Good morning, everyone. Welcome to the CTI BioPharma company presentation. My name is Ethan Taylor. I'm an associate in JPMorgan's Healthcare Investment Banking group. It is my pleasure to introduce Adam Craig, CEO of CTI BioPharma. As a quick note, there will be time at the end for some audience Q&A, please have some questions ready. With that, Adam, take it away. Thank you, Ethan. Good morning to everyone. My name is, as Ethan said, Adam Craig. I'm the Chief Executive Officer and President of CTI. I'm joined today by David Kirske, our Chief Financial Officer. First of all, Ethan, I'd like to thank you and the team for inviting us to this great conference. It's a real privilege for us to be here to present. I will be making some forward-looking statements. I'll refer you to the text in this slide. 2022 was a fantastic year for CTI. It was the year in which we got our first U.S. drug approved, VONJO or pacritinib, for the treatment of patients with cytopenic myelofibrosis. VONJO was approved based for the treatment of patients, adult patients with myelofibrosis with a platelet count below 50,000. It was an Accelerated Approval based on the only randomized trial ever conducted specifically for this kind of patient, the cytopenic myelofibrosis patients, those with the lowest counts. We had a great commercial launch, which I'll go into in a bit more detail, into a quite substantial market. The overall myelofibrosis market is predicted to be around $3 billion in 2026. What is cytopenic MF? It is actually the largest segment of the MF population. myelofibrosis is a disease that typically occurs in the elderly, and it's characterized by low counts, a large spleen, and or what's referred to as constitutional symptoms. Patients have a great deal of lethargy, itching of the skin. It really is quite a pleasant unpleasant, debilitating disease. Most patients, 2/3 of patients on within the MF population, the prevalent population of about 21,000 patients will have low platelet counts. About 14,000 will have platelet counts below 100, and about 7,000 of those patients will have below 50. This is very important because ultimately, myelofibrosis is a disease of the bone marrow. As the disease progresses, the bone marrow fails, and with that, patients will get cytopenias. It's not just reduced platelet counts as you can see with the figure on the bottom right. Patients develop anemia quite quickly in the disease within the first year, and anemia can be very debilitating. As a result of that, patients often need red blood cell transfusions, and that can be quite a burden both to the healthcare system, but to individual patients as well. VONJO, pacritinib, was the only drug that's ever been studied specifically in this population in a randomized clinical trial. The needs of myelofibrosis market are substantial. As many of you know, the first compound to be approved in myelofibrosis in the U.S., specifically as a JAK2 inhibitor, was Jakafi. It's a great drug. It's been a very successful drug for Incyte in the U.S. and very successful for Novartis in Europe. It does, like many drugs, it has limitations, and its main limitations is that when the drug is given at higher doses, it can cause the platelet counts to drop. This toxicity leads to the need for patients to have a reduced dose. As the dose is reduced, the efficacy of the dose reduces, the patients can often get into a vicious circle of platelet count dropping, dose dropping. In the end, many patients end what, on what we refer to as subtherapeutic doses, and that's 20 mg a day or less. As the FDA label points out, when patients are on 5 mg BID, they're unlikely to show any response, as outlined in the text in the box, which comes directly from the ruxolitinib label. In parallel to that, obviously, if the drug is not doing well for patients, physician dissatisfaction or lack of satisfaction will increase. What you see is a small survey that was conducted b y 100 healthcare providers, it shows as the dose goes down, the daily dose from 15 mg-20 mg a day to 5 mg-10 mg today, the level of dissatisfaction goes up and the level of satisfaction goes down, as illustrated by the red line. That's the market. What's unique about VONJO? There are other JAK2 inhibitors, as many of you know. VONJO is a JAK2, IRAK-1, ACVR1 inhibitor, and it spares JAK1. I'll just briefly go through all those mechanisms. JAK2 is obviously a very important mechanism for inhibition is the important mechanism for control of myelofibrosis. IRAK-1 is a pathway that may be involved in controlling the inflammatory component of myelofibrosis. ACVR1, which I'll cover again in more detail in my talk in a few minutes, is believed to be an important pathway in the development of the anemia of inflammation that occurs within myelofibrosis. You may ask, why have I said we spare JAK1? Well, JAK1 inhibition is something that is found with ruxolitinib. It's a JAK2, JAK1 inhibition. Many people believe it's the JAK1 inhibition that leads to the low counts, the cytopenias. The fact that we spare JAK1 may be a mechanistic explanation as to why VONJO can be given at full dose in these patients who already have bone marrow failure. One of the highlights for the company now of the last few years, obviously an approval of a drug. It was a great day. In February 28th of 2022, the FDA granted us Accelerated Approval for the treatment of myelofibrosis patients with a platelet count below 50. Our label is pretty straightforward, no black box warning, very clear dosing instructions. The approval was given as an Accelerated Approval based on spleen volume reduction as a surrogate endpoint. Spleen volume is a way of measuring the benefit of drugs in myelofibrosis. The spleen gets very large. As the bone marrow fails, the spleen tries to compensate for the activity of the bone marrow and gets very large. It's a way it can be measured in clinical trials quite successfully, or you can actually palpate the spleen in clinic and see whether the spleen is enlarged. We were asked by the FDA to complete a confirmatory trial, which is underway. It's called the PACIFICA Trial. PACIFICA because we're a West Coast company based in Seattle, and we're looking at patients with primary or secondary myelofibrosis who have the platelet counts of less than 50,000. It's a 2-to-1 randomization between VONJO at the approved dose of 200 milligrams twice a day versus physician's choice, which includes four options, the most important one of which is low-dose ruxolitinib. 85% of our patients on this trial are receiving low-dose ruxolitinib. The trial is being conducted in Europe and the rest of the world. It's not being conducted in the U.S. The endpoint, we have a co-primary endpoint. 35% spleen volume reduction, as measured by CT or MRI at 24 weeks, and a 50% reduction in what's called the Total Symptom Score, which is a questionnaire the patient fills out every day across a variety of symptoms. You're looking for an improvement in symptoms, a reduction in the score at week 24. The study is well powered to to have a positive outcome, and the data is expected to be available in the middle part of 2026, subject to obviously the constraints that many of us are having in the field of clinical trials at the moment with respect to COVID and obviously the war in Europe. The product label, the safety profile for the drug has always been pretty predictable throughout our clinical trials. The safety profile that's described in the product label, and you see the table from the product label on this slide, shows that diarrhea is the most common side effect that we see with this drug. We've been very proactive in the field commercially to make sure that physicians are educated, nurse practitioners and pharmacists are educated about diarrhea. We've been very successful in making it very manageable. It typically occurs one to two weeks into therapy. It can be treated quite successfully with Imodium and not be an issue. You have to be aware of it, and patients need to be aware of it. There's a big education component to us managing the diarrhea in the commercial setting. In fact, our specialty pharmacists do when they send patients to the patient, the VONJO, they also send them a script for Imodium. The patients are encouraged to get the Imodium and start taking it if they have any evidence of diarrhea. That's been very successful. The approval came from what we call the quintessential study of cytopenia, the PERSIST-2 trial. It's the only trial, randomized trial that's ever been conducted specifically in the cytopenic setting. It was conducted in primary and secondary myelofibrosis, patients with platelet counts less than 100. They were allowed to have received prior JAK inhibitors, which was mainly ruxolitinib. We tested 2 doses at the time. This is some years ago, five or six years ago. There were two doses. The 200 mg dose twice a day is the dose that's the FDA label, and that's because it has the best risk-benefit profile. The data that went into the label and was reviewed by the FDA came from this trial. What we saw was for the surrogate endpoint of spleen volume reduction in the patients with the lowest platelet counts, the greatest unmet medical need, the less than 50,000, we saw a 29% reduction in spleen volume at week 24 for pacritinib and 3.1% in best available therapy. If you look at the waterfall plot on the right-hand side, you'll see that most patients on pacritinib in the red did actually have a reduction in their spleen volume compared to the control arm. You can see a nice, healthy benefit. It's now our job to confirm that benefit in the PACIFICA trial. Another way of looking at the data is obviously to look at symptom score. It's a very important, very important component of the disease. You want the patients to feel better. Using a modified symptom score, we showed a 26% versus 9% improvement in symptoms with a very similar waterfall plot on the right-hand side, again, showing that most patients experienced a reduction in their symptom score when treated with VONJO. At the time this publication came out on the PERSIST-2, which was about five years ago, we did demonstrate a clinical improvement in anemia. We had a hemoglobin of a reduction in hemoglobin, reduction in transfusion-dependent, and this was all published in Lancet Oncology some time ago. We didn't know the full mechanism, the small reason behind the anemia. It really wasn't until ASH of this year, where Dr. Stephen Oh of Washington University presented an oral presentation on the anemia benefit of pacritinib in the context of ACVR1 inhibition, that we really fully understood why we had anemia benefit from the drug. As a reminder, as it says at the top here, ACVR1 has been implicated as having a role in the anemia of inflammation in patients with myelofibrosis. What Dr. Oh showed was that pacritinib is a highly potent inhibitor of ACVR1. We knew momelotinib from GSK was an inhibitor, but it wasn't until the summer of last year when this data was generated that it became clear that pacritinib was four times more potent against momelotinib with respect to this target. Very importantly, it's not just this kind of activity. It's not just about whether you inhibit a target, it's how much you inhibit the target in patients over a day. Some PK/PD analysis was done where they looked at the concentration of pacritinib over time over a 24-hour period with respect to how the drug is handled by patients and whether it exceeded the IC50 for ACVR1. What we showed on the left, the squiggly lines here are the pharmacokinetic levels of pacritinib over a 24-hour period at different doses. It's the same for momelotinib on the right-hand side. The dotted line there is the IC50, and what you'll see here is pacritinib's drug levels exceed the IC50 24 hours a day, whereas momelotinib, it's only for 55% of the day. An important difference in how the, both the drugs in the clinical setting potentially inhibit ACVR1. It's very important if you believe you inhibit ACVR1 that you can demonstrate that you can actually inhibit at factors downstream of it. What Dr. Oh was able to show here was that pacritinib decreases SMAD phosphorylation, which is a downstream component of the ACVR1 pathway, and it also reduces the mRNA levels produced by HAMP, which is the gene that actually produces hepcidin. This is good confirmatory evidence that not only does pacritinib inhibit ACVR1, it reduces hepcidin levels. On the clinical side, there was a retrospective analysis conducted on the PERSIST-2 data, said to look at, is there a clinical consequence of potentially of ACVR1 inhibition? What was found was that to get transfusion, patients attained transfusion independence on pacritinib therapy. Transfusion independence means exactly what it is. The patient is not receiving transfusions over, in this case, I think it was an eight-week period. That's very important because transfusions, as I've already said, are a huge burden for patients, and they're a burden on the healthcare system. What we showed with pacritinib in this study had 37% transfusion independence versus 7% on the control arm. The potential mechanism for anemia is that pacritinib is a potent inhibitor for 24 hours a day of ACVR1, and that it may work in conjunction with IRAK-1 and JAK2 to reduce hepcidin levels, and it's hepcidin that is believed to ameliorate the anemia of inflammation that occurs in myelofibrosis. To finish up, I'm gonna talk about our commercial launch. We're very pleased with how it's gone so far. We reported $32.9 million net sales between March, when we launched the drug, of 2022, and the end of Q3, when we last announced earnings. We did this through deployment of 59 key account managers, our reps in the field. We hired very experienced, which older reps who've been in the field a long time, had a lot of good relationships. They are supported by seven regional business managers, and that's gone very well. We understood the market before we launched. We know that 80% of our patients are covered by 4,700 prescribers and 1,200 accounts, it's quite concentrated in that regard. That we know about 60% of our patients are in the community setting, 40% in the academic setting. We knew that there was a well-defined unmet medical need before we launched. We've been very fortunate in the coverage that's been provided by commercial and Medicare and other organizations. The payers have recognized the unmet medical need, and the drug has pretty broad coverage now according to the product label, which I've spoken about, and also the NCCN guidelines, which are covered in this slide. The NCCN guidelines are a very important tool for treating physicians who see MF patients, and particularly in the community. Whilst we cannot promote VONJO according to the NCCN guidelines, any treating physician at their discretion has the option to treat according to them. The NCCN has a similar recommendation as the product label for first-line use for platelets less than 50,000. For second-line use, there's no platelet count restriction. The key drivers, I think, of the success of the launch to date was the commercial team. Really, one of them was the building awareness. They spent a lot of time educating physicians on the importance and the prevalence of cytopenic MF, the challenges they face, particularly with the current therapies such as Jakafi, and then demonstrating VONJO's value proposition. We drove adoption and we'll continue to drive adoption by in-face, in-person meetings, both, and virtual promotion, but lots of one-to-one interaction. That's the success here. That's where we as a small company can be successful. We have spent a lot of time and effort on peer-to-peer education. In many aspects, the best way of educating a physician and for someone to learn about disease is to hear it from one of their peers. We ought we make a big effort to put physicians who have used pacritinib in front of physicians who haven't used pacritinib and have a discussion. Then, of course, optimizing patient access is important. This isn't just about getting patients on drug. This is making sure that any patient who has, who's eligible and has a need gets the drug, and that does include us giving free drug to any patients who cannot afford it. The other part of the commercialization is obviously optimizing the understanding and the care of cytopenic MF. My commercial colleagues have a very simple saying. They say, "The use of the drug is safe, simple, and effective." It's very short, it's very sweet, but it really does sum up pacritinib. It's safe because we don't have the problems with cytopenias in the low platelet count patients. You can give the drug quite effectively. It's simple because you can give the drug at full dose. You don't have to play with the dose as you do with Jakafi. It's effective because it's the only drug that's ever been shown to have a modification of disease in the setting of cytopenia. We can get platelet count stability in this setting when other drugs will cause the platelet counts to drop. As I finish off, obviously our financial position is very important. We reported $82 million of cash at the end of last quarter. If David and I are successful with our revenues as projected this year, we should get to cash flow positivity by the end of the year, which will be a great milestone for a company of our size. To finish off, I'd like to thank my team and all my colleagues at CTI for a fantastic 2022. I think we're very well positioned for 2023. We got VONJO approved in February of this year. We prepared the marketplace, we developed our relationships, and we actually deployed the team into the field very, very quickly. To repeat, we have $32.9 million sales over nine, seven-month period. We have shown strong quarter-over-quarter growth. Our product is differentiated in the marketplace, and we have considerable awareness of the product. What's really good is we're seeing use of the drug both in the academic and the community settings. Our objective as a company is to become the market leader in cytopenic MF, and I think we're well on our way to achieve that goal and by redefining the treatment paradigm for cytopenic MF in 2023. Thank you. Thank you, Adam. We'll have some time now for some Q&A. I can kick things off with a couple questions from us. What has the VONJO uptake been in the community versus academic setting? Thank you, Ethan. It's an important question. The uptake in the community was very robust at the beginning. We always thought that we would get good community uptake, what we were pleasantly surprised by is how quickly there was uptake in the community. From day one, we launched the drug, we had inquirers in the community demonstrating that there was a patient need there. What's interesting, currently we have about 60% use in academics and 40% in the community, we think over time, that's gonna switch the other way as more community physicians are able to treat these cytopenic patients and won't have to refer them to academic centers. The activity in the community has been really exciting for us, and I think it will be an area of growth. Great. you know, touching on access, are you getting the kind of commercial insurance coverage that you were planning for? Yeah. That's gone very well. The insurance companies will cover the vast majority. It's a very small number that we'll cover according to the NCCN guidelines and the product label. Obviously that's very of use to us. As I've said previously, we cannot promote, you know, the NCCN guidelines, but physicians have the choice whether they want to follow them or not. Yeah. Are you seeing any unexpected safety issues in the commercial setting? No, we're not. My other hat is I'm interim chief medical officer, so I take a look at the pharmacovigilance data quite readily, and we're not. We have a good profile, fairly predictive profile. Importantly, there's no unexpected signals in the pharmacovigilance on the pharmacovigilance side. I can say the same for the PACIFICA trial. The PACIFICA trial has the IDMC is about to meet, and the data shows that the drug is very well-tolerated. Again, no surprises, which is great. Great. Any audience member questions? Kind of along the general tradition of, JPMorgan, do you have any comments on the fourth quarter? Any trends, any comments on how that quarter went relative to before? As I said to about 20 people yesterday at different meetings, we're not gonna comment specifically on Q4. December, I will say, I'll say what I've said to other people. We are seeing increasing number of active patients, new prescriptions. We are seeing an increase in duration of therapy over time, which is important as you get patients coming on the drug commercially who are earlier in disease. We've seen some very good trends. Ed, I'm unable today to comment exactly on Q4. It's super exciting. I was wondering, and I know it's early days, but are you foreseeing any label expansion opportunities in the heme space that excite you? Obviously, this has been a recent approval, and there's still a lot to do in cytopenic MF, but any areas of interest in heme apart from cytopenic MF for VONJO? Yes. Thank you for the question. It's very important. The answer is yes. It's very important that we expand and we look forward and we think about where to go in MF and myeloproliferative neoplasms. I think there's two answers to your question. First of all, we do have a dataset of patients who had platelet counts below 100. That's the PERSIST data. The efficacy data in the label covers the less than 50. The safety data covers less than 100. There's still this efficacy data from 50-100. That's something we're looking at. Can we expand the label according to the PERSIST-2 data? The other way, aspect, we've put our smartest people into a working group to see is there another disease area within the MPN spectrum where we could potentially develop a registration pathway. Very important work for us. If we were successful, we could really have quite a significant impact on the commercialization opportunity for the drug. Thank you. I have, 1 final question from my end, at least. Do you plan to increase the sales force size in the coming year? David and I spoke at with the sales team, the sales leadership at the end of the year, and we reviewed it in quite a lot of detail, the sales team and did we need to make any changes. We actually had put the sales team together in collaboration with ZS Associates, who are one of the market leaders at designing and working out territories. The feedback from the commercial team is no, at this time. They actually think they have the right number of people. We may change things by one or two, but there's, you know, to their credit, I think they've got it about right. It's not a large sales force, but they seem to be able to cover, particularly those larger accounts and more concentrated accounts quite successfully with 59 people. Great. Thank you. We have one question through the webcast here. What is the regulatory path for getting labeled approval in the 50 to 100 platelet count patients? I don't know yet. I think we're looking at the data now. I think now we're nearly a year into the launch. As I said, we're not getting any unexpected signals from pharmacovigilance and safety. It's something we can look at, but the specific regulatory pathway for that would need to be discussed with the FDA. If we have that discussion, then we'll be able to report it to the street. Thank you. Any other final questions from the audience? Okay. Thank you. I think with that, yeah, we can give everyone a little bit of time back. Thank you, Adam, for the time. Thank you.