Okay. Let's get started here. Welcome, everybody, to the Wednesday afternoon of the 41st annual J.P. Morgan Healthcare Conference. My name's Anupam Rama. I'm one of the Senior Biotech Analysts here at J.P. Morgan. I'm joined by Malcolm Kuno and Priyanka Grover from the team. I will start out the afternoon session with a presentation from G1 Therapeutics. Presenting on behalf of the company, we have CEO, Jack Bailey. Jack. Thank you, Anupam. It is great to be here live this year at J.P. Morgan Healthcare Conference. G1's mission statement is about improving the lives of those impacted by cancer. Since the approval of our first product, COSELA, chemical name trilaciclib in 2021, we have been intensely focused on fulfilling that mission, both by commercializing it for our initial indication in extensive stage small cell lung cancer, but also executing on five clinical studies to expand its use, both in different types of tumors and different chemo regimens. 2023 is the year those five studies read out. Obviously, I'll be making forward-looking statements, so the normal safe harbors apply. Of these five studies reading out, two are phase III label expanding opportunities, seen here in the top box on slide three. The pending positive data from these two phase III studies provide a foundation for near-term growth acceleration for COSELA. The first phase III readout is in colorectal cancer, CRC, which will occur next month. CRC is a significantly more prevalent tumor, and in fact, it's the third largest cancer of all cancers. Our other phase III study is a phase III study in triple-negative breast cancer that will read out later this year. As a reminder, this is a replicate study of our phase II randomized study that had survival improvement of 60%-70%. Upon positive data, we would expect to file both of these indications and be promoting in 2024, especially since the TNBC study has already been given Fast Track designation by the FDA. I'll dive deeper into both of these studies later in this presentation. The next box down, you'll see these two near-term phase III studies are complemented by three phase II studies, a combination study with ADC and a neoadjuvant TNBC study, both of which will read out in the 2Q of this year, followed by a bladder combination study, which will read out in mid-2023. All three of these studies have efficacy as the primary focus, the results of these three phase II studies will really guide our near-term or midterm development for COSELA. I'll only briefly touch upon these phase II studies today, given they're a bit further out. In addition to these five study readouts, I will also highlight the actions we're taking to continue to strengthen our performance in extensive stage small cell lung cancer. While one of the smallest tumors that we will actually have for COSELA, as part of our pipeline and the molecule potential with this asset, we believe we have more room to run as we complement the relatively strong breadth of product trial with deeper product adoption. Finally, we believe this unusually rich period of data readouts sets us up very well for exploring partnerships during the year that would enable COSELA to be available outside of simply the U.S. and greater China like it is now, and also to help us accelerate the development of both this unique asset and other near-term, or excuse me, next generation compounds that we're focused on. Let me briefly touch upon why COSELA is so unique and what enabled it to get both Breakthrough designation, a priority review, and be endorsed by two committees of NCCN. As seen on slide four here, trilaciclib is an IV administered CDK4/6 inhibitor that acts directly on the host's bone marrow, proactively protecting it from the cytotoxic damage of chemotherapy. This includes both the myeloid lineage seen on the left of this slide, responsible for the production of white blood cells, red blood cells, and platelets, along with the myeloid lineage responsible for the production of T cells. Because of this myeloprotection, you avoid the costly and debilitating damage of neutropenia, anemia, and thrombocytopenia while also protecting the immune system, each of which should enable patients to get more chemotherapy and hopefully lead to better survival benefit. The potential to enhance antitumor immunity has been seen pre-clinically with trilaciclib, first via T-cell activation, enhanced T-cell activation, creating a more favorable tumor microenvironment. Probably most exciting is improving the long-term surveillance ability of the immune system through the increased production of memory T cells, all of which could result in improved survival benefit. We believe that this can occur with chemo or in combination with other targeted agents. In all cases, we are focused on the goal of improved survival. The unique scientific potential of trilaciclib is why we focused our entire development effort, as seen here on slide six, on providing better survival, again, either through myeloprotection, which enables increased cytotoxic exposure or potentially via this immunomodulation. The work reflected here on this slide, our development staircase, is where we are now on the threshold of getting the five next study readouts. I'd like to spend just a few minutes on those two phase III studies that read out this year. We are very excited next month to be able to have the CRC phase III readout. As noted here on slide eight, this is a tumor that is significantly larger than small cell lung cancer. As seen in clinical studies and through our own market research, physicians acknowledge, oncologists acknowledge that FOLFOXIRI is the most efficacious regimen out there. They will also say it is the most toxic and hence reserve it largely for their healthiest patients with the largest tumor burden. There is a clear interest by those doctors to use more FOLFOXIRI if these toxicities could be managed. With less toxicity, does that enable patients to stay on treatment longer and further improve upon the efficacy of this FOLFOXIRI regimen? If so, we believe this would be truly transformational, a new treatment option for patients living with colorectal cancer globally. The data on the triplet therapy of FOLFOXIRI in combination with bevacizumab, as shown here at the top of slide nine from the Journal of Clinical Oncology, is statistically better across all efficacy measures versus the doublet bevacizumab with bevacizumab, either FOLFOX or FOLFOXIRI. Given its numerous toxicities, this is why the triplet option is only used 10%-20% of the time, given these numerous toxicities. I would draw your attention further down the slide to the dotted boxed area that highlights the significant incidence of both Grade 3/ 4 neutropenia and diarrhea, which occurred at more than twice the rate in the triplet as in the doublet. That's why this was such a logical tumor and regimen to assess trilaciclib use with. Slide 10 shows our phase III colorectal cancer study schema, which is fully enrolled 326 patients. Patients receive up to 12 cycles of induction with FOLFOXIRI and Bev, followed by a maintenance phase of Bev and 5-FU. The primary endpoints are myeloprotection, defined as the rate and duration of severe neutropenia during the induction phase of treatment. We will also have secondary endpoints of PRO, PFS, and overall survival. There are several key areas of focus we are drawing people's attention to that we will certainly be paying close attention to next month with this data readout. As seen here on slide 11. The first, of course, is the reduction in severe neutropenia and achieving the primary endpoint so that we can then engage the agency and look to submit a supplemental New Drug Application. We will also be looking at trilaciclib's ability to reduce the diarrhea, especially that Grade 3/ 4 diarrhea that typically impacts the tolerability of FOLFOXIRI, along with our PRO data. All of which, if positive, would not only enable current target patients to stay on the triplet regimen longer, but should also enable more patients who previously couldn't tolerate the regimen and would therefore be considered ineligible to now be able to access the most efficacious regimen available. Finally, the potential to improve survival. If we see increased duration of therapy with this readout, we believe that is a good initial indicator of leading to potential improved PFS and ultimately OS. I would highlight that we will have initial PFS data available from this study this December, obviously prior to any launch that we would have. Perhaps a better way to visualize this is seen here on slide 12. The current first-line metastatic colorectal market really breaks out to the triplet regimen on the left here that 10%-20% of patients are get it. The doublet Bev option in the middle, which 60% of patients get. Finally, 10%-20% of patients who have left-sided wild type tumor that get the doublet along with an anti-EGFR. Hitting on our primary myeloprotection endpoints and having improved tolerability, we believe not only increases the opportunity for the folks currently on a triplet regimen to stay on therapy longer, seen in the orange on the upper left, but also enables us to begin to access those doublet patients, especially those previously deemed too old or too frail to be able to handle the toxic side effects of the triplet regimen. They could now be able to benefit from this triplet regimen, and they are shown in the middle in the orange. If improved tolerability leads to greater duration of triplet therapy and ultimately improved PFS, we believe all three groups are now eligible to be considered for what is the most efficacious regimen, but that is now also much more tolerable. This is represented on the lower blue-shaded groups below. The ability to improve PFS and OS on the existing gold standard for efficacy, we believe would be transformational and would logically enable not only a broader percent of current metastatic colorectal cancers, but we would look to rapidly explore opportunities in other GI malignancies like pancreatic. This is why we are so excited about next month's readout. Turning to our other phase III readout later this year in first-line triple negative breast cancer. This is an area of extremely high unmet need, a very aggressive tumor, difficult to treat, and where a chemo backbone remains the standard of care. We believe that based upon exceptionally robust phase II randomized data seen here in slide 14, that this was an obvious pivotal study to pursue. Just to orient you, on the left you see the three treatment arms, three study arms. Chemo is the light gray at the bottom, along with two dark blue lines. That is trilaciclib used at two different dosing schedules. As you see on the Kaplan-Meier curves, there is a significant increase in survival for both trilaciclib arms as compared to chemo alone. In fact, for the top blue line, Group 2, as of data cutoff, you can see we have not reached median survival yet. The hazard ratios suggest a reduction in death of 60%-70%, with both groups being highly statistically significant. These results are why the FDA has already granted this study Fast Track designation. Now, in the same study, we also saw an overall increase in survival regardless of PDL1 status. As shown on the left of slide 15 here, we saw nearly a two-year increase in survival for PDL1 positive patients versus chemo alone. As seen on the right, we saw a notable increase in improvement in the PDL1 negative patients with an impressive 0.48 hazard ratio, although not reaching statistical significance given it was a smaller subgroup. The schema for this study can be seen here on slide 16. It is fully enrolled with 187 patients, and the primary endpoint being overall survival. As I noted, the interim survival analysis, whereby 70% of the events are expected to have occurred, is expected in the second half of this year. Again, this is why we're very excited to get the readout for this study later this year. Now let me transition to the three phase II studies and just touch upon those briefly. As all three are listed here on slide 18, you can see the first one is captured in the top box. This is a second third line TNBC study in combination with sacituzumab govitecan, brand name Trodelvy, to evaluate myeloprotection benefits. Cytotoxicities like neutropenia and diarrhea are the biggest challenges facing this therapy. Data shared last year at ASCO confirmed that the effectiveness of saci is clearly tied to exposure. Therefore, maintaining dose intensity and duration and exposure of Trodelvy by myeloprotection and reducing other toxicities like diarrhea, along with any potential synergy, could increase the PFS and OS of this therapy. I'll come back to this one in a moment because we were very encouraged with the initial safety data that we released just a few months ago. The second study in the middle box is neoadjuvant TNBC to confirm both the mechanistic effect Trila is having on immunomodulation and also evaluating antitumor effect based upon pathological complete response. The initial data from this 24 patient study was released last quarter and confirmed the expected changes in the CD8 positive T-cell to Treg ratio in the tumor tissue seven days after a single dose of Trila. We will now await that path CR data in this, in the second quarter of this year. Finally, the third one below is we have a second combination study, this one with a checkpoint inhibitor, avelumab in first-line bladder cancer to see if we can demonstrate increased survival in this tumor and also evaluate any synergistic effects clinically like we have seen preclinically with checkpoint inhibitors. It is a randomized 92 patient study that is fully enrolled that will read out in mid-2023. The initial safety data for this study was shown, was released last week, and it showed similar response rate and a safety and tolerability profile like we would have expected. Look forward to getting more data on this mid-year this year. Now let me just briefly go back to that ADC combination study. The recently released safety data demonstrated precisely the on-target effects in terms of myeloprotection and other benefits that we would have expected to see. Shown here on slide 19, on the right is the published data from the ASCENT trial for Saci, where I would draw your attention on the far right to the grade 3/4 neutropenia, in particular, that occurred in 52% of patients. Shown on the left side of this slide is the data for COSELA, that at the time of this cutoff, showed that any grade neutropenia was cut by more than half, and grade 3/4 neutropenia was only 17%. 52% grade 3/4 neutropenia for Saci, down to 17% when Trila was added. In addition, grade 3/4 diarrhea with Saci shown again on the right, occurred in 11% of patients, while at the time of this data cut, none was seen with Trila. This makes sense given the presence of CDK4/6 cells in the intestinal crypt. As we noted when we released this data, we think there's a logical read-through here to the CRC study, which includes irinotecan as a core component. We certainly look forward to sharing a more comprehensive set of both safety and efficacy data for this study next quarter. To summarize, depending on the final readouts from these ongoing studies, it will dictate what treatment settings we pursue next for COSELA. We remain focused on improving survival, either through myeloprotection to enable greater cytotoxic exposure, as listed on the top row in this slide. Several logical areas we would look to explore include the use of trila with the many different ADCs that are emerging, either as monotherapy or in combination therapy with other targeted agents. The other development area would obviously be in highly myelotoxic regimens, especially across GI tumors such as pancreatic and gastric cancers. As I noted earlier, this would be very exciting area to explore if we have positive PFS for the CRC readout. In addition, as seen on the bottom row of this slide, pending immunomodulation effect that we see with either the bladder or the neoadjuvant TNBC readouts, we would also consider multiple areas of combinations with checkpoint inhibitors there. Again, the focus and the investment further down either of these development paths will be driven by the readouts we see in the coming months. Now I'd like to end with a brief discussion on the performance of COSELA in our initial indication of extensive stage small cell lung cancer. As seen here on slide 22, it is one of the smallest tumor types that we are exploring trial is used for. It's an area with very, very poor patient prognosis. Clearly, COSELA has been able to improve the patient experience here in changing the multi-decades old habit of treating myelosuppression reactively with single lineage agents, is what we continue to remain focused on changing. While we continue to grow the business, as seen here on this quarterly growth slide, we did return to growth in Q4. We believe we have much more room to run with this indication. Let me first underscore, we'll review some of the positive signals we continue to see, and that really is around breadth of product trial. Across the top 100 organizations that treat over half of all small cell lung cancer in this country, we now have 69 organizations that have already used it. The experience of the individual physician remains very, very good, and patients talk about feeling better when COSELA is added to their regimen. Frankly, the 87% physician satisfaction and the 80%+ account reordering numbers, we think confirms that. Certainly, reimbursement by payers is as good, is exceptionally strong, given you save nearly $20,000 when it's used. As shown on the right of the slide, we have relatively low depth of product adoption. Only 14% at this point for these top 100 organizations. Meaning we have a lot of room to continue to grow, and that's what I'd like to speak to next. The main challenge to achieving organizational depth really revolves around the small market, the limited duration of use, and the fact that this is a palliative, focus, patient focus for small cell patients. More importantly, the actions we are pursuing to continue to drive deeper growth include, as seen on the right here, stronger allocation of resources to the community segment. We have seen faster and deeper adoption in the community setting versus the academic setting. We will continue to focus more and more resources there. We have started volume-based contracting, last quarter that we believe will help reinforce COSELA's use across an entire customer's network, but will also enable top-down corporate support when it comes to making sure that physicians align around COSELA as an option. We are also leveraging our PRO data and real-world evidence to underscore to physicians the magnitude of myelosuppression today that exists, and use that in the importance of them using it first time, every time. We have instituted an EMR team that will enable faster incorporation into order sets, and preferably as an opt-out to systematize easier prescribing of COSELA as organizations do move from trial to adoption. For some territories with a lower incidence of small cell lung cancer, we'll adjust the go-to-market model and leverage more of a hybrid and digital approach. Finally, our medical affairs team will increasingly be the main points of contact for academic medical centers that are slower to trial and ultimately adopt, COSELA. I do wanna underscore, we see real differences between the small cell market and the colorectal market, as seen here on slide 26. The inherent differences I've talked about in terms of market size, duration of therapy, but the most critical point I would draw your attention to is toward the bottom. Specifically, there is a much better patient prognosis when it comes to dealing with colorectal cancer than there is with small cell lung cancer. That is which facilitates a more aggressive treatment approach by physicians. This would enable our salespeople, especially if we have PFS data at the time of CRC launch, to challenge physicians to allow more patients to access the most efficacious regimen for the treatment of this tumor. Before I wrap things up, let me just touch upon our cash position. We finished Q3 with $123 million on our balance sheet. We did a small raise in Q4 of just over $50 million. We are confident that this enables us to have enough cash runway to go through these study readouts this year and really identify the best partnering opportunity going forward. In conclusion, we view 2023 as an extremely exciting year for G1. Next month, as I said, starts a robust period of data readouts across five different studies that all occur this year, with two of those being phase III readouts, which are near-term commercial opportunities to continue to accelerate growth. We expect to file and be promoting COSELA in these bigger tumor types around this time next year, pending positive readouts. We believe the nearest one, colorectal cancer, which we'll read out next month, could be transformational if we see that improved duration of therapy given those myelotoxicities, which could ultimately lead to improved PFS. We will gain additional insights from the three phase II study readouts, which will guide us to our next set of pivotal studies, including possible combinations with ADCs. We have ample room to grow in small cell, as I said, we'll be focused on driving deeper product adoption amongst those top 100 organizations. Finally, pending the nature of these readouts, we will be looking to accelerate global expansion of COSELA through potential partnership to make this innovative product more accessible to as many patients globally as possible. Thank you. Thanks, Jack. Just as a reminder, as many of you have heard me say this over 2.5 days, there are three ways to ask a question. You can put it in the digital conference book, and it will show up on this iPad, and I'm happy to ask on your behalf. You can email me, or if you want to do it the old school way, you raise your hand, and we will get a microphone to you. With that I'll kick it off, which is, you pointed to a rebound in Q4 for COSELA sales, i n 3Q, you talked about some seasonality, w as that growth just bouncing back from that seasonality, or did you see some more, you know, deeper penetration, increased use, scripts being driven? How do we work through that? Yeah. No, it's a great question. I'll make a headline, I'll flip it to Andrew. It's really a combination of both. We saw higher flow through of patients getting treated, we also saw some progress on some very notable accounts, which I'll let Andrew comment on. Yeah. Thanks, Anupam. Yeah. I don't know that I would necessarily call it seasonality, but we did see some choppiness of sales month, each month in Q3. Which actually we saw a much more uniform pattern of month-over-month growth in Q4. One of the things that we were most encouraged by, in Q3, we added about 70 new accounts in total across the quarter, whereas in Q4, we've actually added closer to 100 new accounts in the quarter. We added eight top 100 organizations, as Jack said earlier, compared with the four that we added in Q3. Q4 was just a quarter we were able to reestablish momentum with getting new accounts on board, getting new patients on board, getting large organizations on board. Then we actually had multiple instances of where, with those large organizations, we were able to drive quite extensive depth due to the process Jack actually outlined in the presentation of getting on the EMR as the default standard of care. That's really where I see the big difference between Q3 and Q4 was. It gives me some confidence moving into Q1 because those new patients that we develop in Q4, obviously a patient duration of therapy is around about 90 days with first line small cells. That helps us get off to a good start in Q1 when we have a good Q4. I guess in 2023, what are going to be the key sort of education factors for COSELA commercially for driving scripts in small cell? Yeah. I mean, obviously the primary endpoint is the focus of our education and then getting that to the right decision makers within an account. Very often, we still have to focus on the unique mechanism of action. We have no competition as a product. We are the only ones telling this story, and we're the only ones bringing that multi-lineage myeloprotection story forward. We have to make sure that folks really understand our differentiation from any of those legacy interventions that folks might have used in the past. What really brings it home to physicians, to their nursing staff, to pharmacists, and ultimately to patients, is those patient-reported outcomes. There's not a good prognosis in extensive stage small cell, as Jack said. Why are you looking to change what you do today is simply because patients have a better outcome as a result of it. That fitting those into promotion really brings home the fact that this is what it's for, this is what it's worth, this is the impact that patients will feel when you change what you're doing every day in your practice. Questions from the audience? Maybe on PRESERVE 1, which is coming up, I think you said in February, right? Yeah, one of the things that I struggle with is that I understand that severe neutropenia is associated with the FOLFOXIRI regimen here, right? Hence the primary endpoint, right? What about the other myelopreservation markers? Could that show differentiation? If severe neutropenia is the only key marker, like, how do you differentiate from sort of legacy therapies like G-CSF? Yeah. Raj? Yeah. Yeah, Anupam, I can address that. You know, the way we're viewing neutropenia is really as the regulatory endpoint. We're also looking more broadly around tolerability of the molecule in this off this regimen when combined with trilaciclib. If you look at reasons for dose reductions in addition to neutropenia, it's actually diarrhea. That's the other readout that we are very interested in looking at, in addition to patient-reported outcomes. It's more broadly, does trilaciclib make FOLFOXIRI more tolerable, which could then potentially allow it to be used for a longer duration and then improve efficacy s pecifically with regards to the other myelotoxicity parameters, yes, we will be looking at, you know, anemia and thrombocytopenia as well, though these occur relatively less commonly than what you see in the small cell regimens. I think you said you'll get the full PFS update from PRESERVE 1 in the fourth quarter of this year? Yes. That's right. Will you give us any type of PFS look in February at all? Yeah. We've got some markers that we'll be looking at. Raj can speak to those. We'll have an initial sort of sense, but. Then we'll have that initial PFS readout by year-end. You're correct. Raj, you wanna comment on those couple that we'll be looking at? Yeah. Specifically what we'll be looking for is, are patients staying on chemotherapy longer? What does that, you know, what does that look like? Because if we see greater exposure on trilaciclib on the chemotherapy arm, again, that could be a signal that we could improve PFS. Specifically regarding PFS, the data will be too immature in February since we just completed enrollment in June. Median PFS is about one year or so. That's why we'll get that read in towards the end of this year. We think it's important to get some indications of whether that could be, you know, whether that could actually show an improvement in PFS with the types of indicators that I mentioned. Questions from the audience? Another kind of debate out there is that, you know, what is the true antitumor activity of trilaciclib? You recently had a mechanism of action, sort of readout. What were the key read-throughs there that kind of give you confidence as you kind of move from myelopreservation to some more PFS OS type endpoints? Yeah. The main thing we were looking in the tumor biopsy, and this was really the initial readout, if you will, is to look for changes in the CD8 to Treg ratio of the T cells. What we had seen pre-clinically is that the T regulatory cells remain suppressed for a longer duration. The effector T cells, which are the cells that actually kill the tumor cells, recover more quickly. Therefore seeing more CD8 T cells compared to Tregs is actually important for immune priming. That was the primary readout we were looking at from an immunohistochemical perspective, and that is in fact what we saw following a single dose of trilaciclib. We're gonna continue to expand on the immune analyses, but at least, you know, these data are consistent with what we saw pre-clinically. We think that having that increased CD8 to Treg ratio is an important aspect of improving immune priming, which could then result in a better antitumor immune response, and in the immune sensitive tumors could lead to an improvement in efficacy. What would be, you know, I think in the ADC combination study, you showed, a decreased rate of diarrhea and alopecia, right? One of the things that you're looking for in PRESERVE 1 is a decreased rate of diarrhea, potentially. Right. Mechanistically, how should we be thinking about what's driving that? Both of those are on-target effects because those organs actually express CDK4/6. In terms of in the intestine, it's really the cells in the intestinal crypt which express CDK4/6, and these are considered more like the stem-like cells, if you will, in the small intestine. Protecting these cells can result in protecting the gut from damage. In fact, there's some preclinical data that show that four six inhibition can in fact protect from radiation-induced toxicity. The same goes for the hair follicles, where hair follicles also express CDK4/6, so protecting these cells could potentially also reduce alopecia. Both of these are really on-target effects outside the bone marrow. Questions from the audience? Yeah, Malcolm. Your slide 12, that talks about the three buckets, the triplet and the doublet combinations. In that doublet bucket, only half of those patients are highlighted orange. What's the difference between highlighted and not highlighted? Yeah. That's an initial estimate, so we've not done as much formal market research. What we were really trying to highlight there is in that doublet bucket, you've got a lot of frail elderly patients who physicians know they can't tolerate the more efficacious but the more toxic triplet therapy on the left there. You've also got what we read as, see in studies is about 25% of those patients are at high risk of neutropenia. They get put in that doublet bucket, Anupam's point, if you can reduce that, it is a consideration for the triplet therapy. Raj, what else would you add or improve? The other point I'd make is that if we are able to make FOLFOXIRI more tolerable and closer to the tolerability profile of FOLFOX, then that would remove one of the barriers why doctors wouldn't use FOLFOXIRI for patients, and they would get FOLFOX instead. Therefore, those patients could then get the triplet therapy, which actually is more efficacious. For that pool of patients, what you're doing is actually improving their efficacy. Overall, if you look at that population between the FOLFOXIRI bucket and the doublet bucket that now get FOLFOXIRI and have an opportunity for better survival, overall, you're in fact improving the efficacy. Even with a myeloprotection readout, we're actually helping the patients with the FOLFOX do better 'cause they're now able to get the triplet. Great. Thank you. Any final questions? Thanks so much. Great. Thank you all. Thank you.