a good place to start the year.

Okay. That's very helpful. Thank you.

Thank you.

Our next question is coming from the line of Joe <unk> with H C. Wainwright. Please proceed with your questions Hey.

Hey, everybody. Good afternoon, thanks for taking the question.

Just wanted to ask Dr. Pei attic.

Sort of a combination of the questions. That's been asked and also roll made a comment earlier about.

Lot of the same treating physicians that used to have a lease now we'll also look to potentially dose tablet for these patients. So.

Want to look at it of how you look at the evolution of the market and you did touch upon it in certain ways, but the way I wanted to approach. It is if you look at the slide 14 now. This is the one that has the different bar graphs for the different lines of treatment and how headed heterogeneous it is.

The numbers might be different obviously, but the typical view of this chart is virtually identical to what is seen in ETP with multiple.

Approved therapies and it took quite some time to be able to have the ITT at community agree on different treatment guidelines. So even though it's have a lease might be the first approved drug.

Which could gain obviously good traction presumably.

Do you see the heterogeneity still remaining for a while.

Sure.

Okay.

Thank you. Thank you for the question, so I'll ask Dave to comment and I'll add a comment afterwards, yeah, I can just say that Tim.

In and we are currently conducting market research almost on a daily basis at this point.

Talking to clinicians and they are very interested in having some pain.

And then they can use in this disease, it's not even though it has similarities.

To you.

T P. It.

It is it concerns them more and sometimes these patients can get into a lot of trouble and so they want to have new options. Besides think theres going to be a lot of very willing people to listen to.

The message that we're going to bring as we're shaping that message now to clinicians.

If we do have approval and I think it's going to be.

A very solid add to their.

Armamentarium, which is probably a little bit different than an ICP, where they had people's existing for quite a while and probably the unmet need with that theory.

But maybe a somewhat similar to the I T P market pre T bones exactly place to start and you saw how the market evolves there with the people's gaining a predominant or very substantial share of the ICP market over the course of years. So if we could achieve anything near me that we'd be tremendously happy.

That's definitely a good analogy.

Thank you Joe.

Our next question is from the line of Bert Hazlett with BTG. Please proceed with your question.

And thank you for taking the question.

For Dr <unk> and as we considered the phase III data upcoming you had mentioned during your initial comments a focus on the secondary endpoints as being a material as well.

To elaborate just a bit with regard to what might be important cigna.

Significant out of the secondary endpoints that we've seen previously the rapidity of response, the magnitude or even the use of a rescue meds, but a little elaboration there would be helpful and thank you for taking the question.

Sure.

Sure so.

So I think the secondary endpoints are a little bit interwoven, so basically meaning that if you're seeing the hemoglobin response and this in turn.

Less need of of rescue medications.

So if you're roughly thinking are the.

The hemoglobin.

And as the usual transfusion threshold.

At the threshold of our people are starting to feel bad if we're getting people up closer.

Above that that transfusion threshold, that's clinically meaningful.

An improvement from baseline mean, less intensive therapy lesson potential need for transfusions. So so.

What we're trying to do is kind of get our patients out of the hospital.

And feeling like they can do their activities of daily living or if not more than that so.

So the further we can get from these numbers around southern Nevada and for longer periods of time.

Thank you for that.

That concludes my development summary, and I will now turn the call over to Dean.

Dean?

Thank you, Wolfgang.

Thank you Brittany.

I'm on slide 36.

For the first quarter of 2022, we shipped 1,824 bottles to our specialty distributors, resulting in $22.6 million of gross product sales. 1,836 of those bottles were shipped to patients at clinics, while 925 bottles were made in, our distribution channels at the end of the quarter.

Thank you.

We reported net product sales from Tabulis of $16.2 million, a 31% increase compared, to the same period in 2021. Our net product sales from Tabulis were recorded net of estimated discounts, chargebacks, rebates, returns, copay assistance, and other allowances of $6.4 million.

Our gross-to-net adjustment is approximately 28.4% of gross product sales for the first, quarter of 2022.

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

Before we move on from net product sales, let me review our expectations for the second, quarter of 2022. We are pleased with the strength of our bottles shipped to patients at clinics at the end, of the first quarter that Dave described, and expect growth to continue as access to physicians and new patient starts continues to expand.

Incrementally, we currently expect our gross-to-net adjustment to be approximately 30% in the, second quarter of 2022.

We don't typically comment on potential collaboration milestone payments due to payment variability, and uncertainty. We wanted to provide a brief financial update as it relates to Kise's NDA filing in Japan, that Rahul highlighted. With this filing, we expect to receive a $5 million milestone in the current quarter.

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

If approved, we would expect to receive an incremental $20 million milestone in the first, quarter of 2023.

We will continue to provide updates on Kise's progress with this important filing.

In addition to net product sales, Rides with Contract revenues from collaborations were, $500,000 for the three-month-ended March 31, 2022, which consisted of $200,000 from our license agreement with Lilly and $300,000 from our collaboration agreement with Griffles.

Thank you Ed and thank you everyone for joining and for your questions on this and your continued interest in Rigel.

Moving on to cost and expenses, our cost of product sales was approximately $121,000 for, the first quarter of 2022.

Total cost and expenses were $43 million in the first quarter of 2022 versus $39.3 million, in the first quarter of 2021. The increase in cost and expenses was primarily due to increased commercial activities related, to the Salesforce expansion in late 2021, increased research and development costs for the development of Ride's IRAC-1 foreign inhibitor program, and increased personnel-related costs and stock-based compensation expense.

Partially offset by decreased research and development costs related to our phase three, clinical trial of fostamatinib for warm-out immune hemolytic anemia and our ongoing phase three clinical trial of fostamatinib in hospitalized patients with COVID-19.

Finally, we ended the quarter with cash equivalents and short-term investments of $107.5 million.

In addition, I'd like to thank Dr. <unk> for joining us on the call and giving us her thoughts.

On a warm autoimmune hemolytic anemia in total at least very much appreciate it.

And very helpful to all of US as you know we've made great progress this past quarter, and we have exciting milestones coming most importantly.

Thank you Dean.

Rigel's performance in the first quarter has given us a strong start to the year, and we will continue to execute on our strategic priorities as you see here.

Looking forward, we expect the momentum that we were seeing in the commercial front to continue into the upcoming quarters, facilitating ITP sales growth.

Phase III milestone at the IHA in the very near term as you know it.

Most importantly is our upcoming Phase 3 trial readout at WARM AIHA.

We're excited about this readout because it is a key step in building our HEMOG portfolio.

WARM AIHA is complementary to our current commercial focus and so will be highly synergistic and accretive.

It'll be great to be able to deliver a new and helpful medicine for the first time to patients suffering from WARM AIHA and to do so as early as 2023.

I'd also like to thank our employees for their consistent constant commitment to improving the lives of these patients. Thank you.

Now let's open the call to your questions, and given that Dr. Piatik is with us, let's prioritize WARM AIHA-related questions.

Operator?

Thank you.

If you'd like to ask a question, please press star 1 from your telephone keypad and a confirmation tone to indicate your line is in the question queue.

You can press star 2 if you'd 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.

One moment, please, while we poll for questions.

Thank you.

We look forward to updating you on our progress in future calls.

Our first question is from the line of Yoon-Yeon Yang with Jefferies.

We look forward to updating you on our progress in future calls have a great day.

Please proceed with your questions.

Thank you.

I have one question to Dr. Piatik.

So in Phase 3 for the trial, if I remember it correctly, patients have active hemolysis and also they are on some background therapy.

Have a great day.

So with the entry criteria, what do you expect the placebo response to be according to Phase 3 primary endpoint?

Thank you.

Thank you, Yoon.

This concludes today's teleconference.

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

Dr. Piatik?

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

I'd like Wolfgang's input on this as well, but I would anticipate there would be a low response rate for placebo, and the correlate here is that in the Phase 2 data, the non-responders did not achieve a hemoglobin response.

So kind of using that here, we would anticipate a low response rate in placebo for the Phase 3.

Yeah, I would agree with that.

We do not see patients generally just bounce up and down two units. That's a pretty large jump up from any baseline, and to stay up there for three consecutive visits would be very surprising unless the patient is on an effective therapy.

Okay.

And I have a question to the company.

Yeah.

So in Phase 2, I think about 38% of our patients, were second-line, and the remainder of the patients were third or fourth-line, later line of therapies. And although the overall response rate was around 45%, I think there was a higher response in second-line patients.

So my question to the company is that, in terms of baseline patient characteristics by the line of therapy, in Phase 3, is that kind of similar to, Phase 2?

Yeah, so in general, I would say we have probably somewhat more patients in earlier lines, because, as you are aware, we are conducting this trial in the United States, but also in a number of countries in Europe, including Eastern Europe, where compounds such as ritaxin, for example, are a little bit less used or available.

So in general, it's most likely a similar patient population, but maybe somewhat earlier, line, and we do expect certainly comparable or even slightly better data from phase three than what we have seen in phase two.

Thank you.

Our next question is from the line of Yigal Nochomovitz with Citi.

Please proceed with your questions.

Hi, this is Carly on for Yigal.

Thanks for taking our questions.

We have one for Dr. Piatik.

We're wondering how the 46% response rate and the 29% durable responder rate seen in, the phase two study compared to experience with rituximab and other therapies currently used post-steroids.

And I guess if the phase two data are largely replicated in the phase three, could you go, into a bit more detail on how you would think about using Tavleaf in your practice in terms of line of therapy?

Thank you.

Thank you, Carly.

Dr. Piatik?

So, I mean, I think if Tavleaf is approved, it would be the only approved medication for, this indication.

I think in the third line setting, there's a clear role.

In the second line setting, it would also be a reasonable choice, and I would like to, see within the baseline demographics for the phase three, we see a lot of patients who had not received prior rituximab, so it would be beneficial to see the data there to see how these patients benefit.

But our anticipation, similar to the ITP data, is that the earlier on you use Tavleaf, the, higher the efficacy would be, suggesting a role in the second line setting.

Sven?

Go ahead, and Wolfgang, if you have a comment.

Yeah, I would just add to that, and we sort of elaborated a little bit on this.

Again, the primary endpoint that was, you know, acquired by regulatory agencies is a, very high bar, but we have a number of secondary endpoints that also capture clinical benefit.

So we really think there's a substantial percentage of patients that can have clinical, benefit, and it's going to be the totality of the data, and Dr. Paddock will confirm that, the totality of the data that will make a treatment decision, and also in collaboration with the patient.

You know, a patient might want to have an oral drug over an infusion, or vice versa.

So I think we are well positioned to play an important role there.

The last comment that I want to make is, when you refer to other compounds, such as ritaxin, if you want to make comparisons, feel free to do so, but you need to be very, very stringent in really understanding what the endpoints are, and how it's not apples to apples when you talk about overall response rates versus our primary endpoint.

That's not comparable.

So I believe we can certainly come out in a similar ballpark.

Okay, got it.

That's really helpful.

And then just one sort of housekeeping question for the company.

Are you able to refine the timing guidance at all for the forward data from mid-year to maybe around which month this summer we could expect to see the data?

Thanks so much again.

I can clarify that.

I think we could tell you that it's going to be in June, to be more specific.

Not more specific than that, though.

Okay, great.

Thanks.

Our next question comes from the line of Gary Nachman with BMO Capital Markets.

Please receive your questions.

Hi.

For Dr. Piotek, first, you know, when you see Tavalease fitting into the treatment paradigm for warm AIHA, will there be a lot of combination use with this product?

And do you envision any challenges in terms of access with that?

And what would it take for the product to potentially be a first-line drug?

Is that even a possibility over time?

Hi.

Thank you.

I'll ask Dr. Piotek your comments, but also Dave's comments, because we've done some market research in that area.

Go ahead.

Yeah.

So, we don't have any data to inform on combination use.

You know, the clinical trials do have washout periods and time for stability on steroids.

So, the potential is that it would be overlapped more closely with steroids with the effort for it to be a steroid-sparing agent.

We do not have any data in the first-line setting.

There is a role for steroids in WAHA, just as ITP.

So, it's hard to go beyond that.

Thank you.

Dave?

Yeah, Gary.

One thing I would like to mention here is that, you know, it depends on where patients are relapsing.

If they are in acute setting in the hospital, sometimes it's very difficult, as we've learned from recent market research, for clinicians to prescribe Rituxan and administer it in the inpatient setting. So, they have to wait for the patient to be discharged and use it in the outpatient setting.

It's not everywhere, but certainly in the community that that is happening.

And so, you think about a drug like Fosmatinib, which could be used starting in the inpatient setting, patient takes it and moves it, you know, into the outpatient setting.

And then, because of its potentially rapid response, the ability then to taper steroids.

And that appears to be very interesting to clinicians as we talk to them now.

And you saw in the slide that Dave provided earlier, there's substantial mixing and matching, including in first-line therapies with AIHA.

It's a little bit different than ITP in that regard.

Yes.

Okay.

That's helpful.

And then, I guess, for both Dr. Piotrek and the company, for the 14.3 thousand addressable patients in second-line plus, how many of these are easy to tap into?

And will there be challenges getting to any of these patients to get treated in the later lines, or are they readily available for the most part?

So, I'm curious, how much of an effort is required to increase awareness for WAIHA, or, you know, is it well-known and the clinicians are treating most of these patients already?

Thank you, Gary.

I'll ask Dave to come in first, and then Dr. Paddock if you would like to as well.

Yeah, so what I would say, Gary, is that, you know, it is 14,000 patients out there, who are actively undergoing treatment every year, but it will require us to reach a broad number of physicians because particularly in the community, it's pretty evident that clinicians see a handful of these patients over time.

And they manage them, and some will be on treatment, and some won't.

So I think they're aware of patients that are out there.

They know that, you know, if they do relapse, that they're going to need to treat them, but we will have to reach a large number of prescribers in order to get that awareness out there.

Keep in mind on that point, before I ask Dr. Paddock to comment also, is that it's not unlike ITP where it's a rare disease in hematology, benign hematology, and these doctors see a small number of these patients.

When you add these two indications together, it becomes a much more substantial patient population, within that doctor visit. As I said, substantial, almost complete overlap in the doctors who treat both of these indications.

So it's something that we're knowledgeable of and experienced in handling.

Dr. Paddock, anything to add beyond that?

I think that was fairly covered, everything that I would have said.

I would just add that the multiply refractory patients often get referred to an academic center.

And in that setting, then FOSNOTMIT would probably have a higher awareness.

Okay, that's great.

Thank you, Jason.

Thank you.

The next question is coming from the line of Doe Kim with Piper Sandler.

Please proceed with your questions.

Hi, everyone.

This is EK on for Doe.

Thanks for taking the question, and congrats on the continued progress.

For Dr. Paddock, just a quick one.

I don't know if I might have missed it, but if you can just speak on your belief of the receptivity of your colleagues and yourself of tabloids in warm IHA given the current dynamics of how you're treating patients and the relapse rate.

I don't know if there is a kind of entrenchment of sorts with the current therapies, and your colleagues are looking for something novel or, you know, just your brief thoughts on it would be helpful for us.

Sure.

Okay.

So I would say that there is definitely a clinical need for targeted therapies in this disease. You can see from some of the cases we discussed that especially in these multiply refractory patients, we really just don't know how to treat these patients, and it leads to that cycling through therapies with unclear efficacy.

So it's challenging for the patients as well as the physicians to treat these types of patients.

During the COVID times, we found that a preference towards oral therapies, keeping our patients out of infusion centers when possible, and a patient preference for oral treatment.

So I think there definitely is a need, and the targeted mechanism of action is compelling, and is of interest to treating physicians.

Okay, great, and just a quick follow-up on the available treatments or emerging treatments.

I don't know if you have any experience with some of the different therapies that are coming, down the pike, such as like FCRN antagonists.

If you are, I don't know if you can kind of speak to what you think about the mechanisms, of action for those therapies compared to Talvallese.

Sure, so I think what we're seeing is that this is a heterogeneous disease and some patients, may respond to some therapy versus another.

I think it's clear that we're moving to an era of targeted therapy in this disease, but, to really contrast the different mechanisms is a little bit beyond the data that we have right now.

Let me just add on my behalf, is that many of these doctors, and the objective for us, is to have doctors that are already using Talvallese for ITP, so they already know the product, they know its mechanism, they have some experience with it, and I think that'll help the receptivity for a new indication, AIHA, where there's even less available treatments for that indication.

So I think that should help in terms of the receptivity.

In part, the reason we expanded the commercial organization last year is to raise that awareness, for Talvallese and ITP, so as to facilitate the receptivity for AIHA.

Okay, great.

Thanks, Raul.

Just one last question for Dean.

Can you tell us what happened with the non-recognition of the government revenues?

I believe there's $6 million that's left within those contracts, and I didn't see anything, in the queue.

Is there any correlation with the timelines of the current, your COVID sponsor trial, or is it completely distinct from that?

Yeah, thanks, EK, for the question.

So just to remind everyone, we have a $16.5 million overall grant from the DoD, which, is supportive of our Phase III study in COVID, which largely pays for the costs or external costs of that study. To date, we've recognized $10 million of revenue and collected $10 million of cash. That contract specifies that over the course of the study, there are certain milestones, that we get paid for, and therefore, as you point out, EK, we've got $6 million remaining of that $16.5 million that we'll incur during the future of the study, or we'll recognize the revenue and collect the cash over the course of the remainder of the study.

So stay tuned.

That will come out in future quarters.

But there was no recognition, no milestone in Q1, as you highlight.

That sounds good.

Thanks, everyone.

Thank you.

The next question is coming from the line of Kalpit Patel.

This is B. Reilly.

Please proceed with your questions.

Yes, hi.

Thanks for taking my questions.

I'll start with Dr. Pyattick.

For the phase three trial, what is the delta that you're looking for between the active arm and the placebo arm, that would be clinically meaningful in your view?

I mean, is there a percentage, like 20%, 30%, that you would view as impressive in addition to hitting STAT-SIG?

And then I will follow.

Dr. Pyattick, do you have a comment?

There isn't a specific delta that I'm looking for in the phase three.

What I'm interested in is seeing that there's a clear group of responders with durable responses, and trying to parse out, you know, which patients derive benefit from fostamotinib and kind of sorting out those characteristics.

And again, just kind of highlighting that these secondary endpoints, a number of them are clinically meaningful in clinical practice.

Okay, fair enough.

And then I know the protocol allows the use of rescue therapies, but the patients that receive the rescue therapies, they won't be counted as a responder if it's received within a certain time period.

So I guess my question for you, doctor, is that if you were to receive an RBC transfusion, how long is a hemoglobin, you know, improvement good for in the real world?

So the red blood cells that these patients are transfused are also hemolyzed.

So it would, it varies a little bit, but it could be, you can see no response to maybe a response, that lasts for several days, but it does not last the same duration as somebody who is transfused for another reason without hemolysis.

I just want to remind you that you have to be off of that rescue therapy for at least four weeks, after it stops before you can start counting as a responder again, if that's clear.

So like a response for a few days or even a couple of weeks after transfusion is very unlikely, making a durable responder possible.

Okay.

And then one question for the company.

Now that you have three years of experience, launching Tavalisse, do you have any metrics on the median duration of treatment with real world patients?

And then if you can also break down the new starts versus continued treatment in your sales metric for the latest quarter, that would be useful.

Thanks.

I'm not sure that we provided the latter as yet.

So maybe you can comment on the first how long the longevity perhaps of, patients on ITP takes?

Yes.

So currently we have in the mid 50s is our persistency rate, which we've maintained for quite a while for patients at four months of therapy.

So generally about five bottles is what you would say that most patients would get on therapy if you averaged it out over all the patients.

And all I would say is, you know, when we saw this growth in Q1, it was clearly, that we were putting more patients in the top of the funnel than we were actually that patients were going out at the bottom of the funnel as they were coming off drugs.

Although we're not telling you the percent of our business that is new patients right now, it's a growing percent.

As you saw, a good increase in new patient starts, which I think bodes really well for future quarters as we see that entering.

So we're excited about having achieved that in Q1, which is really a good place to start the year.

Okay, that's very helpful.

Thank you.

Our next question is coming from the line of Joe Pantginis with HE Wainwright.

Please proceed with your questions.

Hi, everybody.

Good afternoon.

Thanks for taking the question.

I just wanted to ask Dr. Piotek the sort of a combination of the questions that's been asked, and also Raul made a comment earlier about, you know, a lot of the same treating physicians that use Tavalese now will also look to potentially dose Tavalese for these patients.

So I want to look at it of how you look at the evolution of the market, and you did touch upon it in certain ways, but the way I want to approach it is if you look at the slide 14, now this is the one that has the different bar graphs for the different lines of treatment and how heterogeneous it is, the numbers might be different, obviously, but the typical view of this chart is virtually identical to what is seen in ITP with multiple approved therapies, and it took quite some time to be able to have the ITP community agree on different treatment guidelines.

So even though Tavalese might be the first approved drug, which could gain, obviously, good traction, presumably, you know, do you see the heterogeneity still remaining for a while?

Thank you.

Thank you for the question.

I'll ask Dave to comment, and I'll add a comment after.

Yeah, I can just say that, and we're currently conducting market research on a daily basis at this point, talking to clinicians, and they are very interested in having something that they can use in this disease.

It's not, even though it has similarities to ITP, it concerns them more, and sometimes these patients can get into a lot of trouble, and so they want to have new options.

So I think there's going to be a lot of very willing people to listen to the message that we're going to bring, as we're shaping that message now, to clinicians if we do have approval, and I think it's going to be a very solid add to their armamentarium, which is probably a little bit different than an ITP, where they had T-pos existing for quite a while, and probably the unmet need was not nearly as high.

Yeah, but maybe somewhat similar to the ITP market pre-T-pos.

Exactly.

As a place to start, and you saw how the market evolved there with the T-pos gaining a predominant, or a very substantial share of the ITP market over the course of years, so if we could achieve anything nearly that, we'd be tremendously happy.

That's definitely a good analogy.

Yep.

Thank you, Joe.

Our next question is from the line of Bert Haslett with BTIG.

Please proceed with your, question.

Thank you, and thank you for taking the question.

For Dr. Piotrek, as we consider the Phase III data upcoming, you mentioned during your initial comments a focus on the secondary endpoints as being material as well. I'd love for you to elaborate just a bit with regard to what might be important and significant out of the secondary endpoints that we've seen previously, the rapidity response, the magnitude, or even the use of rescue meds.

But a little elaboration there would be helpful, and thank you for taking the question.

Sure.

So I think the secondary endpoints are a little bit interwoven, so basically meaning that, if you're seeing these hemoglobin responses, this in turn leads to less need of rescue medications.

So if you're roughly thinking of a hemoglobin of seven as the usual transfusion threshold, basically at the threshold of where people are starting to feel bad, if we're getting people up closer, you know, well above that transfusion threshold, that's clinically meaningful. An improvement from baseline means less intensive therapy, less potential need for, transfusion. So what we're trying to do is kind of get our patients out of the hospital and feeling like they can do their activities of daily living, if not more than that. So the farther we can get from these numbers around seven, the better, and for longer periods of time.

Thank you for that.

Thank you, Bert.

Thank you.

There are no further questions at this time, and I'd like to turn the, floor back to Mr. Raul Rodriguez for closing comments.

Thank you, and thank you everyone for joining and for your questions on this and your continued interest in RIGEL.

In addition, I'd like to thank Dr. Piatik for joining us on the call and giving us her thoughts on warm, autoimmune hemolytic anemia and travel.

It's very much appreciated and very helpful to all of us.

As you know, we've made great progress this past quarter, and we have exciting milestones coming, most importantly, a phase three milestone in AIHA in the very near term, as you know.

I'd also like to thank our employees for their consistent, constant commitment to improving the lives of these patients.

Thank you.

Q1 2022 Rigel Pharmaceuticals Inc Earnings Call

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