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Geron (GERN 6.46%)
Q4 2023 Earnings Call
Feb 28, 2024, 8:00 a.m. ET
Contents:
- Prepared Remarks
- Questions and Answers
- Call Participants
Prepared Remarks:
Operator
Good morning. My name is Rob, and I will be your conference operator today. At this time, I would like to welcome everyone to the Geron Corporation's fourth quarter and full-year 2023 conference call. [Operator instructions] Thank you.
Aron Feingold, vice president of investor relations and corporate communications, you may begin your conference.
Aron Feingold -- Vice President, Investor Relations and Corporate Communications
Good morning, everyone. Welcome to the Geron Corporation fourth quarter and full-year 2023 earnings conference call. I am Aron Finegold, Geron's vice president of investor relations and corporate communications. I'm joined today by several members of Geron's management team, Dr.
John Scarlett, chairman and chief executive officer; Michelle Robertson, executive vice president and chief financial officer; Dr. Faye Feller, executive vice president and chief medical officer; Anil Kapur, executive vice president of corporate strategy and chief commercial officer; and Dr. Andrew Grethlein, executive vice president and chief operating 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 imetelstat, anticipated clinical and commercial events and related time lines, the sufficiency of Geron's financial resources, and other statements that are not historical fact.
Actual events or results could differ materially. Therefore, I refer you to the discussion under the heading Risk Factors in Geron's most recent periodic report filed with the SEC, which identifies important factors that could cause actual results to differ materially from those contained in the forward-looking statements. Geron undertakes no duty or obligation to update our forward-looking statements. With that, I'll turn the call over to Chip.
Chip?
Chip Scarlett
Thanks, Aron. Good morning, everyone. Thanks for joining us today. Geron's progress and execution throughout 2023 has paved the way for a potentially transformational 2024 as we plan for the transition to becoming a commercial company.
FDA has assigned a PDUFA date of June 16, 2024, for imetelstat for the treatment of transfusion-dependent anemia in patients with lower-risk MDS and has also provided notice that it's scheduled an ODAC as part of the imetelstat NDA review to be held on March 14, 2024. In addition, a review of our MAA for the same indication is expected to be completed in early 2025. We're focused on and prepared for these critical next steps in the regulatory review process which we hope will result in approval of what we believe is a highly differentiated and important treatment option for patients with transfusion-dependent lower-risk MDS. The publications from our pivotal IMerge Phase 3 clinical trial, including most recently in The Lancet, show a robust response rate and an unprecedented durability of red blood cell transfusion independence with imetelstat treatment across multiple MDS patient subgroups, addressing areas of high unmet need.
Additional unique attributes of imetelstat include patient-reported outcomes of less fatigue and significant reductions in variant allele frequency in commonly mutated MDS gene. With a well-characterized safety profile of generally manageable and short-lived thrombocytopenia and neutropenia, we believe the clinical evidence supporting the benefits of imetelstat is compelling and that it can become a transformational treatment option for currently underserved populations if approved by regulatory authorities. Behind our lead indication, low-risk MDS, is a similarly important program, the Phase 3 IMpactMF clinical trial in JAK-i relapsed and refractory myelofibrosis. An interim analysis is expected for this study in the first half of 2025.
IMpactMF is the first and only MF Phase 3 trial with overall survival as a primary endpoint. If the expected interim analysis in 2025 or the final analysis expected in 2026 is positive, these data could be transformational for patients with JAK-i relapsed and refractory MF who have dismal survival prognoses today. Our two lead indications for imetelstat represent significant commercial opportunities with a total addressable market, or TAM, of $3.5 billion for each indication across the U.S. and EU in 2031, thus representing a combined $7 billion TAM for transfusion-dependent lower-risk MDS and relapsed/refractory MF.
Given this very substantial opportunity amid a deep unmet need in transfusion-dependent lower-risk MDS, we expect to be prepared to launch and self-commercialize imetelstat in this lead indication upon potential FDA approval in the middle of this year. We have also completed multiple long-lead activities to prepare Geron, imetelstat, and the market for our potential launch in the U.S. with the goal of ensuring broad access and reimbursement for important medicine. Moreover, if imetelstat is approved by the European Commission in transfusion-dependent low-risk MDS, we expect commercial launch in Europe would occur in 2025.
We're continuing to evaluate our strategic options for European commercialization, including self-commercialization or partnering, and expect to be able to provide an update later this year. Lastly, we ended 2023 with a strong cash position of approximately $378 million, which, based on our current plans and expected available resources, we expect will enable us to fund a potential successful launch in transfusion-dependent lower-risk MDS in the U.S. and fund our planned operations into the third quarter of 2025. We believe our differentiated product candidates, the very important commercial opportunities in transfusion-dependent lower-risk MDS and relapsed/refractory MF, the excellence and experience of our employees, and the financial resources to execute on our near-term milestones puts us in a strong position for value creation.
With that, I'll turn the call over to Faye for a regulatory and clinical update. Faye?
Faye Feller -- Executive Vice President, Chief Medical Officer
Thanks, Jeff, and good morning to everyone on the call. As Chip mentioned, we are deeply focused on the regulatory processes for our imetelstat NDA and MAA, which are currently under review by the FDA and EMA for the treatment of transfusion-dependent anemia in patients with lower-risk MDS who have failed to respond or have lost response to or are ineligible for ESA. As previously disclosed, the FDA assigned a PDUFA action date of June 16, 2024. On January 30, 2024, the FDA also provided notice in the federal register that it has scheduled an ODAC as part of the imetelstat NDA review to be held virtually on March 14, 2024.
We feel very well prepared for the scheduled ODAC. We've been working for many months with an expert consultancy group which complements our deep in-house regulatory experience. I am personally excited to have the opportunity to discuss imetelstat with experts and peers as we believe imetelstat could be an important and compelling new medicine for transfusion-dependent lower-risk MDS patients. Our readout of positive top-line results from our pivotal IMerge trial in January 2023 was followed last year by a number of additional presentations and analyzes of the data, including at ASCO and EHA earlier in the year and last quarter at ASH.
This growing body of data from the trial continue to give us confidence in what we believe is a meaningful clinical benefit and manageable safety profile with imetelstat in patients with transfusion-dependent lower-risk MDS. As reported at these conferences, the clinical attributes of imetelstat were differentiated, particularly with respect to high RBC-TI reponse rate, durability of response, and the consistency of effect across MDS subgroups that have historically been very difficult to treat. The Lancet published results from our IMerge Phase 3 trial this past December, a strong validation of the importance of the study within the field, as well as a powerful way to reach hematologists and other providers globally with these potentially practice-changing results that offer the possibility of relief for lower-risk MDS patients from chronic reliance on blood cell transfusions. Turning now to our Phase 3 trial of imetelstat in relapsed/refractory MF.
We were excited to have completed 50% enrollment in this study in November of 2023. We continue to expect an interim analysis in the first half of 2025, which will occur when approximately 35% of the planned enrolled patients have died. A final analysis is expected in the first half of 2026 when over 50% of the planned enrolled patients have died. We look forward to continuing to keep you updated on this important study.
Lastly, we are also evaluating imetelstat in a Phase 1 study as a combination therapy with ruxolitinib in patients with frontline myelofibrosis. Our main goal for this combination study, known as IMproveMF, is to determine the safety profile of the combination regimen of ruxolitinib and imetelstat, as well as to explore the potential activity in a frontline MF disease setting. In January 2024, we escalated to the third of four dose cohorts in the study, following a unanimous decision by the study's safety evaluation team, or SET, who reviewed the second cohort data. We are very pleased with this progress and look forward to providing future updates.
With that, I'll turn the call over to Anil for a commercial update. Anil?
Anil Kapur -- Executive Vice President, Corporate Strategy, and Chief Commercial Officer
Thank you, Faye, and good morning, everyone. I look forward to discussing first where we see significant unmet need in the market, and then we'll provide a brief update on our U.S. launch planning. There remains significant unmet need across key transfusion-dependent lower-risk MDS patient populations that are underserved by current available treatment options.
Approximately 10% of lower-risk MDS patients are not eligible for ESAs and represent a very high unmet need subgroup. Rh-negative patients make up approximately 75% of lower-risk MDS patients in RF population particularly vulnerable to poor clinical outcomes. There are no therapies indicated for the treatment of anemia in Rh-negative patients once they are relapsed or refractory to ESAs. Rh-positive patients make up approximately 25% of the lower-risk MDS patients, and most who are high transfusion burden lack effective treatment options.
These underserved subgroups are at a greater risk for disease progression and suboptimal survival and are in the need for more effective treatment options. Moving on to an update on U.S. launch preparations. With a PDUFA date just about three-and-a-half months away, we have completed multiple critical launch readiness activities and plan to be ready to launch imetelstat in the U.S.
market upon potential approval. Long lead time activities, such as securing our global trademark on our brand name, manufacturing of commercial supply, are now complete. In preparation of launch, we have also finalized our distribution network and our patient support providers. In addition, we have onboarded and fully integrated a highly experienced commercial and medical affairs team into Geron.
We continue to transition Geron toward a commercial company with the integration and adoption of systems and processes to recognize and report revenues and the continued refinement of engagement plans with marketing, commercial access, payer, and reimbursement stakeholders. With regards to our field team, all regional business directors were onboarded in early January, and key account manager roles are being recruited. We expect to onboard the sales force in the first and second quarter of 2024. I'm very excited by the caliber of talent we have recruited onto the commercial team and across the organization.
Our cross-functional launch teams have deep oncology expertise and operational experiences, and they have been part of multiple oncology launches. We are excited about the opportunity to bring this innovative therapy to patients and are confident in our readiness to launch imetelstat in the U.S. market upon potential FDA approval. With that, I'll now pass the call over to Michel for a financial update.
Michelle?
Michelle Robertson -- Executive Vice President, Finance, Chief Financial Officer, and Treasurer
Thanks, Anil, and good morning, everyone. For detailed Q4 and full-year 2023 financials, please refer to the press release we issued this morning, which is available on our website. I will now review some highlights from the quarter and full year. At the end of 2023, our cash, cash equivalents, and marketable securities were $378.1 million.
There are approximately $2.5 million warrants outstanding, and the potential proceeds from these warrants is $3.2 million. Total operating expenses for the three and 12 months ended December 31, 2023, were $54.3 million and $194.1 million, respectively, compared to $42 million and $139.1 million for the comparable 2022 periods. R&D expenses for the three and 12 months ended December 31, 2023 were $32.9 and $125 million, respectively, compared to $28.2 million and $95.5 million for the same period in 2022. Expenses have increased year over year, primarily related to supporting our Phase 3 clinical trials IMerge and IMpactMF.
Both personnel and consulting costs increased to support regulatory submissions and increased investment in manufacturing as we prepare for the potential U.S. commercialization of imetelstat in transfusion-dependent lower-risk MDS. G&A expenses were $21.4 million and $69.1 million for the three and 12 months ended December 31, 2023, compared to $13.8 million and $43.6 million for the same period in 2022. The increase in G&A expense is primarily attributed to headcount and external expenses to support the commercial readiness activities.
At the end of December 31, 2023, the company had 141 employees, which we project will grow to approximately 270 employees by the end of 2024, subject to receiving FDA approval of imetelstat. The increase in headcount is primarily in the commercial and medical affairs teams. Our projected full-year 2024 operating expenses are expected to be between $270 million and $280 million. Based on our current operating plans and expectations regarding the timing of a potential approval of our imetelstat NDA that is currently under FDA review and subsequent potential U.S.
commercial launch, we believe that our current cash resources, together with projected revenues from U.S. sales of imetelstat; proceeds from the exercise of outstanding warrants; and funding under our loan facility will be sufficient to support our operations into the third quarter of 2025. I will now turn the call back over to Chip. Chip?
Chip Scarlett
Thanks, Michelle. For Geron, our progress in 2023 represented the culmination of a many-year, multi-faceted scientific and drug development journey, the goal of which is to translate the promise of telomerase inhibition into a potentially powerful medicine. Today we're just 3.5 months away from the PDUFA date for our first-in-class telomerase inhibitor, which we believe has the potential to offer important and potentially life-changing treatment options for patients with transfusion-dependent lower-risk MDS. We believe this is a robust commercial opportunity, and we're on track for a successful transition to becoming a commercial company.
In addition, we're excited by the momentum in our Phase 3 ImpactMF trial, which is 50% enrolled as of November 2023 and for which we expect an interim analysis in the first half of 2025. We believe these programs carry significant value for patients and shareholders alike, and we look forward to keeping you updated on our progress. We'll now open the line to questions. Operator?
Questions & Answers:
Operator
[Operator instructions] Your first question comes from a line of Corinne Johnson from Goldman Sachs. Your line is open.
Corinne Johnson -- Goldman Sachs -- Analyst
Good morning. Maybe one from us and a follow-up to it. How would you characterize the likelihood that you could see imetelstat approved with either a black box warning and/or REMS program? And then perhaps, more importantly, what do you view as the implications from a commercial perspective under either scenario?
Chip Scarlett
Yeah, a lot of suppositions there, Corinne. Let me say, first of all, you're going to hear this over and over, everybody will, so I'll just say once. We're not going to comment on ongoing conversations with regulators and -- for the obvious reasons that we're getting really close to all of these milestone events. Let me just say I don't think it's warranted.
I don't think that from our perspective, either a black box or any REMS program is warranted. But predicting how all of that will go is a little too speculative for us to [Inaudible]. We feel very confident [Inaudible] imetelstat to be used safely and effectively in the cell -- in this target population.
Corinne Johnson -- Goldman Sachs -- Analyst
OK, thanks.
Chip Scarlett
Sorry, yeah, the second part of that question, I think --
Corinne Johnson -- Goldman Sachs -- Analyst
Is it commercial -- the commercial indications if it was to be implemented?
Chip Scarlett
Corinne, pure speculation. I think I'll stay out of that speculation. I think everybody understands that it all depends in the -- and certainly when it comes to either black boxes or warnings or contraindications, these are all nuanced issues, and then I'll refrain from speculation, nuance is never a good thing from my perspective. But again, kind of depends on how that gets together, but that's not where we're focused forward beyond those types of issues, we hope.
Corinne Johnson -- Goldman Sachs -- Analyst
OK, thank you.
Operator
Your next question comes from the line of Kalpit Patel from B. Riley. Your line is open.
Kalpit Patel -- B. Riley Financial -- Analyst
Yeah. Hey, good morning, and thanks for taking the question. There was a letter submitted to the ODAC members by an independent group regarding the hepatic safety for imetelstat. The conclusion on that letter was positive overall for imetelstat, but I guess the question is have you requested any other independent assessments for maybe additional topics, such as evaluating the safety of -- the cytopenias from all the studies before the AdCom?
Chip Scarlett
So I think we ought to clarify for those who aren't aware of those, that letter was sent by the members of our hepatic safety or hepatic evaluation committee, the support agency. That group of liver experts were convened, gosh, almost a decade ago. They're very, very well known to many people in industry, experts on drug-induced literature injury, etc. And we engaged them to oversee all of the imetelstat trials going forward, and I have to say they did a wonderful job.
They have had quarterly meetings. They'll have looked at every scrap of information in the case, as far as I'm aware, they've looked at every scrap of information that relate to any way, shape or form to, to liver -- hepatotoxicity or liver safety. And the letter is there on the docket for people to read. It simply reaffirms their beliefs that imetelstat is a very safe drug for a liver perspective.
So that's really where it came from, and I think we'll just leave it at that. That is kind of a well-confined area of interest that many people are aware of and of interest, especially a decade ago.
Kalpit Patel -- B. Riley Financial -- Analyst
OK. Thanks for taking the question.
Operator
Your next question comes from the line of Stephen Willey from Stifel. Your line is open.
Steve Willey -- Stifel Financial Corp. -- Analyst
Yeah. Thanks for taking the questions. I guess can -- again, I'm not sure if you'll be able to speak to this. But can you remind us just what the frequency of platelet and cell count monitoring in the IMerge trial was? And I guess as you think about a potential product label, would you expect that monitoring requirement to be a bit more stringent than what it was in the trial?
Chip Scarlett
I think the -- if I recall, Steve, it was weekly monitoring for the first several cycles, and I think whatever was in the trial is not unlikely to be looked at by regulators. It's sort of a de facto standard. I won't comment on [Inaudible]. You know where that will go exactly, but I do think that that makes sense.
And it's given us the ability to really interrogate the frequency and the -- sort of the course of these cytokines, which, as you know, are indeed short-lived and well managed -- and manageable, I guess I should say. But we only know that because we've studied them in that way. So I think that's the de facto standard and what I would expect going forward from a cytokine perspective.
Steve Willey -- Stifel Financial Corp. -- Analyst
OK. And do you know, I guess, what proportion of these patients -- I mean, obviously they're low-risk MDS and have dysplastic marrow, but do you know what proportion of them are already doing weekly cell counts, whether it's at home, whether it's in heme office?
Chip Scarlett
[Inaudible] to that. It's an interesting question. I would say that it kind of depends on what -- where they are in their journey. And as you say, kind of where the -- what the level of the no disclosure it is and so forth and what their own experience is.
As you saw in the placebo arm, we have patients who simply also showed meaningful cytopenias, even though they're receiving placebo and whatever other background therapy is allowed. So -- but on the other hand, I think the regular monitoring probably is more associated with different products that these patients take, so -- and the monitoring would be associated [Inaudible]. So my estimate is that this would be something that would get started. When you start a new drug, most histologists would follow very closely.
They just kind of all make sense. And then, ultimately, it will be up to the physician on whatever the label says to decide how the frequency and how that sort of carries out over the course of the treatment with any drug included In those trials.
Steve Willey -- Stifel Financial Corp. -- Analyst
OK. And maybe just kind of a bigger-picture question. I mean, there's obviously, kind of this ongoing narrative among investors regarding the exclusivity runway, and the development program for imetelstat here is still not necessarily expanding, but it's being broadened into some additional indications. And so just curious, I guess, does -- do these Phase 1 studies reflect your internal confidence in the IP? Or do you think that these are opportunities you could bring online quickly, maybe carve out some additional orphan drug designations? Would just be kind of interested in terms of how you're thinking about the longer-term R&D program for this drug.
Chip Scarlett
Sure. So I think you were referring, just to be clear, to IMproveMF and on the AML study. Did I get your question right about that?
Steve Willey -- Stifel Financial Corp. -- Analyst
Yeah, correct. So the rux combo study and just some of the other --
Chip Scarlett
Sure. So I think it's incumbent on every company developing a drug, regardless of kind of whatever the nuances of the IP positions are, I think we study new combinations and study different utilities of drugs. And I'm sorry for being unpleasant about this. I don't mean to be.
But we have to move it at kind of a high level. I think we do that on the basis that we think -- if we think that there is benefit to be derived for patients, that's when we become really interested. The rux is a really good example, as you know and have written about to these people know, there were a whole series of pre-clinical experiments done a number of years ago now. And they were a very good lab of scientists that looked at the question of whether or not there were different ways to exploit some of the intrinsic activity in telomerase inhibitor against some of the cells that are malignantly transformed and ultimately cause myelofibrosis in clinical outcomes.
And what we see is that if you end up treating with [Inaudible] disrupt cells, as I recall, with a JAK inhibitor, you see any damage. And then if you sort of chase that, if you come after that, which you can do in a laboratory [Inaudible] with a telomerase inhibitor, in this case an epoxide, you actually get a higher proportion of animals surviving longer. And also, you see a depletion of the living hematopoietic stem cells. So that was the key for us to start ultimately to do all the work necessary to start this study.
And it's because, a, we can go upfront with this into frontline patients; b, we hope to be able to actually have ultimately improved efficacy, although this study is predominantly a safety study; c, I guess that some people are going to do this. If we don't do it, some people somewhere in the world will start to do it on their own. And we would -- we think we know the drug. We've helped that better than anybody else, and we have control of that.
So sorry to be, again, kind of [Inaudible], but I think that that's the rationale. The same with AML. AML is a terrible disease, and relapsed/refractory patients have very, very few options. There are other drugs in the horizon that I hope for these patients' sake also are [Inaudible].
Our goal is really patients. And then absolutely, if you do something reasonably innovative, which I think these are innovative, ultimately you file for intellectual property protection. That plays out as a completely separate story in one that's not as interesting.
Steve Willey -- Stifel Financial Corp. -- Analyst
OK, makes sense. I appreciate the comments. Thanks.
Chip Scarlett
Sure. Thanks.
Operator
[Operator Instructions] Your next question comes from the line of Gil Blum from Needham and Company. Your line is open.
Ethan Markowski -- Needham and Company -- Analyst
Yeah, hi. This is Ethan Markowski on for Gil. Thank you for taking our question. First one would be how much -- I know you've touched on this before, but how much extra effort do you think you'll have to spend on educating community physicians on managing cytopenias versus academic ones assuming approval? And then do you have any thoughts on how the recent data from morphosis at ASH could impact the myelofibrosis landscape and any future development in the space? Thank you.
Chip Scarlett
I think that's a killer name for Anil Kapur. Anil?
Anil Kapur -- Executive Vice President, Corporate Strategy, and Chief Commercial Officer
Sure. So we have had extensive discussions with both community and academic providers. And just as a reminder for everyone, lower-risk MDS is predominantly treated within the community setting. Physicians tell us they have deep experiences with drugs, such as len HMAs, and are very adept at managing heme-related side effects for patients.
And for them, they point to prolonged myelosuppression with HMAs, etc., as areas which they have managed successfully for a long period of time. With imetelstat, in particular, what is really important is -- which they receive really favorably, is the predictability of the cytopenias, the fact that the cytopenias typically are of finite duration and tend to go away by cycles two and cycle three. And also importantly, there are no clinical consequences associated with these cytopenias in terms of infections and hospitalizations and bleeding events. And when we also provide context on the mechanism of action, this is something that's received very favorably by the practicing hematologists.
So we do not see much differences between the community versus the academic hematologist in terms of their perceptions and management of heme toxicities. They are adept with their training and also their practice experiences. With regards to the question on myelofibrosis, I think this is also an area which is fast-moving. We will obviously wait to see what happens with the BCL-2 and the BET inhibitors in terms of entering the landscape.
But a reminder for myelofibrosis is that we are the only Phase 3 study, the largest effort to the best of my knowledge in the world, which is looking at survival in a patient population that's relapsed and refractory to JAK-is. This patient population is extremely underserved. And every feedback from physicians, academic experts, leading KOLs, is that if our myelofibrosis study is positive, it is going to be transformative for patients with myelofibrosis and really will be rapidly well adopted within the space. So I'll just stop here.
Ethan Markowski -- Needham and Company -- Analyst
Thank you.
Operator
Your next question comes from the line of Joel Beatty from Baird. Your line is open.
Joel Beatty -- Robert W. Baird and Company -- Analyst
Hi. Thanks for taking the questions. For the early access program, can you provide any updates or quantify how many patients are a part of that?
Anil Kapur -- Executive Vice President, Corporate Strategy, and Chief Commercial Officer
Chip, do you want me to take that?
Chip Scarlett
Sorry, yeah, go ahead.
Anil Kapur -- Executive Vice President, Corporate Strategy, and Chief Commercial Officer
So that's a clinical study, Joel. We do not provide updates on the enrollment, etc., projections within that space. The study is ongoing.
Joel Beatty -- Robert W. Baird and Company -- Analyst
OK, got it. Thanks. And then for the guidance of the cash runway into Q3 2025, what sales assumptions are going to that guidance?
Michelle Robertson -- Executive Vice President, Finance, Chief Financial Officer, and Treasurer
Sorry, Joel. I was on mute. We haven't shared any sales guidance or revenue guidance just yet.
Joel Beatty -- Robert W. Baird and Company -- Analyst
Got it. Thank you.
Operator
And we have reached the end of our question-and-answer period. I will now turn the call back over to Aron Feingold for some final closing remarks.
Aron Feingold -- Vice President, Investor Relations and Corporate Communications
Thank you, everyone, so much for joining us today. We appreciate your interest in Geron and look forward to keeping you updated. Be well.
Operator
[Operator signoff]
Duration: 0 minutes
Call participants:
Aron Feingold -- Vice President, Investor Relations and Corporate Communications
Chip Scarlett
Faye Feller -- Executive Vice President, Chief Medical Officer
Anil Kapur -- Executive Vice President, Corporate Strategy, and Chief Commercial Officer
Michelle Robertson -- Executive Vice President, Finance, Chief Financial Officer, and Treasurer
Corinne Johnson -- Goldman Sachs -- Analyst
Kalpit Patel -- B. Riley Financial -- Analyst
Steve Willey -- Stifel Financial Corp. -- Analyst
Ethan Markowski -- Needham and Company -- Analyst
Joel Beatty -- Robert W. Baird and Company -- Analyst
