Good afternoon. My name is Jonathan, and I will be your conference operator today. At this time, I would like to welcome everyone to Kronos Bio Investor Call to discuss the interim data on KB-0742, presented today at the AACR-NCI-EORTC International Conference. At this time, all participants are in listen-only mode. After the speaker's remarks, there will be a question and session. If you'd like to ask a question at that time, you will need to press star one one on your telephone at any time to be placed in the question queue. To remove yourself from the queue, simply press star one one again. Please be advised that today's call is being recorded. I will now pass the conference over to your host, Sarah Connors. Please go ahead. Thank you, operator, and good afternoon, everyone. I'm Sarah Connors, Vice President of Investor Relations and Corporate Communications at Kronos Bio. Earlier today, we issued a press release on Kronos Bio's positive preliminary data from the phase 1 dose escalation portion of the phase 1/2 KB-0742 study at AACR Triple Meeting. You may find this press release on our website, kronosbio.com, in the investor section. Today, you will hear from Kronos Bio Management, including Dr. Norbert Bischofberger, President and Chief Executive Officer, and Dr. Jorge DiMartino, Chief Medical Officer and Executive Vice President of Clinical Development. Norbert and Jorge will provide a brief overview of Kronos Bio, our science, and the KB-0742 program. KB-0742 is Kronos Bio's internally discovered, highly selective oral cyclin-dependent kinase 9 inhibitor being developed to treat MYC-dependent solid tumors. We are very pleased to have trial investigator, Dr. Miguel Villalona-Calero, Medical Oncologist and Director of Early Therapeutics at City of Hope National Medical Center, with us here today to share an overview of the data. Following the presentation, we will open up the call for questions with our speakers. At that time, Dr. Charles Lin, Senior Vice President of TRN Mapping, will join us. Before we get started, let me remind you that we will be making forward-looking statements on today's call. Statements in this presentation that are not statements of historical fact are forward-looking statements for purposes of the Safe Harbor Provisions of the Private Securities Litigation Reform Act of 1995. The presentation, in some cases, uses terms such as on track, plan, potential, will, or other words that convey uncertainty of future events or outcomes, to identify these forward-looking statements. Forward-looking statements include statements regarding Kronos Bio's intentions, beliefs, projections, outlook, analysis, or current expectations concerning, among other things, Kronos Bio's plans to report data for the expansion phase of the phase 1/2 KB-0742 study and the expected timing thereof, and other statements that are not historical fact. Actual results and the timing of events could differ materially from these anticipated in such forward-looking statements as a result of various risks and uncertainties, including without limitation, whether Kronos Bio will be able to progress its clinical trials on the timelines anticipated, including due to risks inherent in the clinical development of novel therapeutics, risks related to Kronos Bio's lack of experience as a company in conducting clinical trials, and the risks that results of the preclinical studies and early clinical trials are not necessarily predictive of future results. These and other risks are described in greater detail in Kronos Bio's filings with the Securities and Exchange Commission, including under the heading Risk Factors in its quarterly report on Form 10-Q for the quarter ended June 30, 2023, filed with the SEC on August 8, 2023. Any forward-looking statements that are made in this presentation speak only as of the date of this presentation and are based on management's assumptions and estimates as of such date. Except as required by law, Kronos Bio assumes no obligation to update the forward-looking statements, whether as a result of new information, future events, or otherwise, after the date of this presentation. With that, I'll turn the call over to Norbert. Well, thank you, Sarah. I would also like to extend a warm welcome to the audience. Thanks for joining us today. For those of you who are not as familiar with our story, I would like to quickly give you a top-line summary. Since the founding of Kronos Bio about five years ago, we have been able to assemble an incredible team and an incredible capability that allows us to map and target transcriptional regulatory networks in a differentiated manner. We have an interesting screening platform called SMM, or Small Molecule Microarray, that allows us to come up with modulators of these transcriptional regulatory networks. And finally, our discovery pipeline is advancing nicely, and we hope to be able to define or announce a development candidate, soon. We have two clinical compounds, KB-0742, that's our CDK9 inhibitor, and that's, of course, gonna be the focus of today's meeting, so I won't further talk about that. Then the second clinical compound is lanraplenib, or LANRA, as we call it, and that is currently in a dose-escalation study, phase 1b/2, in relapsed/refractory FLT3-mutated AML, in combination with the approved compound, gilteritinib. And then just earlier this year, we announced a strategic collaboration with Genentech. Genentech came to us with two transcription factors that they were interested in. They looked at our people and our methodology and concluded that this would be a promising avenue to come up with modulators of these two transcription factors. But today's topic is really, and we're very excited to share with you preliminary positive clinical data on our KB-0742 program. Just a reminder, this is an ongoing dose escalation study, so we tested 10, 20, 40, and 60 milligram doses, and the 60 milligram dose demonstrated on-mechanism, objective, single-agent antitumor activity in heavily pre-treated patients. We're now enrolling, since we haven't reached the maximum tolerated dose, we're now enrolling the next higher dose cohort, that's 80 milligram. And because we saw at the 60 milligram clinical responses, including target engagement, we open up expansion cohorts in MYC-dependent and other transcriptionally addicted tumors. And we hope to be able to share with you data from this dose expansion phase of this study by middle of next year. With that, I would like to hand it over to Jorge Jorge? Thanks, Norbert. I'm really excited to be able to share the first clinical data emerging from our Phase 1/2 trial of KB-0742. The data that we shared earlier today at the Triple Meeting and that Dr. Villalona will be going over with you in greater detail now, is really a snapshot of the first step in the ongoing development of KB-0742, but one that we believe supports our hypothesis that KB-0742's exquisite biochemical selectivity, combined with its favorable PK profile, would allow us to achieve inhibition of CDK9 while maintaining an acceptable safety profile, and that sustained inhibition of CDK9 in a patient with a transcriptionally addicted tumor can be clinically beneficial. KB-0742 was discovered from an unbiased screen using our proprietary SMM platform, and the initial hit declared itself early on as a CDK9 inhibitor with an exceptional selectivity profile and good drug-like properties. This led very efficiently to the development of a clinical candidate, KB-0742. CDK9 is a target that has long been of interest for cancer treatment. Unlike the CDKs that are targeted by currently approved drugs, CDK9 does not directly control cell cycle progression. Because of this, it's important to have selectivity against these other CDKs, which would come with their own toxic side effects. What CDK9 does is controls a key step in transcription, which is a rate-limiting step for the expression of many oncogenes. What creates the opportunity for selectively exploiting a dependency on CDK9 in cancer cells is the reliance of many important cancer driver genes on regulatory sequences that have been termed super enhancers. These long DNA sequences bind transcription factors and their cofactors at much higher density than conventional enhancers that control the expression of housekeeping genes in non-cancerous cells. The disproportionate accumulation of CDK9, the super enhancers, and the keen dependence of the genes controlled by these super enhancers on high rates of transcription, suggested the hypothesis that partial inhibition of CDK9 would have disproportionately deleterious effects on the transcription of these genes and hence tumor cell viability relative to genes that support the viability of normal cells. Although this is a very elegant hypothesis that was supported by preclinical data, actually testing it in patients can only be done using a molecule with the properties of KB-0742, namely, excellent selectivity to avoid off-target inhibition of other cell cycle CDKs, oral bioavailability to enable practical flexibility in dosing, and a long plasma half-life to enable sustained target coverage without potentially toxic spikes in plasma drug concentration. The data that I'll share with you in a couple of slides is so far consistent with our hypothesis and reinforces our belief that KB-0742 is the right molecule for targeting transcriptionally addicted cancers. Now, when we and others talk about transcriptional addiction, we're referring to tumors that have become dependent on very high rates of transcription of specific genes for their growth and survival. The level of transcriptional activity required to sustain expression of these cancer driver genes at levels that support tumor growth are, by and large, far in excess of anything required for normal genes in non-cancerous cells. A classic example of tumors that exhibit transcriptional addiction are tumors that have become dependent on extraordinarily high levels of expression of the MYC family of oncogenes. MYC is an oncogenic transcription factor that requires CDK9 to drive high level expression from its super enhancer. It also requires CDK9 to drive expression of its downstream target genes. Through our collaboration with Tempus, looking at real world data, we've seen that about 87% of ovarian cancers, 79% of triple-negative breast cancers, and 45% of non-small cell lung cancers express high levels of MYC, either through genomic copy number gains or other mechanisms. Another example of tumors that we believe exhibit transcriptional addiction are tumors that are driven by transcription factor fusions. In these tumors, chromosomal translocations literally fuse together two transcription factor genes, creating a dysfunctional transcription factor that drives tumor growth. Like MYC, these fusion transcription factors require CDK9 to maintain high level of expression through their super enhancers and to drive expression of downstream target genes. In the ongoing expansion portion of our trial, we've chosen to focus on patients with these tumor types, and we hope to be able to provide an update on results from this part of the trial sometime next year. In today's presentation, we're focusing on the initial dose escalation part of the trial, up to and including the 60 mg dose level. Because the main objectives of this part of the study were to establish safety and understand PK and target engagement, we did not require patients to have transcriptionally addicted tumors to enroll. This allowed the trial to enroll efficiently at a small number of sites, as is typical for first-in-humans oncology studies. Nevertheless, as you'll see in Dr. Villalona-Calero's presentation, we were fortunate enough to identify a few such subjects in the course of this study, and this has been tremendously informative. Also, as is typical for almost all first-in-humans oncology trials these days, we used a Bayesian algorithm to determine the number of patients at each successive dose level, as well as to establish the maximal increment in dose between cohorts. We've chosen to present this snapshot of the ongoing trial up through the 60 mg dose level because, as I'll show you on the next slide, and Dr. Villalona will expand on, we believe we've entered a pharmacologically and a clinically active dose range at 60 mg, three days on, four days off. For this reason, and to get a better assessment of the antitumor activity at this dose level, we've opened enrollment in our expansion cohorts, selectively enrolling patients with transcriptionally addicted tumors. That being said, we've not yet defined a maximal tolerated dose per the protocol and are continuing to dose escalate in parallel with our expansions. So before turning the presentation over to Dr. Villalona, I wanted to make a couple of additional points to set the stage for his discussion of the clinical data. As I stated earlier, achieving consistent, sustained, partial inhibition of CDK9 in a patient, not in a tissue culture plate, is trickier than it sounds and requires a very specific PK profile. When we first described the PK data up through the 40 milligram dose level in December 2021, we were pleased to confirm that oral dosing of KB-0742 exhibited these properties, namely a 24-hour plasma half-life and all-around good behavior as a drug with very predictable PK. As we've acquired additional data at higher dose levels, this ideal behavior has continued. In addition to measuring plasma drug concentrations and to better guide dose selection, we needed to be able to assess the degree to which we were inhibiting the enzymatic activity of CDK9 at various dose levels. Because it's challenging to obtain repeated tumor biopsies from patients, we developed two custom assays to measure CDK9 inhibition in blood cells. One measures RNA polymerase II phosphoserine 2, which I'll refer to as pSer2, and another measures RNA transcripts from specific CDK9-dependent genes. In this panel, we're looking at the fold reduction in pSer2 from baseline levels on the Y-axis as a function of drug concentration on the X-axis. Each dot represents a unique patient sample and time point, and the dots are color-coded to represent the dose level of the patient. On the previous slide, you saw that plasma concentration increases linearly with increasing dose, and on this slide, we see that the magnitude, magnitude of pSer2 reduction, increases linearly with plasma exposure. At the 60 milligram dose level, we're starting to see sustained and deep reductions in pSer2. When we look at reductions in CDK9-dependent gene expression, which we would expect to result from the reduction in pSer2, we see a nice confirmation of the pSer2 data. In the middle panel, we're looking in changes in Z-score, a composite score across a panel of CDK9-dependent genes relative to a panel of housekeeping genes on the Y-axis versus the AUC of the KB-0742 plasma concentration over time on the X-axis. Again, here we see a nice dose in AUC-dependent reduction in expression of CDK9-dependent genes. Importantly, this is a selective effect. In other words, at these concentrations, KB-0742 is not globally repressing transcription. This is shown for a single patient in the far right panel. Each red line is an individual patient followed over time from KB-0742 dosing, while the gray line represents housekeeping genes. Importantly, this figure shows that the downregulation of these genes is sustained out to 24 hours from the dose. Based on our preclinical work, we believe this kind of sustained inhibition is critical for antitumor activity. These data give us confidence that the safety profile Dr. Villalona will now describe for you is not the result of inadequate target engagement, but instead bears out our initial hypothesis that the key to inhibiting CDK9 safely is sustained partial inhibition. And with that, I'll hand the presentation over to Dr. Villalona, who will walk you through the clinical data. Hello, everyone. Thank you for being here. I am Miguel Villalona-Calero. I am a director of Early Therapeutics at City of Hope National Medical Center and one of the clinical investigators in this study. It's a pleasure for me to present the data that we displayed as poster earlier on today. I would like to start by showing the characteristics of the patients that were accrued on the trial. As you can see and I mentioned before, this was a dose escalation trial in which patients were accrued starting at 10 milligrams and all the way up to 60 milligrams, and a total number of patients were at 28. In terms of the characteristics, you could see that there was a pretty equal split between the males and the females, with a standard age, a median age between 48-60. I can also point that the study was diverse with African Americans, Asian patients, and also Hispanic patients enrolled in this study. These are heavily pre-treated patients. As you can see, the median prior systemic treatment range between 2-6 anticancer regimens. This slide depicts the safety and tolerability and the most common treatment-related adverse event. I want to bring your attention to the column on the right, in which basically all the toxicities reported, broken down by grades 1-2 and grade 3-4, are seen in the patients. As you can see, grade 3-4 toxicities were infrequent. There is a couple of patients that had some mental status changes that was reversible. But in terms of other severe side effects, we did not see. The next slide looks at the hematologic adverse events, which we were very interested in looking, since this could be a class dose-limiting toxicity. But as you can see over here, other than lymphopenia, which is not really clinically relevant, we did not see any events in terms of grade 3 for hematologic toxicity, notably no thrombocytopenia, or anemia, or neutropenia related to the drug. Next slide shows the efficacy across the dose escalation cohort. This is broken down by dose levels. In orange, you can see the 60 milligram dose level. We did see some prolonged stability at 40 milligrams, as you can see in the patient with chordoma, but at 60 milligrams, we also saw a number of patients that have a prolonged stability exceeding 100 days on the study. Is of note, the patient with myxoid liposarcoma that achieve a partial response with a long duration, as depicted in this plot. The next slide, it showed the maximum percentage change in the tumor size. As you can see, the patients with stability and partial response that I pointed out early with a significant tumor shrinkage that was of long duration. They both had myxoid liposarcoma, which is a target for this drug, given that they are mediated by transcription of the factor activation. The overall disease control rate was 47%, and this is when you add together the complete response, partial response, or a stable disease. On the right side panel, you can see the patient with a myxoid liposarcoma that I mentioned earlier. The arrows point to this large mediastinal mass that was present at baseline and had decreased significantly by cycle 10. So both a significant tumor decrease and also a prolonged time in terms of this response. So in summary, we're encouraged by early evidence of on mechanism and on target antitumor activity. KB-0742 was well tolerated at active doses with a manageable safety profile. And we are motivated to continue enrollment in both the ongoing escalation and expansion cohorts. We continue to believe that KB-0742 has potential to benefit patients with difficult to treat tumors. This conclude my presentation. Well, thank you, Dr. Villalona. That concludes the presentation part of today's meeting. I would like to take this opportunity to thank all the presenters, particularly Dr. Villalona, for taking time out of your busy schedule and joining us today. I would also like to thank all the investigators, Dr. Villalona, you are, of course, one of them, but all the others as well. And finally, the patients and their families for participating in our study. Lastly, thanks to the audience for joining us today. And with that, I would like to open the event up to question and answers. Operator? Certainly. As a reminder, ladies and gentlemen, if you do have a question, simply press star one one on your telephone. To remove yourself from the queue, simply press star one one again. One moment for our first question. We ask that you please limit yourselves to one question and one follow-up. Our first question for today's program comes from the line, Salveen Richter from Goldman Sachs. Your question, please. Thank you so much for taking our question. This is Tammy on for Salveen, and congratulations on the result. Given the clean safety that you've seen so far, and you're moving to 80 mg in the dose escalation, can you speak to your confidence in starting the expansion at 60 mg? And are you willing to open other cohorts at 80 mg, pending what the data is there? And, secondly, for Dr. Villalona, did you assess mixed status versus tumor reduction at all? And is there any insight that you could provide into here? Thank you so much. I can take that one, for starters. You know, we're certainly confident in the 60 mg dose, right? We've seen from a target engagement perspective that we had significant reductions in phosphoserine two, essentially two or beyond 50% in some patients. We saw the gene expression changes as we showed on the poster, and very importantly, we saw responses in patients with transcription factor fusion-driven tumors, which is exactly where we would expect to see activity. We know it's an active dose. Because we haven't really defined the MTD yet, you know, we think it's worth continuing to escalate. As we sort of clear higher doses, such as 80 mg, we'll be very interested in exploring those doses in expansion subsequently. If you can repeat the second question, it was about activity? Wondering if just there were any assessments on MYC status in this population, just that it was mentioned before that it was not a required item for inclusion? Yeah. So MYC amplification was not a requirement for the study. This is an all-comers dose escalation on the study, so we do not have the answer in how the MYC amplified you know patients, but this is something that is part of the expansion cohorts. So we have triple-negative breast cancer patients that are MYC amplified, that are part of the cohort, and then we also have ovarian cancer patients that are MYC amplified, in addition to the transcription factor-mediated tumors. Yeah, maybe I can add a little bit to that, Tammy, that, you know, as Dr. Villalona-Calero said, we were not selecting for these patients. So we got a very much an all-comers population. We did get archival tissue to look at MYC retrospectively, but those, those data are incomplete, as of this time. Thank you. Thank you. One moment for our next question. Our next question comes from the line of Michael Yee from Jefferies. Your question, please. Hey, guys. We had a question around your confidence level in the MYC-dependent versus the transcription fusion cohort, and what you think is a relevant bar to push forward. And specifically, whether there's a different bar for transcription fusion sarcomas versus more broader solid tumors, and whether you think you need combination for more broader tumors versus transcription fusions. So could maybe you maybe just talk about the dynamics of each of those two groups and what you think the bar is that you'd want to see, to tell us what you have? Yeah, thanks. So, you know, just to remind, we're seeing really exciting clinical activity in the MYC, which are the transcription factor fusion. We've not yet really enrolled enough of the other type, the MYC-dependent solid tumors, at the 60 or other kind of higher doses to really assess how that's going to look. From a mechanistic and preclinical basis, we think that both are going to be really great places where CDK9 dependence will shine through. From a practical perspective, the transcription factor fusion tumors really represent high areas of unmet need, for which there really are very few approved therapies. So I think that presents a logical route there to think of them, potentially even as a basket across a large number of rare indications. This remains an area of huge excitement for us, and as Jorge alluded to, and Miguel alluded to, it's really now that we're enrolling, a significant number of these ovarian triple-negative and lung MYC high. I think until we see that data, we'll not really, you know, want to keep both of these options open as promising avenues. But to your point, Mike, we are- Yeah. Oh, we are, you know, obviously, as we've discussed before, we are looking actively at mechanism-based combinations, as kind of a next step, certainly for the cohort A tumor types. Preclinically, what makes the most sense? Well, one of the things that we've been most excited about is, you know, the DNA damage effects of CDK9. So there's very good data out there in the literature that suggests that CDK9 inhibition can create a BRCA-like state in a tumor that is BRCA wild type, right? So that sets up the possibility of combining with PARP inhibitors, potentially in indications or subsets of patients where PARP inhibition alone is not giving adequate benefit. There's a possibility that we could essentially create a synthetic lethality sort of situation by inhibiting CDK9 in combination with PARP inhibitors. Thank you. Thank you. One moment for our next question. Our next question comes from the line of Tyler Van Buren from TD Cowen. Your question, please. Hey, guys. Thanks for the presentation. Good to see the increased disease control at the higher doses. Wanted to ask about the expansion portion of the study. Can you tell us where you're at in the expansion and what we should expect to see from the update in the middle of next year? And the follow-up to that, and related to Mike's question, when do you think you'll be able to start dosing patients with the MYC-dependent and larger tumor types in combination? ... Right. So the expansion is ongoing. We're not, you know, necessarily gonna talk about where we are with that right now, except to say that we are planning to present an update on that data, sort of towards the middle of next year. I think, you know, making a decision about starting combination dosing, in part, depends on, you know, the level of single-agent activity that we see in the expansions. What single-agent activity do you think you need to see? Just as a follow-up. Yeah, I mean, that's- I don't know. What would excite you, Miguel? Yeah. So I mean, I have a patient with non-small cell lung cancer who's BRAF dependent, that I just treated and gave it 2 cycles, and the patient had some decrease. And it's a patient that had failed combinations of MEK and BRAF inhibitor treatment, and chemoimmunotherapy. So again, these are patients that are heavily pretreated, and any activity that I see in something like this excites me. So I am a lung cancer doctor, so I see a lot of lung cancer patients. If I would see activity in a small cell lung cancer, which is a cohort that we are accruing to, that would be, you know, very exciting. And one of my colleagues is a sarcoma doctor, and he's getting a lot of referrals with patients with sarcoma. Okay, thanks. Thank you. One moment for our final question for today. Our final question for today comes from the line of Edward Tenthoff from Piper Sandler. Your question please. Great, thank you very much. It's a nice way to end the week and start the weekend with this data set. So, you know, I think the questions have really been asked about, KB-0742 and sort of next steps. I'm wondering, you know, thinking about partnering opportunities here, you know, is this something that you would anticipate partnering? Do you think you need to generate more data, just as you look at sort of the overall portfolio? And I think you maybe mentioned early on that you were looking to either take the next compound into the clinic or even do potential in-licensing. So just wanted to get a broader sense for sort of what you're seeing out there with respect to business development opportunity. Thank you. Yeah, maybe I could take a first stab at it, and Jorge and Charles, if you have anything to add, please do so. You know, we're always looking at partnering opportunities, always. Clearly, you know, 742, if we see continued responders, that might be very interesting to potential partners, so we would certainly entertain that. With regards to in-licensing, you know, at the moment, we would not consider in-licensing without, in the absence of financing. So we absolutely need financing in place in order for us to consider in-licensing opportunities. Jorge, do you have anything to add, or Charles? I mean, I guess the only thing I would say about, you know, partnering is what would excite me about it, is it would allow us to pursue more things in parallel, right? This drug, I think, has so many different opportunities, to be active across a variety of different diseases. We have to focus now because of our size and our stage of development as a small company, but with a large pharma partner, I think we would be able to really look at more opportunities. Makes a lot of sense. Thanks, guys. Thank you. This does conclude the question and answer session of today's brand program. I'd like to hand the program back to Norbert for any further remarks. Yeah, thank you, Jonathan. So I would like to thank everybody again for their great Q&A. Great job, everybody, and thanks for the audience for listening, and again, apologize, apologies for the difficulties, technical difficulties. So with that, we'll adjourn. Thank you very much. Thank you. This concludes today's call. We thank you all for attending. You may now disconnect your lines, and have a wonderful day.