Q4 2021 Geron Corp Earnings Call
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[music].
Operator: Please wait; the conference will begin shortly. Ladies and gentlemen, thank you for standing by, and welcome to the Geron Corporation fourth quarter fiscal 2021 earnings call. All lines have been placed on mute to prevent any background noise.
Please wait the conference will begin shortly.
Ladies and gentlemen, thank you for standing by and welcome to the G Round Corporation fourth quarter fiscal 2021 earnings call.
All lines have been placed on mute to prevent any background noise.
After the Speakers' remarks, there will be a question and answer session.
If you would like to ask a question. During this time. Please press star followed by the number one on your telephone keypad.
If he would like to withdraw your question again press Star one. Thank you Olivia Bloom you may begin your conference.
Operator: After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, please press star followed by the number one on your telephone keypad. If you would like to withdraw your question, again, press star 1. Thank you. Olivia Bloom, you may begin your presentation. Good afternoon, everyone. Welcome to the Geron Corporation fourth quarter and year-end 2021 conference call. I'm Olivia Bloom, Geron's Chief Financial Officer. I'm joined today by Dr. John Scarlett, Geron's Chairman and Chief Executive Officer, Dr. Alexander Rizzo, Geron's Executive Vice President and Chief Medical Officer, and Anil Kapur, Geron's Executive Vice President of Corporate Strategy and Chief Commercial Officer.
Good afternoon, everyone welcome to the John Corporation fourth quarter and year end 2021 conference call I'm, Olivia Bloom Johnson Chief Financial Officer.
I'm joined today by Dr. John Scarlett Geron, Chairman and Chief Executive Officer, Dr. Alexander Rizzo, Gerrans Executive Vice President and Chief Medical Officer, and Andy OCA for Geron Executive Vice President of corporate strategy and Chief commercial officer.
Operator: Before we begin, please note that during the course of this presentation and question and answer session, we will be making forward-looking statements regarding future events, performance, plans, expectations, and other projections, including those relating to the therapeutic potential and potential regulatory approval of Imatelstat, anticipated clinical and commercial events and related timelines, the sufficiency of Geron's financial resources, and other statements that are not historical facts. However, actual results and events could differ material Therefore, I refer you to the discussion under the heading risk factors in Geron's annual report on form 10k for the year ended December 31, 2021, which identifies important factors that could cause actual results to differ materially from those contained in the forward-looking statement. Geron undertakes no duty or obligation to update this forward-looking statement.
Before we begin please note that during the course of this presentation and question and answer session. We will be making forward looking statements regarding future events performance plans expectations and other projections, including those relating to the therapeutic potential and potential regulatory approval and that helped that.
Anticipated clinical and commercial events and related timelines, the sufficiency of John's financial resources and other statements that are not historical fact.
Actual results and events could differ materially.
Therefore, I refer you to the discussion under the heading risk factors and Gerald annual report on Form 10-K for the year ended December 31, 2021, which identify important factors that could cause actual results to differ materially from those contained in the forward looking statements John undertakes no duty or obligation to update or.
Forward looking statements.
Olivia Bloom: And now I will turn the call over to Dr. Scarlett. Chip? Thanks, Olivia. Good afternoon, everyone, before reviewing our significant accomplishments of 2021, and even before discussing how we plan to build on those accomplishments in 2022 and beyond. I'd like to spend a moment putting into context why we believe in the Telstat can potentially be such a transformative, especially in the treatment of hematologic ligaments. Next slide. As many of you know, telomerase is an enzyme that adds length to the ends of chromosomes, thus allowing for continued cell proliferation.
And now I will turn the call over to Dr. Scarlett chip.
Thanks, Olivia good afternoon, everyone before reviewing our significant accomplishments of 2021.
And even before discussing how we plan to build on those accomplishments in 2022 and beyond.
Like to spend a moment putting into context, why we believe <unk> could potentially be such a transformative drug.
Especially in the treatment of hematologic malignancies next.
Next slide please.
As many of you know telomerase is an enzyme that adds links to the ends of chromosomes thats, allowing for continued cell proliferation.
John Scarlett: This enzyme is transiently expressed in normal hematopoietic stem cells during blood cell formation. However, telomerase is continuously expressed in malignant hematopoietic stem and progenitor cells, leading to their uncontrolled proliferation. Imitelstat is an oligonucleotide discovered and developed by Geron that inhibits and limits the proliferation of malignant cells where telomerase is continuously expressed. It thereby selectively induces apoptosis or killing of those malignant cells.
This enzyme is transiently expressed in normal hematopoietic stem cells during blood cell production.
In contrast collaborators continuously expressed in malignant hematopoietic stem and progenitor.
Adding to their uncontrolled proliferation.
<unk> is an oligonucleotide discovered and developed by Jeremy that.
That inhibits telomerase and.
And limits the proliferation of malignant cells, where telomerase is continuously expressed.
Thereby selectively induces apoptosis were killing of those malignant cells.
John Scarlett: This mechanism of action is unique and first-in-class, but what makes this drug so exciting and of very substantial potential value is that data from both Phase II trials in low-risk MDS and MF provide strong evidence of disease-modifying activity. Next slide. Here we summarize that key of- In both Phase II trials, Imitelstats' target engagement of telomerase led to reduction of telomerase activity and depletion of malignant stem and progenitor cells in the bone marrow, as evidenced by elimination of the malignant cells marked by molecular and cytogenetic abnormalities.
This mechanism of action is unique and first in class, but what makes this drug so exciting and a very substantial potential value is there.
Data from both phase two trials in lower risk Mds and MMS provides strong evidence of disease modifying activity.
Next slide please.
Here, we summarize the key evidence.
In both phase II trials Airtel Scott's target engagement of telomerase led to reduction of telomerase activity and.
Depletion of malignant stamand progenitor cells in the bone marrow as evidenced by elimination of the malignant cells marked by molecular insight of genetic abnormalities.
John Scarlett: Importantly, in our phase two trials, the reduction in telomere sectivity and depletion of ligament cells in the bone marrow were reinforced as clinically meaningful to the correlations of those biological effects, clinical benefits such as anemia responses in MDS and in MS, reduction in bone marrow fibrosis, as well as, for the first time, correlation with improvement and overall survival. These data, which are of keen interest to the hematologic community, provide strong evidence of the disease modification potential of imitelstat, which we expect will allow imitelstat to significantly advance patient care in both lower-risk MDS and refractory. Now, let's talk about what happened in 2021.
Importantly, in our phase II trials, a reduction in telomerase activity and depletion of malignant cells in the bone marrow was reinforced as clinically meaningful through the correlations of those biologic effects.
With clinical benefits such as in any responses in Mds.
And in MF reduction in bone marrow fibrosis as well as for the first time correlation with improvement in overall survival.
These data which are of keen interest to the hematologic community provides strong evidence of the disease modification potential loopnet telesat.
Which we expect will allow <unk> to significantly advance patient care in both lower risk Mds and refractory MF.
Now, let's talk about what happened in 2021 next slide please.
John Scarlett: A critical focus in 2021 involved advancing our two ongoing phase 3 trials toward important readouts. These trials are designed to address high-end medical needs in lower-risk MDS and refractory, and are intended to be registration and enabling trials in those indications. In our eMERGE Phase III trial in low-risk MDS, we completed patient enrollment in October of 2020; that milestone achievement enables top-line results for the key efficacy and safety parameters, what we call PLR, to be announced in early January of 2020. If those three top-line results confirm the similar say..., as well as the depth, breadth, and durability of transfusion independence.
A critical focus in 2021 involved advancing our two ongoing phase III trials towards important readout. These trials are designed to address high unmet medical needs in lower risk Mds and refractory MF.
And are intended to be registration, enabling trials in those indications.
And our emerge phase III trial in lower risk Mds, we completed patient enrollment in October of 2021 that milestone achievement enables topline results for the key efficacy and safety parameters, what we call CLR to be announced in early January of 2023.
If those phase III topline results confirm the similar safety as well as the depth breadth and durability of transfusion independence.
John Scarlett: It was observed in our phase two trial in the same lower risk MDS patient population. Ben, we expect to submit an NDA for lower risk MDS within the first half of 2020, and assuming approval, we expect the Mattel Stat to be commercialized as early as the first half of 2020. I can't wait to get to TLR and see the data. The next 10 months cannot come back.
Observed in our phase II trial in the same lower risk Mds patient population.
We expect to submit an NDA for lower risk Mds with the end of the first half of 2023.
And assuming approval, we expect <unk> to be commercialized as early as the first half of 2024.
I can't wait to get to <unk> and see those data. The next 10 months cannot come fast enough.
John Scarlett: In 2021, we also made progress in our second phase 3 trial, impact MF, with 50% of the site being open for no- We also started several new programs with high strategic value and only modest initial costs that are designed to broaden Imitelstat's potential use in additional indications and combination regimens. Alexander will provide more detail on IMPACT-MF and the rest of the Intelstat clinical development programs later in the call. Finally, in 2021, we began the process of transforming Geron into a commercial stage.
In 2021, we also made progress in our second phase III trial impact MF with 50% of the sites being opened for enrollment.
We also started several new programs with high strategic value and only modest initial costs that are designed to broaden <unk> potential use in additional indications in combination regimens.
Alexander will provide more detail on impact MF and the rest of the <unk> clinical development programs later in the call.
Finally in 2021, we began the process of transforming <unk> into a commercial stage company.
John Scarlett: We're doing this by utilizing a comprehensive milestone-driven stage gated commercialization. We've already engaged in preparation of long-lead time items for our first MBA, such as validation of commercial batches by our contract manufacturer, and are beginning to populate several key modules for the Intelstat MD. We have also begun hiring key executives in areas needed to support a commercial organization, including medical affairs, market access, and a chief business officer.
We're doing this by utilizing our comprehensive milestone driven stage gated commercialization.
We are already engaged in preparation of long lead time items for our first NDA such as validation of commercial batches by our contract manufacturers and are beginning to populate several key modules for the <unk> MDI.
We also began hiring key executives in areas needed to support a commercial organization, including medical affairs market access and a chief business Officer.
John Scarlett: Many of our internal activities are focused on keeping to aggressive timelines for submission to an NDA in the U.S. and ultimately an MAA in Europe, assuming the TLR data supports. Both the Lower Risk MDS program and the Refractory MF program are potentially of very significant commercial value. These two indications, assuming regulatory approval and launch in the U.S. and EU5 countries, have the potential to generate annual peak revenue of greater than $3 billion in 2030.
Many of our internal activities are focused on keeping to aggressive timelines for submission of an NDA in the U S and ultimately an MAA in Europe , assuming the DLR data support such submissions.
Both the lower risk Mds program, and the refractory MF program or potentially a very significant commercial value.
These two indications assuming regulatory approval and launch in the U S and EU five countries have the potential to generate annual peak revenue of greater than $3 billion in 2030.
John Scarlett: As a result, [inaudible] and in parallel with our continuing preparations to commercialize NFL, actively investigating potential relationships with appropriate parties. These include exploration of regional and other deal structures, and possible mutual interest, which could potentially further accelerate immatel staff development and commercialization.
As a result.
In parallel with our continuing preparations to commercialize hotel staff.
We're actively investigating potential relationships with appropriate partners.
These include exploration of regional and other deal structures possible mutual interest, which could potentially further accelerate <unk> development and commercialization.
John Scarlett: I'd like to hand the call over now to our Chief Medical Officer, Alexander Richter. He will provide you with an update on our clinical efforts. Following that, our Chief Commercial Officer and Head of Corporate Strategy, Anil Kapur, will share with you his synthesis of the expected differentiated role of Imitelstat in both lower-risk MDS and refractory MDS. Finally, before I make some final comments at the end of the call about upcoming milestones, Olivia Bloom, our Chief Financial Officer, will review our fourth quarter and year-end 2021 results and provide financial guidance for 2022. Thanks, too!
I'd like to hand, the call over now to our Chief Medical Officer Alexandra Reserve, Alex who will provide you with an update of our clinical efforts following that our chief commercial officer and head of corporate strategy and Neal four we'll share with you his synthesis of the expected differentiated role of Intelsat in both lower risk Mds and refractory MF.
Alexander Rizzo: In 2021, our clinical focus was on advancing our two phase 3 trials in low-risk MBS and refractory MS. This focus will continue in 2022 as we prepare for TLR for the Emerge Phase 3 trial and complete opening sides for the impact and death trials. Next slide, for Emerge Phase 3, today and for the rest of the year.
Before I make some final comments at the end of the call about upcoming milestones Olivia Bloom, our Chief Financial Officer will review, our fourth quarter and year end 2021 results and provide financial guidance for 2022.
Alex.
Thanks Chip in.
In 2021, our clinical focus was on advancing our two phase III trials, and Lori MBS and refractory MF.
This focus will continue in 2022 as we prepare for CLR for the emerge phase III trial.
Complete opening sites for the impact MF trial.
Thanks Blake.
Alexander Rizzo: The clinical team will concentrate on executing activities such as data cleaning to enable timely database logs and insured top-line results to be reportable in early January 2023. Given the number of patients and clinical sites around the world, achieving this deliverable requires significant planning, organization, and coordination amongst numerous parties with hands-on oversight by our internal teams. In addition, we have implemented plans to ensure adequate resources for clinical operations, data management, and medical review at our zero and internally.
For emerge phase III to date and for the rest of the year. The clinical team will concentrate on executing activities such as data cleaning to enable timely database lock and ensure a topline results are reported in early January 2023.
Given the number of patients and clinical sites around the world achieving deliverable requires significant planning organization and coordination amongst numerous parties with hands on oversight by our internal team.
In addition, we have implemented plans to ensure adequate resourcing for clinical operations data management and medical review at our CRO and internally.
Alexander Rizzo: Our Biostats team is preparing for the numerous statistical analyses and outputs that will be needed not only for a TLR but also for future regulatory submissions. We and our investigators from the eMERGE study are eagerly looking forward to seeing the top-line results. Given current global events, I would like to make a few comments on the impact of the ongoing conflict in Ukraine and Russia on this trial.
Our bias that the team is preparing for the numerous statistical analyses and outputs that will be needed not only for CLR, but also for future regulatory submissions.
Okay.
And our investigators from the emerge study.
I'm really looking forward to seeing the top line results.
Okay.
Alexander Rizzo: We only have two patients at one site in Ukraine. We know that this site is currently closed to patient visits, and we do not know whether these two patients will be lost for follow-up. In Russia, we have two patients at two sites, and these sites are currently open to patient visits. At this time, we do not expect an impact on the timing of the TLR due to this conflict.
Given current global events I would like to make a few comments on the impact of the ongoing conflict in Ukraine and Russia on this trial.
We only have two patients at one site in Ukraine.
We know that the site is currently close to patient visits and we do not know whether these two patients will be lost for follow up.
In Russia, we have two patients at two sites and these sites are currently open to patient visits.
At this time, we do not expect an impact to the timing of the DLR use of these conflicts.
Alexander Rizzo: Like all of you, we're closely monitoring this evolving situation. Now, on to our second phase 3 trial, Impact MS, which is a refractory MS patient population. I'd like to remind everyone that this is the only phase 3 trial in MS using overall survival or OS as the primary endpoint. In 2021, we opened over 50% of the planned clinical sites for patient enrollment, and we expect to open the remaining selected clinical sites by the end of 2022. For this trial, there are no Ukrainian science participants.
Like all of you we're closely monitoring the evolving situation.
Alexander Rizzo: In Russia, we have two patients randomized and three patients in screening across four sites. However, we are uncertain of the impact this conflict will have on the opening of new sites or patient treatment and enrollment at currently open sites. Under current planning assumptions around enrollment and median arrest for each treatment arm, we expect that the interim analogies for impact MS may occur in 2024. Because this analysis is event-driven, the rate at which death events occur determines the timing for the interim analysis.
Onto our second phase III trial impacts on that which is in refractory Mac patient population.
Alexander Rizzo: As a result, the number of events required to conduct the interim analogies for this study could occur before enrollment is complete, as these events will occur throughout the enrollment period. At the interim analysis, if the pre-specified statistical OS criterion is met, we expect these data could support the registration of hematopoietin in refractory MS, which could occur as early as 2025. If the improvement in OS that we observed in our Telstra-treated patients in our INBARC Phase II trial can be confirmed in the Phase III IMPACT-MF trial, then we believe Imatelstat will be strongly differentiated from other treatments for MS currently approved or in development and will likely change the treatment paradigm for refractory MS patients, as you will hear from the news shortly.
I'd like to remind everyone that the only phase III trial and are now using overall survival or OS as the primary endpoint.
Alexander Rizzo: Physicians consider OS as a key, significant measure of benefits for the treatment of their patients, especially for a month's patients who no longer respond to jacking inhibitors due to their difficult diagnosis and lack of desirable treatment options. Next slide.
Alexander Rizzo: Moving on from our phase three trials to the new programs we announced last November as part of our pipeline development. In 2022, we look forward to the start of three new studies. First, PROVE-MS, our Phase I clinical study of rheumatoid cell start in combination with Ruxolitinib in frontline MS, remains on track to open for enrollment in the first half of 2022. Our interest here is to bring the potential of disease modification seen from Imatelstat to MS patients earlier in their disease.
In 2021, we opened over 50% of the planned clinical sites for patient enrollment and.
And we expect to open the remaining selected clinical sites by the end of 2022.
For this trial there are no Ukrainian sides participating.
In Russia, we have two patients randomized and three patients in screening across four sites. However.
However, we are uncertain of the impact this conflict will have on the opening of new sites or patient treatment and enrollment currently open sites.
Under current planning assumptions around enrollment and median OS for each treatment arm <unk>.
We expect that the interim analysis for impact on that may occur in 2024.
Because <unk> been driven there.
<unk> death events occur determine the timing for the interim analysis as a result, the number of events required to conduct the interim analysis for this study could occur before enrolment is complete.
We have accrued throughout the enrollment period.
At the interim analysis if.
The Prespecified statistical OIS criterion is met.
We expect these data could support the registration of the Mitel is back in refractory MF, which could occur as early as 2025.
If the improvement that we observed in <unk> treated patients in our embark phase II trial.
Can be confirmed in the phase III impact MF trial.
We believe <unk> will be strongly differentiated from other treatments.
Currently approved or in development and will likely change the treatment paradigm for refractory MF patients.
And you will hear from our new shortly.
You should consider OIS as a key.
Do you see kind of a measure of benefit for the treatment of their patients, especially for MF patients, who no longer respond to JAK inhibitors user a dismal prognosis and lack of desirable treatment options.
Next slide.
Moving on from our phase III trials to the new programs, we announced last November as part of our pipeline expansion.
2022, we look forward to the start of three new studies.
First improve and that our phase one clinical study of <unk> in combination with <unk>. So we didn't even frontline lineup.
Based on track to open for enrollment in the first half of 2022.
Our interest here is to bring the potential of disease modification.
Troy Mattel statue MF patients earlier in their disease.
Alexander Rizzo: The protocol is being reviewed and approved by local investigational review boards at each clinical site. Our investigator led studies in AML and higher-risk MDS, called Impress and Telomere, will evaluate Hematopoietis as a single agent and in combination with current standard of care therapy. The principal investigators for both of these studies are highly enthusiastic. Anil continues to be an extraordinarily difficult hemalignancy to treat, and a new mechanism of action, like hematelpsia, that directly affects the malignant stem and progenitor cells driving the disease, could provide an effective treatment option for these patients.
Protocol is being reviewed and approved by local investigational review boards at each clinical site.
Our investigator led studies in AML and higher risk Mds called Empress and two Amir.
We'll be evaluating that tells that as a single agent and in combination with current standard of care therapy.
The principal investigators for both of these studies are highly enthusiastic and now continues to be an extraordinarily difficult chemo agnostic to treat and the new mechanism of action liking that tell us that the directly affects the malignant stem and progenitor cells driving the disease could provide an effect.
Treatment options for these patients.
Alexander Rizzo: Due to increasing requests for participation and the expansion of the studies to more sites than initially planned, we expect the start of these studies in the second half of 2022. In addition to these new studies, we have also some preclinical experiments ongoing. The preclinical work being done at MD Anderson is evaluating the telcel's potential to treat lymphoid-K malignancy. This work allows us to explore the potential use of human telestat beyond myeloid malignancies, which if positive, could open several new indications in the future.
Due to increasing request for participation and the expansion of the studies to more science than initially planned we expect the start of these studies.
And half of 2022.
In addition to these new studies, we have also some preclinical experiments ongoing.
The preclinical work being done at MD Anderson.
Evaluating the telephones potential, which we believe points came mulligan market.
These work allows us to explore the potential user can intelsat beyond myeloid malignancies, which if positive could open several new indications in the future.
Alexander Rizzo: We continue to expect preliminary data from these experiments at MD Anderson at the end of 2022. Our final new area for pipeline expansion is the Next Generation Telomerase Inhibitor Discovery Research Program. Research into the characterization of the different compounds continues, and once a lead compound is identified, we will have more detail on all of these activities.
Continue to expect preliminary data from these experiments at MD Anderson at the end of 2022.
Our final new area for pipeline expansion is the next generation Telomerase inhibitor Discovery Research program.
Research into the characterization of the different compounds continue and once the lead compound is identified we will have more detail.
All of these activities.
Alexander Rizzo: Sets up 2022 to be a busy and rewarding year, not only for Matilda and Geron but also for patients. Now, I will hand the call over to Anil.
Set up 2022 to be a busy and rewarding year, not only frame of Tulsa and Darren but also for patients.
Now I will hand, the call over to Aneel Aneel.
Hi, Neil.
Anil Kapur: Thanks, Alex, and good afternoon, everyone. I share Chip's and Alex's excitement as we get closer to the iMerge top-line results. In my prepared remarks today, I'll first highlight Emittelstat's expected product profile in lower-risk MDS and how this will differentiate the drug in the market. After that, I'll provide insights into the fast-evolving myelofibrosis. We believe that Emetelstat can play a meaningful role in the treatment of patients in both indications. As I'll describe, these indications represent large addressable patient populations and significant commercial opportunities for Geron. Next slide.
Thanks, Alex and good afternoon, everyone.
I shared chipped in Alex's excitement as we get closer to the I emerged topline results.
Anil Kapur: In lower-risk MDS, the mental starts product profile has been favorably received by practicing hematologists. Key attributes identified include Imitalstat's ability to treat a broader set of patients, which includes both Ring-Sideroblast positive and Ring-Sideroblast negative subtypes, as well as the durability of transfusion independence. In addition, Imitalstat's unique mechanism of action and potential for disease modification resonated well with hematologists in our market survey. Given that Lospatacept's approval in lower-risk MDS is restricted to RS-positive patients only, we are seeing a high level of awareness among practicing hematologists about their patients' RS status. We also hear their desire for more effective treatment options for lower-risk MDS patients who are RS negative. Thus, Imitelstat's ability to broadly treat patients across both RS-positive and RS-negative subtypes was seen as important by hematologists.
In my prepared remarks today I'll first highlight them. It does start as expected product profile and lower risk Mds and how this will differentiate the drug in the market after that I'll provide insights into the fast evolving myelofibrosis Margaret.
Anil Kapur: Also, since responses to current treatment options are limited in duration, hematologists seek durable transfusion independence for their patients. As such, the 24-week and the one-year transfusion independence data from our iMERGE Phase 2 trial not only provide strong evidence for the durability of transfusion independence of hematelstat but also were considered by hematologists to be highly clinically relevant for their patients. Next slide. Lower risk MDS represents approximately 70% of the total MDS patient population.
We believe that <unk> can play a meaningful role in the treatment of patients had both indications.
As I'll describe these indications represent large addressable patient populations and significant commercial opportunities.
Next slide.
In lower risk Mds and when it does start to product profile has been favorably received by practicing hematologist.
Key attributes identified include <unk> ability to treat a broader set of patients which includes both ring side auto glass positive.
And ring Sideroblast negative subtypes as well as the durability of transfusion independence.
In addition, it does start to unique mechanism of action and potential for disease modification resonated well with Hematologist and our market service.
Given that <unk> approval in lower risk Mds is it restricted to Rs positive patients only.
We're seeing an high level of add Mitch among practicing hematologist or their patients artist startup.
We also hear their desire for more effective treatment options for lower risk Mds patients what artist Megabits.
Does <unk> ability to broadly to treat patients across both auto as positive an artist. Thank you, Dave subtypes casinos embarking by Hematologist.
Also send to the sponsors to current treatment options are limited in duration Hematologists see durable transfusion independence for the integrations.
The 24 week and the one year transfusion independent data from <unk> phase two trial not only provides strong evidence for their durability of transfusion independence. So Kevin I'll start, but also considered by hematologist to be highly clinically relevant for their patients.
Next slide.
Lower risk Mds represents approximately 70% of the total Mds patient population.
Anil Kapur: Chronic anemia is the predominant clinical problem in patients with lower risk MDI. Typically, retrograde and stimulating agents or ESAs are the mainstay of treatment for the approximately 90% of lower risk MDS patients who have symptomatic anemia and do not have, However, not all patients respond to or are eligible for ESP. Even among responders, responses typically last between 18 to 24 minutes.
Chronic anemia is the predominant clinical problem in patients with lower risk Mds.
And it support and stimulating agents Audi assays are the mainstay of treatment for the approximately 90% of lower risk Mds patients, who have symptomatic anemia, and do not have dilution by SKU.
But not all patients respond to <unk> eligible assets.
Even among responders responses typically lost within 18 to 24 months treatment options remain limited for patients who have failed <unk>.
Anil Kapur: Treatment options remain limited for patients who have failed or are ineligible for ESR. These patients may move on to receive hypomethylating agents or HMAs or Lispatacept if they are ring-sided aeroblast pathogens. It's important, though, to note that HMAs are not a preferred option, given their limited benefits.
Ineligible for Esa These.
These patients maybe want to receive high quality, leading agents on HMA is on the spot.
Are ring Sideroblast positive.
It's important though to note that.
Tim is not a preferred option given their limited benefits. They are also not broadly approved across Europe for this indication.
Anil Kapur: They are also not broadly approved across Europe for this indication. As such, there remains a lack of effective therapies for RS-negative patients, leaving a significant unmet need for effective therapies for the remaining approximately 75% of lower-risk MDS patients and a compelling market opportunity for Emetelstat in this setting. Thus, given the breadth, the depth, and the durability of transfusion independence and the potential for disease modification, as evidenced by our Phase II data, we expect a highly differentiated profile for Emetelstat at launch in lower-risk MDS and expect it to significantly penetrate this attractive market and become part of the standard of care in the syndicate.
As such there remains a lack of effective therapies for <unk> negative patients, leaving a significant unmet need for effective therapies, but the remaining approximately 75% of lower risk Mds patients and a compelling market opportunity and make those start in the city.
Does given the Brett.
And the durability of transfusion independence.
And the potential for disease modification as evidenced by our phase II data.
We expect a highly differentiated profile does start that launch in lower risk Mds unexpected Michael start to significantly penetrate this attractive market and become part of the standard of care in this indication.
Next slide.
Anil Kapur: Now, moving on to myelofibrosis. In myelofibrosis patients, improvement in overall survival remains a key unmet need that was highlighted by community hematologists in our market survey. This is especially important given that patients who discontinue JACI-based therapy have a dismal survival prognosis; therapies that offer disease-modifying potential naturally carry significance in the armamentarium of treatment options offered by physicians, as these therapies have the potential to alter the course of the disease. In addition, physicians are seeking treatments for anemic or severely thrombocytopenic patients, and they also need effective second-line treatments that are non-jack
Now moving on to myelofibrosis.
In myelofibrosis patients improvement in overall survival remains a key unmet need that was highlighted by community Hematologist and auto market service.
This is especially important given that patients who discontinue jakafi based therapy, how did this most survival prognosis.
<unk> that also disease modifying potential naturally gaddy significance in the armamentarium of treatment options offered by physicians as these tenant these have the potential to alter the course of their disease.
In addition, physicians are seeking therapies for anemic are severely thrombocytopenic patients and they also need effective second line therapies that are non JAK high base.
Next slide.
Anil Kapur: Next slide. As Alex pointed out earlier, when we asked hematologists in our surveys for the most relevant endpoint in randomized clinical trials for their JACI-treated or JACI-discontinued patients, the majority cited overall survival as the most relevant clinical endpoint for this trial. Thank you for your time.
As Alex pointed out earlier, when we asked Hematologists and our salaries for the most relevant endpoint in randomized clinical trials.
Jack I treated our jacquard discontinued patients.
A majority of these high grade overall survival as the most relevant clinical endpoint for this population.
Anil Kapur: Thank you. In PACT-MF, our phase 3 trial intended for registration is the first and only phase 3 trial in refractory MF with OS as the primary endpoint. If impact MF can confirm the improvement in overall survival we observed in our face-to-face trial, we expect Immittal Start will transform the care of refractory mylo fibrosis.
In fact, MF, our phase III trial intended for registration is the first and only phase III trial in refractory MF.
Good OS as the primary endpoint.
If impact MF can confirm the improvement in overall survival observed in our phase two embark trial <unk>.
We expect <unk> will start will transform the CAD of refractory myelofibrosis patients.
Next slide.
Anil Kapur: Next slide, on to the expected myelofibrosis market evolution. The decade-old Jaka in Avatar therapy, Raksal Littinip, has been a very successful drug in the Milo Fibrosis market and has established itself as the standard of care and the backbone of, However, we know that patients do not stay on this drug long-term. Real-world data suggests a dismal prognosis for patients who have discontinued ruxolitinib, with median overall survival less than 12 months. As part of the natural evolution of this market, we expect to see significant expansion over the next decade as more drugs are developed to give clinicians more choices to offer tailored patient treatment options. These will include single agent or combination approaches where appropriate.
Onto the expected myelofibrosis market evolution.
The decade oral JAK inhibitor tenant we had accelerated NIM has been a very successful drug in the myelofibrosis market.
<unk> has established itself as the standard of care and the backbone of frontline therapy.
We know that patients do not stay on this drug long term.
Real World data suggest the ESMO prognosis for patients who have discontinued <unk> with median overall survival less than 12 months.
As part of the natural evolution of this market, we expect to see significant.
<unk> expansion over the next decade as more drugs are developed.
Give clinicians more choices to offer tailored patient treatment options.
These will include single agent or combination approaches where appropriate.
Anil Kapur: We believe that the opportunity in myelofibrosis for emetelstrat is driven by the expectation that all JAKI inhibitor-treated patients will become unresponsive to JAKIs over time and therefore become eligible for a medal. Like in lower-risk MDS, we expect imitL-STAT to have a highly differentiated profile in refractory myelofibrosis and thus to potentially become part of the standard of Before I hand over the call to Olivia for the Financial Summary, just a quick update on our preparations for Immittal Starts commercialization, which are stage-cated across all aspects, as pointed out by chips.
We believe that the opportunity in myelofibrosis flooded my goldstrike is driven by the expectation that all JAK <unk> inhibitor treated patients will become unresponsive Jack is overtime.
And therefore become eligible for damage on the stock.
Like in lower risk Mds.
<unk> will start to have a highly differentiated profile in refractory myelofibrosis and thats to potentially become part of the standard of care and back indication.
Before I hand over the call to Olivia for the financial summary, just a quick update on our preparations for them. It does start commercialization recharge stage gated across all aspects as pointed out by chip out yet.
Anil Kapur: In 2022, the key areas of focus for the commercial organization are on activities that have long lead times, such as commercial supply chain planning and third-party logistics set-up, refining our value proposition across all stakeholders, and building a deep understanding of the customer base. Although we have initiated these pre-commercial activities, the bulk of our commercial investments will happen after top-line results from I Merge Facebook. With that, I will now hand the call over to Olivia. Okay?
In 2022, the key areas of focus for the commercial organization add on activities that have long lead times, such as commercial supply chain planning and third party logistics setup.
Finding that value proposition across all stakeholders and building a deep understanding of the customer base.
While we have initiated these pre commercial activities the bulk of our commercial investments will happen after top line results from <unk> phase III.
With that I will now hand, the call over to Olivia Olivia.
Olivia Bloom: Thanks, Anil. Next slide. As expected, overall operating expenses for the fourth quarter and full year 2021 were higher than the same period in 2020. Total operating expenses for the 3 and 12-month-ended December 31, 2021 were $32 million and $115.4 million, respectively, compared to $23.3 million and $77.2 million for the same period in 2020.
Thanks, Danielle next slide.
Olivia Bloom: The increase in research and development expenses primarily reflects increased clinical development costs for our two ongoing Phase III clinical trials, higher Imitelstat manufacturing costs for producing validation batches at contract manufacturers, and higher personnel-related costs for additional headcount. The increase in general and administrative expenses primarily reflects new costs in connection with pre-commercial activities, including modernizing our internal infrastructure to support a potential commercial launch and higher legal costs. We ended the 2021 fiscal year with $212.7 million in cash and marketable securities, which we believe is sufficient to fund current operations through the end of the first quarter of 2023.
As expected overall operating expenses for the fourth quarter and full year 2021 were higher than the same period in 2020.
Total operating expenses for the three and 12 months ended December 31, 2021 were $32 million and $115 4 million, respectively, compared to $23 3 million and $77 2 million for the same period in 2020.
The increase in research and development expenses, primarily reflects increased clinical development costs with our two ongoing phase III clinical trials.
Higher and they tell us that manufacturing cost producing validation batches at contract manufacturers and higher personnel related costs for additional headcount.
The increase in general and administrative expenses, primarily reflects new costs in connection with pre commercial activities, including modernizing our internal infrastructure to support a potential commercial launch and higher legal costs.
We ended the 2021 fiscal year with $212 $7 million in cash and marketable securities, which we believe is sufficient to fund current operations through the end of the first quarter of 2023.
Olivia Bloom: For guidance in 2022, we expect non-GAAP total operating expenses to be in the range of approximately $140 million to $150 million. This guidance reflects expenses for supporting the two ongoing Phase III clinical trials, as well as the new exploratory studies in frontline MF and AML, and finalizing validation batches of imitelset at contract manufacturers to enable future production of imitelset for clinical and commercial purposes. Initial Manufacturing for Commercial Inventory Production, Preparations for Top-Line Results in Low-Risk MDS and Future Regulatory Submissions. Initial commercial readiness activities, projected increases in headcounts, and larger interest payments due to higher outstanding debt.
For guidance on 2022.
We expect non-GAAP total operating expenses to be in the range of approximately 140 million to $150 million.
This guidance reflects expenses for supporting the two ongoing phase III clinical trials as well as the new exploratory study in frontline Mds and AML.
Finalizing validation batches of <unk> that our contract manufacturers to enable future production of Intelsat for clinical and commercial purposes.
Initial manufacturing for commercial inventory production.
Preparations for top line results and low risk Mds and future regulatory submission.
Initial commercial readiness activities.
Projected increases in head count and larger interest payments due to higher outstanding debt.
John Scarlett: With that, I will now hand the call over to Chip to share our key upcoming corporate milestones. Chip? Next slide, please. Thanks, Olivia. As I commented at the beginning of this call, 2021 was a year of critical execution and accomplishments for Geron, as we drive towards significant future readouts in our phase three trials and ultimately commercialization of the mental status. 2022 is equally important.
With that I will now hand, the call over to Jeff to share our key upcoming corporate milestones.
Chip.
John Scarlett: Next slide, please. Our expected key upcoming milestones include ensuring delivery of top-line results for the Phase 3 Emerged Lower Risk MDS trial in time for disclosure in early January of 2023. Assuming positive TLR, we are also preparing for a potential submission of the NDA in the first half of 2023, an MAA submission in the second half of 2023, and subsequent regulatory approval and commercialization in lower-risk MDS as early as the first half of 2024 in the U.S. As well, our team will continue executing on IMPACT-MF with opening the remaining selected sites by the end of the year. If we accomplish this, we expect that the planned interim analysis of IMPACT-MF may occur in 2024.
Next slide please thanks Olivia.
As I commented at the beginning of this call 2021 was a euro critical execution and accomplishment for John as we drive towards significant future Readouts from our phase III trials, and ultimately commercialization of Intelsat <unk>.
2020, twos equally important next slide please.
Our expected key upcoming milestones include ensuring delivery of top line results for the phase III emerge lower risk Mds trial in time for disclosure in early January of 2023.
Assuming positive <unk>. We are also preparing for a potential submission of the NDA in the first half of 2023 and an MAA submission in the second half of 2023.
And subsequent regulatory approval and commercialization in lower risk Mds as early as the first half of 2024 in the U S.
As well our team will continue executing on impact MF with opening the remaining selected sites by the end of the year. If we accomplish this we expect that the planned interim analysis of the impact MF may occur in 2024.
John Scarlett: Taken both separately and together, the upcoming readouts from these two Phase III registration trials have the potential to transform Geron from a late-stage development company into a commercial stage and thus to realize our vision of Geron becoming a leader in the treatment of hematologic malignancies. Finally, we expect the new programs in our expanded pipeline to progress meaningfully this year and to begin the process of potential value accretion beyond our initial indications for Mattelstadt and possibly even beyond Mattelstadt itself.
Taking both separately and together the upcoming Readouts from these two phase III registration trials have the potential to transform Jeremy.
A late stage development company into a commercial stage company and.
Industrialize our vision of.
Becoming a leader in the treatment of hematologic malignancies.
Finally, we expect the new programs in our expanded pipeline to progress meaningfully this year and to begin the process of potential value accretion beyond our initial indications from Intelsat.
Possibly even beyond <unk> itself.
John Scarlett: Looking forward, if we accomplish each of these important value-accreting milestones successfully, we expect Imitelstat will change the treatment of lower-risk MDS and refractory MF with significant improvement for patients. Thanks very much for your interest in the company, and we'll be glad to answer your questions. Operator, please open the call to questions. At this time, I would like to remind everyone, in order to ask a question, please press the star followed by the number one on your telephone keypad. Your first question comes from Gil Blum with Needham and Company. Your line is open. Hi, and good afternoon, everyone.
Going forward, if we accomplish each of these important value accretive milestone successfully we expect them to tell us that will change the treatment of lower risk Mds and refractory MF with significant improvement for patients.
Thanks, very much for your interest in the company and we'll be glad to take your questions. Operator, Please open the call to questions.
At this time I would like to remind everyone in order to ask a question. Please press star followed by the number one on your telephone keypad.
And your first question comes from Gil Blum with Needham <unk> Company. Your line is open.
Hi, and good afternoon, everyone.
Operator: So maybe I have a quick question on myelofibrosis. So there's been a bit of a shift in the treatment landscape with the very recent approval of PacRetMed. Do you think that that's going to extend the amount of time patients spend being refractory, i.e., living a little longer?
So maybe a quick question on myelofibrosis, so theres a bit of a shifting of the treatment landscape for us a very recent approval of <unk>.
I think that it's going to extend the amount of time patients spend being refractory.
E living a little longer.
Gil Blum: Does that potentially increase the market for relapsed refractory? Hi Gil. Thanks very much. This is Chip.
Potentially increase.
Market for relapsed refractory Amit thank you.
John Scarlett: Can you hear me okay? Yes. Okay, great. Okay. So, I think I'm going to let Anil Kapur just take a first crack at that and others may have a few other comments so the question was, will the shifting, would the, will the critinib approval shift landscape in any, in any way, and in particular increase the number of patients who have a.., who are jack-eyed refractory. I think that was the question. Go ahead, Anil.
Hi, guys. Thanks very much. This is chip can you hear me okay, yes.
Yes.
Okay, great Okay.
So I think I'm Gonna West Aneel Kapoor, just take a first crack at that.
Others May have a few other comments. So the question was will the shifting with the Wil <unk>.
Approval ships landscape in any in any way and in particular to increase the number of patients who have a.
Who are Jeff Hi, refractory I think covers the question go ahead.
Anil Kapur: Sure, thanks for the question, Gil. So pecretinib, as you know, was just approved for severely thrombocytopenic patients. These patients represent a small fraction of myelofibrosis patients, and it's different from the population that a metal stack can treat, and we welcome the addition of all of these new jacquit therapies for MF patients. And I think to answer your question, Jill, it all depends on the patient population actually on PICRIT. So if the patient population on pecretinib is less than 50,000, which is their indicated label, that population will remain distinct from the populations of biomes.
Sure. Thanks for the question, Joe So Patrick as you know.
It was just approved for severely thrombocytopenic patients.
These patients represent a small fraction of myelofibrosis patients and it's different from the population that they might sell stock and stuff.
And we welcome. The addition of all of these new <unk> MF patients and I think to answer your question. It all depends upon.
The patient population actually on <unk>.
The patient population on take rate and it is less than 50000, which is net indicated label Dod population will remain distinct from the population served by M. It does start however, repaying that this unmet need is very high and we welcome the opportunity, but the general Gist and <unk> I can say that for all 10.
Anil Kapur: However, we think that this unmet need is very high, and we welcome the opportunity, but the general gist, and I think I can say that for all therapies and developments, is that over time, you will see this market significantly expand and, as we said, provide physicians with multiple choices across all lines leading to a much, much larger second, third line, plus treatments in myelofibrosis. Very similar to this dynamic is an example that we saw even in myelofibrosis. Thanks, Anil. Gil, any follow-up questions on that? Maybe I should sharpen that last point a little further.
Do you think development is that over time, you will see this market significantly expanded and as we said provide physicians with multiple choices across all lines, leading to a much much larger second line third line plus treatment in myelofibrosis very similar to the dynamic is an exam.
That we saw you in myeloma.
Thanks Danielle.
Kill any follow up question on that.
Maybe they've sharpened.
Last point a little further.
Gil Blum: It is my understanding that thrombocytopenia is part of the disease progression as well as an outcome of the treatment of JAKIs over time. And basically, if patients live long enough, they will be confirmed with cytokine X. So it's kind of like a funnel where your patient is constantly progressing to being more and more thrombocytopenic. Am I misunderstanding that?
It was it was minor.
My understanding of that.
Tom Thrombocytopenia as part of the disease progression as.
As well as an outcome of the treatment of Jefferies over time.
And very quickly patients to live long enough. They will become thrombocytopenic. So it's kind of like a funnel, where you're a patient who is going to constantly progressive Martin Warsaw and beside dependent for my misunderstanding.
Okay.
Alexander Rizzo: I'll let Alexandra take that since she's the clinician on the call. Go ahead, Alexandra. Yes. Can you hear me?
Outlet Alexandra take that since you asked the question on the call go.
Go ahead Alex.
Yes can you hear me.
Alexander Rizzo: [inaudible] You're correcting that saying that patients that progress over time become thrombocytopenic. In addition to that, as we know, it is available, for the approved JAK therapy at the moment also doesn't serve these patients or over time these patients, you know, with time the patients that are treated with Duxoetine, for example, become thrombocytopenic. So, um...
Yes.
Yes sure.
Yeah.
You are correct.
That saying that patients that progress over time become thrombocytopenic. In addition to that as we now have available.
And with the approved JAK therapy at the moment Oh, So definitely serve these patients are over time these patients.
Times of patients that are treated with opioids me for example become thrombocytopenic so.
Alexander Rizzo: I think your conclusion is right there. And then these patients, as they progress, if they do have the appropriate number of platelet counts to be treated with imatelsta, they could, you know, they certainly are an option for treatment or could potentially be an option for treatment with imatelsta. I'll conclude with some comments about this Gil. I think that the point, as we see it, is that most of the patients who probably will end up on Christmas, at least early in the course, would come from the front line or near the front line, maybe possibly the second line with low playlists.
I think you're in your conclusion is right there and then these patients as they.
Progress if they do have the appropriate number of percolate challenge to be treated tweak you might tell us that they could you know they they certainly are.
Our option for for treatment or could potentially be an option for treatment with <unk>.
Yeah, maybe I conclude.
Some comments about the scale I think that.
<unk>.
I think the point that as we see it is.
Most of the patients who probably will end up months Clinton or at least early in the course would come from the frontline or near frontline, maybe possibly second line with low platelet counts I think your question presupposes, what will happen as patients become much more ill and ultimately patients.
Alexander Rizzo: I think your question presupposes what will happen as patients become much more ill, and ultimately, patients become trauma-cited, neutropenic all on their own with their bone marrow failing. While it's certainly possible that some of those patients would benefit by the availability of a drug that is not limited by platelet counts, on the other hand, most of those patients are really failing jack out therapy in other ways, symptomatic and otherwise.
Become thrombocytopenia neutropenia, all on their own with their bone marrow fails.
It's certainly possible that some of those patients would benefit by the availability of the drug is not limb.
Limited by.
Platelet counts on the other hand, most of these patients are really failing jakafi therapy, and other ways symptomatic and otherwise so I think that.
John Scarlett: So I think that we will, I think that the dynamic will continue to evolve. And, honestly, as Anil said, we do welcome these other entrants, especially into these areas that are particularly difficult patients to treat. But how exactly is it going to play out in numbers?
We will.
Think that the dynamic will continue to evolve and as.
Honestly as Neil said, we do welcome. These other entrants, especially into these areas that are particularly difficult patients to treat but how exactly it's going to play out in numbers I put my money on the entire market expanding as more and more patients become eligible for frontline page for frontline therapy. That's just my point of view.
John Scarlett: I put my money on the entire market expanding as more and more patients become eligible for frontline therapy. That's just my point. Okay, maybe we could move on to the next question. Yeah.
Okay, maybe we could move on to the next question.
Operator: One additional question and then that would be from me. So do you guys have any timeline on potential readouts from the frontline combo study? This is a very interesting study. Yeah.
Yes.
One additional question.
Sure I can speak for me so.
Doesn't have any timeline on potential readout from the frontline combo study. This is a very interesting.
The study.
John Scarlett: Gil, I think it's a little early to be commenting on that. All we know is that we're feeling comfortable that we'll begin the study or open the site for enrollment in the first half of this year, but we don't know exactly how long it will take to ladder up the different doses, right? So you'd have to take these studies quite slowly in the interest of safety, and that's been true for every combo study I've ever done, really pretty much any indication.
Yeah, Joe I think it's a little early to be commenting on that.
All we know is that we're feeling comfortable that we will begin the study or will open at the site.
Four.
For enrollment in the first half of this year, but we don't know exactly how long it will take to ladder up with different dosing right. So you have to take these studies quite slowly.
In the interest of safety and that's been true for every combo study I've ever done really pretty much any indication.
John Scarlett: So the question will be, how long do we have to stick with it, and what do we see in the way of adverse events as we add on? So I don't think there's a good expectation at the moment. I don't know if Alexander has any further commentary about that.
So the question will be how long do we have to stick and what do we see in the way of of adverse events as we add on so I don't think there is a good expectation at the moment.
I I don't know if Alexandra has any further commentary about that Alex.
Alexander Rizzo: Yeah, thank you, I just wanted to make it clear that we expect to start the study in the second half of 2022, so that was something in my part of the script, just because there is a bit more. And, oh, I'm sorry, I, yeah, so she was correct. I'm sorry, I moved to the, to the, to the investigator that studies. So, she's correct.
Yeah. Thank you.
Just wanted to make it clear that we expect to start.
The study in the second half of 2022, so that was something in my part of the script just because there is a bit more.
And.
I'm, sorry, I got the numbers.
Yeah. So chip was correct I am sorry, I moved to the to the to the investigator led studies. So cheap it's correct the company sponsored study.
From time to start enrollment of the first half.
Alexander Rizzo: That's the component sponsor study on time to start enrollment in the first half. And, as she said, we are first trying to safely combine the two drugs, and we are going to look for the safest route, but with that said, right, it's an open-labeled study, so we will be able to evaluate the potential efficacy of the two drugs as we go. Um, I guess so.
Uh huh.
As chip said.
Aircrafts Medtronic to safely combine the two drugs and we are.
Going to look for the seats goes but we've got a great. It's an open label study. So we will be able to evaluate the potential efficacy of the two drugs as we go thank.
Thank you so.
Alexander Rizzo: That's one addition that I wanted to give. Okay, next slide. And I think that's it from me for now, and we'll continue to watch your program. Thanks very much, Gil. Next question. Your next question comes from the line of Stephen Willey with Stiefel. Your line is open. Hi, this is Ellen on for Steve.
That's why in addition that I wanted to get to.
Yes.
Okay.
Okay.
Thank you. Thanks from me for now and.
Well continue to monitor progress.
Thanks, very much Joe next question.
Next question comes from the line of Stephen Willey with Stifel. Your line is open.
Yeah.
Operator: Thank you for taking the question. So maybe the first one on the work that's being done on the second generation telomerase inhibitor. I'm just wondering what the ideal profile that the second candidate would look like, in your opinion, and you know what key improvements would be made compared to. Could you tell us that?
Hi, This is Ellen on for Steve. Thank you for taking the questions.
First one on the work that's being done on the second generation Telomerase inhibitor I'm just wondering what the ideal profile that second Gen candidate would look like in your opinion and you know what what key improvements would be made compared to Intelsat.
John Scarlett: Yeah, sure. I'll take that one. So, uh, our number one choice, and what we're really going for, is an orally available small molecule that has all the usual benefits, and one that would have all of the usual benefits of small molecule development, both in terms of manufacturing and also in terms of timing, and of course, oral availability would be welcome in certain indications, in certain types of utility. It's a tall order.
Yeah sure I'll take that one so R R.
Number one choice and what were really good.
Going forward is an orally available small molecule that has all the usual benefits.
And one that would have all of the mutual benefits of small molecule development. Both in terms of manufacturing and also in terms of timing.
And of course, the oral availability would be would be welcome.
Certain medications and certain types of utility.
John Scarlett: We started out with a couple of different scaffolds, but we're still looking for a lead compound in that regard. I have a lot of hope here, but honestly, we're not quite ready to report any specificity around this, and we will attempt to give a little bit more specificity once we have a lead compound, and I think we've said in the past that that will likely take us through the remainder of this year.
Tall order.
We started out with a couple of different scaffolds, but we're still we're still looking for a lead compound in that regard I have a lot of hope here, but honestly.
We're not quite ready to report any stuff.
Specificity around this and we will attempt to give a little bit more specificity. Once we have a lead compound and I think we said in the past that.
That will likely take us the remainder of this year.
John Scarlett: Okay, great. Thanks. And then with regard to the frontline MS study, I know, you know, the primary endpoint is really safety and the combinability of these two drugs, but just wondering from an efficacy perspective, you know, total symptom score, kind of what the bar is for moving the program forward. Alexander, do you want to comment on that?
Okay, great. Thanks, and then with regards to the frontline MF study I know you know time endpoint is really safety and the combinability of these two drugs, but just wondering from an efficacy perspective, you know total symptom score kind of what the bar is for success here for moving the program forward.
Okay, Andrew you want to comment on that.
Alexander Rizzo: I just wanted to maybe start off by saying that the enthusiasm on our side for this combination is really to bring the disease-modifying potential or disease-modifying data that we have seen with metastat in the relapse and refractory setting. So while, yes, you know, we have to really look into the endpoints that are easy to evaluate, like a TSS or an SVR, we will certainly be looking into other efficacy endpoints as well, potential CRs, PRs, and improvement of fibrosis as well.
Yeah sure.
Sure, Yeah, and I did hear it and I just wanted to know.
Maybe start off by saying that could really be until jamul.
He is on our side for this.
For these combination was really to bring the <unk>.
He has more to find potential disease modifying data that we have seen within the Palestine relapsed and refractory setting.
Well, yes, we you know we have to really look.
Look into the.
End points that are easy to evaluate like a PSS.
Yes, we are we will certainly be looking into other efficacy endpoints as well potential Trs prs improvement of fibrosis as well so it's really going to be the totality of the data that we will be evaluating.
Alexander Rizzo: So it's really going to be the totality of the data that we will be evaluating in this study. I'll remind everyone, this is a phase one study, so I think that's kind of how we are looking at this. Okay, great, thank you for taking the questions and congrats on the progress. Thank you. As a reminder, if you would like to ask a question at this time, please press star followed by the number one on your telephone keypad. Your next question comes from the line of Joel Beatty with Baird. Your line is open.
A reminder, once phase one study.
I think that's kind of where we how we are looking on this study.
Yeah.
Okay, great. Thank you for taking the questions and congrats on the progress.
Thank you.
Yeah.
As a reminder, if you would like to ask a question at this time. Please press star followed by the number one on your telephone keypad.
Next question comes from the line of Joel Beatty with Baird. Your line is open.
Yeah.
Operator: Hi, thanks for taking the questions. The first one is on the eMERGE Phase 3 trial in MDS. Could you discuss what gives you confidence that the trial is sufficiently powered?
Hi, Thanks for taking my questions.
The first one is on the emerge phase III trial in MBS could you discuss what gives you confidence that the trial.
Joel Beatty: I believe, you know, one example of something that could be successful is a 30% rate in the metaltate arm versus 7.5% in the placebo arm. And could you talk to the team about, I realize it's just an example, but you know, could talk to them about how realistic those numbers are? Go ahead, Alex. Let's try it here, Olly.
Phil.
This only powered.
I believe.
One example of something that could be successful as a 30% rate in the.
Let me tell us that arm versus seven 5% in the placebo arm.
Talk to the I realize there's just an example, but could talk to how realistic both numbers are.
Go ahead, Alex that's a trade up your alley.
Alexander Rizzo: [inaudible] Yeah, to Joel, I'm no tweet by who you're willing to begin, but I think you asked whether we had discussed these with health authorities. And if that's what the question, no, that was not at all. Okay, I'm sorry, I really have. You're having a little bit of trouble hearing.
Yeah.
I'm not sure if I heard you willing the beginning but I think you asked whether we have discussed this with the health authorities.
That was the question no that went on at all Okay, I'm, sorry, really youre, having a little trouble hearing yeah right.
Let me repeat yes, let me repeat the question and maybe I'll take a crack and then Alex you can fill in so Joel I understood. The question to be what gives us confidence in the outcome of the emerge phase III low risk Mds study and you cited the fact that we've commented in the past that.
John Scarlett: Yeah, but let me repeat the question and maybe I'll take a crack at it, and then Alex, you can fill in. So Joel, I understood the question to be, what gives us confidence in the outcome? Of the emergency three low is going to be a study. And you cited the fact that we've commented in the past that we have fairly conservative powering assumptions, meaning that although we saw a 42% rate of eight week TI in our phase two, we put into our powering assumptions a 30% rate, a very conservative rate.
We have a fairly conservative powering assumptions, meaning that although we saw a 42% rate of eight week Ti in our phase two we put into our powering assumptions, a 30% rate with very conservative rate. We also have noted that although.
In other trials the placebo.
John Scarlett: We also have noted that although in other trials, the placebo rate in, for example, MVF 005, which was a competitive study in a similar patient population that had a placebo rate of around, I think it was a 3 to 5% maximum. I think it was 4.5%.
Great.
For example.
<unk> zero, five which was a competitive study.
In a similar patient population that had a placebo rate of around I think it was.
3% to 5% maximum.
John Scarlett: We've actually assumed for statistical powering assumptions, again, a very conservative 75%. So, as we've talked about before, the other elements that make us feel really comfortable going into TLR are the similarity in the patient population. These are all patients who come from very, very similar populations. They're not VEL5Q.
It was four 5%, we actually assume first statistical powering assumptions again, a very conservative 75%. So that we've talked about before the other elements that make us feel really comfortable.
Going into <unk>.
The similarity of the patient population. These are all patients who are come from very very similar populations, they're non Delphi Q.
John Scarlett: They all are relapsing refractory to ESAs. They have, they have, all are naive to HMAs and to lenalidomide. This, by the way, was a very similar patient population to the medalist study for a loose polypeptide which was used for their approval. And then finally, I think that we feel very comfortable that the drug is being used in exactly the same way. Starting doses of 7.5 milligrams per kilogram, we've refined, of course, to phase 3, and during the course of phase 2, we've refined some of the dose modifications to be made during the study.
They all are relapsing refractory to Esa as they have.
They have.
Not all are naive to hma's into Lenalidomide.
This by the way it was a very similar patient population to be to the.
Nevertheless study for loose powder Sept, which was used for their approval and then finally.
I think that we feel.
Very comfortable that the drug is being used in exactly the same way starting doses seven five milligrams per kilogram, we've refined of course to the phase III during the course of pace to refine some of the dose modifications.
To be made during the study, but overall I think we would say we have a very similar patient population very similar treatment regimen.
And conservative statistics.
Great Yeah, that's really helpful. Thanks for those points.
Maybe moving on to a question on the impact MF trial.
Are you able to discuss how the blinded event rate is comparing to the expectations going into the trial.
No I don't think were going to plan to do that we are you're absolutely correct that the study is blinded and at the at this point in time, we don't have any plans to to discuss that.
That event rate.
It's a long trial and we'll see how things progress, but right now we're focused on enrollment.
Okay got it that makes sense.
Thank you.
Okay, great. Thanks.
This concludes our Q&A session I'd like to turn the call back to Dr. Scarlett for closing remarks.
Okay, well, thanks very much for those excellent.
Excellent questions.
Thanks, everybody for joining us today, we really appreciate you taking time to dial in and participate.
Forward to sharing the achievement of a lot of these milestones in the coming year stay healthy everyone and stay safe. Thank you bye bye.
This concludes today's conference call you may now disconnect.
John Scarlett: But overall, I think we would say we have a very similar patient population, and a very similar treatment regimen and concern. [inaudible] Great, yeah, that's really helpful; thanks for those points. Maybe moving on to a question on the impact MS trial, are you able to discuss how the blinded event rate is comparing to the expectations going into the trial? No, I don't think we're going to plan to do that. We are. You're absolutely correct that the study is blinded, and at this point in time, we don't have any plans to discuss that event rate.
Please wait the conference will begin shortly.
John Scarlett: It's a long trial, we'll see how things progress, but right now we're focused on enrollment. Okay, got it. Yeah, makes sense.
John Scarlett: And thank you. Okay, great. This concludes our Q&A session. I'd like to turn the call back to Dr. Scarlett for closing remarks. Well, thanks very much for those excellent, excellent questions.
John Scarlett: Thanks, everybody, for joining us today. We really appreciate you taking the time to dial in and participate. We look forward to sharing the achievements of a lot of these milestones in the coming year.
Operator: Stay healthy, everyone, and stay safe. Thank you. Bye-bye. This concludes today's conference call. You may now disconnect.
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Yes.
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Yes.
Operator: Please wait; the conference will begin shortly. Please stand by for the conference to begin. Please stand by for the conference to begin.
Yeah.
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