Q1 2021 Curis Inc Earnings Call
Good afternoon, and welcome to curious as first quarter 2021 earnings call. All participants will be in listen only mode should you need assistance. Please signal a conference specialist by pressing the star key followed by zero.
Operator: Good afternoon, and welcome to Curis' first quarter 2021 earnings call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key, followed by zero. After the company's prepared remarks, call participants will have an opportunity to ask questions. To ask a question, you may press star, then one on your touchtone phone. To withdraw your question, please press star, then two. Please note, this event is being recorded. I would now like to turn the conference over to the company's chief financial officer, Bill Steincrouse. Please go ahead.
After the Companys prepared remarks, all participants will have an opportunity to ask questions to ask a question you May Press Star then one on your Touchtone phone.
To withdraw your question. Please press Star then two.
Please note this event is being recorded.
I would now like to turn the conference over to the company's Chief Financial Officer Bill Steinkrauss. Please go ahead.
Thank you and <unk>.
Bill Steincrouse: Thank you and welcome to Curis' first quarter 2021 earnings call. Before we begin, I would encourage everyone to go to the investor section of our website at www.couros.com, find our first quarter 2021 earnings release and related financial tables. I would also like to remind everyone that during the call, management will be making forward-looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risk and uncertainties, and actual results may differ materially. For additional details, please see our SEC violence page.
Welcome to cure since first quarter 2021 earnings call.
Before we begin I would encourage everyone to go to the investors section of our website at Www Dot curious dot com to find our first quarter 2021 earnings release and related financial tables.
I would also like to remind everyone that during the call management will be making forward looking statements, which are based on our current expectations and beliefs.
The statements are subject to certain risks and uncertainties and actual results may differ materially.
For additional details please see our SEC filings.
Joining me on today's call are Jim Dentzer, President and Chief Executive Officer, and Bob Martell head of R&D.
Bill Steincrouse: Joining me on today's call are Jim Denser, President and Chief Executive Officer, and Bob Martel, head of R&D. We will also be available for a question and answer period at the end of the call. I'd now like to turn the call over to Jim.
We will also be available for a question and answer parent and other call.
I'd now like to turn the call over to Jeff and Jim.
Thank you Bill.
James E. Dentzer: Good afternoon, everyone, and thank you for joining us today. Every day at Curus, we push to develop the next generation of transformative, targeted cancer therapies that will meaningfully improve and extend patients' lives. In the first quarter of 2021, we took important steps towards that goal, building upon the exciting progress we made last year and expanding into additional areas where we believe we can make a difference. For example, our novel Small Molecule IRAC4 Inhibit
Good afternoon, everyone and thank you for joining us today.
Every day and cure, we push to develop the next generation of transformative targeted cancer therapies that will meaningfully improve and extend patients' lives.
In the first quarter of 2021 we.
We took important steps towards that goal.
Building upon the exciting progress, we made last year and expanding into additional areas, where we believe we can make a difference.
Our novel small molecule Iraq for inhibitor.
And a 49 and 48 is currently being evaluated in three clinical studies.
James E. Dentzer: CA 49-48 is currently being evaluated in three clinical studies. First, the Phase 1-2 monotherapy study, in AMLMDS, I just mentioned, the phase one, two study in combination with ibuputinib for patients with relapsed or refractory NHL or other hematologic malignancies. And third, the Phase 2 Lucas study, evaluating CA 49-48 in patients with lower risk MDS, being led by Dr. Uvei Plotzbecker of the University of Leipzig. We are especially pleased with the progress of CA4948 and the exciting data update published in the European Hematology Association Abstracts this morning from our Phase 1-2 monotherapy study in relapsed or refractory acute myeloid leukemia, or AML, and high-risk myelodysplastic syndrome, or MDS.
First.
The phase one and two monotherapy study in AML Mds I just mentioned.
Second.
The phase one two study in combination with Ibrutinib.
For patients with relapsed or refractory and H L or other hematologic malignancies.
And third.
The phase two Lucas study.
Valuate and CH 49, and 48 in patients with lower risk Mds being.
Being led by Dr. Ebay, plus Becker of the University of life's fish.
We are especially pleased with the progress and see a four nine and four eight.
And the exciting data update published in the European Hematology Association Abstracts. This morning.
From our phase one two monotherapy study in relapsed or refractory acute myeloid leukemia or AML.
And high risk Myelodysplastic syndromes or Mds.
As many of you have been following the long isoform of Iraq for or.
James E. Dentzer: As many of you have been following, the long isoform of Iraq 4, or Iraq4L, has recently been identified as the key driver of disease in the majority of patients with AML and MDF. We at Curus have the first and only drug that directly targets Iraq for to enter clinical testing for these patients.
Iraq for L.
It has been recently identified as the key driver of disease, and the majority of patients with AML and Mds.
We are curious have the first and only drug that directly targets Iraq for to enter clinical testing for these patients.
James E. Dentzer: Today, I am also pleased to announce that we have amended our AML and MDS study to add both a combination dose escalation and a monotherapy dose expansion. Preclinical data supporting the combination study were published by IHA earlier today and will be presented in a poster presentation at the IHA conference next month. We expect to begin enrollment in this portion of the study in Q3.
Today I am also pleased went out.
That we have amended our AML and Mds study to add both a combination dose escalation.
And on monotherapy dose expansion.
Preclinical data supporting the combination study was published by Ehealth earlier today and.
And will be presented in a poster presentation at the heart Conference next month.
We expect to begin enrollment in this portion of the study in Q3.
While there has certainly been a lot of attention on our Iraq Force study.
James E. Dentzer: While there has certainly been a lot of attention on our Iraq forces, it is important to note that we have also been pleased with patients' enrollment in the phase one dose escalation study of our first in-class monoclonal antivista antibody, CI 8993. We look forward to reporting initial clinical data for this study later this year.
It is important to note.
Debt. We have also been pleased with patient enrollment in the phase one dose escalation study of our first in class monoclonal anti Vista antibody.
And I 80 993.
We look forward to reporting initial clinical data for this study later this year.
All told we opened 2021 with strong momentum following our updates and December at Ash and the successful execution of key strategic financing and partnerships.
James E. Dentzer: We opened 2021 with strong momentum following our updates in December at Ash and the successful execution of key strategic financing and partnerships, with premier institutions like the NCI and the European MDS Consortium, that will support the continued advancement and expansion of our clinical programs. With that, let's dig into some detail about our ongoing clinical programs, starting with the IRAC-4 study in leukemia. In April, we were pleased to report that CA4948 had received orphan drug designation from the FDA for the treatment of AML and MBS. This special designation represents a significant milestone for Curus.
With premier institutions like the NCI.
And the European M D S consortium and that will support the continued advancement and expansion of our clinical programs.
With that let's dig into some detail on our ongoing clinical programs, starting with the Iraq Force study in leukemia.
In April we were pleased to report that Ta 49, and 48 had received orphan drug designation from the FDA for the treatment of AML and Mds.
This special designation represents a significant milestone procure us as we work to advance and see a 49 and 48 through clinical testing and in time seek to make it available to the patients who need it most.
James E. Dentzer: As we work to advance CA 4948 through clinical testing and, in time, seek to make it available to the patients who need it most, in the Iha abstract published this morning. We are pleased to report that the data in our AMO and MBS study continue to exceed our original expectations, showing consistent single-agent efficacy across the spectrum of late-line AML and MDS patients, despite these patients having already experienced several unsuccessful prior lines of therapy.
And the Ehow abstract published this morning.
We were pleased to report that the data in our AML and Mds study continue to exceed our original expectations.
Showing consistent single agent efficacy across the spectrum.
Of late line AML and Mds patients.
Despite these patients having already experienced several unsuccessful prior lines of therapy.
To provide some context.
James E. Dentzer: To provide some contact, in conjunction with Ash last year, we reported preliminary data from six patients, as of a November cutoff, showing marrow blast reductions in all six patients, with two of the patients demonstrating marrow complete responses, and none of the patients experiencing a dose-limiting toxicity at either the 200 or 300 milligram BID dose levels. The data published today, which are from 15 patients and a February 8 cutoff, showed bone marrow blast reductions at all tested doses, 200, 300, and 400 milligram BID, and in eight of nine evaluable patients with elevated blast counts at baseline.
In conjunction with Ash last year we.
We reported preliminary data from six patients.
And it's up on November cutoff.
Showing marrow blast reductions in all six patients.
With two of the patients.
Administrative marrow complete responses.
And none of the patients experiencing a dose limiting toxicity and either the 200 or 300 milligram B I D dose levels.
The data published today.
Which are from 15 patients and the February 8th cut off.
Showed bone marrow blast reductions in all tested doses 200, 304 hundred milligram B I D and.
And in eight of nine evaluable patients with elevated blast counts at baseline.
All of these.
One patient experienced a full hematologic recovery C R.
James E. Dentzer: One patient experienced a full hematologic recovery, CR. One patient experienced a CRI with negative minimal residual disease, and two patients had bone marrow CRs. Three of these patients presented with a U2AF1 or SF3B1 spliceosome mutation, and all three of those patients achieved marrow CR or better, validating our belief that these spliceosome mutations are specific oncogenic drivers of the long isoform of Iraq 4, which CA 49-48 is explicitly designed to target. We were also pleased to see that all patients with objective responses showed signs of hematologic Delving a bit deeper on this point.
One patient experienced a cri with negative minimal residual disease.
And two patients had bone marrow and see ours.
Three of these patients presented with a Youtube F. One or S. F. Three b, one spliceosome mutation and all three of those patients achieved a mere OCR or better.
Validating our belief that these spliceosome mutations are specific oncogenic drivers of the long isoform of Iraq for.
Which CAE and 49 and 48 is explicitly designed to target.
We were also pleased to see that all patients with objective responses showed signs of hematologic recovery.
Delving a bit deeper on this point.
The blast reduction data reported in the abstract this morning from.
James E. Dentzer: The blast reduction data reported in the abstract this morning provide further evidence that CA 49-48 is effective at reducing a patient's cancer burden. For this late-line patient population, having a drug that can safely and effectively get the cancer out is the immediate goal. In first-line patients, those patients whose bone marrow has not been irrevocably damaged by cancer or by prior cytotoxic treatment, it has been shown that if given a drug that reduces the level of leukemic blasts, these patients can achieve clear and substantial hematologic recovery within a few months. For the extremely sick late-line population, such as the patients in our study, It is important to remember that their cancer has progressed despite numerous prior lines of therapy. These patients often have deeply scarred dysfunctional marrow, which may delay or even prevent successful hematologic recovery.
I'd further evidence that see a 49 and 48 is effective at reducing a patient's cancer burden.
For this late line patient population.
Having a drug that can safely and effectively get the cancer out.
Is the immediate goal.
And first line patients.
Those patients, whose bone marrow has not been irrevocably damaged by cancer or by prior cytotoxic treatment.
It has been shown that if given a drug that reduces the level of leukemic blasts and these patients can achieve clear and substantial hematologic recovery within a few months.
For the extremely sick late line population.
Such as the patients and our study.
It is important to remember that their cancer has progressed despite numerous prior lines of therapy.
As a result.
These patients often have deeply scarred dysfunctional marrow.
Which may delay or even prevent successful hematologic recovery.
It is therefore, especially encouraging that we have been able to see signs of hematologic recovery. Even in these late line patients after only a few months and treatment.
James E. Dentzer: It is therefore especially encouraging that we have been able to see signs of hematologic recovery, even in these late-line patients, after only a few months of treatment. It underscores our option that CA 4948 may have both a combo therapy and a monotherapy regulatory path. Overall, we are very pleased with the progress for CA49-48, and we look forward to the Iha content, where we will provide an updated and expanded dataset with a later cutoff date to include additional patients, including those enrolled in our 500 milligram VID cohort.
And it underscores our optimism that see a 49 and 48 may have both a combo therapy and a monotherapy regulatory path.
Overall, we are very pleased with the progress foreseen and 49 and 48 and we look forward to the Ehow contracts, where we will provide an updated and expanded dataset with a later cutoff date too.
And to include additional patients, including those enrolled in our 500 milligram B I D cohort.
In addition, we will provide an update on safety pharmacokinetic and Pharmacodynamic data, including Iraq for L expression levels and further genomics information.
James E. Dentzer: In addition, we will provide an update on safety, pharmacodynamic data, including IRAC4L expression levels, and further genomic information. We found that the 500 milligram BID dosing regimen exceeded the maximum tolerated dose, according to protocol guidelines. We observed two patients with dose-limiting toxicity, one of whom had grade 3 CPK elevation or rhabdomyalysis, similar to what we saw in the NHL study, and the other experienced grade three synchres. However, both patients' AEs were reversible and quickly resolved after discontinuation of the dose.
Yeah.
We have found that the 500 milligram B I D dosing regimen has exceeded the maximum tolerated dose according to protocol guidelines.
We observed two patients with dose limiting toxicities.
And one of whom had grade three CDK elevation or rhabdomyolysis similar to what we saw it and the NHL study.
And the other experienced grade three syncope.
Both patients Aes were reversible and quickly resolved after discontinuation of dosing.
Now that we have established the maximum tolerated dose.
James E. Dentzer: Now that we have established the maximum tolerated dose, we will explore the lower dose levels to determine the appropriate recommended phase two dose. I'd like to briefly touch on the preclinical data in our other EHA abstract published earlier today. These data highlighted CA49-48's synergistic antitumor activity in combination with azocydidine and Venetaclox in leukemia cells, and will be presented in a poster session at EHA next. These data demonstrate that CA 49-48 potentiates anti-tumor activity in certain cell lines resistant to clinically relevant concentrations of azicidine and Venetaclach, furthermore. CA 49-48 demonstrated synergistic anti-leukemic activity in combination with Venetaclachyne and azicidine in AML cell lines. Even before we saw these data, we knew that CA 49-48 was unique.
We will explore the lower dose levels to determine the appropriate recommended phase two dose.
I'd like to talk to briefly touch on the preclinical data and our other abstract published earlier today.
These data highlighted CA 49, and 48 synergistic antitumor activity in combination with ease and deciding and panetta clocks in leukemia cells and.
And will be presented in a poster session at <unk> next month.
These data demonstrate that see a 49 and 48 potentiate antitumor activity and certain cell lines Reis.
And to clinically relevant concentrations of he's decided and eat and vanilla clocks.
Further.
<unk> 49, 48 demonstrated synergistic anti leukemic activity in combination with the net of clocks and he's decided inc. In AML cell lines.
Even before we saw these data we knew that C 49, and 48 was unique.
It is all.
James E. Dentzer: It is all, it is disease-modifying. It directly targets the key driver of disease, Iraq4L, which is a novel mechanism of action, and it has demonstrated the ability to provide clear and significant single-agent activity without significant myelosuppression, including complete elimination of detectable cancer burden. With the latest preclinical data adding a possible synergistic effect as well, we and our clinical investigators are very excited to explore the combination of CA 49-48 with Aesin cytidine and Venetacax in the clinic.
It is disease modifying.
It directly targets the key driver of disease, Iraq poor L.
Which is a novel mechanism of action.
And it has demonstrated the ability to provide clear and significant single agent activity without significant Milo suppression.
Including complete elimination of detectable cancer burden.
With the latest preclinical data, adding a possible synergistic effect as well.
We and our clinical investigators are very excited to explore the combination on C. A 49, and 48 with ease and siding and vanilla clocks and a clinic.
As I mentioned earlier.
James E. Dentzer: As I mentioned earlier, this quarter we amended the protocol of our existing study to include an expansion cohort for both monotherapy and combo therapy. The monotherapy dose expansion will begin after the recommended phase two doses are determined and will include four cohorts. Patients with spliceosome mutated MDS who are relapsed refractory to HMA, patients with MDS without spliceosome mutation who are relapsed refractory to HMA, patients with Flit 3 mutated, relapsed refractory AML, and patients with Flip 3 wild type, relapse refractory AML
This quarter, we amended the protocol for our existing study to.
And to include expansion cohorts for.
And for both monotherapy and combo therapy.
The monotherapy dose expansion.
And will begin after the recommended phase two doses determined and will include four cohorts.
Patients with spliceosome mutated M D S.
As relapsed refractory to HMA.
Patients with Mds without spliceosome mutation that is relapsed refractory to HMA.
Patients with flit, three mutated relapsed refractory AML.
And patients with flip three wild type relapsed refractory AML.
Yeah.
The combo therapy study we'll.
James E. Dentzer: The combo therapy study will start dose escalation at 200 milligrams BID and will include two cohorts. CA 4948 plus A's the site of name for patients with AML or MDS who are naive to HMA, and a second cohort, CA 4948 plus Venet o'clock for patients with AML or MDFs who are naive to Venetocl.
We will start dose escalation and 200 milligrams B I D.
And will include two cohorts.
C. A 49 48, plus he's decided inc.
For patients with AML, and Mds, who are naive to HMA.
And the second cohort.
And see a 49 48, plus spinetta clocks.
And for patients with AML or Mds, who are naive to banana clocks.
We hope that the design of these cohorts will help to identify the most appropriate regulatory path or paths.
James E. Dentzer: We hope that the design of these cohorts will help to identify the most appropriate regulatory path or path for CA 49-48. We expect to begin enrolling patients in these combo therapy cohorts in Q3. We may also explore a triple combination of all three drugs, of CA 49-48 plus Cicidine plus Venetoc. But that would, of course, be dependent upon the initial safety and efficacy results from the two-agent combination cohort.
For CH 49 48.
We expect to begin enrolling patients and these combo therapy cohorts in Q3.
We may also explore a triple combination of all three drugs on.
CH 49, and 48, plus he has decided and plus the net o'clock.
But that would of course be dependent upon the initial safety and efficacy results from the two agents combination cohorts.
Before moving on from leukemia, I would like to touch briefly on the ongoing I S. T treating patients with lower risk Mds that we announced in February.
James E. Dentzer: Before moving on from leukemia, I would like to touch briefly on the ongoing IST for treating patients with lower risk MDS that we announced in February. The Phase 2 Lucas study is being led by the co-chairman of Iha's scientific working group on MDS, Dr. Uvee Plasbecker, who will be coordinating this study in 17 sites across Europe to evaluate CA 49-48 for the treatment of anemia in patients with lower risk MDS If this study is successful, it could lead to a potential breakthrough in the MDS field. While current EPO stimulating agents can be effective for patients with lower risk NDS who have low serum EPO, this effect is often transient and is not disease modifying, and it does not affect progression to AMO and further disease complications. With its direct non-milosuppressive targeting of Iraq 4, and its robust safety profile.
The phase two lupus study is being led by the co chairman of <unk> scientific working group on MTS, Dr. Ubani plus Becker.
Who will be coordinating this study and 17 sites across Europe.
To evaluate and see a 49 48 for the treatment of anemia in patients with lower risk Mds.
If this study is successful.
It could lead to a potential breakthrough in the Mds field.
While current Epo stimulating agents can be effective for patients with lower risk Mds, who have low Sara meet though.
This effect is often transient.
And is not disease modifying.
And it does not affect progression to AML.
And further disease complications.
Okay.
With its direct non Milo suppressive targeting of Iraq for.
And its robust safety profile.
We believe C 49, and 48 could potentially offer a safe and transformative disease modifying alternative for patients at earlier stages of disease.
James E. Dentzer: We believe CA 49-48 could potentially offer a safe and transformative disease-modifying alternative for patients at earlier stages of disease. Now moving on to Lymphoma. In an oral presentation at Ash last December, we reported expanded clinical data from our phase one dose escalation study of CA 49-48 for the treatment of patients with relapsed or refractory NHL or other hematologic malignancies. These data highlighted durable reductions in tumor burden in six of seven evaluable patients, treated with 300 milligrams of CA 49-48 twice daily, following a median of four prior lines of therapy.
Now moving to lymphoma.
And an oral presentation at Ash last December.
We reported expanded clinical data from our phase one dose escalation study of CA 49, 48 for the treatment of patients with relapsed or refractory NHL or other hematologic malignancies.
James E. Dentzer: It is important to reiterate that seeing clear efficacy with a novel monotherapy agent and seeing that this efficacy is durable over such an extended period of time for these extremely sick patients is enormously encouraging and has provided powerful affirmation of our intention to launch the current combination study evaluating CA49-48 with Ibrut. This combination study, which began enrolling in Q1, is expected to enroll approximately 18 patients in a 3 plus 3 design, with CA49-48 Ibrutinib dosing will be whatever is appropriate for the patient's respective NHL subtype.
These data highlighted durable reductions in tumor burden and six of seven evaluable patients treated with 300 milligrams of <unk> 49, and 48 twice daily.
Following a median of four prior lines of therapy.
It is important to reiterate that seen clear efficacy with a novel monotherapy agent.
And seen that this efficacy is durable over such an extended period of time for these extremely sick patients.
Enormously encouraging and provided powerful affirmation of our intention to launch the current combination study evaluating CH 49, and 48 with Ibrutinib.
James E. Dentzer: We expect to provide an enrollment update for this study, as well as initial safety and efficacy data, in Q4. Now, I'd like to turn to CI 8993, our first in-class monoclonal antibody for the treatment of patients with relapsed or refractory solid tumors. Checkpoint inhibitors that function to enhance T-cell priming, such as anti-CTLA-4 antibodies, and checkpoint inhibitors that relieve T-cell exhaustion, such as anti-PD1 antibodies, all have two key limitations. T cells stuck in a quiescent state cannot be acted upon by these checkpoint inhibitors.
This combination study.
Which began enrolling in Q1.
And is expected to enroll approximately 18 patients and a three plus three design.
With CA and 49, and 48 doses, starting at 200 and escalating to 300 milligrams B I D.
Ibrutinib dosing will be whatever is appropriate for the patients respective NHL subtypes.
We expect to provide an enrollment update for this study.
As well as initial safety and efficacy data and Q4.
Now I'd like to turn to see I see I 80 993.
Our first in class monoclonal antibody for the treatment of patients with relapsed or refractory solid tumors.
James E. Dentzer: Miloid-derived suppressor cells or MDSCs actively impair the effectiveness of these checkpoint inhibitors. Vista is a primary enforcer of T-cell quiescence and can sequester a large proportion of T cells in a quiescent state, preventing them from being acted upon by anti-CTLA-4 or anti-PD1 antibody. Vista is also a primary driver of MDSCs.
Checkpoint inhibitors that function to enhance T cell priming.
Such as Mtc till late for antibodies.
And checkpoint inhibitors debt relief T cell exhaustion, such as anti PD one antibodies on.
We'll have two key limitations.
First.
T cells stuck in a quiescent state cannot be acted upon by these checkpoint inhibitors.
James E. Dentzer: These cells function to promote T-cell exhaustion and suppress pro-inflammatory tumor-associated macrophages. Finally, we know that Vista expression can increase dramatically as a compensatory mechanism during treatment with anti-CTLA4 or anti-PDworm therapy. For these reasons,
Second.
My alloyed derived suppressor cells or M. D. S sees actively and pair the effectiveness of these checkpoint inhibitors.
Vista is a primary enforcer of T cell quiescent.
James E. Dentzer: We believe that therapeutic targeting of Vista will be a crucial addition to the arsenal of immune oncology therapy. We believe CI 8993 is the most advanced anti-Vista antibody currently in clinical development and has the potential to be a game-changing cancer therapy. The clinical community has already shown deep excitement about this program, and we look forward to reporting initial clinical data later this year. To wrap up, I'd like to extend my utmost appreciation to the entire Curis team who have made all of this progress possible.
And can sequester, a large proportion of T cells, and a class and state preventing them from being acted upon by Mtc till eight four or anti PD one antibodies.
This is also a primary driver of M. D S sees.
These sales function to promote T cell exhaustion and suppress pro inflammatory tumor associated macrophages.
Okay.
Finally.
We know that Vista expression can increase dramatically as a compensatory mechanism during treatment with anti C. T like four or anti PD one therapy.
James E. Dentzer: We are eager to build upon our efforts in the quarters to come and advance our next generation targeted cancer program to help patients in need. With that, I'll turn the call over to Bill to review our financial results for the quarter.
For these reasons, we believe that therapeutic targeting and Vista will be a crucial edition to the arsenal of immune oncology therapy.
Bill Steincrouse: For the first quarter of 2021, we reported a net loss of $9.9 million, or 11 cents per share, on both a basic and diluted basis, as compared to a net loss of $9.7 million, or 28 cents per share, on both a basic and diluted basis for the same period in 2020. Revenues for the first quarter of 2021 were $2.2 million as compared to $2.7 million for the first quarter of 2020 In both cases, revenues comprise primarily of royalty revenues recorded on Genentech and Roche's net sales of Araved.
We believe C. I 80, 993 is the most advanced anti Vista antibody currently in clinical development.
And has the potential to be a game changing cancer therapy.
The clinical community has already shown and deep excitement and interest and this program and we look forward to reporting initial clinical data later this year.
To wrap up.
I'd like to extend my utmost appreciation to the entire curious team who have made all of this progress possible.
We are eager to build upon our efforts in the quarters to come.
Bill Steincrouse: Operating expenses for the first quarter of 2021 were $11 million, as compared to $11.2 million for the same period in 2020, excluding cost of royalty revenues. $1.1 million for both the first quarter of 2021 and 2020. Research and Development expenses were $6.8 million for the first quarter of 2021, as compared to $7.5 million for the same period in 2020. The decrease for the quarter is primarily attributable to the upfront license fee expense from our option and license agreement with Immunex related to CI 8993 that occurred during the first quarter of 2020.
And advance our next generation targeted cancer programs.
To help patients in need.
With that I'll turn the call over to Bill to review our financial results for the quarter.
Bill.
Thank you Jim.
The first quarter 2021, we reported a net loss of $9 $9 million or 11 cents per share on both a basic and diluted basis.
As compared to a net loss of $9 $7 million or 28 cents per share on both a basic and diluted basis for the same period and 2020.
Revenues for the first quarter of 2021 were $2 $2 million as compared to $2 $7 million from it.
First quarter of 2020.
Both cases revenues comprised primarily of royalty revenues.
Bill Steincrouse: These costs were partially offset by a $.3 million increase in employee-related costs. General and administrative expenses were $4.1 million for the first quarter of 2021, as compared to $3.6 million for the same period of 2020. The increase in general and administrative expense was primarily driven by higher costs for stock-based compensation, professional, and consulting services, partially offset by lower legal costs during the three months ended March 31, 2021. For the first quarter of 2021 and 2020, net other expense was $1.1 million and $1.2 million, respectively. Net other expense primarily consisted of imputed interest expense related to future royalty payments.
Courted on Genentech, and Roche's net sales of Arab bench.
Operating expenses for the first quarter of 2021 were $11 million as compared to $11 $2 million from the same period from 2020.
Cost of royalty revenues.
$1 million for both the first quarter of 2021 and 2020.
Research and development expenses were $6 $8 million for the first quarter of 2021.
As compared to $7 $5 million from the.
Same peer and 2020.
The decrease for the quarter is primarily attributable to the up.
Front license fee expense from our option and license agreement with Immunex and why.
And to see I ate and 99 three that occurred during the first quarter of 2020.
These costs were partially offset.
My point $3 million increase and employee related costs.
General and administrative expenses were $4 $1 million from the first quarter of 2021 as compared to $3.6 million from the same period 2020.
Bill Steincrouse: As of March 31, 2021, there were approximately 91 and a half million shares of common stock outstanding. As of March 31, 2021, Kieris' cash, cash equivalents, and investments totaled $168.4 million. We expect that our existing cash and investments should enable us to maintain our planned operations into 2024. With that, I'd like to open the call for questions. Operator? We will now.
The increase and general and administrative expense was primarily driven by higher costs for stock based compensation.
Festival and consulting services.
Partially offset by lower legal cost during the three months ended March 31 2021.
For the first quarter of 2021, and 2020 net other expense was $1 $1 million and $1 $2 million respectively.
Net other expense primarily consisted of imputed interest expense related to future royalty payments.
Operator: We will now begin the question and answer session. To ask a question, you may press star, then one on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the key. To withdraw your question, please press star, then two. At this time, we will pause momentarily to assemble our roster. Our first question comes from Ed White with H.C. Wainwright. Please go.
As of March 31, and 2021, there were approximately 91 and a half million shares of common stock outstanding.
As of March 31, 2021.
<unk> cash cash equivalents and investments totaled $168 $4 million.
We expect that our existing cash and investments and then.
Enable us to maintain our planned operations into 2024.
With that I'd like to open the call for questions operator.
Edward Patrick White: Good afternoon, and congratulations on the data. It's very good news. Just the first question, Jim: how should we be thinking of the path forward to approval for monotherapy and combination therapy?
We will now begin the question and answer session to.
To ask a question you May Press Star then one on your Touchtone phone.
If you are using a speakerphone. Please pick up your handset before pressing the keys to withdraw your question. Please press Star then two.
Edward Patrick White: Maybe, perhaps you can discuss potential timelines for approval for AML and MDS, you know, what's
James E. Dentzer: you know, what strategy? either monotherapy or combo can get 49, 48 to the market sooner. I get it, thanks Ed.
At this time, we will pause momentarily to assemble our roster.
Our first question comes from Ed White with H C. Wainwright. Please go ahead.
James E. Dentzer: I appreciate your thoughts on the question. You know, it's a little preliminary for us to talk about timelines for approval, but I think our overall approach is really the same approach we outlined in December. We're just, of course, we're confident now that the data continues to reinforce it. And that is from initially expecting this to be a combo therapy-only drug that we were going to have in a selected population, you know, 50% of the population.
Yeah.
Good afternoon, and congratulations on the data.
Very good news.
And just the first question Jim.
How should we be thinking and the path forward to approval for monotherapy and combination therapy, maybe protect perhaps you can discuss potential timelines to approval and AML and M. D S and.
You know what strategy.
Either monotherapy or combo can can get 49, and 48 to the market sooner.
James E. Dentzer: You know, the December data and, of course, now the Ash Abstract data seem to support that this is more appropriate for all comers. So I think that that's the primary end use. The other opportunity that was hinted at in December, and now we can see more clearly, is that there may also be a monotherapy path in a selected population. And I think now we can say it looks like the splicesome mutation population would be a good candidate for that.
Oh, Yeah, Hey, Thanks, Ed I appreciate the thoughts on the question and its a little preliminary for us to talk about timelines to approval, but I think our our overall approach.
Is really the same approach we outlined in December. We're just of course, we're confident now that the data continues to reinforce that and that is from initially expecting this was a combo therapy only drug that we were gonna have and a selected population.
James E. Dentzer: All three of the patients that have a spiceosome mutation in this study so far, I've seen MeroCR or Petters. Obviously, given the genomic association, which makes it a very compelling monotherapy opportunity and the idea that in a post-HMA setting, there is no other drug approved. We like the chance of that one as well. Which one will go faster? I don't really know. I think the answer at this point is that both seem to be very compelling opportunities. A combination therapy where this gets added to standard of care. And then, of course, monotherapy in a separate population driven by genomic signatures.
You know 50% of the population.
On the.
The December data and of course now the ash abstract it seem to support that this is more appropriate for all comers. So I think that that's the primary and use.
The other opportunities that are you know with hint to that in December and now we can see more clearly as there may also be a monotherapy path and a selected population and and I think now we can say it looks like the spliceosome mutation population and would be a good candidate for that on.
All three of the of the patients.
That have our spices and mutation and the study so far I've seen Merrill C are better. So obviously that given the genomics Association, which you know is it makes it for a very compelling monotherapy opportunity and the idea that and the post HMA setting and there is no other drug approved.
James E. Dentzer: Jim. Maybe you could just try
James E. Dentzer: Give us your thoughts on this.
James E. Dentzer: The size of these doses
Robert E. Martell: Dose escalation studies, you know, the cohorts in both combination and monoterraic. Yeah, Bob, would you mind taking that one? Yeah, so these
We like the chance of that one as well, which one will go faster I don't really know I think the answer at this point is both seem to be very compelling opportunities a combination therapy, where this gets added to standard of care.
Robert E. Martell: Yeah, so these studies will initially be dose escalation trials using a 3 plus 3 type of design. Fortunately, we're able to start at a very relevant dose that's already been shown to be therapeutically active, 200 milligrams twice daily. And we also have started to define the upper limits as well, as Jim mentioned. You know, we would likely stick within the range of, you know, somewhere in the 200 to 400 range for dosing. So the overall dose escalation for these trials is not likely to take too long.
And then of course and monotherapy and in a separate population driven by the genomic signals.
Yeah.
Thanks, Jim.
And maybe you could just.
Give us your thoughts on the size of these dose escalation and <unk>.
Studies, Yeah, you know the cohorts in both combination and monotherapy.
Edward Patrick White: Great. Thanks for taking my order.
Yeah, Bob would you mind, taking that one.
Justin Walsh: Thanks for that. Excuse me, the next question is from Justin Walsh with B. Riley Securities. Please go ahead. Hi, congrats on the progress and thanks for taking the questions. So first, could you guys elaborate on the steps needed to establish the recommended phase two dose at less than 500 milligrams?
Yeah. So these and these studies will initially be on dose escalation trials using a three plus three type of design and unfortunately, where we're able to start at a very relevant dose that's already been shown to be therapeutically active <unk> of 200 milligrams twice daily.
Justin Walsh: than 500 milligrams, BID and AMLMDFs.
And we also have started to define the upper limits as well as Jim mentioned, you know we would likely.
James E. Dentzer: Sure, again, that's probably the best question for Bob.
Robert E. Martell: Yeah, I can do that. So, you know, so far, we've seen really exciting data in a small number of patients. So part of our efforts now will be to look at a variety of different variables, obviously, including pharmacodynamics. We do know, for example, that pharmacokinetics are very well behaved between, say, the 200, 300, and 400 milligram dose levels. You know, we'll also want to expand somewhat and further understand the efficacy, perhaps, you know, looking at..., you know, perhaps a dosing interval break, things like that. So all of this will take place in the coming months, and hopefully, we'll be able to define a recommended phase two dose going forward, you know, in the near term.
I think within the range of.
Somewhere in that 200 to 400 range for for dosing. So the overall dose escalation for these trials is not likely to take too long.
Great. Thanks for taking my questions.
You bet. Thanks.
Excuse me. The next question is from just and Walsh with B Riley Securities. Please go ahead.
Hi, Congrats on the progress and thanks for taking my question.
So first could you guys elaborate on the steps needed to establish the recommended phase two dose at lower than 500 milligrams, the I D and M. L. M D S.
Sure again, that's probably the best question for Bob and Bob.
Yeah, I can do that so you know so far we've seen you know really are exciting data and a small number of patients. So part of our efforts now will be to.
Look at a variety of different variables, obviously, including and pharmacodynamics and we do know for.
James E. Dentzer: Yeah, I think if I were to add something to that, Justin, I'd say that, you know, the good news from a timing perspective is that we expected to hit MTT, we just didn't know when. The only signal that we had from the NHL study was that it was likely to be CPK elevation of RABD. Sure enough, we did see it at 500 in the leukemia study. So I think, you know, now that we've got the MTD in hand, we're at this high-class headache where 200, 300, and 400 all look therapeutic. I mean, I know that sounds kind of funny to say that that's your headache, but really, it is.
Example, the pharmacokinetics are a very well behaved between.
Sales of 200, 304 hundred milligram dose levels.
We will also want to.
Expand somewhat and and.
And further understand the efficacy.
You know looking at.
Perhaps a dosing interval breaks and things like that so all of this will take place in the coming months and hopefully we'll be able to.
Define a recommended phase two dose going forward.
You know and in the near term.
Yeah, I think if I were to add something to that Justin I'd say that you know the good news from a timing perspective, as we expected to hit M. T. D. We just didn't have win and the only signal that we had from from the NHL study was that it was likely to be see PK elevation of Rab don't sure enough. We didn't see it at 500 and are in the leukemia.
Justin Walsh: So we need to do a little bit of dose exploration at this point to try and figure out which of these really is the best one to take into phase two. Got it. And one more question for me.
So I think you know now that we've you know we've got the M P D and hand.
Justin Walsh: I saw in the abstract that most of the patients were transfusion dependent, which isn't that strange for higher-risk MDS. I'm just wondering, are you guys tracking this? And have you noticed any improvements in transfusion dependence in the MDS patients? Yeah, so hold that thought for the more detailed discussion at EHA, but absolutely, in MDS, transfusion dependence is really important. In fact, a clinical endpoint for a study could be a reduction in transfusion dependence.
Where we're at this high class headache, with 200, and 304 hundred and all look therapeutic I mean, I know that sounds kind of funny to me that that's your headache, but really it is so we need to do a little bit of dose exploration at this point.
To try and figure out.
Which of these really is the best one to take into phase two.
Got it.
And one more question from me I saw on the abstract that that most of the patients were transfusion dependent which which isn't that strange for higher risk Mds and I'm. Just wondering are you guys tracking this and have you noticed any improvements and transfusion dependence and the Mds patients.
Justin Walsh: So we continue to monitor that. That's something that's going to be important, not just for our studies but also, of course, for the low-risk MDS study, the Lucas IFT that's being run in Europe. So hold that thought.
Yeah, So I'll hold that thought for the more detailed discussion that at Ehow, but absolutely and M. D. S. Transfusion dependence is is low.
Really important and factor a clinical endpoint for a study could be reduction of transfusion dependence. So we continue to monitor that that's something that's going to be important not just for our studies, but also of course for the low risk Mds study and the Lucas I S. T. That's being run in Europe, so hold that thought.
Justin Walsh: Got it. Looking forward to it. Thanks for taking the questions. Thank you. The next question is from Salmet Roy with Jones Trading. Please go ahead.
Soumit Roy: Hi everyone, congratulations again on very robust data. Just a couple of questions. Absolutely. And I'm not sure how much color you can share with us, any mutational status on these responders, if we should think they are mostly species of mutants or it looks like both could be both three white type or mutant, and the split between AML or MDS, how many are from the AMS cohort of the responders and how many from the MDS.
Got it looking forward to it and thanks for taking the questions.
Yep.
Thank you and the next question is from Sal that ROI with Jones trading. Please go ahead.
Hi, everyone. Congratulations again on a on a very robust data on just a couple of things and I.
Certainly and I'm not sure how much color you can share with us.
The any mutational status on this the responders if we should think theyre, mostly.
Spaces on mutant and so it looks like both could be bought with three white tech on mutant and the split between him and all in and how many are from the aim of cohort two responders from.
James E. Dentzer: Yeah, so we're going to want to hold off on some of the genomics discussion for the actual EHA presentation. We're going to not go beyond what we've said in the abstract. That said, of course, that's a matter of great interest for us. So you can look forward to having a lot more detailed discussion around that when we get to it.
And yes.
Yeah. So we're gonna want to you know.
Hold off on some of the genomics discussion for the actual Ehealth presentation, we're going to not go beyond what we've said and the abstract.
That said of course, that's a matter of great interest for us. So you can you can look forward to having a lot more detailed discussion around that but when we get to it absolutely understand it but just one last question. When you were sitting up four nine and four eight plus either indeed.
Soumit Roy: Absolutely understandable. Just one last question. When you are setting up 4948 plus ESA in the HMA naive setting, should we think of as frontline patients being included who are not amenable to 7 plus 3 treatment? And how are physicians going to think whether to put the patient on 4948Aza versus Venetoclux plus Aza in these elderly patients?
Each of them and naive setting should we think of as frontline patients being included whoever is not amenable to seven plus three treatment and how would the physicians kind of think whether to put the patient on four nine and four at either of us It benefits X plus as I and dependent elderly patients.
Soumit Roy: Yeah, you know, why don't we ask Bob, our oncologist, to walk us through that? Bob,
Yeah, and you know why don't we ask Scott Barbour oncologists to walk through that bump.
Robert E. Martell: Yeah, absolutely, you know, Aesitine may be a viable treatment for first line for patients. So this combination in first line is something that certainly could be considered. You know, one of the advantages that this drug has over Venetaclax, for example, is the lack of significant myelop suppression. So, you know, this might be a driving factor, especially for a frail elderly patient for a clinician to choose. This combination over Venetaclax. As we mentioned earlier, we were also exploring a combination with Venetaclax itself and may even consider a triplet to treat this combination at some point in the future as well.
Yeah, So absolutely you know azacitidine.
You know maybe a viable treatment for first line for patients and so there's combination in first line as it's something that certainly could be considered.
You know one of the advantages that this drug has over and vanilla o'clock. For example is the lack of significant mindless suppression. So this might be a driving factor, especially for our frail elderly patients.
For a clinician to choose this combination over the nine o'clock.
As we mentioned earlier, we were also exploring and combination with men and a class itself and may even consider a triplet combination and at some point and the future as well.
Alright, thank you so much and congratulations again.
Soumit Roy: Thank you so much, and congratulations again.
Thank you Shannon.
Operator: Again, if you have a question, please press star then one. The next question is from Alethea Young with Cantor Fitzgerald. Please go ahead.
Again, if you have a question. Please press Star then one.
The next question is from Alicia Young with Cantor Fitzgerald. Please go ahead.
Alethea Young: Hey guys, thanks for taking my question and congrats on the progress with the abstract. A lot of them for me. Yeah, good stuff. So, I'm going to ask them one by one because I think they're all equally important. So when you look at the six people you had at Ash, like when we trace back now to how the CRs have deepened, were those the people that had Marrow CRs, and they deepened? Or, you know, how should we think about who had hematologic recovery? The first question.
Hey, guys. Thanks for taking my question and congrats on the progress with the abstract a lot of them from making yeah.
Yeah, and got stopped selling the first I'm going to ask them one by one because I think they're all equally as important so when you look at the six people you had at Ash like you know when we trace back now and how does he ours have deepened where those are the people that had merits the art and they defend our you know how should we think about who had the hematologic recovery. That's the first question.
Yeah, we haven't gone into into the patient by patient detail like say a hold that discussion on.
James E. Dentzer: Yeah, we haven't gone into patient by patient detail. I'd say hold that discussion, you know, on the deeper level of the data for the EHoc conference. I would say that, you know, the high-level observation is really the most important one, and that is that, you know, we were very pleased that we were getting blast count reductions. Remember that this drug is, you know, it's an anti-cancer drug; it's not a marrow stimulant. So we weren't really expecting to see heem recovery in this really late-line population.
And on a deeper level of the data for the Ehow Conference I would say that debt you know at the high level observation is is really the most important one is that.
We were very pleased that we're getting blast count reductions you know remember that this drug is and that's an anti cancer drug and it's not a marrow stimulant. So we werent really expecting to see him recovery and this really late line population that we started to see it.
James E. Dentzer: That we started to see it was fantastic. We would expect that if you can eliminate the tumor burden, and heme recovery is possible depending upon the health of the marrow, it is the sort of thing that you would expect, you know, might come over time. The fact that we've already seen it is, of course, fantastic. So we'll be following those patients and, of course, the additional ones we put on the study in the months to come. But we're very encouraged by what we're seeing so far.
Fantastic.
And we would expect debt if you can eliminate the tumor burden and and.
And he and recovery is possible depending upon the health of the marrow at it is that sort of thing that you would expect you know might come over time. The fact that we've already seen it is of course fantastic.
And so we'll be following those patients and of course. The addition, once they put on you know on.
On the study and the months to come and.
But we're very encouraged by what we're seeing so far.
So to follow that up so so and Ehow and we'll get the information on patient by patient, but just at a high level is it fair to assume that you know your hypothesis is that responsive deepen over time, Mark and you can you say that.
Alethea Young: So to follow that up, so Eha will get the information patient by patient, but just at a high level, is it fair to assume that, you know, your hypothesis is that responses deepen over time, or can you say that?
I think the hypothesis is that this drug directly.
James E. Dentzer: I think the hypothesis is that this drug directly targets the driver of the disease, IRE-4, or IREFOR long, and that should lead to the reduction of leukaine blast, full stop. That's what this drug does. It's an anti-cancer drug.
Targets the driver of disease, Iraq War or I work for a long.
And that that should lead to the reduction of leukemic blasts full stop and that's what this drug does its and anticancer drug and so by hitting the targeted disease or the driver of disease, and you should see a reduction and cancer burden and if the patient's marrow was healthy enough, obviously frontline patients and the marrow is gonna be much healthier.
James E. Dentzer: So by hitting the target of disease or the driver of disease, you should see a reduction in cancer burden. And if the patient's marrow is healthy enough, obviously, frontline patients, you know, their marrow is going to be much healthier than in late line. The marrow gets damaged over time, not just by the cancer but also by the cytotoxic agents. Whether it's chemo or Aza or Ben, all of these agents will cause damage to the marrow.
And then in late line the marrow gets damaged over time.
Not just by the cancer, but frankly by the by the cytotoxic agents, whether it's chemo or or ease up or Ben.
All of these agents will will cause damage to the marrow.
The patient's marrow is healthy enough to be recovered we would hope to see it.
James E. Dentzer: If the patient's marrow is healthy enough to be recovered, we would hope to see it, knowing that that might take some time. But that's going to be, frankly, a patient-by-patient basis, and it's going to depend, of course, on how many prior lines of therapy and how deep the cancer has gone in each patient.
Knowing that that might take some time.
But that's gonna be a frankly, a patient by patient basis, and it's going to depend of course, you know how many prior lines of therapy and and how deep the cancer has gone.
And each patient.
Okay, and so I don't know if you can say this but can you tell us at what doses. They see ours were achieved.
Alethea Young: Okay. I don't know if you can say this, but can you tell us at what doses those CRs were achieved?
And we will be showing that at our conference.
James E. Dentzer: We will be showing that at the Yon Khan. Okay.
Okay and and.
Alethea Young: Okay. I guess maybe this is more just on the toxin at the higher dose. Can you confirm whether there were any responses reported in the 500 milligram cohort? Um, or any more toxicity, I guess, in a way, like, you know, is it like, yeah, you know what I'm saying.
And I guess, maybe this is more just on the tox the toxicity and at the higher dose and can you confirm if there were and whether there any responses reported the 500 milligram cohort.
So or any more toxicity, I guess and a way and like I know it is.
Yeah, Yeah, you know what I'm, saying.
Yeah, I know, what you're saying I'm trying to obviously I'm trying to balance the Ehow rules right, we don't want to be.
James E. Dentzer: Yeah, I know what you're saying. Obviously, I'm trying to balance the Iha roles, right?
James E. Dentzer: We don't want to be bridging the gap between what's in the abstract and what's in the presentation to come. I think what we would say is that we always expected to see talks. We weren't surprised.
And the gap between whats in the abstract and what's in the presentation to come I think what we would say is that we always expected to see talks and we weren't surprised we were pleasantly surprised that we started to get responses even at the 203 hundred dose levels and what I can say broadly is that 200 304 hundred and all.
James E. Dentzer: We were pleasantly surprised that we started to get responses even at the 200 and 300 dose levels. What I can say broadly is that 200, 300, and 400 all look like therapeutics. I would say that we were pleased that we've now established NPD, and we're now going to try and figure out which of the doses has a dose response, is 200, you know, there's 300 better than 200, and 400 better than three. It remains to be seen.
And look like therapeutic doses.
And I.
And I would say that we you know we were pleased that we've now established and T. D and we're now going to try and figure out which of the of the doses is there a dose response is 200 300 and better than 204 hundred better than three remains to be seen and and as Bob said, we may also want to take.
James E. Dentzer: And as Bob said, you know, we may also want to take advantage now that we're in phase one before we go to phase two of exploring different regimens as well. You know, now is the time to learn that. But for now, I would say we're, you know, in this very high-class headache position of seeing three therapeutic doses and trying to evaluate which of the three is the best one to take into phase two.
And now that we're in phase one before we go to phase two and exploring different regimens as well now's the time to learn that and.
And but for now I would say we're frankly.
And in this very high class headache position.
I've seen three therapeutic doses and trying to evaluate which of the three is the best one to take into phase two.
So when you think about the dose response curve here you know like the 304 hundred and now the 500 like you know there was rhabdo at 300 and not in this population and mind you but.
Alethea Young: So when you think about the dose response curve here, you know, like the 300, 400, now the 500, like, you know, there was a RAPDO at 300, not in this population, mind you. But, you know, do you think that you have a predictable kind of dose response curve between 200, 300, and 400 now, and that, you know, basically 500 is where this starts to creep up, or do you think there's more work to be done there?
Now do you think that there and you have a predictable kind of dose response curves between the 200 304 hundred now and that you know basically five hundreds where they starts to creep up or do you think there's more work to be done there.
James E. Dentzer: Yeah, I would say we still have a pretty small number of patients. To be fair, I think we're encouraged that across the board, all of the doses look to be effective, you know, all the doses meaning 200, 300, and 400. But gosh, there are such a small number of patients in each trial that it's hard to say today that there's clearly a dose response and that one dose is clearly preferable to the other two. That's exactly why we've got to continue the dose exploration for the month to come and try to stuff that out.
Yeah, I would say, we still have a pretty small number of patients and need to be fair.
Yeah, I think we're and we're encouraged that across the board all of the doses looked to be effective and.
You know all the doses, meaning 200, and 304 hundred and Oh gosh, it's such a small number of patients and each one and it's hard to say today that theres clearly dose response and that one dose is clearly preferable to the other two and that's.
And that's exactly why we've got and continue the dose exploration in.
In the months to come in and tried to sort that out.
Okay and so when these two cases on the Rab, though what the what the grade three one was there any clinical sometimes I know what the other one there was the same got like can you is this and kind of like is it.
Alethea Young: Okay, and so with these two cases of Ravdo, with the grade 3 one, were there any clinical symptoms? I know with the other one, there was the syncope, but can you, is the syncope, like, is it drug-related? And if so, can you kind of explain what you think that the mechanism of action is?
And travel related and like so like can you kind of explain what you think the mechanism of action of.
Robert E. Martell: Sure, Bob, you're probably the best one to talk about that.
Sure and Ah, Bob you're probably the best one to talk to that.
Yeah. So generally patients can experience. This will have some muscle soreness, maybe they'll notice a little bit of a darkening of yearend.
Robert E. Martell: Yeah, generally, patients who experience this will have some muscle soreness, maybe they'll notice a little bit of darkening of the urine. In all of the cases, the patients have not had any, you know, organ dysfunction like renal failure or anything like that, and they've all recovered fairly rapidly from this.
And in all of the cases.
Patients have not had any you know, Oregon dysfunction, like a renal failure or anything like that and they've all recovered fairly rapidly from this and we think in several of the patients who have been there.
Robert E. Martell: You know, we think in several of the patients, there have been other, you know, factors that may have also contributed to that, for example, heavy exercise or taking a statin, for example, that may have, that has a warning for revobilysis. So, you know, it's possible that this drug pushed those patients to the point where they experienced that. And to that extent, you know, we do feel that it is drug-related, but there are other, you know, potential factors.
Factors that May have also contributed to that for example had the exercise or on.
A statin.
Example, that may have that has a warning for rhabdomyolysis. So.
And so that this drug.
Pushed pushed those patients and a point where they.
<unk> debt.
And from from that day.
We do feel that it is drug related but other potential factors.
Okay, So primary and factor for us at Lithia in and declaring.
Alethea Young: Okay, so the primary factor for us, Alethea, in declaring, um, you know, 400 is our maximum tolerated dose and backing away from 500 was not the syncope. It was RABDO because we were looking for it, frankly, after the NHL experience. We did expect to see it. We were pleased that, as Bob said, we believe, based on the NHL study, that if you are on a statin, this may exacerbate that.
400 is our maximum tolerated dose and backing away from 500 was not was not thinking it was it was the rhabdo because we were looking for it and frankly after the NHL experience and we did expect to see it we were pleased with that and as Bob said.
We we believe based on the NHL study.
That if you are on a statin and this may exacerbate that so if you already have one factor that would push you to see P. Kale elevation that if you stay on the stat and and at our drug and it might push it that much farther in the direction same thing with heavy exercise if you're doing a lot of heavy exercise maybe this exacerbates that so we were looking for that effect.
Alethea Young: So if you already have one factor that would push you to CPK elevation, if you stay on the statin and take our drug, it might push you that much farther in that direction. Same thing with heavy exercise. If you're doing a lot of heavy exercise, maybe this exacerbates that. So we were looking for that effect, and that we did see it didn't surprise us. But even though it's only one of the two DLTs, that's really the one that in our mind says, okay, we saw what we expected to see. Let's back off to 400. And then, of course, you know, take a look at the other doses as well to see which of those is the best. Okay.
And and then we did see it didn't surprise us.
But you know even though it's only one of the two D. L. Ts that's really the one that in our mind says okay. We saw what we expected to see let's back off to 400, and and then of course, you know take a look at the other doses as well to see which of those with the best.
Okay, and so and with the with the grade three Rhabdo that you saw did anyone have like kind of that and exercise baseline things and one of them though.
Robert E. Martell: Okay, and so with the grade 3 Ravdo that you saw, did anyone have, like, kind of staten, exercise, baseline things that would have been on note?
Yeah.
Yeah, Yeah, so the two.
Robert E. Martell: Yeah, Bob? Yeah, so two of the patients in the lymphoma trials, we've mentioned previously, one of whom had grade three rambomyelysis, was also on a statin, and the other patient, in that case, actually felt quite a bit better after being on the study drug for a short time, went out and exercised heavily, and then developed this, you know, muscle weakness and symptoms after that. So we think, what we've advised going forward for the clinical trial is for patients and investigators to discuss with their patients if they are on a statin whether it's necessary to continue that statin.
Two of the pay Samsung the.
And lymphoma trials, we've mentioned previously one of whom had the grade three Rhabdomyolysis was also on a stat and.
And the other patient in that case actually.
I actually felt quite a bit better after being on the study drug.
For a start time.
And went out and and exercised heavily and and then develop to this and you know.
Muscle soreness and symptoms after that so we think so what we've advised going forward for the clinical trials for patients.
And you know and investigators to discuss with their patients. If they are on a statin and there is necessary to continue that statin and <unk>.
And if they can come off that sat and they would you know.
Robert E. Martell: And if they can come off that statin, they would, you know, suggest that they do that. Similarly, to avoid extremely vigorous exercise as well on the treatment. And we think that might be part of the reason why we didn't see this side effect until a higher dose was used in the leukemia study.
Suggest to do that similarly to avoid extremely vigorous exercise well on the treatment.
And we think definitely part of the reason why we you know.
And I didn't see this side effect until higher doses on the leukemia studies.
Got it and then.
Alethea Young: Got it. And then, maybe, my last one.
And maybe my last one do you think there's a differential what kind of monotherapy response between Mds and AML patient.
Alethea Young: Do you think there's a differential kind of monotherapy response between MDS and AML patients?
Yeah, well yeah. So.
Robert E. Martell: Yeah, Bob. Well, yeah, we've actually given a much more detailed description of the specific patients, but obviously, we've treated both patients so far, and we've seen, you know, the achievement of marrow CRs in both groups of patients. So we'll have to see, you know, the MDS population is the population where these splicephal mutations are much more common. And you know that, you know, we've announced as part of this presentation that, you know, the three patients who have splicephal mutations all achieved a mayor of CR or better.
You know we've.
We will actually give us a much more detailed description of the specific patients.
But obviously, we've treated those patients so far and we've seen you know achievement as you know.
<unk> see ours in both groups of patients. So we'll have to see the the <unk>.
M. D. S population is the population and where the spices. So mutations are much more common.
And you know that we have.
We announced as part of this.
Presentation that.
The three patients who had spikes and so mutations all achieved a mere OCR or better.
Alethea Young: All right, great. I'll hop back in Q. Thanks. Thanks, Aletia.
Alright, great and I'll hop back in queue. Thanks.
Thanks Alicia.
This concludes our question and answer session I would like to turn the conference back over to James Dentzer for any closing remarks.
James E. Dentzer: This concludes our question and answer session. I would like to turn the conference back over to James Denser for any closing remarks.
Thank you operator.
Operator: Thank you, operator. I'd just like to thank everybody for joining us on the call today. We greatly appreciate the patients and families participating in our clinical trials. And, of course, as I said earlier, I'd like to thank the team at CURIS for their hard work and commitment. Also, our partners at Origen, Immunex, and NCI for their ongoing help and support. We look forward to updating you all again very soon at the EHOP conference. Operator? The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.
And I'd just like to thank everybody for joining us on the call today and we greatly appreciate the.
Patients and families participating and our clinical trials and of course as I said earlier I would like to thank the team and tourists for their hard work and commitment and also.
So our partners and origin Immunex and the NCI.
Are there ongoing help and support and.
We look forward to updating you all again very soon and be hot topics.
Operator.
The conference has now concluded. Thank you for attending today's presentation you may now disconnect.
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Yeah.
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