Good morning, everyone, and thank you for joining us in the final day of the Needham Healthcare Conference. My name is Gil Blum, and I am a senior biotech analyst here at Needham & Company. It is my pleasure to have with me this morning Jack Bailey, the CEO of G1 Therapeutics. Now, as a reminder, any viewers who are watching through our conference portal are able to submit questions via the Ask a question box below the video feed window. With that, let's start with a bit of an introduction. Just to explain to some of our viewers who are maybe not familiar with G1 and Cosela, about the drug class that you're developing and what is its value proposition in oncology? Well, first of all, thanks for having us, Gil. Real pleasure to be back here at the Needham Healthcare Conference. G1 Therapeutics was formed in 2008. One of its two founders was Dr. Ned Sharpless, a name some of your viewers may be familiar with. He went on to run the National Cancer Institute, the highest-ranking federal body focused solely on cancer, and was also an FDA director. But he had a vision for transforming the chemotherapy experience, and from that vision, Trilaciclib, brand name Cosela, was developed. It's an IV-administered CDK4/6 inhibitor that enables the bone marrow to be protected from the damages of chemotherapy, what's called Myeloprotection. We received our first indication in 2021 for chemotherapy-induced myelosuppression, Myeloprotection, excuse me, in extensive-stage small cell lung cancer. And as we'll talk about over the next 40 minutes here, a lot of damage is derived from chemotherapy. While it does a great job killing the cancer cells, it also does enormous damage to the good cells in the body. Your viewers can think about the white blood cells that fight infection, the red blood cells that transport oxygen, give us energy, or platelets that help us clot in the case of injury. So by protecting those good cells from the damages of chemotherapy, you can avoid hospitalizations, a lot of undue patient suffering, and certainly reduced expenditures in healthcare. So, look forward to getting into that here as we talk a little bit more. Excellent. So yeah, I think a good place to start is with commercial Cosela and maybe diving a little bit into the details. What is the clinical value, from the studies, for approval, that small cell lung cancer patients derive from Cosela? Sure. So as I said, chemotherapy is the backbone of most cancer treatments in this country and around the globe. Over 1 million patients a year in the US get it. For our initial cancer type, extensive-stage small cell lung cancer, it's one of the most aggressive forms of cancer. It's about a year from diagnosis to, unfortunately, patient expiration. Chemotherapy is sort of the backbone for that cancer also, and so unfortunately, as I said, chemo does a great job killing those cancer cells, but it's indiscriminate, kills the good blood cells, the white blood cells, red blood cells, and platelets that are produced by the bone marrow. So what happens is you get an infusion, a 30-minute infusion of Trilaciclib anytime in a 4-hour window prior to that chemotherapy. What it does is it transiently arrests the circulation of those good cells, so as chemo's in the body, it doesn't. It can kill the cancer cells, but it's not killing the good cells. Now, what does this mean? This means less things like infection, including febrile neutropenia, which frequently requires, and usually requires hospitalization for patients. That's where the body doesn't have enough white blood cells to fight off infection. Think about anemia. All of us have had family and friends who have gone through a, you know, a bout of chemotherapy and talk about, "I laid in bed for two or three days in a dark room." It's 'cause they had no energy, 'cause all those red blood cells were killed. They had what's called anemia. Others have to engage in things like platelet transfusion as their platelets get killed from chemotherapy. So, on average, what you see is a significant reduction in all three of those, what are called lineages, white blood cells, red blood cells, platelets. Less damage from chemo keeps patients out of the hospital. We see a significant reduction in hospitalizations that are required, and perhaps most importantly, the patients feel better. This is, again, a very aggressive form of cancer that's really about quality of life, 'cause survival or curative options are not on the table at this point. And so if you're battling something like anemia, if you're having to get rehospitalized multiple times during your treatment sessions, I mean, that's just not what these people want. They want a higher quality of life, be able to get their affairs in order, spend time with loved ones. It's really tough to do that if you're hospitalized or have no energy or having to spend time getting a transfusion. So we, you know, we believe this is a real need. There's zero competition in terms of the marketplace, direct competitors for us. And what we want to do is continue to educate physicians, because it does require, again, the infusion before the chemotherapy. For the last 30, 40 years, what oncologists have largely done is monitor your blood counts, your white blood counts, red blood cell counts, and if they drop, then you get a reactive intervention, good for that lineage. Maybe a growth factor for white blood cells and a transfusion for your platelets or your red blood cells. Unfortunately, again, that costs the system money, can be painful for the patients, and ultimately doesn't enable them to enjoy what time they have here after being diagnosed. Thank you. That's, that was very helpful. So, the company did face some commercial challenges last year, and, and I, I wanna focus specifically on platinum-based chemo shortages. Do you expect most of this pressure to now be resolved, and how, how does the company intend to deal with this sort of volatility in the underlying chemo? Yeah, it's a great point. So last year, for the viewers who maybe weren't as close to the oncology market, in at the end of the or in the first quarter of last year, the largest supplier of cisplatin, which is a form of platinum chemotherapy, and also they were one of the biggest producers of carboplatin. Those are two very common platinums that you would use to Cosela on top of. They ran into some regulatory issues. They had to stop production, so the market supply really dwindled. We talked to just enormous number of customers, some very heartbreaking stories of having to prioritize curative patients or maybe clinical trial patients over supportive care patients, those like with extensive stage small cell that really don't have a cure. What we're trying to do, as I said, is maintain their quality of life and function as possible. Now, mind you, this is, you know, roughly 20,000 patients a year in the U.S. who get diagnosed with extensive-stage small cell lung cancer. So it's not a small population. But the bottom line is, without either Cisplatin or Carboplatin, you really don't need Cosela. And so what we did see is, after a solid first quarter growth of 21%, it dipped down to the low single digits. The FDA was able to approve additional suppliers about September of last year, and we did see again, patients be able to access it more regularly across clinics and hospitals across the country. But to your core point about, you know, how do we avoid this in the future? It's... A lot's been written on it now in terms of some of the incentive challenges, some of the regulatory demands, and some of the market dynamics. So, you know, at this point, we do monitor the FDA website very closely. While it still lists some outages in the platinum market, at this point, in talking to all of our customers literally daily, we feel like it's not impacting, especially the largest clinics, the largest hospital systems, the largest oncology networks. And we did see that last year. They came out of it quicker. And if there was anything that, any bright side to this very, tragic, shortage in the most recent of what has been an ongoing, probably decade-long challenge, and particularly with generic sterile injectables, is. It really gave our sales team the opportunity to educate physicians on the true platinum-agnostic nature of Trilaciclib, can be used with either Carboplatin or Cisplatin. And in many instances, literally, doctors, clinics, and hospitals didn't know what they could access on a particular week. So being able to use Cosela on either one of those, was just a good opportunity to really reinforce that message. And we also saw that our business in those top 100 accounts, the MD Anderson, Texas Oncology, Florida Cancer, that your viewers know, they treat about half of those, 20,000 small cell lung cancer patients a year. And so they were more equipped in terms of storage space, capital, purchasing patterns, to be able to sort of, I think, weather the storm a little bit more. And so we did see our business deepen with those top 100 accounts, which is helpful. So... Excellent. As of the last corporate update, it was noted that Cosela is about 13% penetrated in frontline setting. What actions is the company taking these days to kind of increase penetration? Yeah, great question. It's one that our chief commercial officer, you know, thinks about every day, and we talk about every day. You know, to go back to the market itself, it's about 20,000 patients, just under. It's about a $700 million target addressable market. So it's a, it's a large market. We've only got 13%, as we talked about. The bulk of our use is in first line, which tends to be with, cis or carbo, etoposide, containing... a platinum-containing regimens. We do have an indication for later lines with topotecan, and again, we've had an opportunity to slowly grow that. But in terms of really what's gonna drive it, I think what has resonated over the last quarter or two has been the real-world evidence. You know, this is an indication that a lot of times, again, you're battling 30-40 years of reactive behavior, single intervention application. And when you think about what we call a multi-lineage, so it covers white blood cells, red blood cells, platelets, we use it in a preventative basis. You know, to get that to change, sometimes it's hard, and usually it's data that will convince these physicians and organizations. And we've been able to produce a lot, both in partnership with some of these organizations, but many have produced it on their own, trying to better understand this thing called, you know, myelosuppression or this bone marrow damage. And I think that's really helped us, and we've been able to publish a lot of that data, share that data at ASCO Quality and other meetings, really highlight both clinically the detriments of myelosuppression and the benefits of this Myeloprotection, both clinically in terms of patients and in terms of financially, right? You're saving about $19,000 per patient when you use Cosela to prevent all those, the, the damage to the bone marrow that occurs and those downstream costs like hospitalization. So real-world evidence is really, really important and very impactful because it tends to even be institution specific. This is one of those things where everybody else feels like the, the other institution maybe isn't managing the chemo, the damage from chemo effectively, but they are. But when you show information from their own institution, it really sort of shines a light on the opportunity to improve by using Cosela. I think second, these are complex organizations. We're very much focused on those top 100s. Again, these are, you know, thousands of people and frequently 100+, 200+ sites, if it's a community network. So what we found some success in is continuing to bolster our strategic account management team. These are folks that frequently come from these big, complex organizations. They understand how to navigate them, things like getting on the formulary committees, being able to embed it in the EMR, being able to discuss the benefits of something like an opt-out. So the strategic account team, we've seen a lot of good success, in particular, as they focus on those top 100, both the 75 that we've got writing already and as we've continued to grow that through the beginning of this year. And then the final thing, I think we use volume-based contracts selectively. That really allows us to get sort of C-suite support, whether it be through communications, emails, ongoing monitoring, data reports that can highlight missed opportunities to use Cosela to again, help the patient feel better, be able to have better clinical performance, and then save this $19,000 per patient. So those are three of the big things that we're really driving right now. The real-world evidence that shows your institution can do better, the ability to really navigate it more effectively and quickly get that deeper penetration, and then, of course, selectively use these contracts. So going back a second for the first point, if you have some anecdotal physician feedback, how has it been accepted, and what do you know your individual physicians find most appealing? You know, Gil, I mean, I've launched literally dozens of products over 35 years in life sciences, and I think what's amazing on this one is a couple of things. One is, not all products perform in the real world as they did in clinical trials, and I think in the case of Cosela, it's abundantly clear it operates, it delivers every bit, if not more, than what we saw in our clinical trials. Two, when you hear from physicians, oncologists, when you hear from nurses who tend to be very close to the patients or from the patients themselves, who talk about things like, "I feel like I didn't have cancer," because they understand they're avoiding a lot of those nasty chemo side effects that maybe they experienced something earlier about or they've heard about through other friends and family. So, you know, from our standpoint, the feedback's been tremendous. We knew we started with high awareness because a lot of folks do realize that this is, you know, sometimes the cure is worse than the cause, as they say, when it comes to chemotherapy. And so there was high awareness. We continued to drive trial. Our real challenge is to how to turn this, what is 90+% satisfaction by oncologists in a high reorder rate of over about 85%, continue to use that to drive penetration in an organization. You can have one doctor in an organization, but how do you get all the doctors? You can have one site in the network. How do you get all the sites? And that's really where we talk about driving deeper penetration. That's really the big difference for us from having spectacular quarters to having solid quarters, is how much of that deep penetration, especially in those top 100, we can drive. Again, we're getting, I think, smarter by the day on what drives that. While it's individualized by organization, some naturally have top-down tools, whether it be their EMR system, whether it be their financial incentives, whether it be their communication vehicles. Others, it's a little bit more side by side. So we're getting better at understanding that. These SAMs are critical to that, as I mentioned earlier, but at day's end, clinicians, nurses, and even patients, when they get to experience Cosela, they love it. It's really about operationalizing it so it's systematic, and you're not missing out on opportunities to provide these benefits to these patients. Maybe kind of as a last point here, G1 guided for about $60 million-$70 million in 2024 sales, suggesting about 40% year-over-year growth. What do you think are the tailwinds and headwinds for that eventuality? Yeah, I think, you know, tailwinds include stuff like in last fall, ASCO put it on, the guideline, recommended guidelines. Obviously, when we launched, the FDA had labeled this breakthrough designation, breakthrough therapy designation, got a priority review. NCCN, within six weeks of approval, had dual committee endorsement. So I think it helps over time as these sort of gold standard bodies continue to endorse it. But at day's end, it's gonna be really focusing on these top 100s and being able to drive that deep penetration from the different tactics and tools I referenced earlier. That's where we see... You know, when you can move from, you know, dabbling 15, 20% of the time, pitching, you know, one in five patients, to really having it systematized or operationalized, where literally you get every single patient that comes in the door, that's where we see the real spike up in sales and what we'll continue to focus on to hopefully create more of a tailwind here in 2024. On the investment then, do you guys plan on, you know, increasing your commercial footprint, or are you happy where you are? I think we're pretty good. We've had to make some adjustments over the first couple of years post-launch. Obviously, there are some areas where you just don't have the amount of small cell. And in other cases, it's you know, we had to do a little dabbling, but I think we've got the right folks out there in the right areas with the right tools and the right sort of matrix support partners, whether it be these SAM strategic account managers that I mentioned, or maybe our market access folks. I mean, the good thing we haven't talked about is the reimbursement on this product is spectacular. I've not launched a product in the last 15 years that was this well endorsed by payers. Again, you can understand when you're saving $19,000 per patient in oncology, as we know, is one of the leading therapeutic areas where they're really looking at: how do we, how do we manage each dollar effectively in a sort of a value-based way? And, but more, most importantly, I think it, it's what this can do for patients, right? It represents everything we want in healthcare, and that it's, it's preventative, not reactive. It's good value, and it delivers meaningful benefit to the patient, and I think that's what we all want in a healthcare system. I think that's a very important point of payers. Definitely prefer preventative measures whenever they can get them, and that's been a guideline for a long time now. So I do wanna switch gears to talk about, you know, label Triple-negative Breast Cancer. maybe just to remind our viewers here on the ongoing pivotal study of Trilaciclib plus chemo in Triple-negative Breast Cancer. Yeah. So we're really excited. So this year, again, it's pretty simple. We've got to keep driving sales, be able to, you know, educate those physicians, move them from trial to deep penetration. Clinically, it's two different readouts. The first one we'll talk about here is our phase III readout. This is in Triple-negative Breast Cancer. much like small cell, a very aggressive tumor type, really limited options out there. So it's a great opportunity to really benefit patients and advance the treatment paradigm in a very challenging area. We did have a phase II study that we ran that this is essentially a replicate of. That was first, second, and third line. This is just a first-line study. But the bottom line is that showed a 60%-70% reduction in death, which was unparalleled. So we've got this replicate study. We started enrolling in June of 2021. We completed our enrollment in October of 2022, and so it's fully enrolled. We did have an interim readout in Q1, which as many of your viewers know, especially in oncology, about two-thirds of all interims don't meet the statistical bar, but it's a great opportunity to try and get this product out earlier, and that's really why we had the single interim. But, you know, we feel very good with it. It is planned to hit readout Q3 of this year. And at day's end, if it hits its statistical measurement, 0.67 or a 33% reduction in death, in Triple-negative Breast Cancer, it will be the single biggest improvement in this cancer type, to date. A lot of folks are watching it, whether it be, you know, key opinion leaders, patient groups, et cetera. We certainly feel good with it because we know in the phase II study, it was about 15 months where you started to see separation on what are called the PD-L1 negatives, which make up about 60% of the patients in this study. If you think about that enrollment window I talked about, it ended in October of 2022. The interim occurred beginning of this year. It's about a 15-month timeframe where we hopefully will start to see the PD-L1s that, again, make up over half the study, have time to separate. We also know from San Antonio Breast Cancer last December, that Trilaciclib really has this unique benefit where, you know, when you use it early, you see a sustained benefit over time. So in many respects, we think time is on our side here in terms of moving to the final and hopefully being able to meet this threshold and add, I think, a real step forward in the treatment of first-line metastatic triple-negative. So the study is designed as a frontline combo with chemo. What about the addition of checkpoints to frontline Triple-negative Breast Cancer? does this change the target population? How are you considering this? Yeah, a great question. There's been a lot of movement. It's. We sort of call it the Wild West in metastatic triple-negative these days. I. You know, people are experimenting, trying different things. Some of the science is moving ahead. Again, it's still a limited set of options, to be candid with you, and we think Trilaciclib could add a lot, if it meets the threshold here in Q3. We think it would certainly because that 33% reduction in death is for all comers, so PD-L1 positive and negative. The current checkpoint inhibitor that you referenced is only for PD-L1-positive patients, which again make up about 40%. So, A, we think, you know, this is for all comers. B, at a minimum, you're gonna look at your PD-L1 negatives and say, "This ought to be incorporated into the regimen." But even in those PD-L1 positives, if, if physicians, if oncologists want an option other than an IO therapy, which has got its own baggage, some of those patients are intolerant of it, some of them progress very quickly within 12 months. So we see a whole bunch of subsets underneath that PD-L1 positive that certainly Trilaciclib ought to be thought about pretty quickly. So we think it's a pretty big opportunity, and unlike small cell, where it's an 84, it's a fixed-dose regimen for cycles, here you treat to progression. So again, if we can show survival benefit, we think this is a great addition to a very, very tough cancer type that has limited treatment options right now, and the opportunity to impact those patients, we're pretty excited about. Okay. And speaking of that, interim readout that was reported in February, how much alpha spend was dedicated to that specific readout? And are there really any consequences for the study continuing to its completion? I know there's been a lot of arbitrage around this. Yeah, so, in terms of the final, it's 0.67 is the hazard ratio. There was a, you know, small amount of alpha spent on the interim. The vast majority remains for this final study. So just statistically, when you think about the difference between the interim and the final, you've got more opportunity to hit it. It's not as high of a bar as that interim, and that's what the FDA expects, right? You want a really high bar if you're gonna get something out in a quicker timeframe. Because we have more time, less of a statistical bar to clear, more alpha, and then we've got this 15-month point where we saw in phase II where the PD-L1 negatives only started to separate then, all of that makes us feel, very positive for, a good readout here in Q3. One question we did get a lot, and maybe this one's not best addressed to you, but. What would be the right comparator arm as people try to think about, you know, not that cross study comparison is the best way to do things, but people want to know what the yardstick is for a control arm. I know you guys use KEYNOTE-355 as your reference, but there's quite a few other studies out there as well, with a very wide range of results. Yeah. No, and this goes back to a little bit of the Wild West in triple-negative right now. We, we do believe that KEYNOTE-355 is still the best one or the best comparator for us to sort of think about both because it's the most recent, it's one of the largest. So we think it's a, it's a reasonable comparator to sort of have our folks think about when they're looking at the potential of of our study. So... Okay. And assuming a positive readout here, what would be next steps and timing for sNDA filing? And how much more of a footprint would you need to launch this drug in triple-negative? Yeah, great point. So obviously, we've already actually been given fast track designation by the FDA, again, for all those reasons I talked about earlier, an aggressive tumor type, limited options. For us to hit our statistical bar, it would be the single biggest improvement in survival to date in this particular tumor type. So they're very anxious to work with us to make sure that we can get it out. Our regulatory team would work very quickly to put the appropriate filings together. We'd engage with the FDA, but we would expect that we would be looking at an approval and promotion here in 2025, and hopefully as early in 2025 as possible. So again, as you know, sNDAs are also less demanding than the original filing. So I think all those things speak to, and just our commitment to getting this to, to people with triple-negative. It's, it's a devastating disease, and we'd love to be part of the solution going forward. So I'd like to speak to the other half of the triple-negative equation here, which is, Trop-2 ADCs, so triple-negative plus Trodelvy. A lot of investors are very interested in this, and we get a lot of inbounds on it. Just to help people orient, what is the market proposition here? Yeah. So, much like your, the calls you get, I mean, I think it's interesting, as we've talked to investors, you've got a, a huge slug that, you know, are really excited about the phase III. But there's a, there's a growing contingent here who also appreciate what this phase II signal-seeking study may represent. ADCs are a, a wave that we've never seen in terms of oncology therapy. Over 100 different ADCs in development. It, you know, makes the checkpoint inhibitor wave from 15, 20 years ago seem small in comparison. So just a lot of interest in, you know, this new emerging class. It's got a lot of advantages, right? But it still has a lot of baggage. It's effectively targeted chemotherapy, so much of the side effects that we deal with in, platinum-based, chemotherapy, for instance, you do see with the, the ADCs. Again, it varies by a linker payload, warhead, et cetera, but the bottom line is, you've got some adverse events, neutropenia in particular, but also GI-related, challenges in grade III or IV. So this is life-lifestyle disrupting. This isn't a little bit of inconvenience. So, you know, in our phase II study, we've already seen the initial safety data. That was last summer. We showed the mature, safety data earlier this year that continued to look really good, 50% reductions across the board in a lot of those cytotoxic side effects. But the exciting thing is, is can we improve the survival? Certainly, that's what we saw in our initial efficacy readout that we disclosed in January. ASCENT trial with Trodelvy is probably the sort of gold standard out there, or the one that we benchmarked against. They had 12-month improvement in median OS. We were at 17.9, so a very healthy improvement. I think most of the analysts and investors were looking for 2-3 months, which is sort of typical in oncology. So the fact that we were there I think is a good starting sign. The data has to mature, but I think that, along with the 12-month survival being at 60%, just shy of 60% versus 50% for the ASCENT study, both of those bode very well. Hopefully that we'll be able to maintain that survival benefit in addition to this AE reduction, and I think that provides a lot of opportunity for us in different combinations, starting Triple-negative Breast Cancer, either in later lines or moving up in earlier lines, where again, things like these side effects, right, really inhibit your ability to be on it long term. So we think that the Triple-Negative space itself, both between our phase III, the combination with ADCs, and we've even, you know, done some earlier work with checkpoint inhibitors, to your point, that, you know, we think we've got a lot of opportunity here to really plant a pretty big flag and help out patients with Triple-Negative. As to news flow, for this combination, what should investors be looking to? The ADC data will be reading out midyear this year, and as we said, the Phase III will read out in Q3, so to be a pretty exciting middle of the year for G1. Excellent. You did mention potential combinations with checkpoints. There's a little bit of an underlying, you know, mechanism there. What can you comment there about what the company has looked at so far? ... Yeah, we did do a bladder combination study, and while in the induction phase, it didn't have a checkpoint. In the maintenance phase, it did, and we did see a benefit there. So at day's end, this is a continued area of interest for us. I think right now, just based upon the phase III coming due in Q3 and this sort of huge wave of ADCs, we've sort of prioritized those two as the areas of development and commercialization focus in the near term. But we continue to explore what are the opportunities as it relates to combination checkpoints. We've got some ISSs underway looking at that. We'll continue to keep it on the burner, but we really believe right now, in the next near-term period, it's really about planting that Triple-negative Breast Cancer, either with, you know, chemotherapy and/or in combination with ADCs. On the financial side of things, can you remind our viewers of G1's cash position runway, and does the company expect additional cost control measures that were enacted earlier? Yeah, so we finished our Q4 earnings call. We highlighted, we finished 2023 with $82 million in cash on our balance sheet, that would give us runway into 2025. As far as sort of ongoing cost control, I think we take a lot of pride in our cost discipline. I think your investors and folks have seen that. After the CRC study, we did it again here following the interim. You know, we really wanna make sure we're spending every shareholder dollar wisely and extending that runway as far as possible, so. Excellent. Of course, we don't want to impact commercial. That's the one thing I would say, is we know driving the top line, getting more patients, on this product, making physicians aware is key. Maybe as a point to stop here, is there any additional topics that maybe we have not visited that you would like to highlight? No, I think for us, it's... We know what we've got to do, right? This is a unique product. As we said, it's well reimbursed. It delivers incredible value to the healthcare system and really represents where healthcare should go. We know it's hard to change, you know, decades-old habits, but we're encouraged with the progress we're making. I think it'll continue to be a little lumpy, depending if you get these big top 100 accounts to really drive deep penetration adoption, but we know it's possible. We've got dozens and dozens of accounts where literally they're at 100% or nearly 100% penetration, so we know it's possible. It's about doing it. Right now, in the supportive care space, you go organization by organization. I think moving over to the therapeutic side, which is what would happen with a positive phase III, as many of your viewers know, it's those tend to get adopted quicker, tends to be various vehicles to drive it top-down more, and so we look forward to the combination of both of those. I didn't get to your question about with a positive TNBC, what does this entail? We've got a really good commercial chassis right now, so it would be marginal what we would have to add. A couple of the geographic pockets that aren't covered right now that don't see a lot of small cell, but clearly see incidences of triple-negative, we'll have to add there. But, you know, there's a lot of synergy to be, I think, reaped upon getting this additional label expanding opportunity in triple negative. Yeah. So this, this year should be exciting for you guys. Yeah, yeah. It's, we're, we're excited for 2024. All right. With that, Jack, I'd like to thank you for attending today. Thank you, Gil. Always a pleasure.