Q2 2022 Rigel Pharmaceuticals Inc Earnings Call

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

Greetings and welcome to the Rigel Pharmaceuticals Financial Conference Call for the second quarter 2022.

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

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

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

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

If anyone should require operator assistance during the conference, please press star zero on your telephone keypad.

Welcome to our second quarter 2020 financial results and business update conference call. The financial press release for the second quarter was issued a short while ago and can be viewed along with the accompanying slides for this presentation and unusual events section of our Investor Relations site Www Dot Rigel dotcom.

As a reminder, this conference is being recorded.

During today's call we may make forward looking statements regarding our financial outlook, and our plans and timing for regulatory and product development. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted a description of these risks can be found in our most recent annual report on Form 10-K for the year ended December.

For 31, 2021, and subsequent filings with the SEC.

In our Q2 quarterly report in 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.

It is now my pleasure to introduce our first speaker,

Thank you Dolly and thank you everyone for joining today.

Dolly Vance, who is Rigel's Executive Vice President, Corporate Affairs and General Counsel.

Also with me today are Dave Santos, our Chief Commercial officer, Dr. Wolfgang Dummer, our Chief Medical Officer, and Dean <unk>, Our Chief Financial Officer.

Thank you, Ms. Vance.

You may begin.

On slide five we are also very pleased to have Dr. Jorge Cortes, joining us today to provide a clinical perspective on our recently acquired pipeline addition, although suiting you talked to Cortez is an internationally recognized experts in the leukemia and has led the development of numerous leukemia treatments, including <unk>.

<unk> seen rebel and inclusive were used towards the treatment of chronic myeloid leukemia, or CML and the reasonable whose treatment for older patients with acute myeloid leukemia or AML Dr.

Dr. Cortez is currently the director of the Georgia Cancer Center, which he joined in 2019 after spending 23 years at the University of Texas, MD Anderson Cancer Center, where we held he held many roles in the department of Leukemia Division of cancer Medicine, including Deputy Department Chair and the chair of the AML and CML.

In addition, he was the Deputy Division head for the cancer network and chair of the executive IRB.

Importantly for US today, he is a clinical trial investigator on the trial.

Beginning on slide six.

I am pleased to report that we have made significant strides this quarter in growing our commercial hematology oncology business.

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

With our first value driver on this slide growing <unk> sales during.

The financial press release for the second quarter was issued a short while ago and can be viewed, along with the accompanying slides for this presentation, in the news and events section of our investor relations site on www.rigel.com.

During the second quarter <unk> achieved the highest quarterly net product sales for <unk> at least in ITB since launch.

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 risk and uncertainties.

They may cause actual results to differ from those forecasted. A description of these risks can be found in our most recent annual report on Form 10-K, for the year ended December 31, 2021, and subsequent filings with the SEC, including our Q2 quarterly report on Form 10-Q on file with the SEC.

This demonstrates the continued momentum we are driving through our commercial activities, where Piedmont prescribers as.

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.

As you May recall last year, we undertook a sales force expansion to broaden our reach improve efficiency and increase in person interactions.

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

These initiatives are yielding results and we believe that we have all the components in place to drive continued growth in <unk> sales.

Raul?

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

Additionally in May we entered into a collaboration agreement with night, they're reputed to.

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.

<unk> been Latin America, including Mexico, Central and South America, and the Caribbean It.

It will be great to have be able to provide access to foster imatinib for patients suffering from my GP in these countries as well.

In addition to our collaboration partner Tc in.

In April we announced that Keisha had submitted its NDA in Japan for <unk>.

We look forward to a potential approval in Q1 of 2023.

Our new value drivers Rigel is all of this.

On slide five, we are also very pleased to have Dr. Jorge Cortez joining us today to provide a clinical perspective on our recently acquired pipeline addition, Olasutinib.

We are very pleased to announce that we have entered into an exclusive worldwide licensing agreement with <unk> therapeutics for Elisa.

Dr. Cortez is an internationally recognized expert in leukemia and has led, the development of numerous leukemia treatments, including for Vasulif, Sinribil, and Inclusive, who were used for the treatment of chronic myeloid leukemia, or CML, and Darizmo, whose treatment for older patients with acute myeloid leukemia, or AML. Dr. Cortez is currently the Director of the Georgia Cancer Center, which he joined in 2019 after spending 23 years at the University of Texas MD Anderson Cancer Center, where he held many roles in the Department of, Leukemia, Division of Cancer Medicine, including Deputy Department Chair and the Chair of the AML and CML Sections. In addition, he was the Deputy Division Head for the Cancer Network and Chair of the Executive IRB.

Well it certainly is a potential market, leading oral therapy for the treatment of relapsed or refractory acute AML or acute myeloid leukemia.

Importantly for us today, he is a clinical trial investigator on the Olasutinib trial.

This collaboration will broaden our near term portfolio and is highly synergistic with our current commercial infrastructure.

Beginning on slide six, I am pleased to report that we have made significant strides this quarter in growing our commercial hematology-oncology business.

I will talk more about this program right. After I review the balance of the pipeline and Dave will also provide detail on the commercial opportunity.

I'll start with our first value driver on this slide, growing ITP sales. During the second quarter, RIGEL achieved the highest quarterly net product sales for Talvalese in ITP since launch. This demonstrates the continued momentum we are driving through our commercial activities with, Hemong prescribers. As you may recall, last year, we undertook a Salesforce expansion to broaden our reach, improve efficiency, and increase in-person interactions. These initiatives are yielding results, and we believe that we have all the components in place to drive continued growth in ITP sales.

In June we reported top line data for our pivotal phase III forward trial in warm AIA check.

The trial missed a primary endpoint in the overall patient population. However in a post hoc analysis response rates in western countries favorite Foster mandate over placebo.

We are continuing to evaluate this data and plan to share our findings with the FDA to determine the best path forward for warm AIA trip.

With no currently approved.

Approved therapies in this indication we continue to believe that there is an opportunity for <unk> to improve the outcomes for patients with this disease.

We have also advanced our post Amanda COVID-19 program, we have completed enrollment of our pivotal phase III trial in July with 280 patients, which we believe sufficiently powered the study and we expect to report top line data in Q4.

Post Imatinib is also being evaluated in a phase III trial sponsored by NIH and <unk> as a potential treatment in high risk patients hospitalized with COVID-19.

These trials have the potential to show the benefit of foster imatinib as a treatment in patients with severe COVID-19.

Wolfgang will discuss this program later on in the call.

Lastly, turning to our earlier pipeline programs, Iraq, one four and reporting.

Due to everything we want to cover today I will just give a short overview on the status of these programs.

As we had shared with you before we are evaluating our two week nine Iraq, one and four dual inhibitor in low risk Mds. We believe <unk> has the potential to provide effective suppression of the inflammatory environment that causes low risk Mds.

<unk> startup study startup activities are currently ongoing and we are targeting the third quarter of this year for study initiation.

We are also excited about the advancement of our Rip one inhibitor or <unk> being developed in collaboration with our partner Eli Lilly into phase two development.

We see a mechanistic clinical and scientific rationale for <unk> in several large immune indications such as psoriasis are a in IBD.

The initial phase II study is anticipated to start in Q2 of 2023 <unk>.

<unk>.

We will disclose the indication closer to the initiation of that study.

Additionally, we are completing our work on a rip one inhibitor that can cross the blood brain barrier for the treatment of CNS diseases. Lilly will then lead the development of these <unk> inhibitors.

Additionally, in May, we entered into a collaboration agreement with Knight Therapeutics to commercialize fostamatinib in Latin America, including Mexico, Central and South, America, and the Caribbean. It would be great to be able to provide access to fostamatinib for patients suffering from ITP in these countries as well.

In addition to our collaboration partner, Kise, in April, we announced that Kise had submitted its NDA in Japan for fostamatinib and, ITP.

Moving on to <unk>.

I would like to discuss our new collaborations with former therapeutics for all of a sudden.

We look forward to a potential approval in Q1 of 2023.

<unk> newest value driver I.

I would like to provide a brief overview of the transaction and Dave will provide our commercial and strategic rationale and why we feel that <unk> has the potential to be a meaningful therapeutic option for patients with AML.

A new value driver for Rigel is Olasutinib. We are very pleased to announce that we have entered into an exclusive worldwide, licensing agreement with Orma Therapeutics for Olasutinib. Olasutinib is a potential market leading oral therapy for the treatment of relapse or refractory acute AML or acute myeloid leukemia.

This collaboration will broaden our near-term HEMOC portfolio and is highly synergistic with, our current commercial infrastructure.

Under the terms of the agreement <unk> received an exclusive worldwide licensing rights to <unk> in all indications with an initial focus on relapsed or refractory <unk>.

I will talk more about this program right after I review the balance of the pipeline, and Dave will also provide detail on the commercial opportunity. In June, we reported top-line data for our Pivotal Phase III forward trial in warm AIHA. The trial missed the primary input in the overall patient population. However, in a post-hoc analysis, response rates in Western countries favored fostamatinib over placebo.

We are continuing to evaluate this data and plan to share our findings with the FDA to determine the best path forward for warm AIHA.

<unk> positive AML patients.

With no currently approved therapies in this syndication, we continue to believe that there is an opportunity for Tavalis to improve the outcomes for patients with this disease.

We have also advanced our fostamatinib COVID-19 program.

We have completed enrollment of our Pivotal Phase III trial in July with 280 patients, which we believe sufficiently powers the study, and we expect to report top-line data in Q4.

This includes the right to grant sub licenses in ex U S territories.

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

Wolfgang will discuss this program later in the call.

And exchange Roger will pay former a $2 million upfront payment.

In addition, former will be eligible to receive an additional $17 5 million upon the achievement of certain near term milestones.

Lastly, turning to our earlier pipeline programs, IRAC1.4 and RIP1.

The deal also includes potential future development and commercial milestone payments.

As well as tiered royalties on net sales of older students.

<unk> has submitted the new drug application to the U S. FDA following positive results from our phase II Registrational trial.

With a <unk> action date of February 2023, less than seven months from now.

The mid cycle review with FDA has been completed.

Just on that meeting we were told that we are there is currently no plans for an advisory Committee meeting.

No major safety issues have been identified and currently no Rems program is likely to be required.

If approved <unk> will expand our haemonchus product portfolio and enabled detailed two important therapies to our hemo positions.

Roger will leverage our haemonchus abilities to maximize the potential of the commercial potential of all the suit, which we believe can become an important and differentiated product in this space, particularly given that AML is an aggressive and very difficult to treat disease.

Results from the Phase II Registrational study of all the students as a mono theory monotherapy demonstrated promising efficacy, including a $13 eight month median duration of response and a favorable tolerability tolerability profile.

Rigel plans to initially focus on the commercialization of <unk> as a monotherapy in mutant <unk> positive relapsed or refractory AML setting.

There is also the potential to explore a suite in the first line <unk> positive AML setting as well as in combination.

Both of which were explored in the phase II study.

Beyond AML all the student has been explored as a monotherapy in glioma.

Or ending Cholangiocarcinoma.

We look forward to advancing <unk> through the regulatory process and potentially bring this important therapy to patients who need.

Due to everything we want to, cover today, I will just give a short overview on the status of these programs.

As we had shared with you before, we are evaluating R289, IRAC1 and 4 dual inhibitor in low-risk MDS.

With that I will turn the call over to Dave for a commercial and therapeutic area overview Dave.

We believe R289 has the potential to provide effective suppression, of the inflammatory environment that causes low-risk MDS.

Study startup activities are currently ongoing, and we are targeting the third quarter of this, year for study initiation.

We are also excited about the advancement of our RIP1 inhibitor, R552, being developed in collaboration with our partner, Eli Lilly, into phase two development. We see a mechanistic, clinical, and scientific rationale for R552 in several large immune, indications, such as psoriasis, RA, and IBD. The initial phase two study is anticipated to start in Q2 of 2023.

Lilly will disclose the indication closer to the initiation of that study.

Thank you Raul.

I'd like to take a few minutes just to highlight why we're so excited for the prospects of expanding our <unk> portfolio with <unk>.

Additionally, we are completing our work on a RIP1 inhibitor that can cross the blood-brain, barrier for the treatment of CNS diseases.

Moving to slide nine our collaboration with format aligns with our strategy of expanding our portfolio of Hematological therapies, while leveraging our existing commercial infrastructure.

Lilly will then lead the development of these RIP inhibitors.

As Raul touched upon in the past year, we made key strategic investments in our commercial organization to expand our sales force and sharpen our BD focus to prioritize late stage development programs that would be a good strategic fit for us as a result, we are well positioned to add Alicia.

Moving on to slide two, I would like to discuss our new collaboration with Forma Therapeutics for olasutinib, Rigel's newest value driver.

To our product profile.

On the left we have strategically experience business operations and marketing teams that can quickly gather insights and synthesize data into actionable plans that will ensure a strong launch even with a short runway.

In addition, we have a highly experienced and customer focused patient access team that has everything in place to efficiently distribute OLED pseudonym and ensuring patients have access to coverage reimbursement and assistance.

Finally, we have a very oncology tenured field team already calling on the majority of Hematologists and oncologists in the U S, enabling us to realize cost efficiencies, while potentially bringing two important products alluded said nib and top of lease to the attention of our customers our proposition we believe.

We can increase the overall awareness and utility of both.

In summary, we have the team in place to successfully launch elite Sydney, which is critical since we have a product that could be approved in just six five months.

I would like to provide a brief, overview of the transaction, and Dave will provide our commercial and strategic rationale and why we feel that olasutinib has the potential to be a meaningful therapeutic option for patients with AML.

On slide 10, I wanted to share why AML was a very interesting disease for us to enter.

Under the terms of the agreement, Rigel receives an exclusive worldwide licensing rights to olasutinib in all indications. With an initial focus on relapse or refractory, IDH-positive AML patients. This includes the right to grant sub-licenses in ex-U.S. territories. In exchange, Rigel will pay Forma a $2 million upfront payment. In addition, Forma will be, eligible to receive an additional $17.5 million upon the achievement of certain near-term milestones. The deal also includes potential future development and commercial milestone payments, with as well as tiered royalties on net sales of olasutinib.

As you May know AML is an aggressive highly complex malignancy and primarily a disease of older adults.

In 2020 to the American cancer Society estimates that more than 20000 patients will be diagnosed with AML and Unfortunately 11500 patients will die from AML This year.

So even though we now have several new agents that have helped to transform the treatment of AML patients. There is still progress to be made.

One of the biggest advances over the last five years has been that AML patients now undergo guideline driven molecular inside the genetic analyses for immediately actionable mutations of chromosomal abnormalities.

Patients in <unk> H, one are seen in around 6% to 16% of AML patients and although this is a small population of AML patients. They are very well defined based on standard widespread testing that is done upon diagnosis and prior to initiation of a new line of treatment.

Thus leukemia treating physicians are aware of their <unk> positive patients.

And within this well defined patient population about 60% our patients clinicians considered fit for intensive therapy with the goal of hopefully getting those patients to transplant, if they have a complete remission.

The remaining 40% of patients are not able to be or choose not to be treated with intensive therapy and they are given less intensive outpatient therapy.

In both cases, there are substantial number of patients who are refractory to their upfront treatment or relapsed after getting a response those patients would be in the dark green boxes in the bottom row and that represents an opportunity to impact the lives of as many as 1090 <unk> positive.

Outpatient each year.

Forma has submitted the new drug application to the U.S. FDA following positive results from a phase two registrational trial. With a PDUFA action date of February 2023, less than seven months from now, the mid-cycle review with FDA has been completed. Based on that meeting, we were told that we are, there is currently no plans for an advisory committee meeting, no major safety issues have been identified, and currently no REMS program is likely to be required.

Moving to slide 11, we believe the data from the phase III Registrational trial for <unk> in patients with relapsed or refractory <unk> positive AML is compelling and if approved would be viewed by physicians as a meaningful treatment option for <unk> positive AML patients.

If approved, olasutinib will expand our Hem-Onc product portfolio and enable Rigel to detail, two important therapies to our Hem-Onc physicians.

Rigel will leverage our Hem-Onc capabilities to maximize the potential, the commercial potential of olasutinib, which we believe can become an important and differentiated product in the space, particularly given that AML is an aggressive and very difficult to treat disease. Results from the phase two registrational study of olasutinib as a monotherapy demonstrated promising efficacy, including a 13.8 month median duration of response and a favorable tolerability profile. Rigel plans to initially focus on the commercialization of olasutinib as a monotherapy in mutant IDH1 positive relapse or refractory, AML setting.

Despite having new treatments over the last five years healthcare providers continue to perceive a significant unmet need since many patients still do not achieve remission.

They can also suffer from unfavorable treatment profiles, particularly in later lines of therapy.

Clinicians are continuing to look for new therapeutic options that can provide incremental survival improvements longer duration of response, and a better balance of efficacy and toxicity, especially since these are off in older patients with other comorbid conditions.

We believe <unk> can better meet clinicians needs and has <unk> positive AML market, leading potential with its long duration of response and the potential for patients to forego cardiac monitoring as key differentiating factors compared to existing therapies.

We see a significant opportunity for <unk> in patients with relapsed or refractory <unk> positive AML and Furthermore, believe there is meaningful full potential for <unk> to move into earlier therapy.

Turning to slide 12, we are extremely excited about the opportunity to bring <unk> to patients and our launch planning is already well underway.

Although we're just announcing the collaboration today, a small and highly dedicated team has been working on launch planning during diligence and we will now expand that effort and put our planning into high gear.

We already have a high level strategic plan for launch and we will spend time this quarter refining that strategy with additional customer insight.

We will have a full tactical readiness plan by year end. So we are ready to launch upon approval.

Our team is up for the challenge of a short runway potential launch and we will be ready to go if and when an approval comps.

Look forward to talking more with you about our plans as we move through the remainder of 'twenty two.

There is also the potential to explore olesutinib in the first-line IDH-positive AML setting as well as in combination, both of which were explored in the Phase II study.

Now I'll turn the call over to Dr. Cortez to talk about the findings from the alluded fit nib Registrational phase II study Dr. Cortez.

Thank you very much.

My name is Jorge Cortes mentioned I'm currently the director of the Georgia Cancer Center, and formerly at MD Anderson and the department of leukemia, whereas the Deputy Chair and I was there for 23 years on faculty plus my Trey.

Training before that so.

Beyond AML, olesutinib has been explored as a monotherapy in glioma and in cholangiocarcinoma.

That'd be very glad to discuss with you.

Drug Eluting Sydney.

And their role in patients with <unk> mutated acute myeloid leukemia.

We look forward to advancing olesutinib through the regulatory process and potentially bringing this important therapy to patients in need.

So I'll start with the background on slide 14.

With that, I will turn the call over to Dave for a commercial and therapeutic area overview.

Dave.

A reminder, I D H D H one mutations occur.

In somewhere around 8% to 12% of patients with acute myeloid leukemia, you can see the printing of different sources and different patient populations. The range, maybe expand a little bit more from somewhere to 6% to 16%.

Thank you, Raul.

Now I'd like to take a few minutes just to highlight why we're so excited for the prospects of expanding our HEMOM portfolio with olesutinib.

Moving to slide nine, our collaboration with PhRMA aligns with our strategy of expanding our portfolio of hemological therapies while leveraging our existing commercial infrastructure.

And.

As Raul touched upon, in the past year, we made key strategic investments in our commercial organization to expand our sales force and sharpen our BD focus to prioritize late-stage development programs that would be a good strategic fit for us. As a result, we are well-positioned to add olesutinib to our product profile.

That's about where we see the city's type of mutation.

On the left, we have strategically experienced business operations and marketing teams that can quickly gather insights and synthesize those into actionable plans that will ensure a strong launch, even with a short runway.

In addition, we have a highly experienced and customer-focused patient access team that has everything in place to efficiently distribute olesutinib and ensure patients have access to coverage, reimbursement, and assistance.

Finally, we have a very oncology-tenured field team already calling on the majority of hematologists and oncologists in the U.S., enabling us to realize cost efficiencies while potentially bringing two important products, olesutinib and tovalys, to the attention of our customers, a proposition we believe can increase the overall awareness and utility of both.

In summary, we have the team in place to successfully launch olesutinib, which is critical since we have a product that could be approved in just six and a half months.

As already mentioned <unk> is a very potent and very selective inhibitor of I D. H one mutated.

And I will remind you how I D. H one mutations work in acute myeloid leukemia is very important because he sees.

On slide 10, I wanted to share why AML was a very interesting disease for us to enter.

One of those mutations that are consider.

Initiating mutations there's some mutations that happened really later after the leukemia has been developed and some better initiating mutations and we think that <unk> mutations are one of those that's important because that goes to the root of the development of acute myeloid leukemia normally.

As you may know, AML is an aggressive, highly complex malignancy and primarily a disease of older adults. In 2022, the American Cancer Society estimates that more than 20,000 patients will be diagnosed with AML, and unfortunately, 11,500 patients will die from AML this year. So even though we now have several new agents that have helped to transform the treatment of AML patients, there is still progress to be made.

One of the biggest advances over the last five years has been that AML patients now undergo guideline-driven molecular and cytogenetic analyses for immediately actionable mutations or chromosomal abnormalities.

Mutations in IDH1 are seen in around 6-16% of AML patients, and although this is a small, population of AML patients, they are very well defined based on standard, widespread testing that is done upon diagnosis and prior to initiation of a new line of treatment. Thus, leukemia treating physicians are aware of their IDH1 positive patients. And within this well-defined patient population, about 60% are patients clinicians consider, fit for intensive therapy with the goal of hopefully getting those patients to transplant if they have a complete remission.

As you all may remember from the.

From biochemistry, we have these crabs.

Cycle, which is the metabolism of normal sales and it goes through alpha keto glittery and win.

The remaining 40% of patients are not able to be or choose not to be treated with intensive, therapy, and they are given less intensive outpatient therapy. In both cases, there are a substantial number of patients who are refractory to their upfront, treatment or relapse after getting a response.

Those patients would be in the dark green boxes in the bottom row, and that represents, an opportunity to impact the lives of as many as 1,000 IDH1-positive AML patients each year.

I D H, which normally metabolize alpha ketoglutarate when it is mutated E transforms alpha ketoglutarate into two hydroxy grocery toward two H G.

And when it does.

That Natalia <unk> is usually not present in normal cells in the normal cycle. When it is formed it.

Has the potential to transform itself into leukemia cells hematopoietic cells into leukemia cells through epigenetic mechanisms. So actually two HG become some marker a biomarker of the mutation you'll go up when there is a mutation of <unk>.

One and if you inhibit a D H one.

The levels of two HG will go down which is a good thing because again that is what drives the development of the leukemia. So having allude to Sydney are very potent very active drug.

Moving to slide 11, we believe the data from the Phase II Registrational Trial for lutecidinib, in patients with relapse to refractory IDH1-positive AML is compelling, and if approved, would be viewed by physicians as a meaningful treatment option for IDH1-positive AML patients.

Selective for I D H one.

Being available.

Ken.

Reverse that's malignant phenotype.

Despite having new treatments over the last five years, healthcare providers continue, to perceive a significant unmet need since many patients still do not achieve remission.

So.

We've been understanding of the potential of these drug on slide 15.

You can see that we have from the very beginning when I started I started getting involved with these drug for them at very early stages of the development.

They can also suffer from unfavorable treatment profiles, particularly in later lines of therapy.

Clinicians are continuing to look for new therapeutic options that can provide incremental, survival improvements, longer duration of response, and a better balance of efficacy and toxicity, especially since these are often older patients with other comorbid conditions.

And we very quickly developed a very comprehensive plan for the development of Oh good to see.

We believe lutecidinib can better meet clinicians' needs and has IDH1-positive AML market-leading, potential with its long duration of response and the potential for patients to forego cardiac monitoring as key differentiating factors compared to existing therapies.

Both as a single agent as a mono therapy.

And in combination with other agents knowing that sometimes in leukemia, you need combination for certain settings. So the mono therapy includes refractory relapse in other settings, including some exploration of the treatment naive patients patients who had not received prior therapy dose with the orange boxes, and we explored that also.

We see a significant opportunity for lutecidinib in patients with relapse to refractory IDH1-positive, AML, and furthermore believe there's meaningful potential for lutecidinib to move into earlier therapy.

Turning to slide 12, we are extremely excited about the opportunity to bring lutecidinib, to patients, and our launch planning is already well underway. Although we're just announcing the collaboration today, a small and highly dedicated team has, been working on launch planning during diligence, and we will now expand that effort and put our planning into high gear.

We already have a high-level strategic plan for launch, and we will spend time this quarter, refining that strategy with additional customer insights.

We will have a full tactical readiness plan by year end, so we are ready to launch upon, approval.

Now, I'll turn the call over to Dr. Cortes to talk about the findings from the Illudicid Nib Registrational Phase II Study.

Our team is up for the challenge of a short runway to potential launch and we will be ready to go if and when an approval comes.

I look forward to talking more with you about our plans as we move through the remainder of 2022.

In the combination therapy for.

Dr. Cortes?

For the purposes of these presentation.

The data that is most mature.

What you'll see in slide 16 date, the refractory or relapsed patients monotherapy.

Thank you very much.

We choose the primary indication what that's gonna be pursued again, because that is where most of the data east at the moment, that's where we usually would start to diverge.

And my name is Jorge Cortes, as mentioned.

I am currently the Director of the Georgia Cancer Center and formerly at MD Anderson in the Department of Leukemia where I was the Deputy Chair. And I was there for 23 years on faculty plus my training before that.

Element offer drove so for this cohort the primary endpoint was the achievement or what is called a CR or a CRH I'll get to the definition of that.

So I'll be very glad to discuss with you this drug, Illudicid Nib, and their role in patients with IDH1-mutated acute myeloid leukemia.

So I'll start with the background on slide 14.

As a reminder, IDH1 mutations occur in somewhere around 8 to 12 percent of patients with acute myeloid leukemia. You can see, depending on different sources and different patient populations, the range may expand a little bit more from somewhere to 6 to 16 percent.

And that's about where we see this type of mutation.

As already mentioned, Illudicid Nib is a very potent and a very selective inhibitor of IDH1-mutated.

And I will remind you how IDH1 mutations work in acute myeloid leukemia. It's very important because this is one of those mutations that are considered initiating mutations.

There are some mutations that happen a little bit later after the leukemia has been developed and some that are initiating mutations. I think that IDH1 mutations are one of those that's important because that goes to the roots of the development of acute myeloid leukemia.

In a couple of minutes.

Normally, as you all may remember from biochemistry, we have this Krebs cycle, which is the metabolism of the normal cells. And it goes through alpha-ketoglutarate. And when IDH, which normally metabolizes alpha-ketoglutarate, when it is mutated, it transforms alpha-ketoglutarate into 2-hydroxyglutarate, or 2-HG. And that metabolite, 2-HG, is usually not present in normal cells in the normal cycle. When it is formed, it has the potential to transform cells into leukemia cells, hematopoietic cells into leukemia cells through epigenetic mechanisms. So, actually, 2-HG becomes a biomarker of the mutation. It will go up when there is a mutation of IDH1.

And if you inhibit ADH1, the levels of 2-HG will go down, which is a good thing because, again, that is what drives the development of the leukemia.

So, with the understanding of the potential of this drug on slide 15, you can see that we have, from the very beginning, when I started getting involved with this drug, from the very early stages of the development, and we very quickly developed a very comprehensive plan for the development of elutacidinib, both as a single agent, as a monotherapy, and in combination with other agents, knowing that sometimes in leukemia you need combination for certain settings.

So, having elutacidinib, a very potent, very active drug selected for IDH1 being available, it can reverse that malignant phenotype.

But that's essentially the responses, but do we have important secondary endpoints. The overall response rate the duration of the remission the transfusion independence, the overall survival and of course the safety.

So, the monotherapy includes refractory, relapse, and other settings, including some exploration of the treatment-naive patients, patients who have not received prior therapy.

Those are the orange boxes.

All federal so let me describe the resell.

On slide 17, you can see the patient characteristics of those that are included in these evaluable cohorts that's being presented now are.

And we explore that also in the combination therapy.

Now, for the purposes of this presentation, the data that is most mature is what you'll see in slide 16, the refractory, relapse patients, monotherapy, which is the primary indication that's going to be pursued, again, because that is where most of the data is at the moment.

These are mostly older patients.

The median age of 71, we do have some younger patients, but you can see at the upper end of the spectrum. We had patients are way up into their eighties included on these in this study two.

That's where we usually would start the development of a drug. So, for this cohort, the primary endpoint was the achievement of what is called a CR or a CRH.

Two thirds of the patients are what we call. The novel email, meaning this is a disease that happens for the first time as opposed to the secondary AML, which is about a third of the patients that he sent emails that evolves from other malignancies or Myelodysplastic syndrome, most frequently but it could be from other.

And you apply shows sort of smaller perspective neoplasms in August and a few that had treatment related AML.

Male patients that had other cancers breast cancer lymphoma et cetera are you, giving chemotherapy they develop their email if those were just a few.

It's most typical that these mutation happens in patients that have either no chromosomal abnormalities or very frequently.

Extra chromosome eight are those are what we call intermediate risk chromosomal abnormalities I need represents a majority of these patient population, but theres a good.

A little over 20% that have a poor risk chromosomal abnormalities.

By definition all of the patients had an IV H one mutations of different variations of the IV H one.

Nation. The most common is these are 130 to see.

That's a little over half of the patients and then some of the others that you see on this slide.

We also know that patients with acute myeloid leukemia do not always only have one mutation. They mutations in other genes could coexist with I D. H one mutation. The most frequent that we saw in this cohort was N. P. M. One that occurred in almost 30% of the patients.

We spent mutations in all their genes three and all of those as you can see on this slide we're talking about refractory or relapsed patient population, referring to amines you gave them initial therapy. They did not respond at all.

The largest cohort and <unk>.

A little over 40% of the patients.

The others are relapsed that means you gave them. Some initial therapy. They responded but the disease is call me back.

The worst case scenario is that either the disease comes back quickly before 12 months that is the highest risk.

Patients that tend to have the worst prognosis and that is the next largest cohort 37%.

There also could be patients that have had.

Our response in relapsed, you'll give them something else responded again, they relapse the game, so two or more relapses. That's all it's a pretty bad 20% of the patients in this cohort are like that and the best case scenario is the patients will have a first relapse and the first remission lasted more than 12 months, that's a smaller.

A subset of these patients only.

11% of the patients you can see actually that most of the patients had received the median number of prior regimens was too. So if they had received at least two prior therapies before they came to be studied film had received as many as seven and.

11% had received actually a stem so twice.

I'll get to the definitions of that in a couple of minutes.

Let's jump to be a response rate in D. C on slide 18.

And you can see here that I mentioned the primary endpoint was C. R plus CRH, let me define that for those of you who may not be as familiar.

And that's essentially the responses.

But we have important secondary endpoints, the overall response rate, the duration of the remission, the transfusion independence, the overall survival, and, of course, the safety.

T R means that the blast count those fees.

The blasts are essentially the leukemia cells.

Slide 17 You can see the patient characteristics of those that are included in these evaluable, cohorts that's being presented now.

Uh huh.

The nor.

Normal is less than 5%.

More than that would be the leukemia. So CR means that the blast count has gone down below 5% and the platelets have recovered to at least 100000 and the neutrophils to at least a thousand that's a CR.

These are mostly older patients, the median age is 71, we do have some younger patients, but you can see at the upper end of the spectrum we have patients way up into their 80s included in this study.

Two-thirds of the patients are what we call the novel AML, meaning this is a disease that, happens for the first time, as opposed to the secondary AML, which is about a third of the patients, that is an AML that evolves from other malignancies, a myelodyspastic syndrome most frequently, but it could be from other hematologic neoplasms, sort of neoplasms and others, and a few that had treatment-related AML, patients that had other cancers, breast cancer, lymphomas, etc., you give them chemotherapy, they develop AML, those were just a few.

It's most typical that this mutation happens in patients that have either no chromosomal, abnormalities or very frequently extra chromosome 8, those are what we call intermediate risk chromosomal abnormalities, and it represents the majority of this patient population, but there's a good, a little over 20% that have a poor risk chromosomal abnormality.

By definition, all the patients had an IDH1 mutation, the different variations of the, IDH1 mutation, the most common is this R132C, that's a little over half of the patients and then some of the others that you see on this slide.

We also know that patients with acute myeloid leukemia do not always only have one mutation, the mutations in other genes could coexist with IDH1 mutations.

The most frequent that we saw in this cohort was NPM1, that occurred in almost 30% of the, patients, but we saw mutations in other genes, R3 and others, as you can see on this slide.

Now, we're talking about refractory or relapsed patient population. Refractory means you gave them initial therapy, they did not respond at all, that is the largest, cohort and it's a little over 40% of the patients. The others are relapsed, that means you gave them some initial therapy, they responded, but the disease is coming back.

If there is some recovery of the neutrophils and platelets, but not completely so the neutrophils are more than 500, but not quite more than a thousand and the platelets more than 50000, but not quite more than 100000 with velocity was less than 5%. That's a C. R. H. So you can see here that 33.

The worst case scenario is that either the disease comes back quickly, before 12 months, that is the highest risk, the patients that tend to have the worst prognosis, and that is the next largest cohort, 37%.

There also could be patients that have had a response, then relapsed, you gave them something, else, responded again, they relapsed again.

Percent of the patients achieved that primary endpoint.

Importantly, the great majority of these are the food C are 30% so only four of them.

So two or more relapses, that's also pretty bad, 20% of the patients in this cohort are, like that.

The 41 patients who responded or see our age of CRH is are good but certainly see are easily ultimate response, we.

We also have some patients that have <unk>.

Some recovery of the neutrophils and platelets, but they've been not quite make it to that.

Those thresholds that 550 of the CRH, we called go see our ice.

And the best case scenario is the patients who have a first relapse and the first remission, lasted more than 12 months, that's a smaller subset of these patients, only 11% of the patients.

11% of patients who have these.

Our response and then a couple of other smaller categories MLR fares means morphologic leukemia free state the blast counts went down to less than 5%.

You can see, actually, that most of the patients, the median number of prior regimens was two, so they had received at least two prior therapies before they came to these studies, some had received as many as seven, and 11% had received, actually, a stem cell.

But theres no really much recovery in the platelets or neutrophils and the PR means that the blast kind of wind down but it did not go all the way down to less than 5%, let's say somebody started with 90% plus of new went down two 8% well that's a partial response it doesn't quite make it to the full criteria of ways then.

All right, let's jump to the response rate then.

This is on slide 18.

5% if you take all of these together are almost half of the patients respond at 46% of the patients had.

He is one of these categories of response.

But very importantly, where do you see on slide 19 is the duration of response you you want to see that these responses are lost for some time not just happened one time and then immediately the patient relapses as you can see here the duration of response.

The median duration I E.

He has.

It has not yet been reached at the time of this analysis.

If you do a very conservative approach, what's called a sensitivity analysis and say well because some of these patients went toward twice spent I'm going to and the response at the time they went to try and spend so I don't have to.

Judy Kate to the drug something that was partially.

Attributed to the Trust fund than the median duration is 13.8 still a very very good outcome and again, it's not that they relapse at that point, we just stopped content because they went to a trust fund.

And you can see, here that I mentioned the primary endpoint was CR plus CRH.

And then on Slide 20 also something very important that I mentioned that the primary endpoint of a CR in CRH and this shows the survival of the patients. According to the response at the hub.

Let me define that for those of you who may not be as familiar.

A CR means that the blast count, the blasts are essentially the leukemia cells. The normal is less than 5%.

The patients who had a CR or a CRH their median survival has not yet been reached by 18 months.

The 87% of patients are still alive, which is I've notwithstanding outcome now very important to see some of these lesser responses that I mentioned to see a rise in morphologic leukemia free there.

More than that would be the leukemia.

They also have a survival benefit these patients have a median survival of 15 months for more than a year.

Prior to the patients who did not respond with a median survival of only four months so that means that.

The even the lesser responses have value to the patients add to their survival probability significantly from four months to 15 months as the as the.

So CR means that the blast count has gone down below 5% and the platelets have recovered, to at least 100,000 and the neutrophils to at least 1,000.

The median.

Let's talk now a little bit about the safety of allude to Sydney.

That's a CR.

I'm showing you here what is called treatment emergent adverse events E S.

And what that means is any toxicity that happens while the patient is anything that happens while the patient is taking to grow we're not making assumptions that he was related or not related we just say it happened eat you know we reported.

So anything that happens in.

20% of patients for more or that was grade three or four in at least 10% grade three or for the more severe instances of these adverse events. When you treat patients with leukemia, it's very typical with any treatment that they're neutral foods go down to play let's go down the hemoglobin goes down. So so that is a fairly standard with chemotherapy.

If there is some recovery of the neutrophils and the platelets, but not completely.

So the neutrophils are more than 500, but not quite more than 1,000.

And the platelets more than 50,000, but not quite more than 100,000.

With the blast still less than 5%, that's a CRH.

So you can see here that 33% of the patients achieved that primary endpoint. Importantly, the great majority of these are the full CRs, 30%. So only four of the 41 patients who responded are CRHs.

CRHs are good, but certainly CR is the ultimate response.

There's an additional 11% of patients who have this response.

We also have some patients that, have some recovery of the neutrophils and the platelets, but they do not quite make it to those thresholds, the 500 and the 50 of the CRH. We call those CRIs.

It's 100% of patients have these things with the great majority of the adverse events that you see here reported on these on these slides.

And then a couple of smaller categories.

MLFS means morphologic leukemia free state.

The blast count went down to less than 5%, but there's not really much recovery in the platelets or the neutrophils.

<unk> anemia.

Thrombocytopenia neutropenia and actually those are the only ones that reached any significance in terms of grade three or grade four and of course, the patients who dropped their neutrophils for frequency have a fever as well, but other than those.

And the PR means the blast count went down, but it did not go all the way down to less than 5%. Let's say somebody started with 90% blast and it went down to 8%.

Well, that's a partial response, doesn't quite make it to the full criteria of less than 5%.

If you take all of these together, almost half of the patients responded.

46% of the patients had at least one of these categories of response.

The only ones that are that stand out or any great.

Some nausea.

A little over a third of patients constipation in a quarter of the patients.

But very importantly, what you see on slide 19 is the duration of response. You want to see that these responses last for some time, not just happen one time and then immediately the patient relapses. As you can see here, the duration of response is the median duration has not yet been reached at the time of this analysis.

Some fatigue and 20% of the patients, but none of these really make it to any grade three or four. So these were mild side effects that are clearly manageable.

If you do a very conservative approach, what's called a sensitivity analysis, and say, well, because some of these patients went to a transplant, I'm going to end the response at the time they went to a transplant. So I don't adjudicate to the drug something that was partially attributed to the transplant, then the median duration is 13.8. Still, a very, very good outcome. And again, it's not that they relapsed at that point, we just stopped counting because, they went to a transplant.

Slide 20 I mentioned that the primary endpoint was, CR and CRH, and this shows the survival of the patients according to the response that they had. The patients who had a CR or a CRH, their median survival has not yet been reached.

By 18 months, 87% of patients are still alive, which is an outstanding outcome.

For these patients they are much better than what you would expect with a chemotherapy for example.

Now very importantly, some of these lesser responses that I mentioned, the CRIs, the, morphological leukemia-free, they also have a survival benefit. These patients have a median survival of 15 months, or more than a year, compared to the, patients who did not respond, who have a median survival of only four months. So that means that even the lesser responses have value to the patients, add to their survival, probability significantly from four months to 15 months as the median.

Now moving to slide 22, I went to point some of the adverse events of special interest. Some some things that are of particular importance first qt prolongation with Q T C.

Slide 21 Let's talk now a little bit about the safety, of elutocinib.

I am showing you here what is called treatment emergent adverse events, DEAEs, and what that, means is any toxicity that happens while the patient is taking the drug.

We're not making assumptions that it was related or not related.

Q T E sand interval in the electrocardiogram, you've seen those graphics and electrocardiogram.

You measure from one quite a wave that's that's called the <unk> waiver.

Wave that's called a T wave you see the interval between dose if it gets very long there is always a very severe a REIT that can be even fatal and and we see that sometimes.

Fortunately here it happened very infrequently less than 10% of patients had any qt prolongation, but most importantly, the ones that we worry the most about the grade three and agreed for the very long intervals. It happened in only one patient and was a grade three.

We just say it happened, we report it. So anything that happened in 20% of patients or more, or that was grade three or four in, at least 10%, grade three or four, the more severe instances of these adverse events.

When you treat patients with leukemia, it's very typical with any treatment that their, neutrophils go down, the platelets go down, the hemoglobin goes down.

So that is a fairly standard with chemotherapy, 100% of patients have these things.

But even that did not lead to discontinuation of the drug. So it was very low rate and very manageable.

Well that's the great majority of the adverse events that you see here reported on this, slide.

It's anemia, it's thrombocytopenia, it's neutropenia, and actually those are the only, ones that reach any significance in terms of grade three or grade four, and of course the patients who drop their neutrophils very frequently have fever as well.

And then we have lever abnormalities is where perhaps the adverse events other than the blood counts that we saw more frequently you see any great happened.

We were between 27% for bilirubin to 42% with one of the transaminase is a S T a.

Fortunately these were grade three.

Small percentage of patients. So overall, 20% of patients had any earlier.

Patients of liver enzymes.

But only a 12% had grade three or grade four most of these are actually great three but very importantly of these 32 patients 25 of those 32 did not require any dose modification or if they had those modification that was enough for the patient to continue on therapy.

On these seven patients who discontinued.

Treatment for.

Recurrent three others and basically get or did not want to re challenge. We thought there was a judgment or anything so we don't know what would have happened there.

And then differentiation syndrome is something that we've learned happens with I D H inhibitors.

And as part of the process of maturation, but it can come with symptoms with problems that happen, but fortunately it happening only 14% of these patients and the most and and about half of these were grade one grade two the oldest were grade three or grade four 8% total only three pay.

However, discontinued treatment because so far the differentiation syndrome meeting the great majority of these are very they can be managed well with treatment interruptions. We know some drugs that you use corticosteroids from Myles that chemotherapy like hydroxyurea and things like that so.

Very very manageable toxicity because of the low rates and the.

Low.

Density of the civic so.

My conclusion is that with these interim analyses.

We see that the root cause.

<unk> has a very high response rate very high rates of CRC CRH, but very importantly, most of these are true see ours and they're durable remissions that even with a very conservative analysis accounting for twice what the median duration.

He is more than more than a year are indeed there.

Heavily pretreated patient population.

And that these benefits extents to even patients that do not have the full cri CRH with all the responses. They also have a survival benefit and this comes with a drug that's oral that's very well tolerated that most of these toxicities are very manageable very mild.

But other than those, the only ones that stand out of any grade are somnolence in a little, over a third of patients, constipation in a quarter of the patients, some fatigue in, 20% of the patients, but none of these really make it to any grade three or four. So these were mild side effects that are clearly manageable for these patients, much better, than what you would expect with a chemotherapy, for example.

And that makes it a very applicable very welcomed drug.

The management of these patients with a D. H one mutation with acute myeloid leukemia. So this is my presentation and thank you for your attention.

Find it over to our next speaker.

Thank you very much Doctor Cortez for your thorough review of our data.

Now moving to slide 22, I want to point some of the adverse events of special interest, some things that are of particular importance.

Really appreciate all of your insights and.

I know there will likely be questions as we move to the end of the call. So I just have a few brief comments on <unk> progress in Q2.

First QTC prolongation. QTC, the QT is an interval in the electrocardiogram, you've seen those graphics of an electrocardiogram, you measure from one wave that's called the Q wave and another wave that's called the, T wave, you see the interval between those. If it gets very long, there is a risk of very severe arrhythmias that can be even fatal, and we see that sometimes.

Now fortunately here, it happened very infrequently, less than 10% of patients had any QTC prolongation, but most importantly, the ones that we worry the most about are the grade three and the grade four. The very long intervals, it happened in only one patient, and it was a grade three, but, even that did not lead to discontinuation of the drug. So it was very low rate and very manageable.

We're actually quite excited about that as well on slide 25, you'll see our FDA approved indication, which is for adult patients with chronic immune thrombocytopenia or <unk>, who have had an insufficient response to a previous treatment.

Unknown Executive, Farzin Haque, Nalin Tejavibulya, Richard Miller, Raymond Furey, Nalin Tejavibulya, and unfortunately it happened in only 14% of these patients, and about half of these were grade 1 or grade 2, the others were grade 3 or grade 4, 8% total.

Only three patients, however, discontinued treatment because of a differentiation syndrome, meaning the great majority of these are very, they can be managed well with treatment interruptions.

Slide 26, Q2 was the third quarter in a row that we achieved the high in bottles shipped to patients and clinics, we were happy with the growth trajectory. We saw in Q1 and then it accelerated in Q2 are.

We know some drugs that use corticosteroids on mild chemotherapy, like hydroxyurea and things like that.

So a very, very manageable toxicity because of the low rate and the low intensity of these events.

Our 2054 bottles shipped to patients and clinics represented 21% growth over Q2 of last year and 12% over Q1 of this year that was our highest sequential demand growth in two years or.

Our demand growth continued to be driven by the increased new patient starts we've been generating since Q4 of last year.

We achieved net sales of $18 6 million, a 9% increase over the same quarter last year.

So we're very pleased with the continued positive momentum we're seeing in our ICT sales and I'd like to thank our commercial team for all of their collaborative work to grow tallis.

On Slide 27, you see how our customer interactions have also continued to grow in Q2, particularly with respect to our in person interactions. Our team grew our in person interactions another 30% beyond Q1, and those made up more than three quarters of our total interactions with customers. So overall in.

Q2, you are double digit demand growth over Q1 created a new quarterly high in net sales for <unk>, we've been focused on leveraging every opportunity to impact customers with our key messages on tower leases efficacy and safety along with our preferred status on key national Formularies.

These messages have been effective in raising awareness and reimbursement confidence among prescribers and resulted in more new patient Sunpower Louise.

Thanks for your attention and I'll now turn the call over to Wolfgang to provide a brief update on our development progress Wolfgang.

Thank you, Dave I will provide the update on the other ongoing programs in stores with a phase III.

So my conclusion is that with this interim analysis, we see that the elutocidin has a very high response rate, very high rate of CR, CRH, but very importantly, most of these are true CRs and they're durable remissions, that even with a very conservative analysis accounting for transplant, the median duration is more than a year in this very heavily pretreated patient population.

Study.

And that this benefit extends to even patients that do not have the full CR or CRH with other responses, they also have a survival benefit.

Slide 29.

In June we reported that the forward phase III study in warm.

<unk> did not meet its primary efficacy endpoint.

And this comes with a drug that's oral, that's very well tolerated, that most of these toxicities are very manageable, very mild, and that makes it a very applicable, very welcome drug for the management of these patients with IDH1 mutation with acute myeloid leukemia.

Fortunately the safety profile was consistent with prior clinical experience and no new safety.

<unk> was discovered.

So this is my presentation.

Overall, we have shared our belief that the results are negatively impacted by a large placebo response rates, particularly in eastern Europe .

Since the topline announcements, we did a large number of additional analyses in order to understand the data in greater detail.

We will discuss the previously shared data and all new reanalysis data in detail with the FDA. This fall to determine the path forward and AIG.

We continue to believe the totality of these data may still allow for a positive overall benefit risk assessment for post imatinib.

Hey.

Shifting gears now to our COVID-19 program.

Moving to slide 31, we are still confident that post imatinib can provide therapeutic benefits in COVID-19. Most importantly based on the published positive clinical data from the NIH NHL phase two study in hospitalized patients with severe COVID-19.

Given persistent resistance to vaccination in some places and the possibility of new virus variance there will continue to be severely ill hospitalized patients who need effective treatment options.

We have two ongoing phase III trials that will provide us with pivotal data.

And if approved in this indication tower lease would be available for immediate use for these patients.

Slide 32.

Due to the recent slow enrollment we completed randomization into our pivotal phase III study of 280 patients, which is 91% of targeted enrollment.

The original enrollment target was 308 patients however.

However, we determined the trial would be sufficiently powered it was 280 patients who potentially provide a clinically meaningful result in determining the efficacy and safety of post imatinib in COVID-19.

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

There are also multiple secondary endpoints to assist the important mortality risk as well as improvement from severe disease and duration of hospitalization ICU stay.

The follow up period is through the 60 after the last dose. So we expect to have top line data in the fourth quarter. This year and plan to file in UAE. If the data is positive.

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

I thank you for your attention, and I'll hand it over to our next speaker.

Thank you very much, Dr. Cortes, for your thorough review of our data.

Thank you Wolfgang I'm on slide 34 for the second quarter of 2022, we shipped 2053 bottles to our specialty distributors, resulting in $26 $4 million of gross product sales 2054 bottles were shipped to patients and clinics, while 924 bottles.

We really appreciate all of your insights, and I know there will likely be questions as we move to the, end of the call.

So I just have a few brief comments on Tavalee's progress in Q2.

And in our distribution channels at the end of the quarter.

We reported net product sales from <unk> of $18 6 million, a 9% increase compared to the same period in 2021.

Our net product sales from <unk> were recorded net of estimated discounts charge backs rebates returns co pay assistance and other allowances of $7 $9 million, our gross to net adjustments of approximately 29, 8% of gross product sales for the second quarter of 2022.

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

We're actually quite excited about that as well.

On slide 25, you'll see our FDA-approved, Moving to slide 26, Q2 was the third quarter in a row that we achieved a high in bottles shipped to patients in clinics.

We were happy with the growth trajectory we saw in Q1 and that it accelerated in Q2. Our 2054 bottles shipped to patients in clinics represented 21% growth over Q2 of last year and 12% over Q1 of this year. That was our highest sequential demand growth in two years.

Our demand growth continued to be driven by the increased new patient starts we've been generating since Q4 of last year. We achieved net sales of $18.6 million, a 9% increase over the same quarter last year. So we're very pleased with the continued positive momentum we're seeing in our ITP sales.

We also expect to receive a $2 $5 million milestone payment during the third quarter relating to the enrollment completion in the phase III COVID-19 study, which is supported by the U S Department of Defense government grants incrementally. We currently expect our gross to net adjustment to be approximately 30% in the third quarter of 2022.

And I'd like to thank our commercial team for all of their collaborative work to grow Tavalese.

On slide 27, you see how our customer interactions have also continued to grow in Q2, particularly with respect to our in-person interactions. Our team grew our in-person interactions another 30% beyond Q1, and those made up more than three-quarters of our total interactions with customers.

So overall in Q2, our double-digit demand growth over Q1 created a new quarterly high in net sales for Tavalese. We've been focused on leveraging every opportunity to impact customers with our key messages on Tavalese's efficacy and safety, along with our preferred status on key national formularies. These messages have been effective in raising awareness and reimbursement confidence among prescribers and resulted in more new patients on Tavalese.

Thanks for your attention, and I'll now turn the call over to Wolfgang to provide a brief update on our development progress.

<unk>.

Under the next slide in addition to net product sales Rogers contract revenues from collaborations were approximately $11 3 million for the three months ended June 30th 2022, which consisted of $7 $5 million from key say, which included the $5 million milestone for the NDA filing in Japan.

$2 million related to our license agreement with Tonight.

$4 million from our collaboration agreement with referrals and $300000 of our license agreement with Lilly.

Moving on to costs and expenses our cost of product sales was approximately $1 million for the second quarter of 2022.

Approximately $900000 of this related to the delivery of fast imatinib supplies for our distribution partners.

Total costs and expenses were $42 $8 million in the second quarter of 2022 versus $39 $3 million in the second quarter of 2021.

The increase in costs and expenses was primarily due to increased commercial activities related to our sales force expansion and increased research and development costs for the development of our Iraq, One four inhibitor program.

Partially offset by decreased research and development costs related to our phase III clinical trial of fast Imatinib for warm autoimmune hemolytic anemia, and our ongoing phase III clinical trial of fast Imatinib in high risk hospitalized patients with COVID-19.

We ended the quarter with cash cash equivalents and short term investments of $89 $2 million.

Finally, we announced today that we drew an additional $10 million on our mid cap financial credit facility.

Please note that this draw occurred during the third quarter as a reminder, $20 million remains available to draw through March 31, 2023. We also extended the maturity terms. This credit facility is now our interest only through September 2024 monthly principal amortization that extends 24.

Months through September of 2026.

Onto the next slide let me highlight for you some of the key terms of the agreement with former Therapeutics, Roger will pay form a $2 million upfront payment with an additional $2 $5 million for near term regulatory milestone of $5 million upon approval and 10 million.

Upon first commercial sale.

Not finalized our review of the accounting treatment of these various payments. We currently expect the preapproval milestones to be treated as operating expense in the period incurred incrementally.

Incrementally our collaboration agreement also includes additional regulatory and commercial milestone payments as well as tiered royalties on net sales.

Finally, incorporating the pre approval milestones noted above launch preparation activities that Dave highlighted let me update you on our expectations for operating expenses through the end of the year.

We expect to see a small incremental increase in operating expenses in the third and fourth quarters of this year as compared to the first two quarters of this year.

As we continue to develop our launch plans and prepare for launch we expect to see strong synergies and leverage and we will provide operating expense updates into the future with that I'd like to turn the call back over to Ralph.

Wolfgang?

Thank you Dean to conclude this quarter, we made significant advancements in growing and expanding our hemo focused business.

Thank you, Dave.

I will provide the update on the other ongoing programs and start with our Phase III AIHA study.

Slide 29.

First we achieved the highest quarterly net product sales for <unk> since launch and we are well positioned to maintain that momentum in upcoming quarters.

Second we are very excited about our strategic in licensing a whole a pseudonym and.

We bring a new and important treatment for patients with AML.

Next year, you may see Roger with two highly synergistic products.

Each may enable greater success of both and more fully leverage our commercial capabilities.

We also remain committed and focused on advancing our other portfolio of programs.

In June, we reported that the forward Phase III study in warm AIHA did not meet its primary efficacy endpoint. Importantly, the safety profile was consistent with prior clinical experience, and no new safety signals were discovered. Overall, we have shared our belief that the results were negatively impacted by a large placebo response rate, particularly in Eastern Europe. Since the top-line announcement, we did a large number of additional analyses in order to understand the data in greater detail.

We continue to analyze the phase III trial data and look forward to discussing our findings with the FDA.

We will discuss the previously shared data and all new reanalysis data in detail with the FDA this fall to determine the path forward in AIHA. We continue to believe the totality of this data may still allow for a positive overall benefit risk assessment for fostamatinib in AIHA.

We believe that foster Magnum has the potential to help patients with warm AIA <unk> in a very meaningful way.

Shifting gears now to our COVID-19 program, moving to slide 31, we are still confident that fostamatinib can provide therapeutic benefits in COVID-19.

Most importantly, based on the published positive clinical data from the NIH NHLBI Phase II study, it hospitalized patients with severe COVID-19. Given persistent resistance to vaccination in some places, and the possibility of new, virus variants, there will continue to be severely ill hospitalized patients who need effective treatment options.

With our phase III COVID-19 trial, having completed enrollment we expect to report topline results in the fourth quarter of this year.

We have two ongoing phase 3 trials that will provide us with pivotal data, and if approved, in this indication, Tavalis would be available for immediate use for these patients.

Slide 32.

And lastly, we continue to drive our two earlier clinical programs are to ignite our Iraq <unk> four inhibitor.

Due to the recent slow enrollment, we completed randomization into our pivotal phase 3 study, at 280 patients, which is 91% of our targeted enrollment. The original enrollment target was 308 patients. However, we determined the trial would be sufficiently powered with 280 patients to, potentially provide a clinically meaningful result and determine the efficacy and safety of fostamartinib in COVID-19.

As mentioned earlier this year, we updated the inclusion criteria for the trial to focus, on more severe patients and changed the primary endpoints to days on oxygen for a more sensitive measure and better comparison to the NIH active trials. There are also multiple secondary endpoints to assess the important mortality risk, as, well as improvement from severe disease and duration of hospitalization or ICU stay.

We expect to enter phase one slash two trials in Q3 and with arc 505 to our Rip inhibitor. We look forward to this program moving into phase II clinical development, which we expect to happen in the first half of next year.

The follow-up period is through day 60 after the last dose.

So we expect to have top-line data in the fourth quarter this year and plan to file, an EUA if the data is positive.

So with that let me turn the call over to your questions.

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

And if I may ask since Dr. Cortez who's with US if you have questions for him.

Let's put those first in your in your call sequence.

Operator.

Thank you if you'd like to register for a question. Please press star one on your telephone keypad, a confirmation tone will indicate your line is in the question queue.

Dean?

Thank you, Wolfgang.

I'm on slide 34.

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For the second quarter of 2022, we shipped 2,053 bottles to our specialty distributors, resulting in $26.4 million of gross product sales. 2,054 bottles were shipped to patients at clinics, while 924 bottles remained in our, distribution channels at the end of the quarter.

We reported net product sales from Tavlis of $18.6 million, a 9% increase compared to, the same period in 2021. Our net product sales from Tavlis were recorded net of estimated discounts, chargebacks, rebates, returns, copay assistance, and other allowances of $7.9 million.

Our gross to net adjustment is approximately 29.8% of gross product sales for the second, quarter of 2022.

One moment, please while we poll for questions.

Sure.

Thank you. Our next question is from Union Yang with Jefferies.

Before we move on from net product sales, let me review our expectations for the third, quarter of 2022. We are pleased with the continued strength of our bottles shipped to patients at clinics, that Dave described, and expect growth to continue as access to physicians and new patient starts continues to expand. We also expect to receive a $2.5 million milestone payment during the third quarter, relating, to the enrollment completion in the phase three COVID-19 study, which is supported by the U.S. Department of Defense government grant.

Please proceed with your question Hi, Thank you so for this AML ARPA Kennedy.

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

In addition to net product sales, RIGA's contract revenues from collaborations were, approximately $11.3 million for the three months ended June 30, 2022, which consisted of $7.5 million from Kisei, which included the $5 million milestone for the NDA filing in Japan.

You guys, you're mentioning at least on the fly the nearer term opportunity.

Hum.

How about 1000 patients pay in the U S. What are you thinking about how long are you thinking about the pricing number one.

So anyhow.

Faster you can actually penetrate 1000 patients.

Once you launch the product upon approval.

$2 million related to our license agreement with Knight, $1.4 million from our collaboration, agreement with Griffles, and $300,000 for our license agreement with Lilly.

Moving on to cost and expenses, our cost of product sales was approximately $1 million, for the second quarter of 2022. Approximately $900,000 of this related to the delivery of Fostamatinib supply to our, distribution partners.

Total cost and expenses were $42.8 million in the second quarter of 2022 versus $39.3, million in the second quarter of 2021. The increase in cost and expenses was primarily due to increased commercial activities related, to our Salesforce expansion and increased research and development costs for the development of our IRAC1.4 inhibitor program, partially offset by decreased research and development costs related to our Phase 3 clinical trial of Fostamatinib for warm water immune hemolytic anemia and our ongoing Phase 3 clinical trial of Fostamatinib in high-risk hospitalized patients with COVID-19.

We ended the quarter with cash, cash equivalents, and short-term investments of $89.2 million. Finally, we announced today that we drew an additional $10 million on our MidCap financial, credit facility. Please note that this draw occurred during the third quarter. As a reminder, $20 million remains available to draw through March 31st, 2023.

And the second question is if a dean that $2 million from pay monies that are gonna be amortize always you wont have it booked at one.

We also extended the maturity terms. This credit facility is now interest-only through September 2024. Monthly principal amortization then extends 24 months through September of 2026.

On to the next slide.

And I guess I like.

Regulatory milestone or did they book there was but I cannot comment on all from payment and how it's going to be booked in the income statement. Thank you.

Thank you and appreciate that let me ask <unk> to answer that one first and then I'll ask Dave to answer your first two questions on pricing and how quickly might you might be able to penetrate that relapse refractory market an idea it's positive AML.

Let me highlight for you some of the key terms of the agreement with Forma Therapeutics. Roger will pay Forma a $2 million upfront payment with an additional $2.5 million for, near-term regulatory milestone, $5 million upon approval, and $10 million upon first commercial sale.

Yes, hi, Yoon the upfront payments, we expect the preapproval milestone payments that I just described we expect to.

While we've not finalized our review of the accounting treatment for these various payments, we currently expect the pre-approval milestones to be treated as operating expense in the period incurred. Incrementally, our collaboration agreement also includes additional regulatory and commercial, milestone payments, as well as tiered royalties on net sales. Finally, incorporating the pre-approval milestones noted above and launch preparation activities, that Dave highlighted, let me update you on our expectations for operating expenses through the end of the year.

Included in operating expense.

And therefore, the upfront $2 million that $2 $5 million of the near term regulatory milestone we expect those in that in the back half of this year.

We expect to see a small incremental increase in operating expenses in the third and fourth, quarters of this year as compared to the first two quarters of this year.

And the.

The guidance I gave with respect to operating expense in this small increase from the Q1 Q2 levels are inclusive of those that $2 million and $2 $5 million cost. So that's built into that in the operating expense feedbacks I provided.

As we continue to develop our launch plans and prepare for launch, we expect to see strong, synergies and leverage, and we'll provide operating expense updates into the future.

Thanks, Dave.

I think thanks for the question Hugh I think from a pricing standpoint, obviously, we just.

Did the transaction so we're not going to release any information on price, but I would say that if you look at targeted therapies in AML, that's probably a good target for you I mean theyre all in the in the in a similar neighborhood and so that's probably the best that I would I would say there's been seven approvals of oral <unk>.

Agents over the last five years.

<unk>.

Particularly when you look at targeted agents and IH, one IV HQ and flip three and particularly even in the relapsed setting.

I think those are those are sort of the numbers that.

We've been looking at and we'll be discussing as we move forward, but certainly no decision has been made.

In terms of uptake I guess, the best thing I can tell you is that the first quarter on launch with another <unk> inhibitor and this was when there was less information out there on IV H, one less testing unless identification today it standard and widespread there were 100 inpatient.

On the product at least that's what the original if you look back at that earnings call and the first partial quarter of launch 100 prescribers of the drug so.

I think that this is obviously a question of.

Are the patients out there they are well identified and the question is going to be you know.

There's oh Lucent they've offer.

An advantage over other therapies that might be used in this relapsed refractory space, but we plan to differentiate it as best we can.

Thank you.

Thank you Ian.

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

Thank you. Our next question comes from <unk> <unk> with Citi. Please proceed with your question.

Thank you, Dean.

This is carly on for Yigal. Thank you for taking our questions. We have one for doctors Cortes can you talk about how you think that.

To conclude, this quarter, we made significant advancements in growing and expanding our, HEMONC-focused business. First, we achieved the highest quarterly net product sales for Tabolisse and ITP since, launch, and we are well-positioned to maintain that momentum in upcoming quarters.

Second, we are very excited about our strategic in licensing of Olasutinib and potentially bringing, a new and important treatment for patients with AML.

Next year, you may see Rigel with two highly synergistic products, which may enable greater success of both and more fully leverage our commercial capabilities.

We also remain committed and focused on advancing our other portfolio programs.

Efficacy and safety of.

Although this had net compared to either fitness and.

I guess, assuming membership Chris how do you see it sort of being used alongside either.

Okay.

We continue to analyze the phase three AIHA trial data and look forward to discussing our findings with the FDA.

We believe that Foster Magnum has the potential to help patients with warm AIHA in a very meaningful way.

Dr. Cortez, if you would.

With our phase three COVID-19 trial having completed enrollment, we expect to report top line results in the fourth quarter of this year.

And lastly, we continue to drive our two earlier clinical programs, R289, our IRAC1.4 inhibitor.

We expect to enter phase one slash two trials in Q3.

Sure.

And with R552, our RIP inhibitor.

Hello.

We look forward to this program moving into phase two clinical development, which we expect to happen in the first half of next year.

Dr Cortez.

So with that, let me turn the call over to your questions.

Can you hear me.

And if I may ask, since Dr. Cortez is with us, if you have questions for him, let's put those first in your call sequence.

Oh, Yes, there you go yes, there you go.

Operator?

Thank you.

I'm, sorry, I was saying that you know certainly I would see it anyway. So it's a very good drug and we've been fortunate to have it for some time.

If you would like to register for a question, please press star one on your, telephone keypad.

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And also we need to.

Highlight the fact that there were acknowledged the fact that it's difficult to compare when you when you're looking at two different studies, but if we look at the characteristics of the studies, which are essentially very similarly conducted in a similar patient population.

I think that there is many reasons to believe why that's almost a certainty.

It compares favorably to I proceeded and number one in terms of the patient population that was in this study.

The two are refractory or relapsed acute myeloid leukemia.

One moment, please, while we pull for questions.

But the.

Characteristics of the patients are there are little bit older and they are going to see it in each study.

Thank you.

There are a lot.

It'll be more difficult to treat for example would be there.

I mentioned these are fully refractory patients.

They are there.

Their or their relapsed patients there were very few patients that have relapsed within 12 months, which as I mentioned the harder patient population there were less than 10% here. We have a third of the patients were like that so so many of the features are equal or worse we've.

We'd be sitting here, so we're starting with a worse with a more difficult patient population and yet the overall response rate lukes.

Similar if not better than the overall the response, the CR plus CRH was 30% without <unk>.

It's 33% here, but most importantly.

The CR rate, which was 21% type of Sydney is 30% or with the Sydney the duration of Oh for a remission.

Which was.

About eight months with a with a receipt of need it's 13 eight months with a good precedent so yeah.

There there's differences between the studies and again you cannot make too much but every.

Free item points to some benefit compared to.

Where do we have.

With that I would see it it keeps you see prolongation very uncommon, we'd say with.

The city in which folks are very very important not that it's that's common with Apple Sydney, but it is more than than we see with our with Republic. The Sydney. So overall I feel very good about the potential of these drugs because he these drug because it adds.

It has many aspects that seem to suggest.

A further improvement over what we already have with that I will see it and if so I think that I would certainly if it was available today.

I would use it quite a bit.

Okay, Great. That's that's very very helpful. And then we just had a question for Rigel as well you highlighted the synergies with the existing I T. P. South fourth are you are you expecting to add sales reps in order to support the AML launch and I guess, just curious you know how much we could expect opex.

<unk> to ramp.

All into 2023, thanks, so much.

Thanks, Charlie I'll ask Dave to answer that question and then Dean in terms of the Opex piece of it.

Yes, great question and actually we're not going to be expanding our sales force at all for this because <unk>.

Is it much.

Much bigger patient population treated across a community. So we've got significant coverage out there with our current team and so what we now have to do obviously in and by the way.

In the relapsed refractory setting with an oral therapy and this can be used in the community and patients are being treated in the community. So that'll be good but well Additionally have to pick up.

Leukemia, treaters and institutions, which were already call. It God, but the answer is no additions to our sales force I think they've got quite the capacity.

After announcing this today I'm pretty sure I can say without any furbearer, they're gonna be tremendously excited.

To have something else in their bag so.

That answered your question and that's exactly why we looked at a drug like <unk> that we think it fits perfectly into our bag.

Seeing hematologists oncologists community, we were in the institutions, where leukemia treaters are and we can spread the word rapidly.

And currently with respect to operating expense, we expect limited clinical spend so Dave described the significant leverage on the commercial commercial side. So limited clinical spend I'd just remind you also with respect to our just overall operating expense as we've as we roll off.

And we've just completed our phase III study in AI H E.

We're wrapping up the phase III study in Covid.

We expect to see some some some leverage some savings into the future on clinical spend there too. So so that's a.

A bit of a bit of feedback on the oldest suite nib.

Impact on operating expenses.

So again.

Thank you Carla.

Thank you. Our next question is from Joe Pan Kenneth with H C. Wainwright. Please proceed with your question.

Our next question is from Yun Yang with Jeffries.

Please proceed with your question.

Thank you.

So for this AML opportunity, you guys are mentioning, at least on the slide, the near-term opportunity is about 1,000 patients in the U.S.

Hey, everybody. Good afternoon. Thanks for taking the question an interesting transaction and thanks for the details.

So how are you thinking about the pricing, number one, and how fast you can actually penetrate 1,000 patients once you launch the product upon approval?

And the second question is for Dean.

So first for Dr. Cortez I guess when you were talking about the slides regarding the AE profile.

The $2 million offer on payment, is that going to be amortized or is it going to be booked at once?

Physicians, such as yourself and at centers of Excellence. You said, obviously these are a very manageable toxicity profile. When you look at things such as the liver elevations and even things like the differentiation syndrome, how is the broader physician community in AML.

Equipped to be able to treat these M aes.

Thank you I think that's it.

By now we are very well equipped no liver toxicity is something that a general oncology.

Many other drugs that they use for solid tumors I know things.

Have you been higher incidents, Susan and and and severity than these he's where do we see here.

You know one other area that I that I manage a lot of patients who see a male than some of the drugs that we usually see them they'll have higher easy things this will be season yet.

Zebra toxicity, specifically and I think physicians manage that well.

The differentiation syndrome.

E a little bit more unique and not something that you've seen with many other countries.

Cancer therapies.

But number one it's not that.

Come Unfortunately, with a group of Sydney and I think that's a little by little they have become much more aware of these and they can manage well I've seen them manage with some of the other drugs that we're using to induce hematologic malignancies.

And they become much more aware and alert them than when we started seeing these things initially with an I D. H two inhibitor, which was the first one it was approved that was sort of a bit more of a surprise even for us when we started developing the drugs, but then over time I think they've become very familiar.

And are able to manage these and you know if if not manage themselves at least call for help so I feel comfortable with how they will be able to manage it well.

We're going to see it and you'd be in the clinic.

And I guess the regulatory milestone will be booked at once, but can you comment on offer on payment, how it's going to be booked in the income statement?

No. Thank you for that very much and then to.

<unk> questions for the company please.

Thank you.

Regarding way how are you able to I know it's ahead of your FDA interactions in the fall that you mentioned, but are you able to give us any additional information or <unk> for that matter regarding additional analyses that you've been conducting.

Thank you, Yun.

Yeah, Joe Thanks for that question, we've done a great deal of analysis on the data since our since we announced that we've worked hard on that and at this point, what we prefer to do is to share that with FDA first before sharing more broadly that would be the appropriate steps.

Appreciate that.

Let me ask Dean to answer that one first, and then I'll ask Dave to answer your first two questions on pricing, and how quickly you might be able to penetrate that relapsed refractory market and IDH-positive AML.

View as the next step to do and have those discussions and after that interaction be able to report to you in the investor community. What FDA feedback is on that based on that analysis, rather than showing ensuring additional analysis at the FDA not view that favorably as a result.

So the timing is.

Not that far out by the way, we hope to meet with the FDA in the fall and after that we would have had.

Have some feedback from them and be able to share more.

Totally fair and then just quickly I wanted to see if how things are being maintained or improving regarding.

The current refill rate based on prior quarters, you had been hovering around the mid fifties.

Dave do you want to comment on the persistency.

Assistance C Hasnt changed.

It takes a long time to move that curve, obviously, we've been adding new patients it's too early to assess.

Whether those patients have longer persistency, but for right now we're maintaining in the mid fifties.

Yeah.

Great. Thanks, guys.

Thank you Joe.

Thank you. Our next question comes from Gary Nachman with BMO capital markets. Please proceed with your question.

Hi, Yun.

The upfront payments we expect, the pre-approval milestone payments that I, described, we expect to be included in operating expense. And therefore, the upfront $2 million, the $2.5 million of the near-term regulatory milestone, we expect those in the back half of this year. And the guidance I gave with respect to operating expense and the small increase from the Q1, Q2 levels are inclusive of those, that $2 million and $2.5 million cost. So that's built into the operating expense feedback that I provided.

Hi, good afternoon, and congrats on the deal first for Dr. Cortez, where do you see the most opportunity in additional indications for alluded fitting in.

Going forward in particular, how important will combination therapy over time.

I think from a pricing standpoint, obviously we just did the transaction, so we're not going to release any information on the price, but I would say that if you look at targeted therapies in AML, that's probably a good target for you.

What's the timing of that data and at what point will physicians start to experiment with that and how many more patients are out there beyond the 1000 that could be good candidates overtime.

I mean, they're all in a similar neighborhood, and so that's probably the best that I would say.

Yeah. Thank you first thing in terms of the opportunity you know where were her next.

Definitely frontline I think this is a drug that you know of course, you start starting it in refractory relapsed that's the nature of drug development in AML, but it has a lot of potential for frontline both as a single agent and in combination.

You know, there's been seven approvals of oral agents over the last five years, and I think particularly when you look at targeted agents in IDH1, IDH2, and FLT3, and particularly even in the relapse setting, I think those are sort of the numbers that we've been looking at and will be discussing as we move forward, but certainly no decision's been made.

Because those patients where you're aiming for different things so.

For very.

On fit patients, who are not able to take combinations, where you don't want to minimize myeloid suppression and all these things.

Even though I mentioned when I was a person who is the most common this is far less than you would see with any chemotherapy so far.

So, you know, I think that this is obviously a question of, you know, are the patients out there, they're well-identified, and the question's going to be, you know, does illusive offer an advantage over other therapies that might be used in this relapse refractory space, but we plan to differentiate it as best we can.

Thank you.

Far less than you would see with for example, as a in anthro clocks for example, which is so mindless of proceeds so a single agent could be very very good for some of these patients but a combination then would be a very valuable addition for the for the patients where you were aiming for a little bit more more responses deeper responses.

Thank you.

And so on so that definitely would be a trajectory to follow I also like the.

Our next question comes from Yigal Nachomowicz with Citi.

Please proceed with your question.

I went fast through the development, but there was one of the arms, we choose for for patients that have what we call measurable residual disease or <unk> D. So these are patients who had achieved a remission, but they still have you can find by these sensitive test.

Detectable disease.

And this is very well suited for that purpose because it's just it's an oral.

Agent you would use it as a single agent by itself you don't have to worry about differentiation syndrome that concept.

So it is a very very well.

Very good.

It fits very well for that for that for that purpose. Both after some other sort of chemotherapy or after a stem cell transplant patients that relapse.

And you gave them whatever these drug or something else and then they went through a constant maintenance after transplant.

He becomes very valuable if you have something that's effective.

You see that's safe et cetera. So I think that those are some of the areas where were you would fit well.

Can it grow more than those patients I think it can because number one if you moved it upfront number two I think that as we have more of these treatment options that physicians identify us well tolerated effective.

Et cetera.

The testing for the mutation starts picking up and although a lot of the patients are being assessed for mutations nowadays, it's not 100% it can be a lot better than it is now so I think that.

Physicians will start looking more and more for these mutations because they know that it could be a big difference for their patients in terms of the treatment strategies that they could use.

Okay, Great. That's very helpful and then one for the company.

I'm curious how competitive was the process.

For this drug how did you evaluate the economics for the deal relative to the overall opportunity I mean, if you could try and quantify that for us at a high level I think that would be helpful. And do you have capacity to do more deals in the humongous space and get the full synergies are likely to get.

With this transaction and then just comment on the IP for the drug that would be helpful. As well. Thank you.

Sure.

Tony why don't you comment on the IP I'll answer the other questions I'm sure on the composition of matter without any extensions. It is protected through September 2035, and then there's another a number of very useful methods of treatment as well as certain forms of the compound.

As well that have protection through 2039.

Thank you Tony.

We've been engaged with our colleagues in pharma for a bit on this drug we looked at this and we thought it was a very attractive molecule with compelling data that could make it the leading agent in this category in AML and so for that reason we were very attracted to it. It is a constraint product, it's not a $1 billion product by any means but it's a.

Very exciting product for a company like Rigel and in particular, our franchise that we're building in <unk> with that foundation being ITB with top Elyse. This is a perfect add on molecule to that and we have.

Our commercial organization in place boots on the ground now that can deliver value to this asset and so it made it an attractive proposition for our colleagues at former as well I believe.

And as a result, we found a way to mitigate some of the risk minimize some of the payments upfront for us, we're particularly sensitive in the short term.

And allow them to recapture some of the value of their tremendous work. They did in filing the NDA in prosecuting that NDA.

With FDA to this point, so I think the economics makes sense as well for us and they are commensurate with that theres opportunities here beyond.

Relapse refractory AML.

<unk> positive AML and as Dr. Cortez said in early therapy, either as a single agent or combo therapy, there's opportunities in glioma as well, where some work has already been done. So there's other things we could explore here. So it offers opportunities even beyond the initial potential indication that we.

We're the <unk> date is in February .

Can we do more absolutely we can do more here once we've laid a good foundation and we've leveraged that.

We will be in a position to continue to build in this area and this sets a precedent for what we might do going forward no promises no promises on timing of course, but it's a pretty exciting next step for us as a company.

This is Carly on for Yigal.

Okay, great. Thank you.

Thank you our next question comes from.

Kristen <unk> with Cantor Fitzgerald. Please proceed with your question.

Thank you for taking our question.

Good afternoon. This is Rick on for Chris and Thank you for taking our questions. We have two for you on the topic of potential sub licensing around the AML opportunity are you able to give any color on what rigel could look for in a potential partner for bringing I'll, let Ned forward ex U S.

We have one for Dr. Cortez.

Sure I can take that.

We have rights to.

Ex U S sub licenses and there is a very good opportunity and obviously this disease is not solely a U S issue, it's a very severe disease globally.

So we will look to in the future do deals with partners outside of the U S. There may be an additional trial required in some territories and that would be part of the discussion with those parties. We do know that there are investigators that participated in the trials. The registrational trial in Europe that are very enthusiastic about work.

Continuing to work with this molecule and so that'll be part of the discussion as well, but that's an exciting facet to this to this agent that I think allows us to do that a bit further and frankly devote additional resources to its further development.

Fitting us here in the U S tremendously from a commercial perspective.

Understood, Okay, and one more after completing COVID-19 enrollment are you able to say anything about any potential effect that the recent increase in transmission rate across the U S has had or had had in the last stretch of enrollment.

I'll ask Wolfgang to maybe comment on that.

No we did not really see that reflected in hospitalizations at the sites that we were working with in the in the countries that we were working with so while it's possible that there might be some additional hospitalizations coming.

Are you comfortable with the sample size that we have and with the team's primary endpoint, where you have a little bit more sensitivity than the original.

Primary endpoint and therefore, we decided to sell.

Nope enrollment it's 280.

Yeah.

Thank you Rick.

Thank you. Our next question is from <unk> Patel with B Riley Securities. Please proceed with your question.

Hey, good afternoon, congrats on the deal with pharma and thanks for taking the questions.

Can you talk about how you think the efficacy and safety of elutocitinib compared to ivositinib?

Starting out with Doctor Cortez I guess when you compare the two <unk> inhibitors.

Stick out from a tolerability perspective that might position one molecule favorably to the other.

I know you talked about efficacy differences, but curious to hear your perspective on safety.

Yes.

I think that there there are some differentiators.

Hum.

That I like four or from the perspective of the Oh.

Of the safety profile, the the incidents of Qt prolongation, he's he's very low and and that is that that is a you know.

That'd be gas.

You know in particular, because you don't have to be doing decent these things because they happen out patient it's hard to get them.

As I mentioned, there was only one patient in the whole study so that's less than 1%.

Whereas in the type of Sydney.

It was reported an almost 8% of patients I'm talking about the great three of the most severe.

Conditions, so 8% is not a huge percentage, but it is definitely a number that starts making you pay attention because it can be.

Is it severe so baddies one.

And the D.

I think that the.

The liver toxicity doesn't worry me I think it is something that is highly manageable.

And for.

For the general oncologists, especially because most of these can be managed through speeches.

Crunching treatment interruptions, sometimes those adjustments and as I mentioned most of the patients can really continue being treated so.

I think that the safety profile is equal or better for all of <unk>.

With excuse me compared to the receipt of any <unk>.

And you know I.

I really I.

Manage many of these patients that I told you about them.

And it's been very easy to manage.

We don't combination we've reported some of those early research in combination are in some of the meetings and the combination where they used to say because of the good safety profile. It's also easy to combine with other drugs, which are supposed to work.

Have a great value.

Okay, and that's the Cortez if the data are available from the respective trials of these two ADH inhibitors.

Do you see any differences.

And the number of patients that are eligible to receive a transplant or actually go on and receive a transplant after.

All right.

Well one of the criteria that you need for for getting a patient to a transplant these to get them to at the very least a partial response.

And then of course, all the way up to a complete remission. So so for that matter I mentioned that the overall response rate E <unk>.

46%. When you include all of these responses. So all of these patients could potentially be eligible for transplant. Then of course comms. They issue of age comorbidities donors or other factors and many patients drop out because of these conditions, but at least from the perspective of the D C.

And the response that you get with the drug.

That's that's.

Almost half of the patients with become potentially eligible for transport.

And then one question for the company sort of building on one of the previous questions.

And I guess, assuming elutocitinib is approved, how do you see it sort of being used alongside ivositinib?

Since Pip Soho moved.

Dr. Cortez, if you would.

So far in that elderly chemo ineligible patient population in the frontline setting does that approval in the frontline impact your development efforts to move moving your aviation inhibitor earlier on or even your commercialization efforts in the late line setting for this new asset.

Hello, Dr. Cortez.

Yes.

Dave why don't you address our commercial focus and now and maybe in the future and maybe I can comment on.

On future development.

Yes, I think for us that was another thing obviously that attracted us to this opportunity.

One is now well proven.

In the in the newly diagnosed patients with category one evidence in the <unk> guidelines, So I think obviously.

That would be something that as I said earlier would be would be good if we could move into the earlier line setting but for right now.

The relapsed setting for us is a perfect entry it.

Where are there.

Targeted agents have started and I think thats, where the most needed and so we'll do that obviously, we don't have any comparative trials to another IV H one inhibitor and so we can only we can only discuss our data but at the end of the day I think you know as.

You've heard I think clinicians might see some differentiating pieces here.

That could.

<unk>.

It could.

Allow them to use it in different settings in AML, but we're going to wait until we see what the label is.

And then we will be.

It is approved and if it is.

Made available at that time, we will we will pursue that with vigor.

Yeah. This is working just to add to that as you've heard from the Cortez.

The data in the refractory relapsing population looks compelling rate was high.

Response rates and long duration of disease, and a manageable safety profile, so if others.

You know.

This study is going on in earlier patients in frontline patients.

Doctors, usually follow the data and if they believe there's something promising.

I'm optimistic that the that we could engage them in discussions about earlier use.

Yeah.

Okay. Thank you very much.

Thank you.

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

Can you hear me?

Oh, yes.

There you go.

Yes, there you go.

Sorry.

I was saying that, you know, certainly, ivositinib is a very good drug, and we've been fortunate to have it for some time.

And also, we need to highlight the fact that or acknowledge the fact that it's difficult to compare when you're looking at two different studies. But if we look at the characteristics of the studies, which are, you know, essentially very similarly conducted in similar patient population, I think that there's many reasons to believe why that elutocitinib compares favorably to ivositinib.

Number one, in terms of the patient population that was in the study, the two are refractory relapse, acute myeloid leukemia.

Thank you for your questions and for the positions that we've made in terms of your time I appreciate that so an exciting quarter, we accomplished some really important milestones this past quarter.

But the, Characteristics of the patients, they're a little bit older in the Olutacidenib study.

They are a little bit more difficult to treat. For example, I mentioned these fully refractory patients.

Or the relapse patients, there were very few patients that had relapsed within 12 months, which is, I mentioned the harder patient population, there were less than 10%.

Here we have a third of the patients were like that.

So many of the features are equal or worse, with the Olutacidenib.

So we're starting with a worse, with a more difficult patient population.

And yet, the overall response rate looks similar, if not better. The overall, the response, the CR plus CRH, was 30% with the Olutacidenib. It's 33% here, but most importantly, the CR rate, which was 21% with Olutacidenib, is 30% with the Olutacidenib.

The duration of remission, which was about eight months with Ivocidinib, it's 13.8 months with the Olutacidenib.

So there's differences between the studies, and again, you cannot make too much, but every item points to some benefit compared to what we have with the Ivocidinib.

QTC prolongation, very uncommon with Olutacidinib, which is also very, very important.

You highlighted the synergies, with the existing ITP sales force.

Not that it's that common with Ivocidinib, but it is more than we see with Olutacidinib.

Are you expecting to add sales reps, in order to support the AML launch?

So overall, I feel very good about the potential, of these drugs, because it adds, it has many aspects that seem to suggest a further improvement over what we already have with the Ivocidinib.

Regaining momentum and growth in <unk> sales I think that is foundational to the company in terms of the he Mont business overlay that on top of that this in license providing leverage with an existing organization. We're incredibly excited about those those two events this quarter and I think it bodes really well for this year and.

So I think that I would certainly, if it was available today, I would use it quite a bit.

Okay, great, that's very, very helpful.

And then we just had a question for Rigel as well.

And I guess just curious, how much we could expect OpEx to ramp as we go into 2023.

Thanks so much.

Thanks, Carly.

Into next and then progress on some of our pipeline programs with fast Imatinib.

I'll ask Dave to answer that question, and then Dean in terms of the OpEx piece of it.

Dave?

Yeah, Carly, great question.

And actually, we're not going to be expanding, our sales force at all for this, because ITP, it's a much bigger patient population, treated across the community.

So we've got significant coverage out there, with our current team.

With FDA coming soon with Covid data coming soon and advancements into patients with our earlier two programs are two things. We're very excited about so thank you for your questions and look forward to providing you more information as appropriate take care.

And so what we now have to do, obviously, and by the way, in the relapse refractory setting with an oral therapy, this can be used in the community, and patients are being treated in the community.

So that'll be good.

Our next question is from Joe Pantginis with HC Wainwright.

But we'll additionally have to pick up leukemia treaters, in institutions, which we're already calling on.

Please proceed with your question.

But no, the answer is no additions to our sales force.

Hey, everybody.

I think they've got quite the capacity.

Good afternoon.

And after announcing this today, I'm pretty sure I could say without any fear of error, they're going to be tremendously excited to have something else in their bag.

Thanks for taking the question and interesting transaction and thanks for the details.

So that's the answer to the question.

So first, for Dr. Cortes, I guess when you were talking about the slides regarding the, AE profile, physicians such as yourself and at centers of excellence, you said, obviously, these are very manageable toxicity profiles.

And that's exactly why, when we look at a drug like glutathione, we think it fits perfectly into our bag.

When you look at things such as, you know, the liver elevations and even things like, the differentiation syndrome, how is the broader physician community in AML equipped to be able to treat these AEs?

Thank you for your questions and for the imposition that we made in terms of your time.

We're seeing hematologists, oncologists in the community.

Thank you.

I appreciate, that.

We're in the institutions where leukemia treaters are, and we can spread the word rapidly.

I think that by now, they are very well equipped.

It's an exciting quarter. We accomplished some really important milestones this past quarter, you know, regaining momentum and growth in ITP sales.

And Carly, with respect to operating expense, we expect limited clinical spend. So Dave described the significant leverage on the commercial side, so limited clinical, spend.

You know, liver toxicity is something that a general oncologist sees with many other, drugs that they use for solid tumors and other things at even higher incidences and severity than what we see here.

I think that is foundational to the company in terms of the Hemant business.

I just remind you also with respect to our just overall operating expense, as we roll, off and we've just completed our phase three study in AIHA, we're wrapping up the phase three study in COVID, you know, we expect to see some leverage, some savings into the future on clinical spend there too.

You know, one other area that I manage a lot of patients is CML and some of the drugs that, we use in CML have higher incidences of these things, and yet liver toxicity specifically, and I think physicians manage that well.

Overlay that on top of that, this in-license providing leverage with an existing organization.

Take care.

So that's a bit of feedback on the OLA-SUTNIV impact on operating expense.

The differentiation syndrome, it's a little bit more unique, not something that it's seen, with many other cancer therapies, but number one, it's not that common, fortunately, with aglutasidinib, and I think that little by little, they have become much more aware of these and they can manage well.

We're incredibly excited about those two events this quarter, and I think it bodes really well for this year and into next.

Thank you again.

I've seen them manage with some of the other drugs that we use in these hematologic malignancies, and they become much more aware and alert than when we started seeing these things initially with an IDH2 inhibitor, which was the first one that was approved.

And then progress on some of our pipeline programs with Foster Matinib, with FDA coming soon, with COVID data coming soon, and advancements into patients with our earlier two programs are two things we're very excited about.

Thank you, Carly.

That was a bit more of a surprise, even for us, when we started developing the drugs, but then, you know, over time, I think they've become very familiar and able to manage these and, you know, if not manage themselves, at least call for help, so I feel comfortable with how they will be able to manage aglutasidinib in the clinic.

So thank you for your questions and look forward to providing you more information as is appropriate.

Thank you.

Now, thank you for that very much, and then two Tavilis questions for the company.

Yeah.

Please.

This concludes today's conference.

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

Regarding WHA, are you able to, I know it's ahead of your FDA interactions in the fall that you mentioned, but are you able to give us any additional information or tease for that matter regarding additional analyses that you've been conducting?

You may disconnect your lines at this time.

Yeah, Joe, thanks for that question.

Thank, you for your participation.

You know, we've done a great deal of analysis on the data since we announced it.

We've worked hard on that.

But at this point, what we prefer to do is to share that with FDA first before sharing it more broadly.

That would be the appropriate step we view as the next step to do and have those discussions.

And after that interaction, be able to report to you and the investor community what FDA feedback is on that based on that analysis, rather than sharing additional analysis and have the FDA not view that favorably as a result.

So the timing is probably not that far out, by the way.

We hope to meet with the FDA in the fall. And after that, we would have some feedback from them and be able to share more.

No, totally fair.

And then just quickly wanted to see if, you know, how things are being maintained or improving regarding the current refill rate based on prior quarters, you'd have been hovering around the mid 50s.

Do you want to comment on the persistency?

Yeah, persistency hasn't changed.

You know, we've it takes a long time to move that curve.

Obviously, we've been adding new patients.

Uh huh.

It's too early to assess whether those patients have longer persistency.

But for right now, we're, we're maintaining in the mid fifties.

Great.

Yeah.

Thanks, guys.

Thank you, Joe.

Thank you.

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

Please proceed with your question.

Hi, good afternoon and congrats on the deal.

First for Dr. Cortez, where do you see the most opportunity in additional indications for eludafitinib going forward?

In particular, how important will combination therapy be over time?

You know, what's the timing of that data?

And at what point will physicians start to experiment with that?

And how many more patients are out there beyond the 1000 that could be good candidates over time?

Yes, thank you.

First, in terms of the opportunity, you know, where we're next, definitely frontline.

I think this is a drug that, you know, of course, you start starting it in refractory relapse.

That's the nature of drug development in AML.

But it has a lot of potential for frontline, both as a single agent and in combination, because there's patients where you're aiming for different things.

So, you know, for very unfit patients who are not able to take combinations where you don't, where you want to minimize myelosuppression, all these things, even though I mentioned myelosuppression is the most common, this is far less than you would see with any chemotherapy.

So, you know, far less than you would see with, for example, azavananthoclax, for example, which is so myelosuppressive.

So, single agent could be very, very good for some of these patients, but a combination then would be a very valuable addition for the patients where you're aiming for a little bit more, more responses, deeper responses, and so on.

So, that definitely would be a trajectory to follow.

I also like the, I went fast through the development, but there was one of the arms, which is for patients that have what we call measurable residual disease or MRD.

You know, if a patient that relapsed and you gave them whatever, this drug or something else, and then they went to a transplant, maintenance after transplant usually becomes very valuable if you have something that's effective, that's easy, that's safe, et cetera.

So, I think that those are some of the areas where it would fit well.

Now, can it grow more than those thousand patients?

I think it can, because number one, if you move it up front, number two, I think that as we have more of these treatment options that physicians identify as well tolerated, effective, et cetera, the testing for the mutation starts picking up.

And although a lot of the patients are being assessed for mutations nowadays, it's not 100%.

It can be a lot better than it is now. So, I think that physicians will start looking more and more for these mutations because they know that it could be a big difference for their patients in terms of the treatment strategies that they could use.

Okay, great.

That was very helpful.

And then one for the company.

I'm curious, how competitive, was the process for this drug?

You know, how did you evaluate the economics for the deal relative to the overall opportunity?

I mean, if you could try and quantify that for us at a high level, I think that would be helpful.

And do you have capacity to do more deals in the HEMONC space and get the full synergies like you're getting with this transaction?

And then just comment on the IP for the drug.

That'll be helpful as well.

Thank you.

Sure.

Dolly, why don't you comment on the IP?

I'll answer the other questions.

Sure.

On the composition of matter without any extensions, it is protected through September, 2035.

And then there's a number of very useful methods of treatment as well as certain forms of the compound as well that have protection through 2039.

Thank you, Dolly.

You know, we've been engaged with our colleagues in pharma for a bit on, this drug. We looked at this and we thought it was a very attractive molecule with compelling data that could make it the leading agent in this category in AML.

And so for that reason, we were very attracted to it.

It is a constrained product.

It's not a billion dollar product by any means, but it's a very exciting product for a company like Rigel and in particular our franchise that we're building in HEMONC with that foundation being ITP with Tavalisse. This is a perfect add-on molecule to that.

And we have a commercial organization in place, that has boots on the ground now that can deliver value to this asset.

And so it made it an attractive proposition for our colleagues at Pharma as well, I believe.

And as a result, we found a way to mitigate some of the risk, minimize some of the payments up front for us.

We're particularly sensitive in the short term and allow them to recapture some of the value of the tremendous work they did in filing the NDA and prosecuting that NDA with FDA to this point.

So I think the economics makes sense as well for us.

And they're commensurate with that.

There's opportunities here beyond relapse refractory AML, IDH positive AML.

And as Dr. Cortes said, in early therapy, either as a single agent or combo therapy, there's opportunities in glioma as well, where some work has already been done.

So there's other things we could explore here.

So it offers opportunities even beyond the initial potential indication that where the PDUFA date is in February.

Can we do more?

Absolutely.

We can do more here.

Once we've laid a good foundation and we've leveraged that, I think, we'll be in a position to continue to build in this area.

And this sets the precedent for what we might do going forward.

No promises and no promises on timing, of course, but it's a pretty exciting next step for us as a company.

Okay, great.

Thank you.

Thank you.

Our next question comes from Kristen Klitschke, with Cantor Fitzgerald.

Please proceed with your question.

Good afternoon.

This is Rick on for Kristen.

Thank you for taking our questions.

We have, two for you.

On the topic of potential sub-licensing around the AML opportunity, are you able to give any color on what RIGEL could look for in a potential partner for bringing all its Sure, I can take that.

We have rights to do IQS sub-licenses and there's a very good opportunity, and obviously this disease is not solely a U.S. issue, it's a very severe disease globally.

And so we will look to, in the future, do deals with partners outside of the U.S.

There, may be an additional trial required in some territories and that would be part of the discussion with those parties.

We do know that there are investigators that participated in the trials, the registrational trial, in Europe that are very enthusiastic about continuing to work with this molecule and so that will be part of the discussion as well.

But that's an exciting facet to this agent that I think allows us to do that a bit further and frankly devote additional resources to its further development, benefiting us here in the U.S, tremendously from a commercial perspective.

Understood.

Okay.

And one more.

After completing COVID-19 enrollment, are you able to say anything, about any potential effect that the recent increase in transmission rate across the U.S, has had or had had in the last stretch of enrollment?

Thanks.

I'll ask Wolfgang to maybe comment on that.

Yeah, no, we did not really see that reflected in hospitalizations at the sites that we were, working with in the countries that we were working with.

So while it's possible there might be some additional hospitalizations coming, we feel comfortable with the sample size that we have and with the changed primary endpoint, we have a little bit more sensitivity than with the original primary endpoint and therefore we decided to stop enrollment at 280.

Thank you, Rick.

Thank you.

Our next question is from Kalpit Patel with B. Riley Securities.

Please proceed with your question.

Hey, good afternoon.

Congrats on the deal with Forma and thanks for taking the questions.

Starting out with Dr. Cortez, I guess when you compare the two IDH1 inhibitors, does anything stick out from a tolerability perspective that might position one molecule favorably to the other?

I know you talked about efficacy differences, but I'm curious to hear your perspective on safety.

Yes.

I think that there are some differentiators that I like from the perspective of the safety profile.

The incidence of KTC prolongation is very low and that is a big asset in particular because you don't have to be doing EKGs and these things, if they happen outpatient, it's hard to get them.

As I mentioned, there's only one patient in the whole study, so that's less than 1%.

Whereas with typhus sydney, it was reported in almost 8% of patients and I'm talking about the, grade three, the most severe conditions.

So, 8% is not a huge percentage, but it is definitely a number that starts making you pay attention because it can be severe.

So, that is one.

I think that the liver toxicity doesn't worry me. I think it is something that's highly manageable, in for patients, again, for the general oncologists, especially because most of these can be managed just with just transient treatment interruptions, sometimes those adjustments, and as I mentioned, most of the patients can really continue being treated.

So, I think that the safety profile is equal or better for Olatucinib compared to the Ivocidinib.

I've managed many of these patients that I told you about, and it's been very easy to manage.

We've done combination. We've reported some of those early results in combination, in some of the meetings, and the combination with ACES, because of the good safety profile, it's also easy to combine with other drugs, which is also a great value.

Okay, and Dr. Cortes, if the data are available from the respective trials of these two, IDH inhibitors, do you see any differences in the number of patients that are eligible to receive a transplant or actually go on and receive a transplant after?

Well, one of the criteria that you need for getting a patient to a transplant is to get them, to, at the very least, a partial response, and then, of course, all the way up to a complete remission.

So for that matter, I mentioned that the overall response rate is 46% when you include all of these responses.

So all of these patients could potentially be eligible for transplant.

Then, of course, comes the issue of age, comorbidities, donors, you know, other factors, and many patients drop out because of these conditions.

But at least from the perspective of the disease and the response that you get with the drug, that's almost half of the patients would become potentially eligible for a transplant.

And then one question for the company, sort of building on one of the previous questions.

Since PIPSOVA moved so far in that elderly, chemo-ineligible patient population in the, frontline setting, does that approval in the frontline impact your development efforts to move moving your IDH inhibitor earlier on, or even your commercialization efforts in the late-line setting for this new asset?

Dave, why don't you address our commercial focus now and maybe in the future, and maybe Rupgan and I can comment on future development.

Yeah, I think for us, that was another thing, obviously, that attracted us to this opportunity.

IDH1 is now well proven in the newly diagnosed patient with Category 1 evidence in the NCCN, guidelines.

So I think, you know, obviously, that would be something that, as I said earlier, would be good if we could move into the earlier-line setting.

But for right now, the relapse setting for us is a perfect entry.

It's, you know, where other targeted agents have started.

And I think that's where the most need is.

And so we'll do that.

You know, obviously, we don't have any comparative trials to another IDH1 inhibitor. And so we can only discuss our data.

But at the end of the day, I think, you know, as you've heard, I think clinicians might see some differentiating pieces here that could allow them to use it in different settings in AML.

But we're going to wait until we see what the label is.

And then we'll be, if it is approved, and if it is made available at that time, we will pursue that with Yeah, this is working.

Just to add to that, as you've heard from Dr. Cortes, the data, in the refractory relapsing population looks compelling, right, with high response rates and with a long duration of disease and a manageable safety profile.

So even if others, you know, have studies going on in earlier patients or frontline patients, doctors usually follow the data. And if they believe there's something promising, I'm optimistic that we could engage them in discussions around earlier use.

Okay.

Thank you very much.

Thank you.

Thank you.

There are no further questions at this time.

I would like to turn the floor, back over to Mr. Raul Rodriguez for any closing comments.