Good morning, welcome to the Ambrx Analyst and Investor Day. At this time, all attendees are in a listen-only mode. A question-and-answer session will follow the formal presentations. If you'd like to submit a question, you may do so by using the Q&A text box at the bottom of the webcast player or by emailing your questions to questions@lifesciadvisors.com. As a reminder, this call is being recorded and a replay will be made available on the Ambrx website following the conclusion of the event. I'd now like to turn the call over to your host, Dan O'Connor, Chief Executive Officer of Ambrx. Please go ahead, Dan. Thank you, Tara. Good afternoon, everyone. I'm Dan O'Connor. As Tara said, I'm the CEO of Ambrx. I would like to welcome you to our Analyst and Investor Day. Joining me on the call from Ambrx is Dr. Sandra Aung, our Head of Clinical, and Dr. Shawn Zhang, our Chief Scientific Officer. We are also joined today by two of the leading breast cancer oncologists in the United States, Doctors Hope Rugo and Paula Pohlmann. Next slide. During this presentation, we will be making forward-looking statements. Please take a moment to read this slide. Thank you. Next slide. I'd like to talk about ARX788, our proprietary anti-HER2 ADC. Since joining Ambrx as CEO last November, we've had the opportunity to speak with our 788 clinical investigators, key internal personnel involved with the 788 clinical development program, and have also had the opportunity to review additional clinical data from our existing 788 clinical trials. Based upon these discussions and review, including preliminary antitumor activity, we've seen post-Kadcyla, post-Enhertu, and in HER2-low patients observed in our recently paused clinical trials, as well as other published data. We believe 2 things. First, 788 is active in metastatic breast cancer patients. Second, based upon what we've observed from the paused studies, we believe that there may be a meaningful clinical efficacy with 788 in the post-Enhertu and HER2-low patient populations. Slide 5, please. With the approval of Enhertu and its successful commercial deployment in the second line, the third line treatment landscape has changed, and in doing so, it's created an opportunity for a novel drug therapy to enter the third line. Moreover, as you see on slide 5, approximately 25% of patients still progress following Enhertu treatment within the first 12 months. To date, we're not aware of any reports of efficacy in the post-Enhertu setting, and as such, we believe there may be an opportunity for 788 to fill this gap. Slide 6. As outlined on this slide, we believe there's a significant market value in the third-line HER2-positive post-Enhertu breast cancer patient population. Slide 7. In light of the considerations set out on this slide, specifically an efficacy signal observed post-Kadcyla, post-Enhertu and in HER2-low patients, the published data from I-SPY 2.01, that mechanistically ARX788 kills cancer cells with a different payload than Enhertu. That 25% of the patients progress on Enhertu within the first 12 months, and the fact that this is likely a very large market opportunity. For these reasons, we think ARX788 could be positioned to be among the first to deliver clinically meaningful results in the post-Enhertu patient population. We believe conducting a small signal finding study in the post-Enhertu patient population is therefore warranted. In other words, our investment in evaluating ARX788 in a small study, we believe, is far outweighed by the potential upside value creation for our shareholders. Slide 8, please. The study design we are planning to conduct will be approximately 30 patients in HER2-positive metastatic breast cancer that have progressed following Enhertu. We plan to enroll only patients who have had no more than three prior lines of therapy, and we also want to ensure that the enrollment criteria ensures that patients have had recent assessments of HER2-positive status. We currently plan to have a 2-to-1 randomization schedule, ARX788 against physician's best choice or choice of best supportive care. We estimate that enrollment will take approximately 18 months from the first patient dose. If the data are compelling, we'll evaluate next steps and potentially conduct a registration-enabled study. We're joined today by two of the leading breast cancer oncologists in the United States, as I said earlier, Doctors Hope Rugo and Doctors Paula Pohlmann. We really appreciate Hope and Paula you joining today. Thank you so much. To provide additional context regarding our plan to conduct a study in the post-Enhertu patient population, we've asked Dr. Rugo to share her experience and perspective with ARX788, as well as her point of view regarding our plan to conduct this small signal finding study in the post-Enhertu patient population. Dr. Rugo has firsthand experience in treating patients with ARX788. Dr. Pohlmann is a leading investigator for ARX788 on the I-SPY 2.2 clinical study. As many of you may know, I-SPY 2.2 is prestigious, internationally renowned clinical trial in breast cancer. We are very pleased that ARX788 was selected for participation in the I-SPY 2.2 program in the neoadjuvant setting. Like Dr. Rugo, Dr. Pohlmann also has hands-on experience in treating patients with ARX788, and she'll provide her perspective on ARX788's participation in the I-SPY 2.2 TRIAL. Now I would like to introduce Dr. Rugo. Dr. Rugo is a hematologist oncologist who specializes in breast cancer treatment and is a Professor of Medicine in the Division of Hematology and Oncology at UCSF Helen Diller Family Comprehensive Cancer Center, where she is also the Director of Breast Oncology and Clinical Trials Education. Her career is focusing on combining novel therapeutic targets, targeted therapeutics with standard treatments to improve the treatment of both early and late-stage breast cancers. She has published widely in this area. In addition to her research, Dr. Rugo is an active clinician and is committed to education, regularly lecturing on subjects relating to the treatment and supportive care for breast cancer. As I said a moment ago, Hope has firsthand experience treating breast cancer patients with our product candidate seven eight eight, which is, an anti-HER2 ADC. She's here to share her experience and her perspective on where the drug could be used in the current treatment landscape. I'd now like to turn the call over to Dr. Rugo. Hope. Thank you, Dan. It's really a pleasure to be here to talk about ARX788. We're really excited about the future development possibilities and place in the treatment paradigm for our patients for this novel antibody-drug conjugate. I think it's first important to just think about the antibody-drug conjugate itself and what it can offer our patients that's different from what we have established now in our paradigm for treating breast cancer patients, Trastuzumab deruxtecan or Enhertu, which I think will move into the first line setting for metastatic HER2-positive patients within the next couple of years and already has moved earlier in patients with more resistant disease. I think what's important when we start moving effective agents earlier in the course of therapy is that we know we need subsequent treatment options. Right now, we really don't have a good feeling for the efficacy of, for example, our previously established ADC, Trastuzumab emtansine or Kadcyla, in patients who've already received Enhertu. I think that the subsequent therapies, we have tyrosine kinase inhibitors, but we still really need treatments that have efficacy for our patients who have HER2-positive disease. Of course, in the HER2-low setting, which is a subsequent area of study here, this is a very large population of patients where we definitely need subsequent therapies. Really important for us. My experience with ARX788 is, I think, really based on this need for having additional therapies in sequence for our patients, and that this really represents a growing population of patients worldwide who need sequential therapies. As we think about ARX788 and what it can add, when we're thinking about giving sequential chemotherapy for our patients, we're looking for non-cross resistance. We want agents that work a little bit differently and have different characteristics. That's sort of the hallmark of how we give chemotherapy to patients with metastatic breast cancer, both in the metastatic and early-stage setting. In advanced disease, ARX788 offers us some additional advantages, which is that it delivers a toxin or payload which patients will not have seen. It has a different mechanism of action than the toxin that's attached to Enhertu. I think that that has a big benefit. In addition, the toxin itself is highly potent, which means that you can deliver a fairly small amount of toxin, per antibody-drug conjugate, essentially, in order to have efficacy. There's high uptake of the antibody-drug conjugate within the tumor cell. We use this idea in our clinical practice in terms of understanding how these drugs can benefit our patients. In clinical practice, the drug is given every 3 weeks, which is very convenient for our patients. It doesn't cause stomatitis mouth sores, it doesn't really cause much bone marrow suppression, so we don't see a lot of decreased blood counts, which is a real hallmark and difficulty, of our management with chemotherapy. It's kind of funny for us as clinicians to think that we can now give toxic drugs that kill cancer cells and not really suppress the blood counts, which is amazing. One of the big issues with patients when we treat them in the metastatic setting is quality of life. Of course, it's important in early-stage disease, but you can see the light at the end of the tunnel. For metastatic disease, patients are on treatment until they die of their cancer. Quality of life takes on an even more critical role. One of the things that patients really suffer from is neuropathy. This is not just tingling, of the fingertips and toes, but loss of sensation and pain. That means that patients can't function. They can't, walk a long distance, wear specific shoes, most shoes. They can't type, open bottles, close their buttons, things like that. This is really a big deal. The fact that ARX788 delivers this, we know already effective toxin, but that this type of toxin doesn't cause neuropathy is really critical. We do see some. You know, we see efficacy, so this is great. You know, it's a very effective drug. We already know that from the data at hand, and we need to see specifically in the population after Enhertu, that it retains that efficacy. Although we already have a little bit of data that suggests that the drug is efficacious after other ADCs. Next part of that is, what other toxicities do we deal with? Well, the unique toxicity to ARX788, which is seen with other ADCs actually, some upcoming that are in clinical trials now, is some eye toxicity. It's kinda weird to say eye toxicity because it's actually not long-term. It just, patients get irritation of their eyes, and we found that using eyedrops and now using these very low concentration steroid eyedrops have a huge effectiveness in treating. We hope, and we'll look at this in preventing this eye effect or adverse event rather than toxicity. You know, we worked really closely with our ophthalmologist. There doesn't seem to be any permanent damage. It doesn't permanently affect any aspect of vision. That's really encouraging for us as we manage. What's also interesting for our patients is they generally manage it, and they don't complain about the eye toxicity. They have the side effect, but we can manage it with them as we move forward. Lastly, I think the, concern of investigators overall has been, do we cause inflammation of the lungs, so-called interstitial lung disease or pneumonitis? That appears to be a very, very low risk with this drug. You know, we've seen this as a specific toxicity with trastuzumab deruxtecan, or Enhertu that we know is specific for this drug and some other ADCs. My sort of take on heavily pretreated patients too with ARX788 is that this is a less of an issue and less of a toxicity We need to follow patients over time to truly understand this risk, but we're really good at identifying it and managing the risk early and effectively in our patients. So that's, I think, encouraging. Just to summarize, I'm really excited about the now plan to reinvigorate ARX788 in breast cancer patients. I think it has a really important role, and I look forward to the study in HER2-positive disease as well as further exploration in patients who have so-called HER2-low disease. Of course, I'm looking forward to hearing Paula talk about our really exciting experiences in the early stage setting as neoadjuvant therapy in I-SPY 2. Sorry, I was on mute there, Hope. Thank you, very much for that. Maybe if I could just follow up with a couple quick questions. How do you feel about our study design? When you look at our study design, 2-to-1 randomization, probably total of 30 patients, 20 on the drug arm and then maybe 10 patients on a best supportive care physician choice. How do you react to that? I think that that's a, to me, a great way of studying this drug now. I like the 2 to 1 because, we always want the experimental drug. Patients want the experimental drug, so they're more likely to join on a study if you have 2-to-1 randomization. That works, I think, in terms of assessing signal. I think giving lots of options in terms of the investigators and patients about what the next line therapy is great. I think that, you know, allowing 3 lines of therapy is also quite reasonable because, we have some data that adverse events increase and, you know, we don't know that this is really true for. For example, I don't think it's true for the eye effect. There may be some toxicities that are enhanced if you treat patients very late in the course of therapy. End up with problems with patients having progressive brain metastases or other issues that limit their ability to receive drug, and maybe their cancer grows and, you know, before you even really had a chance for the drug to have an effect. I think limiting the exposure to three lines of prior therapy is quite reasonable. You don't wanna make it so tight that you can't enroll patients, but you also want to give yourself the best chance for success. Thank you, Hope. Maybe kind of similar question around, relatively recent HER2 status and how you think about that? You mean the whole HER2-low area of controversy as well? Well, maybe just like we're planning on having relatively recent assessments of HER2 positivity. Oh, I see. Yes. Yeah. I mean, just any thoughts around that. Yeah. No, really important. I mean, if you're doing a study for HER2-positive disease, you wanna know that patients have HER2-positive disease. people have sometimes trouble, I think, internationally assessing HER2. I will say in the United States that we don't have as much of a problem because we have very robust testing and use laboratories that have a high volume, which seems to be really important in detecting HER2 positivity. In the large HER2-low study with Enhertu that was recently presented and published, there was a small number of cases, and relatively small, that were thought to be HER2-low and actually were HER2-positive. It's interesting that if you look at those cases, these are internationally determined and I think on very old samples. I think, you know, being able to confirm that you have HER2-positive disease is important, that, that it's confirmed, relatively recently, in the patient population. I will say that one thing about HER2, which is reasonably unique, for example, it's not true of ER, is that HER2 is very conserved, so that if you had HER2-positive disease in the early stage and metastatic stage, you tend not to lose it. You could keep testing HER2 forever, and it will still be positive. That's a very different marker than, for example, HER2-low, which is not conserved, and ER, which is not conserved. Patients lose ER, expectedly over time as their cancer progresses, but HER2 is maintained. Got it. Thanks, Hope. Another question around, kind of, what you think would be a clinically relevant response rate in the drug arm with ARX788. Well, it's a good question. You know, how we assess response in small numbers of patients, of course, is always a question for us because we've seen responses go up as patient populations increase. This is a relatively small study, but we're looking at a patient population who can't have a limitless number of lines of treatment, which I think is important, and following them very closely. You know, I think that response rate in general that, we see at least in the 25% range is reasonable because what you're going forward with is a large population of patients who received T-DXd. It's hard for me to keep saying Enhertu because I'm so used to using the generic names. Apologies. For T-DXd, we generally, know if you figure all of these patients are gonna receive the drug earlier and earlier, even a modest response rate would be really encouraging for us to move forward with treating patients right after T-DXd and seeing what the efficacy is in patients with metastatic disease. Obviously, the higher the response rate, the better we are. Responses, it's a funny thing as we look at RECIST response, because we were really motivated by looking at waterfall plots for T-DXd, because even in patients who didn't meet RECIST criteria for response, we also saw shrinkage of disease. And a lot of times that shrinkage or clinical benefit rate also is very important for our patients. You know, a modest response rate for me is going to be very encouraging in this patient population. Do you think ARX788 could deliver that based upon your experience? I think it's quite likely to. I think we have, we have the expectation that this drug will have efficacy after T-DXd because we're using a different payload and a different construct. We may be able to overcome some of the resistance that occurs, and we know occurs to T-DXd over time by using this alternate antibody-drug conjugate. I think that, it does have a very good potential for offering efficacy in this setting. You know, we'll see as we treat patients, but you wanna go into a study like this with the, a little bit of seed data that suggests the drug will be efficacious, and we have that. Great. Awesome. Hope, thanks so much. Really appreciate that. You know, with that, I'd like to now introduce Dr. Paula Pohlmann. Like, Dr. Rugo, Dr. Pohlmann has had hands-on experience treating patients with ARX788 and we're asking Paula to if you could describe kind of ARX788 participation in I-SPY 2.2. In, in terms of your background, I'm reading this, so I just wanna make sure I get it, get it right, and same thing for you, Hope, it's amazing. Both of your careers are really amazing. Dr. Pohlmann is an American Board of Internal Medicine diplomat specializing in I clinical trials and breast cancer research and treatment. Pohlmann currently serves as the Chief of Breast Medical Oncology Research at University of Texas MD Anderson, as an associate professor at the Department of Breast Medical Oncology, with a joint appointment at the Department of Investigational Cancer Therapeutics, Division of Cancer Medicine. Did I get that right, Paula? Yeah, that's right. Good. Excellent. After Dr. Pohlmann speaks, we'll spend a few minutes providing a brief update regarding what we call ARX517, which is our proprietary anti-PSMA-targeting ADC, and then we'll go into a Q&A. Paula, I'd like to turn it over to you. Thank you, Dan. It is, again, a pleasure to be here and be able to speak about the I-SPY structure and how ARX788 comes into play. Just to review, I-SPY 2 is a clinical trial that evaluates new agents that are combined with standard therapy in patients with stage 2 and 3 breast cancer, early-stage disease, and patients that are candidates for surgery. The primary endpoint of I-SPY is the probability of pathologic complete remission. This is the probability of the complete disappearance of the tumor from the breast and regional lymph nodes as a result of this systemic therapy that is done before the surgery. I-SPY 2 uses a heavy clinical biomarker program, classifies the different diseases in actually 10 different subtypes of breast cancer. There is where each drug is evaluated. It also has this Bayesian adaptive randomization plan that allows individualized patient assignment to each specific treatment arm to maximize the treatment effects for each individual patient. We have cumulative data from our group and from others at that document that when the patient achieves the PCR, which is the complete remission with the systemic therapy, this will correlate with the survival outcomes that are better than if there is a still residual disease by the time of the surgery. In I-SPY 2, all the patients will have the opportunity to receive the standard of care backbone chemotherapy before the surgery if needed, right? The new drugs will come on study in addition to the backbone, and this is done sequentially. The main aims are really to improve the probability of pathologic complete remission with the addition of the new drug or to get the patient to that PCR without the need of exposure to the more toxic standard of care backbone chemotherapy that is established. How a new drug comes to I-SPY. It's a very formal process for evaluation. With multiple committees that evaluate the drug with a vote all the way from a concept of a new drug to get to activation. I want you just to review this because it's we have several drug candidates, but not endless slots on I-SPY to test a new drug. It's quite difficult for a drug to get there. The first step, of course, after we learn of a new drug, we evaluate the efficacy data and the safety data that is already available. This will include understanding the experience in earlier phase clinical development like Phase I and Phase II. It will involve experience in other malignancies and also in breast cancer, mostly metastatic disease. With that information, we start the conversation with the pharma partner that has the drug, and then we trigger the formal concept design and the formal process for approval. The first committee that this new concept has to go through is the New Agents Committee. We have a group of seasoned oncologists with a lot of experience in clinical trials that sit in this committee. The concept is, discussed at length. At the end of the evaluation, there is a vote. For those concepts that are approved in that committee, the next step is the independent agent selection committee, which is a similar committee, but now of investigators that are not part of I-SPY. It's independent. The same process takes place, the concept is evaluated and there is a vote. For the concepts that go through this committee, of course, we go with the contracts, we sign the CTA and the safety data exchange agreement. We get the protocol and informed consents all written. This goes to the FDA. We get the FDA feedback, this material goes to the central SRC, which is for the scientific review of the new arm of the protocol. After that, it goes to the IRB. As you can see, it's a stepwise process that is very formal to get a drug from a concept to activation in the study. ARX788 of course, went through all this process and got activated. Honestly, as a chaperone of the arm, as I-SPY investigator, it was surprising to us to hear that, we would have a halt on the development and the drug was going to be placed on hold. The first thing that we wanted to know was the reason for that. With, of course, a lot of, hopes that, the drug would continue on I-SPY. We were very glad that, we were able to continue the treatment of the patients that we have on and continue to enroll patients, new patients at that point. We are hoping and very well, first of all, we are very excited about the agent, as Dr. Rugo has just mentioned. We are hoping that we can complete the I-SPY arm so that we can get the results on that. Paula, thank you so much for explaining that. Just with respect to our pausing, that was, it's a call I had to make to let that we had made a decision based on strategic reasons, not anything to do, obviously, with the product candidate. We're really glad that we were able to kind of reverse that decision now. We're really excited to see the participation in the program. You know, I from prior experience, I know it's highly selective. I guess I'm curious, as you described that funnel of all the committees getting down to a selected candidate because you don't have, unlimited spots. How did you think about 788? Why did the group, all the committees come to a view that it should be a candidate to participate in 2.2? Of course, we are very excited about the drug because it has a very specific construct in terms of the ADC. You have a specific location for the conjugation of the chemotherapy payload to the antibody, and we have a different payload than what the patients are typically exposed to. Our hope would be that we could get the patients to PCR without the need for exposure to, for instance, anthracyclines that have a lot of side effects early and long-term, potential side effects, including, heart failure, secondary malignancies like leukemia. I think, we all, respect a lot our, backbone chemotherapy, but, if we could get a more specific and less toxic, agent to get the same results, that is what we would like to see. We felt that the ARX788 has this potential, and that's why we decided to move forward on I-SPY. Awesome. Thanks, Paula I'll ask you a question that I always get asked, which is when can we expect to see data? I know this is your study. It's not our study. again, we really appreciate all the work that I-SPY and the team have done on it. Do you have any insights towards when we might be able to see some, some data coming out of the program? Dr. Rugo can help me on that, but typically the arms, take about a year to enroll. Mm-hmm. We are very quick to start reporting on the experience. Okay. Awesome. Do you have something to add to that? Yeah. I mean, one of the things that's a hallmark about I-SPY, which makes it possible, is that we don't actually, as investigators and, as the chaperones and as members of our safety analysis, we don't track the number of patients that are enrolled in each arm, which it sounds ridiculous, but it isn't. It actually. What it means is that you can't sort of bias yourself towards one arm or another as you're going on, and we're not comparing experimental drugs to experimental drugs. The bottom line is that we don't know when an arm will close. You know, certainly we've used the drug in patients and been really excited, I mean, very excited about what we've been seeing, which is great. We report very quickly after the last patient has gone to surgery, looking at our primary endpoint of pathologic complete response. Then because we are doing an exploratory look at ARX788, we'll have information sooner than we would have for some of the other arms that have a larger planned accrual, and then we can choose to expand and add more patients so that we have even a more robust analysis. Thanks. That's super clear and appreciate. I actually didn't understand that part about not knowing enrollment. Paula, maybe a couple quick questions around some of the topics I was asking Hope, which is, how do you think about us doing this signal planning study post Enhertu, and, study design and those kind of things. What are your thoughts? I think this is critical, right? T-DXd is a active drug, as Hope said, it's moving up into the lines of therapy, and the patients will need other therapies after that. I feel that it's important to allow prior Enhertu exposure to the study so that you can provide that information and get to, the next line after that exposure. I feel that, the other thing is that, as you mentioned, 25% of the patients will be off Enhertu after the first, what is it? The first, six- 12 months. 12 months. Yeah. Then 50% will be off after the first 24 months. Yep. Right? Yeah. I think this is important because it is an active drug, but unfortunately, not everyone will get the very prolonged exposure to that drug, and we do need to treat the patients that come off. Mm-hmm. Then again, how do you feel about ARX788 in that context, the post Enhertu patient population? Well, I think it has the potential to be effective and useful. As Dr. Rugo said, the toxicity profile doesn't seem to be overlapping. I feel that the patients will have another non-traditional chemotherapy option that tends to be better tolerated than, just a naked antibody with some chemo. Got it. Awesome. I really appreciate that. Sandra, Shawn, any questions you wanted to ask? I'm good right now. Yeah. You're good? Yeah. Good. Great. Excellent. Okay, Hope and Paula, if you can, if you don't mind, we're gonna have a Q&A after I just give a brief update on our PSMA targeting ADC. If you can hang in with us for a little bit longer, we would appreciate that. Thank you so much for your comments. We really appreciate it. It was very informative. Let's turn to 517. You know, we'd like to provide a brief update regarding what we call ARX517, which as I said, is our proprietary anti-PSMA targeting ADC. Importantly, 517 is the only PSMA targeting ADC in clinical trials in the United States currently. PSMA is highly expressed in metastatic castration-resistant prostate cancer. As you may know, prostate cancer is the second most common form of death from cancer in the United States, which is obviously creating a need for better treatment options. Recently, Pluvicto, which is a radiopharmaceutical, from our point of view, both a validated PSMA as a good target and an effective target in prostate cancer, and also established what we think is a very meaningful commercial opportunity in the metastatic castration-resistant prostate cancer patient population, which is great. Those are two terrific things. However, when we look at Pluvicto and we recognize that it's a radiopharmaceutical, we think that there may be some challenges or conversely, some advantages that five one seven, which is an infused ADC and not a radiopharmaceutical, may have vis-à-vis Pluvicto. Recently, we provided our first clinical update for what we call APEX-01, which is our first in human dose escalation and safety study of ARX517. This was our first opportunity to provide preliminary data on this study, which had started back in June of 2021. Just taking a look at the criteria, the eligibility criteria for APEX-01, I think there's 2 things I want to highlight. The first is that the patients must have at least 2 prior FDA-approved treatment options for prostate cancer. Also patients must have 1 of the following 3 criteria, either PSA progression defined by a minimum of 2 rising PSA values, or radiographic progression by RECIST, or disease progression by the presence of new bone lesions. Given that enrollment criteria, the patients enrolled in APEX-01 were ended up being heavily pre-treated and also because this was a dose escalation study, there's a tendency to enroll patients that are being evaluated not necessarily at a therapeutic dose, but instead to determine the safety of the drug in a first-in-human study. Patients were heavily pre-treated. When we look at how heavily pre-treated, we see that the patients had a median of five prior lines of therapy coming onto this study, including that some patients had experienced Pluvicto. As I said, the study started in July of 2021. Since starting, we've seen PSA reductions, in PSA level reductions of 30% or more in one or more patients in all previous cohorts, starting at 0.64 ngs per K. Because of this, because we've not seen any drug-related serious adverse events in the study since July, we have been steadily increasing into higher doses. As we put in our recent press release, of the 22 patients evaluated for safety, there were no drug-related serious adverse events or Grade 3 treatment-related or greater than Grade 3 treatment-related AEs have been reported. In essence, ARX517 has been very well tolerated with only Grade 1, Grade 2 treatment-related adverse events being reported. The maximum tolerated dose, or the MTD, has not yet been reached. When we look at the first 3 patients in cohort 6, we observed a PSA reduction of more than 50% and no drug-related serious adverse events. 2 of the patients went on to see a 90% reduction in PSA levels, all of these responses were confirmed. Based upon this data, we're now expanding into cohort 6 up to an additional 15 patients. Excuse me, up to 15 patients. 1 of the 3 patients, this is again something we mentioned previously in our press release. 1 of the 3 patients in cohort 6 had a soft tissue visceral disease and experienced a RECIST partial response on the first treatment scan. Now, we're also into cohort 7. In cohort 7, patients have been dosed and there have been no DLTs observed. Let's take a step back. We believe that the preliminary data we've seen thus far is primarily attributed to the strength of our proprietary conjugation technology, specifically the stability and precision of how we link our cancer-killing payload to our monoclonal antibody. Clinical safety PK/PD data are planned to be presented at a major medical meeting later this year, in the second half of this year, and we are targeting ESMO to do so. We would also like to provide a pre-clinical update or pre-clinical data update for 517 at AACR, which I believe is going to be in March. When we think about the positioning of 517 in prostate cancer, we're currently evaluating a target product profile of similar or better efficacy than Pluvicto, with better tolerability and convenience of administration. We think that makes sense based upon what we're currently seeing. As we said in our February 16th press release, we believe at this point we're seeing early evidence of proof of concept for a single agent ARX517 as an ADC treatment for advanced prostate cancer. While not all patients have undergone a complete assessment and the data is still preliminary, we're very encouraged, particularly considering that the activity observed to date is both as a monotherapy and importantly, we're not assessing PSMA level or the presence of target in these patients, so we don't know PSMA positivity. When we think about the data, we think it's, not only encouraging from what we've also seen, but particularly when taken into consideration that this is monotherapy data and it's without PSMA targeting confirmation. Overall, we like our positioning here. We have the financial resources to achieve our objectives. We have two programs, 517 and 788, which we believe are well-positioned to potentially address important unmet medical needs. We believe that this is attributable to the work that's been done over the years, over the past several years at Ambrx. As I said, I've recently joined as the CEO back in November, and one of the things I was very struck by was the amount of work that's gone on to really perfect our platform technology and in particular our core technology, which is the strength of conjugation of our toxic payload to our antibodies. With that, I would like to first thank all the investigators who are participating on our clinical studies. Hope, Paula, and all of your colleagues, we really appreciate what you've done for our studies and our programs, as well as those doctors who have been working on 517. We really appreciate their efforts. We appreciate all the efforts of your staff. We know there's, it takes many people to do what we're doing, and we really appreciate everything that your staffs have been doing for the advancement of these two programs. Lastly, and perhaps most importantly, we want to thank the patients who participate on our clinical studies. Okay, good. With that, I'd now like to move into a question and answer period. Again, Hope and Paula, thanks for hanging in with us to go through Q&A. Let's go to the first question. This is from Phil Nadeau from Cowen. Phil, thanks for writing your question. We appreciate that. Phil asks, on ARX788, can you discuss what results must be produced in HER2 failures in the next study to support further development? Specifically, is it an ORR or a duration of response hurdle that you think of? If I could, I would ask really, both Hope and Paula to respond to that question, and Hope, perhaps we could start with you. Can you just say the question one more time again? Sorry about that. I'm sorry about that. I caught you off guard. If the question is on ARX788, and we kind of touched upon this a little bit earlier, Hope, maybe just to kind of re-review it. What results do you think must be produced in the HER2 failure patient population to support the next level of development? I think, it's the same as we evaluate any drug in this setting. We need to see efficacy, and we need to see tolerability. I don't have any concern about the tolerability in this situation because we have had, quite a bit of experience giving the drug. I think that our experience helps us manage this as we move forward, in, in terms of preventing and treating moderate adverse events easily. The efficacy, I think we already have a very, very nice efficacy signals, even in the patient population who previously had received trastuzumab emtansine or Kadcyla, and then had progression of disease, which we presented at San Antonio last year. You know, it's a small number of patients, but seeing that kind of efficacy is very encouraging. We just need to continue to follow up and now see ongoing efficacy in this population, and that will, I think, give us the information we need to move forward and also to appropriately educate how we move forward in what patient population. Great. Thank you, Hope. Paula, same question. What do you think? Yeah, sorry. I agree with Hope. You know, we want to see some efficacy. I would like to remind everyone that, not every patient is a candidate for Enhertu. Some people come with, interstitial lung disease and, or they develop that. You know, you don't want to wait until the patient have, shortness of breath, is symptomatic, because then the outcome is really, much worse. We have a sort of a low threshold to stop Enhertu. I feel that, if we have efficacy, it's, that's what we need. Great. Awesome. Thank you, Paula. I appreciate it. Let's go to the next question, which is Marc Frahm from Sectoral Asset Management. Marc asks, what catalyst do we expect for 2023, and what data is expected at major oncology conferences in 2023? This is Hope and Paula, this is probably a company question, but, Sandra, maybe I'll start with you on this. If you can address the second part of that question, what data can we expect at major medical conferences in 2023? Right. Our target is to present some of our more mature data in the Pano-01 study that we had completed enrollment and pause, but complete enrollment. We have the most mature data there at a major medical meeting at the second half of this year. We'll have breast patients with HER2-low post Enhertu and post Kadcyla data that we'll present there. That'll be our most mature data. For ARX517, our expectation, similarly in the second half of this year, is to present data on our dose escalation, the safety and efficacy, the PK/PD data that we're collecting. We're very hopeful that we'll have the recommended Phase II dose identified by then and perhaps even, dose escalation or dose expansion started, excuse me. Great. Great. Okay, that's good. Shawn, maybe, same question vis-à-vis preclinical data. Right. What we are planning here is actually in the AACR in April, we are going to present preclinical data on the ARX517, mainly focused on the in vitro testing profile of the drug. The second thing is the efficacy in the animal model. Third thing is the toxicity study, and therefore, the basically the rationale to start a Phase I human trials. Okay. Excellent. Thanks, Shawn. You know, maybe a corollary question, are you planning on publishing that data as well? Correct. We actually have a manuscript in preparation. We are targeting to submit this year. Okay, excellent. Thank you, Shawn. You know, maybe just, in terms of catalysts, I think we've touched upon the medical conferences. I think, Sandra, you identified establishing the recommended Phase II dose. I think I would agree. I think that's an important event for the 517 program. I also think another catalyst is, you know, being able to put data out at, again, likely ESMO. I think, from what we've seen so far, we're excited to continue and gather data and present that data as it becomes available at that conference. You know, thinking of other catalysts, I think of first patient, first dose in this now signal finding study with 788 post HER2. You know, when I think about our ability to start that study, I like some of our positioning. One is we already have sites that are open. We had many sites open in the ACE-Breast-03 study that we paused. You know, our plan there is to amend that protocol. You know, to amend the ACE-Breast-03 protocol, add this study design in, and then really jump right back into those sites that we already opened and, obviously did our site initiation visits, et cetera, to get to patients. So, I like that. It's really kind of leveraging the footprint that we've already established with these patients or, excuse me, these sites. We can really kind of, post a protocol amendment, jump right into those sites and get enrolling. We think enrollment... Again, in terms of catalysts, we think enrollment for seven-eight-eight is probably 18 months approximately from first patient, first dose. I think we're, you several months from getting to that point. We've got to go to FDA for the amended protocol. I think that takes about 3 months. Sandra, correct me if I'm wrong. So, you know, we kind of bring all that together. You know, I think it's, hopefully we'll be in the position to start dosing this year and then get the data, as soon as we possibly can. I think it's gonna be hard to say that, but we think enrollment is approximately about 18 months for this study. Again, hopefully, because we've got studies up and sites up and running, we can compress that timeline. You know, that's the first patient, first dose in that study. Open label study, so we'll have an opportunity to review the data as its forthcoming. You know, we'll see how we present that. Our preference is to present data at medical meetings. On that topic, PAN01 is the PAUSE study. We have data that we're analyzing, gathering, and looking to present most likely at San Antonio Breast Cancer Symposium later this year, in November of this year. PAN01 data, which is a relatively mature study, as another data update at a medical conference and, again, targeting San Antonio Breast for that. I think those are some of the anticipated catalysts for 2023. Again, appreciate the question mark. That kind of wraps up the questions we had. Maybe I would just go back to Hope and Paula for another moment and see if there's any other comments that you wanted to provide. Not on my side. I mean, I think that except for what I mentioned earlier, which is that, I think that this next step in HER2-positive disease is critical, and it's also going to be exciting to see additional studies in HER2-low disease as well. I think this is a really exciting field. We really think that we're going to be replacing much of our naked chemotherapy treatment in the next decade with antibody-drug conjugates and having these different types of ADCs, because we know that tumors are really smart and keep developing resistance, is gonna be critical for our path forward to optimize treatment for our patients. Excellent. Thank you, Hope. Paula? Yeah. I wanted to say that apart from the metastatic setting, I do have a lot of excitement. We all have a lot of excitement when we are talking about the potential use of this drug in the early stage. I think it represents the potential for us to spare our patients from the old-fashioned chemotherapy that has long-term side effects. We'll, it remains to be proven, but we have the means to do that. Excellent. Thank you, Paula. I appreciate that. Again, thank you to both Paula and Hope for not only participating here but also for being so supportive to the development of our product candidate in this important patient population. We really appreciate that. Last words, Sean and Sandra, if you guys have anything you wanna add vis-a-vis ARX517 or seven-eight-eight. Sean, I'll start with you. Yes. I think, really, I think supporting what Dr. Hope and Dr. Abram, really mentioning here what our ADC works with other ADCs, particularly the Enhertu. We have the stability, we have a different payload, we have a potency, and also we are not a MDR drug-resistant substrate. It's non-cell permeable, which is can minimizing all the toxicity when you have a premature release of the payload in the blood. I think that those aspects really is gonna be make the difference between our ADC versus other ADCs on the market. What our conjugation chemistry is based on synthetic amino acid incorporation in antibody with a chemistry that is not in-licensed system. It's the oxime chemistry based on synthetic amino acid incorporate in the antibody. I think that's the same thing applies for both ARX788 and ARX517, and that's probably where we should be able to see how can we really separate the toxicity versus, basically the efficacy. Thank you. That's helpful, Sean. To kind of reinforce, one thought here and really one of the things that made me very excited to join Ambrx, which was the real potential to deliver chemo-like efficacy without chemo-like toxicity. When I look at what we're achieving in both of these programs and perhaps in particular with respect to five-one-seven, with no DLTs, no grade 3s that are drug-related, I think it really starts to tell the story that conjugation is extremely important, that stability of conjugation is extremely important, and that premature release of payload yields those unwanted chemo-like side effects that, so far, we're not seeing certainly in the five-one-seven program. I would say to Sean, any thoughts or comments about that? I think you covered that very well, Dan. I think the key things here, the technology from Ambrx is what we can do to the incorporation of synthetic immunogen, which can enable complete novel chemistry and create a stable ADC is what we are different from anybody else. Thank you, Dan. You got it. Thanks, Shawn. Sandra, you know, you're on the front lines with our clinicians. You know, if you can provide some of the feedback you've gotten with respect to, 517 and 788, since joining the company. Maybe if you could start with, feedback that you've gotten on 517, from the clinicians working with the programs. Right. Dan, thank you. I just wanna say I'm very lucky and fortunate to be able to work with not just one drug, but two drugs that are active in these, this very high unmet need patient population. You know, 517, it's not every day that you can work on a program where, the slots are being filled every second it's open. That's a very good place to be from both a patient perspective, because they're getting access to drug and from the development perspective, because we can move very quickly. Our, the investigators on the study are very, I'll just say very excited about the 517 program. Are looking to get this, through dose escalation so we can focus on the randomized trial. ARX788, certainly you've heard from, Dr. Rugo and Dr. Pohlmann, that sentiment is all throughout the program. I think Dan alluded to his kind of deep dive into ARX788 when he joined. Essentially, the program and the investigators on the program across the board were not very happy about pausing the program because what they have been seeing in their patients. I'm excited to bring this back and give an opportunity to patients to benefit from our drug. I think that all the investigators on both ARX517, ARX788, I can say feel the same. Excellent. Thanks, Sandra. You know, now we've described today that we're going up to 15 patients in cohort 6. Can you provide, your thoughts around that and rationale for doing so? Right. You know, when you're looking for a signal in your dose escalation, you have to ask yourself, what are the checkboxes you wanna see, especially in prostate. One checkbox is, do you see PSA reductions? We check that box. The other checkbox is, if you have soft tissue to measure, do you have a response there? We check that box. With cohort 6, we feel, at this point is checking the boxes we will wanna see, and therefore we made a decision to expand that cohort up to 15 patients. We have a safety monitoring committee meeting next week. We're gonna discuss whether we're gonna go up or remain in the lower dose cohorts and expand more. That remains to be decided. You know, we're very much looking forward to the ESMO meeting, preparing for that. The focus is all on that right now and getting data prepared for that meeting. Got it. With respect to cohort 7, obviously we've not seen any DLTs, but is that a cohort that you might also consider expanding up to, again, up to maybe 15 patients? That's possible. You know, the data's still coming in. It's still early. We wanna make sure, we have, a robust discussion around it next week. It's possible. Okay, great. You know, we talked about seeing, as low as, 0.64 mg/kg, starting to see, reductions in PSA levels. You know, any thoughts about that as you move, from that second cohort up through the higher cohorts? Yeah. You know, I think one thing to keep in mind is that this is a biomarker unselected patient population. Some of the, the data that we've been seeing is in the lower dose cohorts is encouraging, and I don't wanna discount even the lower dose cohorts potentially expanding on. Because once we understand the PSMA status, we can understand more about all the full data set. You know, I think it's very encouraging that we're seeing, reductions in PSA at the lower dose cohorts. You know, we could expand in, know, additional patients in even in the lower dose cohorts. You know, we have to look at the totality of the data that's all coming in. This is all very, new. I think, we wanted to get the data out there because we felt it was compelling and exciting. We're putting our head down right now, gathering the data, and preparing for the meeting. Excellent, Sandra. Thanks so much. I guess that will be it. I really want to again, thank you all for participating in this call. Dr. Pohlmann, again, thanks for hanging in with us. You're the best. We appreciate it. Shawn and Sandra, thanks. We'll sign off now. Again, thanks everybody for participating in this Analyst Investor Day call, and also thanks again to our patients for participating in our clinical studies. Take care, everyone. Thank you. Thank you.