Good day, and thank you for standing by. Welcome to the Aileron Therapeutics phase I-B NSCLC Interim Analysis conference call. At this time, all participants are on a listen-only mode. After the speaker's presentation, there'll be a question-and-answer session. To ask a question during the session, you'll need to press star one on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star zero. I would now like to hand the conference over to Liz Melone, Head of Communications and Investor Relations. Please go ahead. Thank you operator, and good morning, everyone. Thank you for joining us to discuss the interim data from our phase I-B trial of ALRN-6924 in patients with advanced p53 mutated non-small cell lung cancer and our strategic focus on our ongoing phase I-B breast cancer trial. On the call with me today with prepared remarks is Dr. Manuel Aivado, President and CEO of Aileron. During this call, we will refer to our press release issued this morning, as well as accompanying slides, which are available in the events section of the investors and media page of our corporate website at www.aileronrx.com. We remind you that during this call, we will be making forward-looking statements, including those detailed on slide two and any other statements that relate to future events or our future performance rather than historical fact. These forward-looking statements involve numerous risks and uncertainties that could cause actual events, performance, and results to differ materially from those described. These risks and uncertainties are identified and described on slide two and in today's press release, as well as under the caption Risk Factors in our Annual Report on Form 10-K for the year ended December 31st, 2021, which can be found on our website. In addition, any forward-looking statements represent our views only as of the date of this recording and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so even if our views change. I will now turn the call over to Dr. Aivado to discuss today's announcement. Manuel. Thank you, Liz, and thank you everyone for joining us on today's call. To provide context for today's announcement, I want to quickly highlight a slide from our corporate presentation that outlines our clinical development strategy. We are developing ALRN- 6924 as a selective cell cycle arresting agent to protect patients with p53 mutated cancers from multiple chemotherapy-induced side effects. Our strategy has involved conducting two randomized clinical trials with the goal of clarifying an optimal path to phase III. There's a phase I-B clinical trial in patients with p53 mutated non-small cell lung cancer receiving carboplatin plus pemetrexed, and a phase I-B clinical trial in patients with p53 mutated neoadjuvant breast cancer receiving doxorubicin, cyclophosphamide, and docetaxel. Now, we know that all chemotherapies cause toxicities in patients because they all kill healthy cycling cells. However, we also know that the type and the magnitude of these toxicities vary significantly across chemotherapies. The non-small cell lung cancer trial and the breast cancer trial afford us the opportunity to evaluate two very different chemotherapies with two very distinct toxicity profiles that enable us to test different endpoints. Presented with these two distinct clinical development opportunities, our aim is to identify a sufficiently toxic chemotherapy and hand in hand with that chemotherapy, an applicable primary endpoint that allows us to efficiently evaluate the potential of our drug in order to advance it toward phase III and approval for this critical unmet medical need. Today, armed with critical learnings from the non-small cell lung cancer trial interim analysis, we believe we have clarified that our path forward will be breast cancer, where we can proceed in accordance with clinical and regulatory precedents in the development of supportive care drugs in breast cancer. Before I highlight the summary of our announcement today, I want to remind everyone of exactly what we set out to measure in the non-small cell lung cancer trial and why. Historically, carboplatin pemetrexed is not known to be a highly toxic chemotherapy regimen. In addition, there is no single hematologic standout toxicity with carboplatin pemetrexed. As a result, we devised an exploratory and admittedly somewhat unusual primary composite endpoint with the hypothesis that the cumulative number of toxicities and the associated events would give us the chance to achieve a statistically significant signal on chemo protection without having to enroll hundreds of patients. We created a composite primary endpoint consisting of the proportion of treatment cycles free of Grade 3/4 neutropenia, thrombocytopenia, and anemia, as well as blood transfusions and the use of growth factors, dose reductions, and dose delays in the first four cycles. In addition, we used lab values instead of AE reporting for hematologic toxicities. We also required more frequent blood testing, and we conducted the trial with carboplatin dosed at the highest possible dose level, which is AUC six. By incorporating all these measures into our protocol, we hypothesized that we might discover more toxicities than seen in historic trials with carboplatin pemetrexed, and that a single toxicity might emerge such that we could then modify the trial protocol to reflect a more traditional primary endpoint. We selected a 0.3 milligram per kilogram dose based on our proof of concept chemo protection trial in small cell lung cancer patients receiving topotecan. Finally, we did set the primary analysis at four cycles. Why did we do that? Because the standard of care for patients receiving checkpoint inhibitors is four cycles of chemotherapy, whereas patients without checkpoint inhibitors receive six cycles. Given that none of the 20 patients in this interim analysis ended up receiving a checkpoint inhibitor, an analysis of the first six cycles of chemotherapy was indicated. Now, turning to the key highlights of our announcement today. The non-small cell lung cancer interim analysis revealed two inextricably linked key findings. First, ALRN- 6924 treated patients were able to stay on chemotherapy longer, completing 93% of the first four cycles of carboplatin pemetrexed, compared to 78% on placebo. Obviously, this is a very encouraging finding, but it also causes a potential statistical disadvantage that favors placebo. How? Well, the more cycles patients completed, the more opportunities they had to experience toxicities. The less cycles patients completed, the less opportunities they had to experience toxicities. This created an imbalance of completed cycles between the active arm with ALRN- 6924 and the placebo arm, which we believe to have introduced a bias against ALRN- 6924 on the composite endpoint. What's more, this imbalance increased when looking at the percentage of completed cycles in patients completing up to six cycles of treatment, with 79% of completed cycles on ALRN-6924 versus 57% on placebo. The second key finding is regarding our composite primary endpoint. ALRN-6924 treated patients demonstrated 56% of cycles free from Grade 3/4 hematologic toxicities and related events, compared to 50% on placebo. The interim analysis showed relatively few severe hematologic toxicities overall, with no single toxicity rising to the top. Despite the measures we put in place in our protocol to maximize the opportunity to detect hematologic toxicities, what we saw in this interim analysis was very similar to historic AE reporting. Combined, these early findings enable critical, actionable learnings for us that have significantly helped to clarify p53-mutated breast cancer as our optimal development path for ALRN- 6924. Despite the encouraging extension of treatment duration observed with ALRN- 6924 in the non-small cell lung cancer trial, we plan to stop further enrollment in the trial, and we will apply key learnings from this interim analysis to strengthen our breast cancer trial in accordance with clinical and regulatory precedents. Moving on, here is a quick overview of the non-small cell lung cancer trial design. The trial was designed to randomize a total of 60 patients with advanced disease who were scheduled to receive frontline chemo. The trial is double-blind, placebo-controlled. It has open sites in the U.S. and in five European countries. Patients must, of course, have p53 mutant disease, and patients receive ALRN- 6924 or placebo the day before, the day of, and the day after chemotherapy. As I referenced, none of the 20 patients in the interim analysis received immunotherapy. In addition, as of June 16 this year, that was the interim analysis data cut-off date, three patients remained on treatment on each arm. Looking at demographics. The demographics were balanced across the active and placebo arms, with the exception of a higher percentage of male patients enrolled in the ALRN- 6924 arm versus placebo. Now moving on to Grade 3/4 hematologic toxicity data. This slide gives a comprehensive and completely transparent overview of the per patient, per cycle hematologic toxicity data observed in the interim analysis. To orient you, we break each of the hematologic toxicities down across cycles one through cycle six for each patient. The top portion of the table shows patients on ALRN- 6924, and the bottom portion shows placebo patients. Grade 3/4 hematologic toxicities are indicated in orange and red, respectively. Cells in the table that are blank represent missed cycles. Of the 83 cycles administered across cycles one through six, Grade 3/4 toxicities were observed in about 30% of cycles. Again, while there certainly are toxicities, 30% is not a very high frequency, and Grade 4 toxicities were particularly infrequent. They occurred in one patient on ALRN- 6924, and two patients on placebo, as indicated in red. There are two more observations that deserve to be highlighted. As indicated in purple to the right side of the table, five of 11 patients treated with ALRN-6924 completed six planned cycles or 45%, whereas only one out of nine placebo patients, or 11%, completed six planned cycles. Second, as you can see, there is a single patient here indicated as patient four, who was randomized to ALRN-6924, who accounted for 53% of all Grade 3/4 instances on the ALRN-6924. Despite patient four recording so many severe hematologic toxicities, this patient was able to complete six cycles of chemotherapy and achieved a partial response, and the investigator reported that the patient felt great while on study while the trial was still blinded. Here we have now summarized the key numbers for you. Since we have already introduced the most important results on our summary slide earlier, let me highlight only two things on here. Number one, looking at the hematologic toxicities, there is no real difference. Number two, as indicated in the subtitle, the average cycles completed was pleasantly in our favor, 4.7 cycles on ALRN- 6924 compared to 3.4 on placebo. Now, moving on to safety. ALRN- 6924 continues to demonstrate a highly favorable tolerability profile with no safety signals consistent with our previous evaluations. There were very, very few non-hematologic toxicities reported thus far, with fatigue being by far the most common side effect, which is why we highlighted fatigue beneath the table. Interestingly, more than 50% of patients on placebo reported fatigue, in contrast to less than 20% of patients on ALRN- 6924. You may recall that Dr. Eric Anderson in our KOL event in May called out fatigue as one of the key subjective side effects that often cause patients to stop chemotherapy. Definitely for us, a very encouraging finding and something we'll continue to monitor as we evaluate non-hematologic toxicities in our trials. Also, consistent with our previous approach and studying ALRN- 6924, there was no evidence that ALRN- 6924 protects p53 mutant tumors. While we recognize that this is a finding in only 20 patients, we are very pleased to see a favorable trend on progression-free survival with 4.6 months on ALRN- 6924 compared to 3.2 months on placebo. Now let's talk about what might be going on with the dose in this trial. Does the 0.3 milligram per kilogram dose generate a optimal durable effect to protect against carboplatin pemetrexed? Based on what we know today from the very recently generated data from our healthy volunteer study, we have reason to believe, and you can clearly see the data on the right-hand side of this chart here, that a higher dose level of ALRN- 6924 will produce a more durable effect of our drug. Clinically, it can be expected that a more durable effect of our drug is likely going to translate into greater chemoprotection and perhaps even longer treatment duration. What do we make of these findings, and what are our strategic next steps? Undoubtedly, there are some very encouraging trends in these data, most notably the fact that ALRN- 6924 treated patients were able to receive more chemotherapy and stayed on treatment longer than placebo. While we, of course, would have preferred to have seen an even more robust trend on the composite endpoint, we believe that the combination of several factors led to the composite primary endpoint finding in the interim analysis, as I have outlined throughout this presentation, and which are summarized on the left-hand side of the slide. As I explained at the outset of the call, our aim is to identify a sufficiently toxic chemotherapy and hand-in-hand with that chemotherapy, an applicable primary endpoint that allows us to efficiently evaluate the potential of our drug in order to advance it towards phase III and approval for this critical unmet medical need. It's clear now that our breast cancer trial is far more suitable than our non-small cell lung cancer trial to fulfill all these characteristics. Despite the very encouraging extension of treatment duration on the ALRN- 6924 arm in the non-small cell lung cancer trial, we will stop further enrollment in this trial and focus on the breast cancer trial. Furthermore, we will apply key learnings from the non-small cell lung cancer interim analysis to strengthen our breast cancer trial in accordance with clinical and regulatory precedents. What do I mean by that? First, neoadjuvant chemotherapy for breast cancer is associated with frequent severe neutropenia in cycle one. Thus, we are revising the primary endpoint for the breast cancer trial to duration of severe neutropenia in cycle one. This is a well-precedented primary endpoint that has been used to secure FDA approval of multiple supportive care drugs. Second, the breast cancer trial gives us the ability to evaluate protection against chemotherapy-induced hair loss, given that more than 90% of breast cancer patients receiving neoadjuvant chemotherapy experience alopecia, compared to less than 10% of non-small cell lung cancer patients receiving carboplatin pemetrexed. Alopecia is a devastating chemotherapy-induced side effect for millions of cancer patients. Please recall that last month we reported promising ex vivo data demonstrating that 604 protected human hair follicles and their stem cells from chemotherapy-induced acute and permanent damage. Those new data suggest ALRN- 6924's potential to protect against chemotherapy-induced hair loss, something we are very keen to evaluate clinically in the breast cancer trial. Third, we will be adjusting our chemotherapy regimen. As I mentioned earlier in the presentation, the breast cancer trial, we are evaluating chemoprotection against the combination of doxorubicin, cyclophosphamide, and docetaxel. The original protocol design called for a sequential administration of four cycles of doxorubicin, cyclophosphamide, followed by four cycles of docetaxel, a regimen known as ACD. We will be revising the protocol to simultaneously administer these three chemotherapies as a regimen known as TAC. We are making this modification because TAC is associated with much more frequent incidents of severe neutropenia in cycle one than ACD, and likely for that reason, TAC has been used in a number of pivotal trials for now approved supportive care drugs. Fourth, we're actively working to modify the dosing strategy based on the clinical learnings from the lung interim analysis and the recent MC1 data from the healthy volunteer study. As part of that process, we will stop enrolling patients in the 0.3 and 0.6 milligram per kilogram dose cohorts. We are evaluating additional modifications to optimize our opportunity for success in the breast cancer trial, and we plan to provide an update detailing these modifications in the near term. Before I conclude, I'd like to review a slide from our corporate presentation that I believe really helps to visualize the clear precedence tied to our path forward in breast cancer. Looking at drugs approved for chemotherapy-induced neutropenia since 1991, starting with Neupogen, followed by Neulasta, then several Neulasta biosimilars. Most of these drugs were approved following pivotal trials conducted in neoadjuvant or adjuvant breast cancer. Similarly, most of these pivotal trials used a primary endpoint of duration of severe neutropenia in cycle one, and most of these used TAC chemotherapy. In closing, I want to emphasize that our vision to deliver selective chemo protection to all patients with p53 mutated cancer, regardless of type of cancer or chemotherapy, remains intact. All patients receiving chemotherapy experience some level of toxicities, from life-threatening to quality of life limiting. Patients have few options to address these toxicities and even fewer to prevent them. The first step toward realizing our vision is to ensure we're in the best possible position to evaluate and demonstrate ALRN-6924's potential as a chemoprotective agent. As I have outlined this morning, armed with key learnings from our non-small cell lung cancer trial, we can now focus our efforts and resources on our breast cancer trial to set ALRN-6924 up for success more than ever before. Thank you all again for joining today's call and for your support of Aileron Therapeutics. We look forward to providing you with further updates related to our breast cancer trial in the coming weeks. I would now like to open the call for questions. Operator. Thank you. As a reminder, to ask a question, you'll need to press star one on your telephone. To withdraw your question, please press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from Soumit Roy with Jones Research. Your line is now open. Hi. Thank you for taking the question. Could you tell us the duration of the Grade 3 neutropenia you had, maybe on cycle one or overall versus placebo? Any color on that? Yeah, thanks, Soumit, for that question. We had one case of a Grade 4, one patient who experienced Grade 4 neutropenia on the ALRN- 6924, and we don't have that data yet. That's something that we are happy to provide in subsequent disclosure. No problem. No, I meant to say, Grade 3 for neutropenia. Oh, for Grade 3. What was the duration? Oh, for Grade 3. No, actually, we have not looked at the Grade 3. We didn't see that clinically there would be a lot of interest in the duration for Grade 3s. But it's certainly one of the follow-up assessments that we will be doing in coming days. Sorry, I meant, I thought you meant Grade 4. Then as you are thinking about possibly changing the dose level for the breast cancer trial, do you see any problem going up to like maybe when you go to 0.9 milligram per kg reactivating the apoptotic pathway, and that is gonna backfire, or any thoughts on that? Thank you very much for that thought. That's obviously always something that comes up when you have a p53 activating agent. The answer is no. Basis for that confidence is that we have not only good amount of preclinical data that suggests that at these low dose levels, we are safely in the realm of cell cycle arrest induction and not apoptosis induction. Probably more importantly, in our topotecan study in small cell lung cancer patients, we went all the way up to 1.2 mg/kg body weight, and data presented last year at ESMO, and I'm happy to say that there was absolutely no evidence for any safety findings. In fact, if anything, the opposite might be true. The protection looked as good or even better, slightly better at 1.2 milligram per kilogram body weight than at the lower dose level of 0.3. One more item of information is important in that context. In that topotecan study, we gave our drug five days in a row, and in these subsequent cycles ahead of us in the breast cancer trial, we will be giving our drug three days in a row. Even there, in that regard, there's absolutely no reason for us to be worried because we're gonna be giving the drug fewer days than we have previously given in a safe and tolerable fashion. Got it. Thank you so much for taking the questions. Thank you. Thank you. Our next question comes from the line of Matt Phipps with William Blair. Your line is now open. Hello, Manuel. Thanks for the update. I guess, just how confident are you that you now have the dose to move into this breast cancer trial? Do you need to do any more healthy volunteer work either around dose or schedule? Why not at least keep, you know, some, you know, two doses, maybe a higher and lower or something to help build more confidence coming out of the breast trial? Yeah. Great question, Matt. We, first of all, haven't decided yet exactly what the modification to the dosing strategy is gonna look like. There's certainly the possibility that we go with one or with two dose levels, moving forward. As it relates to the necessity for healthy volunteer data, we feel pretty good about the strength of the data. We have now, I think, exceeded 100 healthy volunteers in total, that we have treated in that healthy volunteer study. The MC1 data, the latest MC1 data that we presented for the first time last month, at our last investor call, right, that MC1 data gave us very strong confidence because we did a very thorough every four-hour evaluation in these healthy volunteers. Based on that, I think we see now that time window that we need to cover. Let's keep in mind, for us, we only need to cover 24 hours since we give our drug once a day. I think we have the data that we need from the healthy volunteer study. Okay, thanks. Have you already treated any patients in the breast study? I realized there was a different chemo schedule and lower doses. Have you treated patients, and then just when do you think you'll provide additional updates on, from the breast trial? Yeah. We have enrolled two patients already, and we will give an update on the breast cancer details in the coming weeks. We haven't made a final determination yet, on that, but, we can expect it to be in the coming weeks. Okay. Thanks, Manuel. Thanks, Matt. Thank you. Our next question comes from Ed White with H.C. Wainwright. Your line is now open. Good morning. Thanks for taking my questions. You had just mentioned that two patients were enrolled in the breast cancer trial so far. Were those both at the 0.3 dose, or is one of them at the 0.6? Yeah. No, we haven't. Great point, Matt, Ed. Thanks for that question. We have not disclosed any details on those two patients. At this point in time, we can't comment on that. Sorry. Okay. For the non-small cell lung cancer patients, you still have some patients in that trial. I'm just curious, did you enroll more than the 20, or was the 20 it? Should we expect to see more data in the fourth quarter of this year? I remember earlier you had said in past calls that you were expecting to have data on 60 patients in the fourth quarter. I'm just curious if we're gonna see more data from the non-small cell lung cancer trial. Yeah, great point, Ed. The first answer is that we have a total of 36 patients enrolled now in the lung cancer trial, and those patients are continuing on treatment. In that regard, you're right, there's gonna be more data available to us. Whether the data is gonna be of relevance to provide additional information that is worth to communicate is something that we'll have to see when we get to the data. At this point in time, I wouldn't rule out that there is another disclosure coming, but we haven't made that determination yet. As such, I would currently not guide that there will be a disclosure on those patients. We'll just have to look at the data and see if those 16 additional patients change the story in a relevant fashion, and if so, then we would, of course, come forward with that. Okay, thanks for taking my questions. Thank you, Ed. Thank you. Our next question comes from Aydin Huseynov with Ladenburg Thalmann. Your line is now open. Good morning, Manuel. Thank you for the update and appreciate taking the question. I have one on ALRN-6924. If this drug candidate is extending the PFS by 1.4 months or 50%, do you think the drug may actually have a therapeutic effect rather than just chemoprotection? If that's the case, why don't you pursue a therapeutic path for the drug in non-small cell lung cancer? Aydin, thank you very much for that question. Yes is the short and simple answer. There is a lot of published literature showing that activation of p53, which is the well-documented mechanism of action of our drug, activates the immune system. Since we are dealing here with p53 mutated cancers, obviously our drug isn't gonna activate anything inside cancer cells, right? The immune system is still p53 wild-type and therefore fully amenable to activation of p53. In fact, we had published on a couple of instances and even in a very well-featured paper a year ago that our drug has shown evidence for activating the immune system, which might indeed play a role here. We have been very cautious to represent to the public. This is early days, right? We think it's fair to be very balanced on that finding. It is absolutely possible and we have data to support that. Now in mice we have seen a lot of evidence for this to support these findings. There are other MDM2 inhibitors that activate p53 that are currently in the clinic combining with immune checkpoint inhibitors. This is certainly a feature, a theme that is out there that isn't just seen with ALRN- 6924. That's just a long-winded way to say that, yes, you're absolutely right. There might also be a therapeutic effect going on behind the surface. Got it. Actually. In light of- Actually, Aydin, actually, if I can quickly address the second part of your question. Why not continue the lung cancer trial in that context? I want to be very clear. If we were in a different environment, as a biotech company, in a different equity capital market situation, with all the resources available to us, we would absolutely continue this trial. I mean, we see a clear extension of treatment, and it goes hand in hand with a favorable trend in progression-free survival. What we would do under those circumstances, since you asked the question, we would increase the dose, pause enrollment, increase the dose, and then resume enrollment. We just have to understand that as we increase the dose and then start the enrollment, we would be seeing an even stronger statistical bias being introduced, because now if you increase the treatment duration even longer, you're gonna be favoring the placebo arm even more. We would have to find ways how to account for that, for instance, by penalizing every single cycle that can't be given on placebo but that can be given on ALRN-6924 in order to somewhat correct for that. It's not a one-to-one correction, but it's somewhat of a correction. In that regard, I would be very confident that we would see also something that didn't stand out here, which is an improvement in hematologic toxicities as we saw in topotecan. If we continue to see that separation in the PFS curves, well, then that would be a beautiful result. Again, I mean, we have so many advantages moving this forward in the most capital efficient way. We have so many advantages doing that in breast cancer compared to lung cancer that at this point in time, I think, even though it might seem a tough decision, it certainly is, but I think it's the right strategic decision, and we're very excited about this path forward. It's the most promising situation we have ever found ourselves in now that we have this clarity, that we have these learnings from the lung cancer trial for the breast cancer trial. You may actually see the OS data by the end of the year for these 20 patients, how this may have affected the overall survival. In light of today's data, how does it affect your view on your drug as a pan-tumor agent? How do you think it would affect FDA's decision when it will be time for the FDA labeling? Would it be just limited to the trial that you're going to conduct, whatever that trial would be, the pivotal, the breast cancer? Do you think that the FDA will be more inclusive and will provide the labeling similar to Neulasta and Neupogen? The honest answer, of course, is that we can't know, right? We maintain that if we follow prior precedents, if we do trials in the same cancer patient population with the same endpoint as others have done before us, that it gives us a chance to get to the same label. As you saw on the last slide, the vast majority of supportive care drugs were approved with a broad label. The ones that didn't get a broad label, well, A, those are the exceptions, and B, there's a very clear theme why they didn't get a broad label. It's the question whether you are protecting also tumor cells with your drug or whether you have an effect on tumor cells, because in the case of other drugs, that question has been raised also. For us that goes back to the mechanism of action. We are the only ones who have a selective mechanism of action. We have a drug that is designed to not have an effect on tumor cells. We have a biomarker that enables that, and it is a biomarker that we mandate patients to be tested. It's the biomarker that defines the target patient population, and it's in that patient population that we will be developing our drug. How broad the label's gonna be after the first set of data and put in front of the FDA is, of course, gonna be everybody's guess and up to their judgment. Since we are the first supportive care drug ever developed with a biomarker, we think that should be held in our favor, and therefore we are pretty optimistic about our conversations with the FDA moving forward. Understood, Manuel. Thanks so much for the update. Thank you, Aydin. Thank you. I'm currently showing no further questions in the queue at this time. I'd like to hand the conference back over to Dr. Aivado for any closing comments. Thank you, Norma. Thanks again for joining us today. We look forward to providing more details on next steps related to our breast cancer trial in the near term as we work to advance ALRN-6924 as an important chemoprotective agent for patients with p53 mutated cancers. Bye. Ladies and gentlemen, this concludes today's conference call. Thank you for your participation.