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spk07: Good afternoon, ladies and gentlemen. My name is Abby, and I will be your conference operator today. At this time, I would like to welcome everyone to the Jerron Corporation first quarter 2022 conference call. Today's conference is being recorded, and all lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press the star key, followed by the number one on your telephone keypad. If you would like to withdraw your question, press star one once again. Thank you. And at this time, I would like to turn the conference over to Erin Feingold, Vice President of Investor Relations and Corporate Communications. You may begin.
spk01: Good afternoon, everyone. Welcome to the Geron Corporation First Quarter 2022 Conference Call. I am Erin Feingold, Geron's Vice President of Investor Relations and Corporate Communications. I'm joined today by the following members of Geron's management team. Dr. John Scarlett, Chairman and Chief Executive Officer. Olivia Bloom, Executive Vice President of Finance and Chief Financial Officer and Treasurer. Dr. Alexander Rizzo, Executive Vice President and Chief Medical Officer, and Anil Kapoor, Executive Vice President of Corporate Strategy and Chief Commercial Officer. 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 Immatel-STAT, anticipated clinical and commercial events and related timelines, the sufficiency of Geron's financial resources, and other statements that are not historical facts. Actual events or results could differ materially. Therefore, I refer you to the discussion under the heading Risk Factors in Jaron's quarterly report on Form 10-Q for the quarter-ended March 31, 2022, which identifies important factors that could cause actual results to differ materially from those contained in the forward-looking statements. Jaron undertakes no duty or obligation to update our forward-looking statements. And now, I will turn the call over to CEO Dr. Scarlett. Chip?
spk04: Thanks, Aaron. Good afternoon, everyone. Thanks for joining us today. This quarter, we continue to build on the momentum from our clinical execution throughout 2021. We believe we're well positioned to realize the transformative potential within the Telstat inhibitor-launched malignancies. Most importantly, we're only eight months away from the top-line results from our eMERGE Phase III trials in low-risk MDS, which we expect in early January 2023. This is the first of two significant data readouts for imitelstat over the next two years. I'll speak about the other one in a few minutes. In their lower-risk MDS patients, key opinion leaders and community hematologists underscore the significant unmet need for durable transfusion independence. If the durability and safety data from our Phase II study are confirmed in the Phase III trial, imitelstat could represent a significant treatment advance for these patients. because we believe no other product has provided the rates of 24-week and one-year transfusion independence seen in the eMERGE Phase II study. In addition, unlike currently approved therapies, Imatelstat offers the potential to treat both RS-positive and RS-negative patients, as well as to provide potential disease modification. We expect these characteristics to strongly differentiate Imatelstat in the lower-risk MDS treatment landscape and to create a broad commercial opportunity. We're also making steady progress in opening clinical sites for our IMPACT-MF phase three refractory MF trial, which is expected to enable an interim analysis in 2024. This interim analysis will be the second significant data readout for Intel step. With the recent start of our improved MF phase one combination study, our pipeline expansion program is picking up momentum. That pipeline expansion program, including the IMPROVE-MF Phase 1 study in frontline MS and the two investigator-led studies in AML, enables us to study the potential to limit Telstat as a combination therapy and an additional indication. A key objective for this quarter was to raise additional capital to provide financial flexibility as well as to broaden our investor base. We're pleased that we achieved both goals with the closing of a $70 million net public offering on April the 1st. This public offering garnered keen interest from biotech specialist investors, including Vivo Capital, RA Capital, TCGX, EcoR1, New Enterprise Associates, and HealthCore Management. We believe that Geron represents a strong investment opportunity for these and other investors due to our compelling Phase II data the nearness of our lower risk MDS Phase III readout, the commercial opportunities of our potential indications, and the strength of our internal capabilities and management team. Our current financial resources, plus the net proceeds from this financing, plus the additional funding in 2023 from potential warrant exercises, are expected to provide the financial resources necessary to support our planned key milestones through the end of 2023. Assuming positive top-line results from the MERGE Phase III trial, these key milestones include submission of a U.S. new drug application, or MDA, in the first half of 2023, submission of a European Marketing Authorization application, or MAA, in the second half of 2023, and preparatory activities for a potential 2024 U.S. commercial launch of Imatelstat and lower-risk MDS. We also expect these current and projected financial resources will provide us the cash runway to consider various strategies to maximize the value of the Mittelstat for patients and shareholders. These could include partnering, additional debt, structured instruments such as royalty monetization, or other strategic options. Before I turn the call over to my colleagues, I'd like to highlight my very strong confidence in and appreciation for my remarkable Geron colleagues. It's the collective excellence in execution across the company as we approach significant milestones that will unlock value for patients and for shareholders. With that, I'll turn the call over to our Chief Medical Officer, Alexandra Rizzo, for a clinical update. Alex?
spk07: Thanks, Chief. and good afternoon to everyone on the call. As Chip mentioned, we're excited to be just eight months away from the plan, top plan results of our phase three lower risk MDS trial. As such, our teams are focused on preparations for a high-quality data readout, which requires collaboration and execution across the clinical operations, data management, and biostat teams, as well as partnership with our CRO, investigators, and study sites. We remain confident that the readout will occur in early January 2023. I'd like to remind everyone that the eMERGE Phase III trial is designed to confirm the Phase II results since the trials use the same patient population, dosing regimen of hematostats, primary and secondary endpoints, and geographies for clinical sites with many of the same investigators. We believe that if the Phase III trial confirms similar depth, breadth, durability of transfusion, independence, and safety, Imatelstat could meet significant needs for all patients with lower risk MDS who have failed or are refractory to ESA treatment. Moreover, Imatelstat would address the approximately 75% of lower risk MDS patients who are RS negative and are underserved by current treatment options. Furthermore, The unique telomerase inhibition mechanism provides disease-modifying potential, which we believe differentiates Imatel-STAT from other currently approved or investigational treatments for low-risk MDS. In addition to preparing for top-line results, our regulatory team has initiated MDA submission preparations. As Chip mentioned, Assuming the results of eMERGE Phase III support regulatory submissions, we plan to submit an NDA in the U.S. in the first half of 2023 and an MAA in Europe in the second half of 2023. With regards to our Phase III refract CMS clinical trial, we continue to make progress with site activation and remain confident we'll open the remaining selected sites in 2022. We believe this progress will enable completion of enrollment and a potential interim analysis in 2024. As a reminder, IMPACT-MS is the only Phase III trial in MS using overall survival as the primary endpoint. We believe that if the improvements in OIS observed in our Phase II trial can be confirmed in IMPACT-MS, Imatelstat would represent a potentially transformative treatment option for MF patients who no longer respond to JAK inhibitors given their dismal prognosis and lack of treatment options. Of note, a recent publication in Cancer Journal, co-authored by Dr. Moscarenas and Dr. Rostovshek, both principal investigators in our Phase III IMPACT-MF trial, describes the clinical dilemma for treatment of JAK inhibitor failures. This paper reinforces the poor outcomes in the many MS patients who are refractory to JAK inhibitors and highlights the unmet need for survival improvement in this patient population. Moving on to the earlier stage programs in our pipeline. This month, we opened our first clinical site in the IMPROVE-MS study. This Phase I study is designed to evaluate the safety and clinical activity of imetalastad in combination with ruxolitinib in patients with frontline MS. In this study, we want to explore the potential for disease modification with imetalastad treatment in the earlier frontline MS disease setting. As a reminder, IMPROVE-MF is a single arm, open-label study in patients with frontline MF consisting of two parts. Part one will enroll up to 20 patients with the objective to identify a safe dose for the combination of imetalastat and ruxolitinib while efficacy data are being collected. In part two, we also plan to enroll approximately 20 patients with the objective to confirm the dose identified in part one and collect further safety and efficacy data. In both parts, patients will receive ruxolitinib followed by imotelastat, a dosing schedule that showed synergistic and additive effects of the two drugs in preclinical experiments. For our investigator-led trials in high-risk MDS and acute myeloid leukemia, or AML, we continue to expect a start in the second half of 2022. A recent non-clinical publication in the Journal of Clinical Medicine, although in pediatric AML, further supports the development of metastatic in these diseases. Lastly, and in anticipation of likely questions, I want to comment that we have limited clinical trial activity in Ukraine and Russia across all of our ongoing trials. At the moment, we believe that the conflict will have no significant impact on our trials or on our timelines, including top-line results for eMERGE Phase III and enrollment and interim analysis for impact MS. I would now like to turn the call over to our Chief Financial Officer, Olivia Bloom, for a financial update. Olivia? Thanks, Alex, and thanks to everyone on the call for joining us today. please refer to the press release we issued this afternoon, which is available on our website for detailed financial results. As expected and in line with our financial guidance, overall in our first quarter 2022 financials, there was an increase in operating expenses compared to the same period in 2021, which was primarily driven by higher development expenses. The increase in R&D expenses for the first quarter of 2022 compared to the same period in 2021 primarily reflects higher personnel-related costs for additional headcounts. The decrease in general and administrative expenses for the first quarter of 2022 compared to the same period in 2021 primarily reflects the net results of reduced costs related to modernizing the internal infrastructure to support commercial launch, and lower legal fees, partially offset by higher personnel-related expenses for additional headcounts. Turning to our financial resources, as of March 31, 2022, we had approximately $177.8 million in cash and marketable securities. On April 1, we closed the underwritten public offering of common stocks and warrants that Chip mentioned earlier on the call. The estimated net proceeds are approximately $70 million after deducting the underwriting discount and other estimated operating expenses payable by us. We continue to expect non-GAAP total operating expenses up to $150 million for the full year of 2022. The fiscal year 2022 financial guidance reflects costs to support clinical execution in eMERGE Phase III, Impact MF Phase III, and new clinical studies associated with the IMITEL Stats Pipeline expansion, as well as readiness activities for top-line results, future regulatory filings, and pre-commercial preparations. With the additional capital from the recent financing and our existing financial resources, We expect to have approximately $130 million in cash and marketable securities at the time of the lower risk MDS top line results in early 2023. We also project up to $125 million in additional funding in 2023 from potential exercises of currently outstanding warrants. When added to the projected $130 million on the balance sheet at the beginning of 2023, we expect the projected financial resources to be sufficient for planned milestones through the end of 2023. These milestones include regulatory filings in low-risk MDFs in the U.S. and in Europe, as well as preparatory activities for potential U.S. commercial launch of Imatel stats in low-risk MDFs in the first half of 2024. With that, I will now hand the call back to Chip for closing remarks. Chip?
spk04: Thanks, Olivia. As you've heard throughout this call, 2022 marks an important year of execution for Geron to deliver on key milestones, which we believe will bring significant value to patients and shareholders. So I'd like to end this call by reiterating our excitement for where we stand as a company today. We believe we have two well-designed Phase III trials with registrational intent that are supported by compelling Phase II results in commercially attractive markets and with data readouts expected to create significant value over the next two years. We have a pipeline expansion program representing opportunities for additional Imatel set indications and combination regimens. We believe we're financially well positioned to execute on key clinical and regulatory milestones with a projected cash runway through the end of 2023. We expect that runway will provide for strategic optionality to maximize shareholder value following top line results from our lower risk MDS phase three trial expected in early January 2023. We're building the capabilities to establish ourselves as a commercial company and to prepare for a potential U.S. launch as early as the first half of 2024. And we have a highly experienced management team, as well as a passionate, focused employee base that is deeply committed to bring intimate health staff to patients and create value for our shareholders. I hope you share in our enthusiasm for the future of Geron and understand our deep belief in our ability to help patients suffering from hematologic malignancies. Thank you for listening today, and operator, please open the call to questions.
spk07: Thank you. At this time, I would like to remind everyone in order to ask a question, press star, then the number one on your telephone keypad, and we'll pause for just a moment to compile the Q&A roster. And we will take our first question from Gil Bloom with Niedermann Company. Your line is open.
spk05: Good afternoon, everyone, and thanks for taking our question. Maybe a quick one on, for the MF study, how do you think the positioning of MS health that might look like in, you know, additional drugs that may be approved by that time in the second-line setting, for example, momolitinib? I think Anil's going to take that question.
spk00: Thank you, Jill, for the question. So, Jill, I think, importantly, the space continues to evolve with multiple mechanisms under investigation. We expect patients to be treated with combination therapies, therapies that address symptomatic patients and also addressing the needs of severely cytopenic patients. Mamelotinib approval is in a transcription-dependent population, which represents a fragment of the eligible patients for our study. Our study, as you know, Jill, is the largest effort ever in myelofibrosis, looking at a jack-eye refractory patient population, and it remains the only study with overall survival as a primary endpoint. In all our market research, discussion with physicians, KOLs, This is expected to be a highly compelling study, and if the results are proven, we would expect to become part of the standard of care for myelofibrosis.
spk05: That makes a lot of sense. The NOS endpoint is definitely differentiated. Maybe a related question. So we're going to be looking at a frontline combination study with rocks, and i noticed that the primary endpoint is tss and svr 35 which is kind of the usual endpoint but any thoughts on other assessment like response rates or you know something a little more outside of the svr realm thank you for
spk04: Yeah, Alex will take that, Gil.
spk07: Yeah, thanks, Gil. So, again, let's repeat that this is a Phase I dose-finding study. We want to first confirm that we can combine the two drugs. to identify a safe dose. And then in the second part of the study, we want to confirm this dose. So while we're doing this, we will be collecting every efficacy data that is out there known for myelofibrosis in addition to SVR and TSS. We will be collecting all the biomarker data for which we believe we distinguish from other drugs in development. So that is one. We will be collecting fibrosis data or improvement in fibrosis data as well. And we will be conducting narrow assessments for potential PRs and PRs as well. So it will be a comprehensive data collection that we believe will inform us on the next steps.
spk05: Thank you. That's very helpful. And thanks for taking our questions. You bet. Thanks, Gil.
spk07: We'll take our next question from Stephen Willie with Stiefel. Your line is open.
spk03: Yeah, thanks for taking the questions. Maybe just to follow up on the last question with respect to improve MF, I know the intention here is to evaluate the potential for disease modification in frontline patients. just curious what you think uh the efficacy bar and tolerance for incremental toxicities is here just uh given the the treatment of frontline patients with rocks is is is currently very focused on symptomatic improvement and then just have a follow-up yeah go ahead alex i can take that intensity so i mean a couple of points i believe here are also important to me
spk07: So thresholds in terms of safety or toxicity are very important. Our drugs do have overlapping thrombocytopenias, and for that reason, we are starting very carefully with the dosing of the two drugs. We are stabilizing RUX first, and then we are adding gematelstat. And we believe that with this approach, we will find the best tolerated dose for the combination. In terms of efficacy, the bars are set in front line. They're being set in second line as well. But we believe that, again, we will see or we hope to see other improvements in addition to the SPR and the TSS. I think the disease-modifying potential that we hope for in terms of reduction in allele burden, improvement in fibrosis, is something that will take our drug in a different position than the other drugs in development.
spk03: Okay. And then just on the disease modification front, are you going to be requiring patients to undergo – marrow assessments and fibrotic assessments. And I guess with respect to fibrosis, I know it's kind of a bit of a subjective endpoint. Would you also be looking at mutant allele frequencies in these patients? And if so, can you remind me, is the rate of secondary mutations in these frontline patients, are those observed at the same rate? at the same kinetics that is seen in the JAK refractory mutations?
spk07: So I think you had a couple of very good points, but let me address them one by one. So we do or we will be collecting marrows to assess fibrosis as well as allele frequencies for various mutations. The fibrosis assessment that we have done on our studies so far, and we plan to continue assessing it the same way, is done by an independent review committee. So while it is, you know, some people say it's subjective, I think we're doing a fairly good job in, you know, having that done by an IRC, which kind of, you know, makes us confident about the fibrosis data that we will be collecting and assessing. So yes to fibrosis, right? So we are doing this in an independent review manner. And we will be collecting samples to assess allele frequency. And in addition to that, we will be coordinating these two with disease outcomes. Now, your last question, whether these mutations occur in the same frequency in frontline and second-line setting, I think we'll have to discuss which ones, because as the patients progress, I would say in their disease, They tend to have the high-risk molecular characteristics. But nevertheless, a lot of these mutations are linked to the disease itself, right, and like the driver mutations itself. So I don't know exactly about the frequency of each of them, but I would say that at least a combination of all of them, and, for example, the HMRs, do increase over time as the patients progress.
spk03: Okay, that's very helpful. Thanks for taking questions. Thanks, Dave.
spk07: And we will take our next question from Joel Beatty with Baird. Your line is open.
spk02: Hello, this is Benjamin on for Joel. Just a few questions for us. Could you maybe describe the level of physician engagement in enrolling patients in IMPACT-MF, and maybe you can provide a little bit of color on the number of sites coming online? Thank you.
spk07: I'll take that one as well. So I think that what we've guided so far is that we've opened more than 50% of our sites, and we do remain confident that we will open the rest of the selected sites by the end of the year. I don't think we have really put a number there, This is what we are expecting to do. The space is competitive, as I'm sure you know. However, taking the fact that we have an overall survival as a primary endpoint, which has been multiple times repeated at EDs, an endpoint that is needed in this space and our PIs really remain enthusiastic about it, we do see enrollment moving in the right direction.
spk02: Great. Thanks. And then just one more. On the lower risk MBS, are there any early commercial prep underway for the readout anticipated in early January? Thank you. Next slide.
spk00: Joel, this is Anil. I'll take that question. So yes, there is extensive effort underway for us to characterize the market. understand the physician base, really see where all the treatments are coming from, and also extensive efforts, which you will start to see over the next 12 months as we bring Immetal stat data to the market and start to educate physicians around the unique mechanism of action from our perspective. All of these events are stage-gated. They are all tailored post low-risk MDS, and I want as a reminder one more time that vast majority of our commercial hiring is a gated post-ELR as well. So I'll just stop here to see if I answered your question.
spk02: Yep, all set. Thanks.
spk07: Another reminder.
spk02: Thanks, Sam.
spk07: It is star one if you would like to ask a question. And we will take our next question from Justin Walsh with B. Reilly Securities. Your line is open.
spk06: Hi. Thanks for taking the questions. With respect to improved MF, do you anticipate frontline MF patients having any hesitancy about starting with a frontline combo, given that RUX alone can provide benefit in patients for some time before they inevitably relapse?
spk07: Thanks for that question. I don't see why. I think that, you know, just in addition to the benefits that they can have with RUX, you know, they might have, you know, additional benefits from treatment with the Metelstat. So we have not heard that concern, nor we have any hesitancy about that.
spk00: So just to add on to what Alex said, there are multiple trials underway in myelofibrosis, upwards of 10 phase 3 trials, six of them in frontline with combination strategies with JAKIs. So our expectation is what we would hope to bring to the table is the potential for disease modification with a novel non-JAKI mechanism, you know, over time as the improved MF data starts to establish itself.
spk06: Got it. And maybe building on that as my last question, do you have any concern that there'll be challenges in enrolling patients since you'll be competing with all of those other trials that you just mentioned?
spk07: I'm not sure for which study you... Improve MF. Improve MF for the frontline study?
spk06: Well, improve MF, but I guess we could... That's true for impact as well.
spk07: Right. I don't think so. I don't think so. I mean, again, the drug offers a really different benefit and distinct value, right, for the patient. You know, the potential for overall survival in the refractory space It's really received with enthusiasm and bringing the disease modification to the frontline setting where patients should respond even better, right, because these are less sick patients, I think it's still uniquely attractive to both PIs and investigators. So with that, at least I don't expect any problems with enrollment. The field is competitive, nevertheless, but we do stand out for a couple of good reasons, I believe.
spk05: Great. Thanks for taking questions. Thanks, Justin.
spk07: And there are no further questions at this time. I would like to turn the call back to Aaron Feingold for closing remarks.
spk01: Thanks so much to everyone for joining us today and for your questions. We look forward to keeping you posted on our progress. Be well.
spk07: And ladies and gentlemen, this concludes today's conference call. We thank you for your participation, and you may now disconnect.
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