Geron Corporation (GERN) Q2 2019 Earnings Report, Transcript and Summary

Good afternoon. My name is Annie, and I will be your conference operator today. At this time, I would like to welcome everyone to Geron Q2 2019 Earnings Conference Call. [Operator Instructions]. Thank you. I would now like to turn the call over to Ms. Suzanne Messere, Investor Relations. You may begin the call, ma'am.

Thank you, Annie, and good afternoon, everyone. Thank you for joining us for our second quarter conference call. I'm joined today by Dr. John Scarlett, Geron's Chairman and Chief Executive Officer; and Olivia Bloom, the company's Chief Financial Officer. Dr. Aleksandra Rizo, our Chief Medical Officer, is with us today as well and will be available during the Q&A portion of the call. After the market closed, we announced our second quarter 2019 financial results via press release. It is available on our website under www.geron.com/investors. In the press release, we also provided an update on the Phase III portion of IMerge. This afternoon, management will discuss the information from today's press release. A live webcast of the call is available on our website and will be archived for 30 days. Before we begin, please note that except for statements of historical fact, this presentation and question-and-answer session contains forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such forward-looking statements include any of the company's plans, expectations, timelines, beliefs, statements of potentiality and projections and without limitation, those regarding that the Phase III portion of IMerge is planned to open for patient screening and enrollment in August 2019. That statistical analysis of IMbark data and real-world data suggest potential favorable overall survival and a lower risk of death with imetelstat myelofibrosis treatment; that there will be an end of Phase II meeting with the FDA by the end of the first quarter 2020; that Geron will potentially develop imetelstat for relapse/refractory MF patients; and that Geron's 2019 operating expenses will be in the range of $80 million to $85 million. All of these 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 comparative analyses between real-world data and IMbark clinical trial data have limitations and cannot be relied upon as demonstrative; that the company may be unable to overcome all the clinical, safety, efficacy, technical, scientific, operational, manufacturing and regulatory challenges to enable Phase III IMerge screening and enrollment in August 2019; that regulatory authorities may not permit the further development of imetelstat on a timely basis or at all; that the company may decide not to develop imetelstat for relapsed/refractory MF patients; and that there may be unexpected operating expenses or events that cause the $80 million to $85 million in 2019 financial guidance to be revised. 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 under the heading Risk Factors in Geron's quarterly report on Form 10-Q for the quarter ended June 30, 2019, 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. Except as required by law, Geron disclaims any obligation to update these forward-looking statements to reflect future information, events or circumstances. With that, I'd like to turn the call over to Dr. John Scarlett, Geron's Chairman and CEO. Chip?

Thanks, Suzanne, and good afternoon, everyone. In this last quarter, we continued to achieve our 2019 milestones and advanced the development of imetelstat. We remain on schedule with our previously communicated timelines. Completion of the IND transfer in May was an important step to enable us to accelerate our startup activities for the planned Phase III portion of IMerge. As a reminder, the Phase III portion of IMerge is designed as a randomized, double-blind, placebo-controlled clinical trial to test the hypothesis that imetelstat improves the rate of transfusion independence compared to placebo. Approximately, 170 patients are planned to be enrolled and randomize in a 2:1 ratio to receive, either imetelstat or placebo. Many key aspects from the Phase II portion of IMerge will remain the same for the Phase III portion. During the Phase II, a target patient population of non-del(5q), lower-risk MDS patients who were relapsed after or refractory to treatment with an EFA and naive to treatment with hypomethylating agents and lenalidomide were identified. The same target patient population will be enrolled in the Phase III portion of the study. In addition, the primary and secondary endpoints, the dose and schedule of imetelstat administration and many other clinical sites will remain the same in Phase III. We plan that the trial will be conducted at multiple medical centers globally, including North America, Europe, Middle East and Asia. We expect the trial to be initiated upon the opening of screening enrollment later this month and plan to issue a press release at the time that occurs. In addition to the clinical operational activities that have been underway this past quarter, at the 24th European Hematology Association Annual Congress in June, we also reported compelling data from the Phase II portion of IMerge and new statistical analyses of the overall survival data from IMbark in comparison to real-world data. I'll highlight key aspects of these presentations later on the call. Both of these data presentations provide further support of our clinical plans, including the start of the Phase III trial in lower-risk MDS and further evaluation of the potential for late-stage development of imetelstat in relapsed/refractory MF. We couldn't have accomplished all of this without having recruited the right team to execute our development plans. Our recent hiring of Vice President of Global Regulatory Affairs further expands our development leadership group, and it brings our total development team headcount to 16. We now have an in-house multifunctional development team that has deep relationships within the oncology community and great expertise in late-stage hematology-oncology drug development. We credit a strong belief in imetelstat's future potential as being a key driver for such top talent to decide to join Geron. Now I'd like to turn the call over to Olivia, our CFO, who will review financial results for the second quarter. Olivia?

Thank you, Chip, and good afternoon, everyone. For the second quarter of 2019, we reported a net loss of $14.2 million or $0.08 per share compared to $6.9 million or $0.04 per share for the comparable 2018 period. Net loss for the first six months of 2019 was $24.3 million or $0.13 per share compared to $14.1 million or $0.08 per share for the comparable 2018 period. Revenues for the three and six months ended June 30, 2019, were $101,000 and $158,000, respectively, compared to $208,000 and $526,000 for the comparable 2018 period. Revenues for the three and six months ended June 30, 2019 and 2018 included royalty and licensee revenues under various non-imetelstat license agreements. The decrease in licensee and royalty revenues compared to the same periods in 2018 reflect a reduction in the number of active research license agreements in 2019 related to our human telomerase reverse transcriptase, or hTERT, technology as a result of patent expirations on the underlying technology. Total operating expenses for the three and six months ended June 30, 2019, were $15.3 million and $26.7 million, respectively, compared to $7.5 million and $15.2 million for the comparable 2018 periods. Research and development expenses for the three and six months ended June 30, 2019, were $10.1 million and $16 million, respectively, compared to $3.2 million and $5.6 million for the comparable 2018 periods. The increase in research and development expenses compared to the same periods in 2018, primarily reflects cost for the transition of the imetelstat program, including resuming sponsorship of the ongoing imetelstat clinical trial, higher personnel-related costs for the expanding development team and expenses for the startup activities for the Phase III portion of IMerge. General and administrative expenses for the three and six months ended June 30, 2019, were $5.2 million and $10.6 million, respectively, compared to $4.2 million and $9.6 million for the comparable 2018 periods. The increase in general and administrative expenses compared to the same periods in 2018, primarily reflects higher corporate and patent legal costs and increased personnel-related expenses for additional headcount to support the development organization. Interest and other income for the three and six months ended June 30, 2019, was $1.1 million and $2.3 million, respectively, compared to $717,000 and $1.1 million for the comparable 2018 period. The increase in interest and other income compared to the same periods in 2018, primarily reflects higher yields on our increased marketable securities portfolio. We ended the second quarter of 2019 with $162.3 million in cash and marketable securities. Since May 2019, we have raised cumulative net cash proceeds of approximately $2.6 million from the sales of approximately 1.9 million shares of common stock under an At Market Issuance Sales Agreements after deducting sales commissions and other offering expenses payable by us. We expect these net cash proceeds to provide additional financial flexibility as we advanced the imetelstat development program. The funds will support future development costs, including conducting the Phase III portion of IMerge. We are reaffirming our 2019 guidance and continue to expect total operating expenses to range from $80 million to $85 million of which approximately $20 million to $25 million represents onetime costs that include imetelstat program transition activities from Janssen to Geron and purchases of materials to supply the Phase III portion of IMerge and prepare for new drug manufacturing. As you know, we began the year with approximately $182 million in cash and marketable securities. When considering our 2019 guidance, we expect our year-end 2019 cash and marketable securities to be approximately $100 million. We expect to complete the imetelstat program transition by the end of the third quarter. The final transition activities will include a transfer of the remaining nonclinical manufacturing and ex-U.S. clinical and regulatory responsibilities from Janssen. In June, we signed a clinical supply agreement with Janssen to purchase certain inventories of drug product, drug substance and raw materials for imetelstat manufacturing. Under the supply agreement, we will pay Janssen approximately $7.5 million for drug product upon shipment of the product to our specified drug storage and distribution centers, which is expected to occur in the third quarter of 2019. We have also agreed to pay up to approximately $6.7 million for drug substance and raw materials. Upon testing and confirmation, such materials meet certain specification and expect such testing to occur in the third and fourth quarters of 2019. We are not obligated to purchase materials that do not pass testing and conform to our quality specification. Today, Geron has 38 employees and plans to grow to a total of approximately 45 to 50 employees by year-end 2019, of whom half will be research and development personnels. With that, I will turn the discussion back to Chip.

Thanks, Olivia. I'll finish today's discussion with highlights from the data presentations in June at the EHA Annual Congress. As you know, we also hosted the KOL event on June 25 with two of the investigators who reprised the EHA presentations and participated in the question-and-answer session with sell-side analysts. We were encouraged by the interactive dialogue at the KOL event that discussed the significant unmet medical need in both lower-risk MDS that's relapsed and refractory to ESAs as well as in relapsed/refractory MF, and the important role imetelstat can potentially serve in meeting those needs. For lower-risk MDS, Dr. Platzbecker emphasized the meaningful and durable transfusion independence, broad activity and disease modifying potential of imetelstat treatment. For relapsed/refractory MF, Dr. [indiscernible] described how real-world data corroborated the potential OS benefit with the imetelstat treatment that's been observed in IMbark. So now I'd like to review the highlights. First, let's review the updated efficacy and safety data from the 38 target population patients in the Phase II portion of IMerge. The data cutoff date for the presentation at EHA was April 30, 2019, at which time the median follow-up was 15.7 months. As a reminder, IMerge is a two part Phase II/III clinical trial. The primary efficacy endpoint is an eight week TI rate, or simply stated, the proportion of patients who achieved transfusion independence or TI for a period of eight consecutive weeks. Key secondary endpoints include the rate of TI lasting at least 24 weeks or 24-week rate TI and duration of TI. The EHA presentation of the updated IMerge data reported meaningful and durable transfusion independence achievable with imetelstat treatment in heavily transfusion-dependent, lower-risk MDS patients. The importance of all of these was emphasized by both investigators who participated in the KOL event. In particular, the clinically meaningful responses for both eight week and 24-week TI rates and high transfusion-burden patients highlighted imetelstat's potential role as a much-needed alternative treatment in lower-risk MDS. At the American Society of Hematology, or ASH, annual meeting in December 2018, the reported eight week TI rate was 38%. With the addition of two new responders, the reported rate at EHA increased to 42%. The durability of the transfusion independence also improved with the 24-week TI rate of 26% reported at ASH and then increasing to a rate of 29% as reported at EHA. With longer follow-up for patients in this data set compared to ASH, the median duration of transfusion independence for responders was 86 weeks or over 20 months with the longest duration of response reported to be more than 2.5 years. In addition, a total of 26 of 38 patients in the target patient population experienced at least a four unit reduction in transfusion burden. And there was a mean relative reduction of red blood cells transfusion burden of 68% when compared to baseline. These reductions in transfusion burden should lead to an improved quality of life, less time in the infusion chair, less cost and reduced exposure to potential iron overload. Next, as was also emphasized at the KOL event, the updated data from EHA indicated that transfusion independence achievable with imetelstat was broadly distributed among different patient subgroups. This included similar results in patients with baseline transfusion burdens that were either greater than or less than six units. In addition, similar results were observed in both ring sideroblast patient subgroups, that is, RS positive and RS-negative patients. Likewise, patients with baseline serum or erythropoietin levels, both above and below 500 million units per ml, achieved similar transfusion independence with imetelstat treatments. We're encouraged that imetelstat demonstrates activity across these different subgroups, and therefore, that it can potentially be used broadly for the treatment of lower-risk MDS patients. Finally, the updated data from the Phase II portion of IMerge presented at EHA also provided further evidence of potential disease-modifying activity with the imetelstat treatment. This was evidenced by improvement after imetelstat treatment in the cytogenetics of cells and the bone marrow and by reduction in the proportion of cells carrying the SF3B1 mutation, both of which are hallmarks of malignant MDS cells. In addition, the EHA presentation reported 75% of the eight week TI responders also experienced a rise in hemoglobin of more than 3 grams per deciliter, suggesting potential recovery of neural pneumatic [indiscernible]. With these data, we now have three hematologic myeloid malignancies with the evidence of potential disease modification associated with imetelstat treatment. The first was in essential thrombocythemia, the second was in myelofibrosis, and now in the third, in lower-risk MDS. On the safety side, there were no new safety signals. The most frequently reported adverse events were Grade 3 or 4 cytopenias. More than 90% of the neutropenias and thrombocytopenias were reversible within four weeks. To put IMerge Phase II results in the further context, I'd like to say a few words about the data presented at ASH in December from the MEDALIST trial with luspatercept, which was a Phase III clinical trial and compared those data to the data that I just described for imetelstat-treated patients in the Phase II portion of IMerge. We acknowledge the limitation of comparing results from an open-label Phase II trial to a blinded placebo-controlled Phase III trial, and also that luspatercept has a relatively benign safety profile. However, the IMerge Phase II data does suggest that imetelstat efficacy is differentiated from that of luspatercept. For lower-risk patients -- sorry, the lower-risk MDS patients studied in MEDALIST had many similarities to the patients studied in IMerge. They have failed ESAs and had become transfusion-dependent, they were non-del(5q), and they were naive to both lenalidomide and HMAs. However, there was an important distinction. The patient population enrolled in IMerge had a higher disease burden, specifically the median baseline number of pretreatment transfusions for MEDALIST patients was 5 units of packed red blood cells per eight weeks compared to 8 units per eight weeks for the IMerge patients. Notably, 29% of the MEDALIST patients had a baseline transfusion burden of less than 4 units per eight weeks. Those patients would not have been eligible for the IMerge trial, where we required a transfusion burden of greater than or equal to 4 units per eight weeks. Another distinction between the two patient populations is that enrollment for IMerge was open to both RS positive and RS-negative patients, while MEDALIST was limited to RS-positive patients only. When we look at the efficacy results for the two drugs in the two studies, the overall eight week TI rates were similar, 42% for imetelstat-treated patients and 38% from luspatercept. However, upon further analysis of the data from the ASH presentation, in the luspatercept patients with the transfusion burden of greater than or equal to 4 units per eight weeks, that is the population with the baseline transfusion burden consistent with that of the imetelstat patients in IMerge. The eight week TI rate was only 20% for luspatercept. In conclusion, if our upcoming Phase III portion of IMerge is able to demonstrate eight week and 24-week transfusion independence rates within a similar range as was seen in the Phase II portion of IMerge, we expect imetelstat will compare favorably with other drugs, including luspatercept within a broad population of lower-risk MDS patients who were relapse or refractory ESAs. I'd like to next turn to the data presented at EHA and at our KOL event from IMbark. Our Phase II trial of imetelstat in relapsed/refractory intermediate to or high-risk myelofibrosis. In order to further assess the potential overall survival benefit observed in relapsed/refractory MF patients treated with 9.4 milligrams per kilogram of imetelstat every four weeks in the IMbark trial, a series of analyses was conducted in collaboration with the Moffitt Cancer Center, a leading academic cancer hospital in Florida. In the analyses, the median OS from IMbark was compared to the OS calculated from real-world data, also abbreviated RWD, in patients who had discontinued treatment from ruxolitinib and who were subsequently treated with best available therapy such as steroids or chemotherapeutic agents. To make a better comparison between the IMbark data and real-world data, a patient cohort from the Moffitt data set was identified that closely match the IMbark patients using guidelines for inclusion and exclusion criteria as defined in the IMbark clinical protocol, so that's just platelet counting spleen size. A statistical technique known as propensity score analysis was then used to balance key baseline patient characteristics for the two analysis cohorts. Using these statistical approaches, the median overall survival for imetelstat-treated relapsed/refractory MF patients in IMbark was more than double that for the closely matched real-world patients treated with best available therapy. The calculated median OS for the imetelstat-treated patients was 30.7 months, which was more than twice the calculated median OS of 12.0 months using real-world data patients treated with best available therapy. The analyses also indicated 65% to 67% lower risk of death for the imetelstat-treated patients compared to the real-world patients treated with best available therapy. So these analyses corroborated the potential OS benefit observed in the 9.4 milligram per kilogram arm of the IMbark Phase II clinical trial. Although, there are limitations of comparative analyses between real-world data and clinical trial data, these analyses give us confidence that further evaluation of the potential overall survival benefit in relapsed/refractory MF may be warranted. As such, we've been evaluating potential late-stage development approaches and regulatory strategies as we prepare for an end of Phase II meeting with the FDA. We are planning to conduct that meeting by the end of the first quarter of 2020. In summary, we've made great progress since regaining the rights to imetelstat less than a year ago. We've completed the IND transfer. We've assumed full responsibly for the drug. We've built world-class drug development leadership team to achieve future milestones. We reported compelling data at EHA that supports the future development of the imetelstat program in MDS and expect to open the Phase III portion of IMerge later this month. We're also strategically preparing for an end of Phase II meeting with FDA to discuss potential late-stage development scenarios and possible regulatory paths for imetelstat in relapsed/refractory MF. 2019 is proving to be a critical year for Geron, and we look forward to achieving these milestones as we progress through the second half of the year. And with that, we're now happy to answer your questions. I'll turn the call back to our operator.

[Operator Instructions]. Our first question is from Chad Messer from Needham.

I was wondering if you could talk a little bit more about what you're doing to prepare for the end of Phase II meeting that you hope to have in the first quarter. I know you've brought in some KOL, you've been having discussions. Sort of what's the emerging story you think you need to get in there and tell the FDA about imetelstat in these patients? What data do you think it's important to emphasize? And kind of what questions you -- do you hope to get answered?

Chad, we have been pretty resolute in not discussing the content of the specifics of analyses that we're doing or really the kinds of specific questions that we'll be asking the FDA. I think that's really both confidential information and also best shared with the regulators before we share them with everyone else. So I think I'm going to -- unfortunately have to demur. I can certainly tell you that a successful meeting would be where we gain insights into how the FDA views potential registration strategies for imetelstat. But exactly how we're preparing for that discussions, I think, has to remain uncommented on at this point in time.

All right. That's fair enough. I've known you long enough to respect your conservatism on issues like that. Maybe one just for Olivia then. How -- what is still available to you on your aftermarket?

On our aftermarket, it's -- approximately $57 million is still available.

We have another question from the line of Tom Shrader.

I have a question, a little bit related to Chad's question. But the recent guidance CTI got where they basically have a pivotal trial, and it's a straight spleen end point. Is that a complexity for you? Or do you think the drugs are so different that it's kind of irrelevant?

Tom, thanks for the question. I think that they are very different drugs. Both the mechanism of action are quite different. We know that JAK inhibitors in general are -- seem to have an activity against spleen size. And we have the potential disease-modifying activities that we've talked about, which may or may not be represented as well in just the pure spleen size but certainly, we believe, have a potential role or a potential overall survival benefit and also other activities. So I don't -- I think that's about probably all I can say right now about it. And I'll just say they are quite different drugs. And I think regulators probably look at them or we hope they’ll look at them as different drugs, maybe I'll say.

All right. Okay. Perfect. And then a question on IMerge. Based on your prior data, you've focused on patients that are HMA and lenalidomide naive. Do you have any sort of sense why those drugs interfere? Are they -- is there any -- they seem very different drugs and that prior treatment shouldn't matter. Or is it just sort of a general effect that if you've gone through HMA as your bone marrow was even more beat up, is there any sort of logical toehold to why you've chosen that group? I know the data tells you to, but I'm just looking for some mechanistic underpinning.

So I think you actually hit on an important one. I'll say the way I think about it's sort of a two-fold issue. The first one is that in the current treatment paradigm, patients who -- patients when they get the HMAs and for that matter, lenalidomide and non-del(5q) patients where it's not even -- lenalidomide, Revlimid isn't even approved, they're really pretty far along in the course of their disease. So I think right there, that's probably an important concept as we both know and oncology in general the further down the therapeutic spectrum you go usually the sicker the patients and the more resistant to treatment in general. I think the second is exactly as you said, all of these drugs exert some degree of toxicity, and HMAs certainly have substantial toxicity, including bone marrow toxicity. So I think it's probably a combination of both of those things.

Would you say that's well enough accepted, your second point that maybe physicians would be steered away from trying HMA or Revlimid first? Is that obvious? Is it something you hope to be the case? Just where does that fall on the current standard?

When we've talked to physicians, both in formal market research and also anecdotally, I think they would all love to have something before they have to go to HMAs or to an off-label drug like Revlimid. And HMAs are off-label in Europe as well, just to be clear. They are on label in the U.S. So I think they really like to have something that they could turn to first. And if there was a compelling story, which I think we believe is developing for imetelstat in patients before they get to HMAs or Revlimid, I think all of our market research suggests they'd be very excited and pretty thrilled to have that. So I don't think it's a matter that they feel like they have to trudge through HMAs and lenalidomide. It's simply they don't have anything else today really available to speak of. So that's the way I view it at least.

We do have another question from the line of Wayne Wu [ph] from B. Riley FBR.

So I have a question for about the IMerge Phase III trial. So the primary endpoint of IMerge Phase III is eight week TI rate and 24-week TI rate. And the quality of life is correlated with the frequency of RBC transfusions. Key secondary endpoint is the amount in relative changing the RBC transfusion, particularly since your patients are heavily transfusion-dependent. So how much weight does this secondary endpoint have with the regulators? And was it considered a [co] [ph] primary endpoint?

You want to -- Aleksandra might want to comment.

Sure. I can comment on that. Let me clarify first that the study has one primary endpoint and that is the eight week TI rate. So just to make that clarification straightforward, first. Then yes, key secondary endpoints are 24-week TI rate, and we know that regulators specifically are looking for durable TIs, which is something that we seem to offer from the Part 1 data as we know. And then yes, the quality of life. It's always very important, especially in terms of reimbursement path down the road. And that will be as well analyzed and looked into in our study as well.

All right, everyone, this ends our question-and-answer session for the call. I would now like to turn back the call over to Dr. Scarlett.

Well, thanks, everybody, for joining us today. We look forward to sharing more progress on our next quarterly call. Thank you. Have a good day.