Geron (NASDAQ:GERN) Q2 2020 Earnings Call

0:00 Ladies and gentlemen, thank you for standing by and welcome to the JRON Second Quarter 2020 Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker's remarks, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. If you would like to withdraw your question, press the pound key. If you require further assistance, please press star 0. I would now like to hand the conference over to your speaker today, Suzanne Massari, Head of Investor Relations. Thank you. You may begin. Thank you, Dorothy, and good afternoon, everyone. Thank you for joining us for today's conference call. I am joined today by Dr. John Scarlett, Charon's Chairman and Chief Executive Officer, Olivia Bloom, the company's Chief Financial Officer, and Alexander Rizzo, our Chief Medical Officer.

0:52 After the market closed today, we announced our second quarter 2020 financial results and recent events via press release. It is available on our website under www.geron.com slash investors. In addition, a live webcast of this call is available on our website and will be archived for 30 days. Before we begin, please note that this presentation and question and answer session will contain forward-looking statements relating to Jaron's plans, expectations, timelines, beliefs, statements of potentiality, and projections. These include, without limitation, those regarding the timelines for completion of enrollment of the ongoing Phase III eMERGE and planned refractory MF clinical trials, the top line results from the ongoing Phase III eMERGE trial, and the results from the interim and final analyses from the planned Phase III refractory MF trial.

1:53 that Imatelstat has potential disease-modifying activity, that Jaron's existing financial resources will be sufficient to fund operations into the second half of 2022, that Jaron's 2020 operating expense burn will be in the range of $70 to $75 million. These and other forward-looking statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. These risks and uncertainties include, without limitation, those regarding that the company may be unable to overcome all the clinical, safety, efficacy, technical, scientific, operational, manufacturing, and regulatory challenges to enable expected timelines for eMERGE and the planned refractory MF clinical trial.

2:43 That regulatory authorities may not permit the further development of Emetelsta on a timely basis or at all. that the COVID-19 pandemic may significantly impact the timeline for both the enrollment and the results of the clinical trial and or drug supply, as well as expectations of operating expenses, and that there may be unexpected operating expenses or events or changes in Jerron's plans that cause either the $70 to $75 million 2020 financial guidance to be revised or the existing financial resources to be insufficient to fund operations into the second half of 2022. Detailed information on the above risks and uncertainties and additional risks, uncertainties and factors that could cause actual results to differ materially from those in the forward-looking statements are explained under the heading Risk Factors Endurance Quarterly Report on Form 10-Q for the quarter ended June 30th, 2020 filed with the SEC. Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made, and the facts and assumptions underlying the forward-looking statements may change.

3:59 On today's call, Dr. Scarlett plans to make a few introductory comments, after which Ms. Bloom will cover the recent financing, second quarter financial results, and 2020 guidance. Dr. Rizzo will provide an update regarding the effects of the COVID-19 pandemic on the enrollment in our phase three trial in lower risk MDS and discuss key takeaways from the KOL event we hosted last month and cover other recently announced clinical development activities in MDS and MS. Dr. Scarlett will then finish the call with an EU regulatory update and closing remarks. I will now turn the call over to Dr. Scarlett. Jaron's Chairman and CEO. Chip?

4:44 Thanks, Suzanne. I'd like to welcome everyone to our second quarter 2020 conference call. Before we begin, I'd like to make a few comments on the COVID-19 pandemic and how we're managing it. In compliance with state and local rules and for the health and safety of our employees, we're restricting access to our offices. Our employees are continuing to work from home and we are limiting business travel to essential business needs only. Despite these challenges, employee productivity and efficiency continues to be very high. Later in the call, Alexandra will comment on the effect of COVID on our clinical activities. So during the second quarter, we achieved several significant milestones that have helped to establish a very positive trajectory for the company.

5:30 First, after a successful meeting with the FDA, we announced plans to move forward with the phase three clinical trial in refractory MF using a primary endpoint of overall survival. The OS data from Embark suggests Imatelstat treatment could potentially double the remaining life expectancy for patients who become refractory to JAK inhibitors, which today are the only approved therapies for intermediate to and high-risk MF patients. Second, maturing data from the EMERGE Phase 2 trial in lower-risk MPS presented at EHA highlighted extraordinary durability of transfusion independence, including our first time reporting a one-year transfusion independence for a significant number of patients. Also at EHA, we reported new analyses from the Embark Phase 2 clinical trial in myelofibrosis that correlated the median overall survival observed with other clinical endpoints from the trial, such as improvement in fibrosis.

6:24 Overall, the EHA data and analyses continue to support the potential disease-modifying activity of Imatel-STAT treatment, as evidenced by clinically meaningful, durable transfusion independence and lower-risk MDS, and improvement in overall survival in relapsed refractory MF. A third major milestone was achieved when we completed our recent public offering, which netted approximately $140 million, giving us the financial resources to execute our current development plans and potentially reach two significant value inflection points that are expected in the second half of 2022. Those are achieving top line results from the eMERGE phase three in MTS, and completion of enrollment for the planned phase three in refractory MS.

7:11 This financing also brought on board a number of very well-respected biotech specialist investors, including Eco R1 Capital, Great Point Partners, NEA, RA Capital Management and Samsara Bio Capital. We believe their investment shows a strong affirmation of both Imatelstat and Jira. So I'd like to hand the call over to Olivia to discuss what the financing needs for our cash position as well as the second quarter financial results. Olivia. Thank you, Chip. And good afternoon, everyone. As of June 30, 2020, we had approximately $265 million in cash, cash equivalents and current and non-current marketable securities. Our cash position reflects net proceeds of approximately $140 million from a public offering of securities in the second quarter.

8:01 Based on current planning assumptions, We expect such funds to be sufficient for our operations into the second half of 2022. And as Chip just mentioned, this is when we expect to have top-line results for the Emerge Phase III clinical trial and lower-risk MDS and completion of patient enrollment for the planned Phase III clinical trial and refractory MS. Overall, the financial results for the second quarter and year-to-date periods were in line with our expectations. Operating expense for the three and six months ended June 30, 2020 were generally higher in comparison to the same period in 2019 due to headcount increases in 2019 across the company, increased activity for the Emerge Phase 3 trial in lower-risk MDF, and new costs associated with validating the Imatel set manufacturing process with contract manufacturers.

8:58 We expect operating expenses to be higher in the second half of 2020, in comparison to the first half as we begin to support two Phase III clinical trials of Imatel staff, the ongoing Emerge Phase III trial and the planned Phase III trial in refractory EMF. Regarding financial guidance for 2020, we are reiterating our expectations of operating expense burns to range from $70 to $75 million. This guidance reflects cash conservation measures implemented in April due to the COVID-19 pandemic such as suspending travel and postponing a planned MSL-STAT proof of concept study. It also includes new costs for startup activity associated with the planned phase three trial in refractory MS and additional costs for the expansion of clinical sites for the emerged phase three trial.

9:53 Financial guidance is based on a set of assumptions at a point in time and if the company's plans change, causing assumptions to be revised, then we expect to update guidance at that time. With that, I will now turn the call over to Alexandra to discuss our recent KOL event and to provide an update on our phase three clinical development activities. Alexandra? Thanks, Olivia, and good afternoon, everyone. Before I describe the key outcomes from our KOL event, I'd like to give a brief update on the enrollment status in the eMERGE Phase III trial in low-risk MDS. As of the end of July 2020, approximately 93% of the 90 clinical sites originally planned for the trial were open for screening and enrollment, compared to 68% reported in May.

10:47 The momentum of patient enrollment has begun to improve. as the effects of the COVID-19 pandemic begin to wane in majority of the countries where eMERGE clinical sites are located. We continue to expect patient enrollment to be completed by the end of the first quarter of 2021, subject to potential future delays or interruptions associated with COVID-19. Under current enrollment assumptions, we continue to expect top-line eMERGE results to be available in the second half of 2022. To ensure achievement of these goals, we are expanding the trial from 90 to approximately 130 clinical sites, and we expect a majority of the 14 new sites to be open for enrollment by the end of the year.

11:36 Next, I will highlight key takeaways from the very successful KOL event we had hosted in June, where three key opinion leaders reprised the total of four presentations from this year's IHA Annual Congress. First, Dr. Valeria Santini, Associate Professor of Hematology at the University of Florence, presented more mature data from 38 patients in the eMERGE Phase II trial in low-risk MDS. As previously reported, the patients in this trial had a very high median transfusion burden of 8 units for 8 weeks at baseline, and 16 of 38 patients, or 42%, achieved at least an 8-week period of transfusion independence. The most important observation reported with this more mature data set was longer durability of transfusion independence, including 11 of 38 patients, or 29%, being transfusion-free for more than one year, and a median duration of transfusion independence of 20 months.

12:41 Transfusion independence with such durability is unprecedented, especially given the high baseline transfusion burden, which indicates disease modifying activity from a TELSTAT. Furthermore, similar TI and HIE rates were observed in both ring cedar blast positive and negative patient subgroups. These eMERGE Phase II data have been well-received by the heme malignancy medical community, and we believe they will generate even more enthusiasm about our ongoing eMERGE Phase II trial, as well as favorably, in fact, impact patient enrollment. Our second presenter was Dr. John Moscarenas, Associate Professor of Medicine and Director of the Adult Leukemia Program at Newport-Sinai.

13:29 Dr. Moscarenas reviewed very exciting new analysis from the EMBARQ trial in relapsed refractory MS patients, which, as expected, showed that Imatelstat achieved dose and exposure-dependent reductions of all of the previously known pharmacodynamic markers of telomerase inhibition, such as telomerase activity, and expression of H3, confirming the on-target mechanism of action of metelstat. Furthermore, this was supported by analysis indicating better clinical outcomes in patients with shorter telomeres or higher telomerase activity levels. And as previously established, these patients are more amenable to a telomerase inhibitor compared to patients with longer telomeres and lower telomerase activity levels.

14:22 In addition, other analogies presented by Dr. Ana Mascarena showed improvement in overall survival that was now correlated with clinical benefits after a metastatic treatment, most notably with improvement in bone marrow fibrosis. Significant dose-dependent reductions in JAK2, CAR-LAR, and lipol allele burden were also reported. Taken together, these new analogies highlight that the observed improvement of fibrosis Reduction in allele burden and the improvement in median OS indicate potential disease-modifying activity of the metelstat by targeting the underlying malignant myofibrosis clones. The third key opinion leader at our event, Dr.

15:09 Rami Komrokchi, Vice Chair of the Malignant Hematology Department at the Moffitt Cancer Center, reviewed new analysis of the clinical outcomes from metelstat treatment in triple negative myelofibrosis patients in EMBARC. MS patients who do not have the JAK2, KAL-R, and needle mutations are called triple negative and represent 10% to 15% of the myelofibrosis population. This type of population is associated with shorter survival compared to patients carrying these mutations. The in-depth data presented by Dr. Kamroji showed an improved overall survival of 35.9 months in patients with triple negative myofibrosis compared to 24.6 months for non-triple negative patients.

16:03 Screen and symptom response rates were also higher for the triple negative patients compared to the non-triple negative ones. Finally, The triple negative patients involved in the study had short telomere length and high telomerase expression levels at baseline. These patients with poor outcome to current treatment options represent a suitable patient population for hematostasis and such patients will be eligible to enroll in our planned phase 3 trial in refractory myelofibrosis. To summarize, these analyses further support our planned phase 3 clinical trial and Jack and Hugh with a refractory MF, which will be led by two principal investigators, Dr. John Mascarenas from Mount Sinai and Dr.

16:51 Serge Vrstovsik from MD Anderson Cancer Center. We're honored to have them on board as collaborators. The PLAN FACE-3 study is a global, randomized, opal-labeled trial in approximately 320 patients with intermediate to or high-risk MF who are refractory to JAK inhibitor. The study will compare metelstat treatment to best available therapy such as hydroxyurea and anazole while excluding JAK inhibitors. We expect to include over 150 sites across North America, South America, Europe, and Asia. Startup activities are ongoing such as identifying potential clinical sites for participation as well as finalizing the protocol and obtaining clearance from institutional review boards or ethics committees and regulatory authorities.

17:47 We plan to open the trial for screening the enrollment by the end of the first quarter of 2021. The trial is designed to have a final analysis for overall survival after more than 50% of the patients planned to be enrolled have died. An interim analysis of overall survival is planned to be conducted after approximately 70% of the total projected number of death events for the final analysis have occurred. If the pre-specified statistically significant difference in OS between the two treatment arms is met at the interim analysis, we expect such data could support a registration file. Our current expectations for this study are to complete patient enrollment in the second half of 2022, to conduct the interim analysis in the first half of 2023, and final analysis in the first half of 2024.

18:48 However, as you know, both the interim and final analysis are event-driven and could occur at different times than currently projected. If this Plan phase 3 trial in refractory method is successful, We believe Imatelstat will be the first drug to demonstrate a survival benefit in this poor-prognosis high unmet need MS patient population. Now I'd like to hand the call back to Chip. Thanks, Alexandra. I'd like to end with a late-breaking positive milestone that was recently reached. At the end of July, the European Commission formally granted orphan drug designation for Imatelstat in MDS in the European Union. and Mattelstat has already been granted orphan drug designation by the FDA as a potential treatment for MDS. So both of these designations provide for potential market exclusivity.

19:42 In the case of the EU orphan drug designation, it allows for potential market exclusivity of 10 years from the date of first approval in the orphan indication, making this latest designation a very welcome milestone to achieve. So in closing today, I'd like to comment that Geron is a fundamentally different company than we were a year ago. We have data to show that very meaningful clinical activity and indications where they're significant on that need. We have an ongoing phase three trial in low-risk MDS and a planned phase three trial in refractory MF for which we expect to begin screening and enrollment activities by the end of the first quarter of 2021. And we have the financial resources to reach significant value inflection points.

20:27 We believe these achievements, along with our experienced development team, have strategically positioned Geron to become a leader in the treatment of hematologic myeloid malignancies over the next several years. So with that, we'd now be happy to answer questions. I'll turn the call back over to our operator. At this time, if you would like to ask a question, please press star then the number one on your telephone keypad. That is star one to ask a question. Your first question comes from the line of Gil Bloom with Needham and Company. Hello, everyone, and thank you for taking my questions and congratulations on all the progress. So maybe a quick one on the 40 additional sites that were added to the MDS study.

21:18 I'm assuming the COVID spread was maybe a criteria here, if you can comment on this. Hi, I can take that question. Yeah, absolutely. It was, you know, the COVID moment that, well, actually made us change the guidance, as you might remember, that enrollment will be completed by the end of the first quarter 2021. And just to make sure that we meet the goal in front of us, we decided to go ahead and open additional sites for the study. Thank you for the caller. Another question I have is about the validation process you discussed with CMOs.

22:05 Is the company looking at the production at this site with an eye on commercial production and also to support the two pivotal studies that are ongoing? Yes, Gil. This is Chip. I'll take that. Absolutely. We are involved in putting together a complete validation program for the commercial scale process. And of course, materials made in that validation program, which will include final validation runs, et cetera, will also be used for clinical trial activities as well. But the primary purpose is really to validate the commercial process.

22:52 Great. And kind of a last one on the myelofibrosis pivotal. As Alessandra mentioned previously, there were some really interesting data at EHA showing kind of different responses from different genetic makeup populations. Is there any look prospectively into, let's say, triple negative patients? Go ahead, Alex. I can take that question, Gil, yes. We, of course, as you indicate, plan to enroll our patients, the triple negative patients will be enrolled as well in the refractory myelothalibrosis study. And we have planned or we are planning to conduct a subgroup analysis on this patient population as well as other relevant populations. So absolutely, we will be looking into this.

23:50 All right, excellent, and congratulations on all the progress, and keep safe. Thanks, Gil. Our next question comes from the line of Ellen with Stiefel. Hi, this is Ellen Sands on for Steve Worley. Thank you for taking my questions. So maybe just the first one is just a follow-up related to the increase in trial sites for the MBS study. Are these trial sites mostly U.S.-based, or are they international, or both? They are distributed globally. So we are looking to the new 40 sites will be across and internationally. Okay, great. Thank you. And then can you just remind us what the key differences are in the patient populations between the population that was enrolled in the Phase II EMBARQ study versus the patient population you'll be looking at for the phase three study in relapsed MF. I know they're quite similar, but just any of those key differences would be helpful.

24:55 Well, the patients in both of our MF studies are similar and are defined as being non-responsive to JAK inhibitor. There are technical differences in the eligibility criteria between the two studies, but fundamentally, all these patients are not responsive to a JAK inhibitor. And as you might know, I mean, 50% of the patients will discontinue, for example, Rax after three years, 75 will be discontinued after five years, you know. So eventually all patients that discontinue treatment with a JAK inhibitor will become eligible for treatment with Imatelstat on our new study. And they were the same ones that were eligible for treatment with Imatelstat on the Imbart study.

25:44 Okay, guys, just very technical differences in eligibility criteria. So maybe just one last question about the Phase 3 relapsed MF study. So there's a number of other assets in development for relapsed MF, and I know patients are required to have seen a prior JAK inhibitor. Are patients allowed to have participated in a previous clinical trial for an investigational product that is not a JAK inhibitor or is that prohibited from enrollment? As long as the patient had refractory to a JAK inhibitor, that patient is allowed on the clinical trial irrespective of other prior treatments. Okay, great. Thank you.

26:31 Our next question comes from the line of Andrew De Silva with Beat Riley. Hey, thank you for taking my questions. Congrats on the progress and sorry if you answered any of these. I was jumping between calls here. So I was just going through my notes and not to delve too deep with already discussed topics, but I'm just trying to get a sense of how you see things playing out here given how encouraging the data has been. So I know low risk is the overwhelming majority of MDS patients and RS positive is around 10% of total MDS patients, but what percent of low-risk MDS patients have 5Q syndrome and are refractory to ESAs but are also RS positive? And then I'll have just a follow-up question to that.

27:25 Okay, I just have to clarify something. It's actually only 5% of the patients that are ZEL5Q positive and Approximately 70% of the patients are RS positive, which is why I think that's important. So it's 5% of the patients that are Delphi Q positive, whereas our study is involving non-Delphi Q positive patients. I just wanted to clarify that. Also, our study and our current efficacy data shows that we are able to induce transfusion independence as well as HIEs in both RS-positive and RS-negative patients.

28:21 So, I would ask you to repeat the question. What was exactly that you were asking us? I was just trying to get a sense of a positive patient breakout within your specific patient population criteria. I know it's a small percent of the overall population for MDS, but what part of the population is it in your specific low-risk population that you're targeting for your phase 3 trial? We are going to enroll patients irrespective of the RS status. I think that's the key to understand, right? So it doesn't matter whether you're RS positive or RS negative.

29:10 You can be enrolled on the IMATEL phase three study. Olivia, I think you had a comment. I think, Andy, I think your question is from What percentage of low-risk MDS patients are RF positive? Correct. Also, within your specific criteria for enrollment. Oh, well, I think that's what Alexander was trying to say, that there is no criteria to exclude or include based upon RF positive or negativity because we're allowing both to come in. So whether you're RS positive or RS negative, you're allowed to come into, you're eligible for our trial, which if you're trying to contrast potentially to other trials or other agents, you know, it is true. So for example, the most recent drug that was approved in low-risk MDS was PowerSept.

30:16 Their trial was focused solely on RS positive patients. Right, so really the thing I was trying to get at was even though they've received approval, you did have amazing transfusion independence in HIE relative to them when you look back at the Phase II data that you presented recently. And I was just trying to figure out, did you really think that it'll be a hindrance in being able to enroll RS positive patients because the RS positive population in the Phase 2 study actually did, I think, better. And so just the data that came out would lead me to think that you'd still be able to enroll a pretty hefty amount of RS positive patients.

31:08 Right. Let me take that, Andy. So I think our view is that The RS positive patients make up a minority, but nevertheless an important minority of patients who have lower risk MDS. As we've said numerous times now, we are not inhibited in enrolling either RS positive or RS negative patients. With regard to the availability of patients for the clinical trial, I think that we are very likely to see a reduction a distribution of patients, plenty of whom will have RS positivity because we seem to have a better profile than some other products in high transfusion burden patients. And so I think because of that, it's very likely that some investigators will choose to put even RS positive patients who are obviously indicated to be treated with, for example, Reblosal I think that they will preferentially put some of those patients with very high transfusion burden into the M12 stop trial. So I think we're not anticipating a major issue in that regard.

32:28 Okay, that's great to hear. Perfect. And my last question, as it relates to the 40 new sites, since these are all post-COVID sites that are coming up, Could you let me know what kind of differences are taking place as far as discussions or what they need to happen before they feel comfortable actually joining the trial? I'm not sure Alexandra is suffering a little bit from IT challenges post-hurricane. She's on the East Coast. Alex, are you back online there? Yeah. I'm here. So did you hear any of these questions?

33:13 I did. I did. I mean, the new sites that we are adding on the study, we're really approaching them with the new data that we have, showing the durability and the high transfusion dependence rate. So honestly, I don't think that there is any additional requirement As I said, the new data has generated enthusiasm across the HIN community, and we've added these sites, and we are expecting most of them, if not all, to be open for screening and enrollment by the end of the year. Okay, great. Hey, congrats again on all the progress year-to-date, and best of luck back after the year.

34:01 Thank you so much. As a reminder, if you would like to ask a question, please press star, then the number one on your telephone keypad. Our next question comes from the line of Tom Schrader with BCIG. Hi, good afternoon. Thanks for holding the call. Just one question. At each KOL event, John Muscarenas invariably goes on and on about how high your burden is for JAK failure, and it makes patients hard to enroll. Given you got OS as an endpoint and JAK inhibitors have a very modest OS benefit, do you think you can relax that? Partly relevant to the previous question about how many things there are competing for MF patients now. Just your thoughts. Does OS free you up a little bit there?

34:51 Go ahead, Alec. Yeah, I can take that. I mean, I don't know. It's an interesting way to put the question. I don't believe we, you know, We are experiencing difficulties or we will be experiencing difficulties based on the street criteria. Just one point to remember is that when the in-park study started five years ago, there were no studies in relapsed refractory patients. It was kind of really paving the way for this study. The definition of relapsed refractory patients, which has been evolving over time. I believe that nowadays the MS community, the MS treating community is used to these criteria. They understand that it's needed for conduct of a trial and therefore I don't think that would cause difficulties in enrollment.

35:53 In addition to that, as you say, I mean, overall survival is the golden endpoint or the golden outcome that everybody would expect from clinical trials. So that certainly creates enthusiasm and we believe will be driving interest and enrollment on the study. I don't know, Chip, if you have anything to add to this. Yeah, actually I do. Just sort of a technical nature, Tom. I think that the field is moving in the direction that we're leading in here. I think that if you think about it, we're really requiring a certain number of months of russolidinib treatment, and then we require at least two months out of that to be at stably dosed RUX levels in order to make sure that patients have had an adequate trial of JAK inhibitor. And if they then meet the criteria for being refractory, then they are qualified for the study. I see this in some other protocols as well that are coming out, probably because it's a relatively small KOL group that promulgates a very a very tight inclusion criteria and exclusion criteria for these types of studies.

37:20 So I don't think we're really at a disadvantage there. I think we will be at a big advantage when it comes time to looking at the data because I think we'll have patients who really did get into the study only if they were truly refractory. And that will obviously tend to heighten the differences, we hope, between active treatment and VAT treatment. I don't know if I got any of your questions or not. Yeah, no, no, absolutely. Thanks for all the color. There are no further questions at this time. I will now turn the call back over to Dr. Scarlett. Well, I'd like to thank once again all of our covering analysts, their colleagues, and their banks. And I'd also like to thank our recent investors in the company. We appreciate very deeply the Show of support and enthusiasm, as mentioned before, and our very, very hardworking community of investigators, study site coordinators, and of course, our own internal employees.

38:28 COVID is a challenge, but interestingly, I think we're finding ways around many of these issues, and we feel good, as commented on more directly in the and the previous comments about going forward. So I'd like to thank everybody for that effort and thank everybody for joining the call today. I think we'll ring off with that. Thanks. Bye-bye. Thank you, ladies and gentlemen. That does conclude today's conference call. You may now disconnect.