As a reminder, this call, this call is being recorded today. I will now turn the call over to Shirley Liang from BeyondSpring. Thank you everyone for joining today's call. I would like to advise listeners that comments made on today's call may reflect forward-looking statements that are related to such matters as BeyondSpring's clinical and preclinical research and development activities and results, regulatory and commercial plans, industry trends, market potential, collaborative initiatives, and financial projections, among others. While management believes that its assumptions, expectations and projections are reasonable in view of the currently available information, you are cautioned not to place undue reliance on these forward-looking statements. The company's actual results may differ materially from those discussed during this call for a variety of reasons, including those described in the forward-looking statements and risk factor sections of the company's 20-F and other filings with the SEC, which are available on the investor section of BeyondSpring's website. Joining us on today's call is Dr. Lan Huang, BeyondSpring Co-founder, Chairman, and Chief Executive Officer, and Dr. Steven Lin, Professor and Radiation Oncologist from MD Anderson Cancer Center. It is now my pleasure to turn the call over to Dr. Lan Huang. Lan? Good morning everyone, and thank you for joining today's call. It is a pleasure to be here to share with you new clinical development programs for Plinabulin, a first in class agent. We have been developing Plinabulin for over 15 years, and it has been used in over 700 cancer patients with good tolerability. First, it can induce innate and adaptive immunity, so it has the unique and dual clinical benefit of anti-cancer efficacy and prevention of chemotherapy-induced neutropenia. Second, it's easy to use as an intravenous infusion, used once or twice in a cycle. Finally, Plinabulin has a very strong patent portfolio, with patent protection to 2038 in 48 jurisdictions. Next slide. I'm delighted to introduce to you Dr. Steven Lin from MD Anderson, who we have been working with for the last six years on understanding Plinabulin's mechanism and how to translate into clinical regimen in unmet medical needs. Dr. Lin is a professor and a physician scientist with a focus on thoracic malignancies. Dr. Lin runs a translational research team that evaluates biomarkers for treatment response and disease outcomes after chemoradiation therapy and immunotherapy. Hi, everyone. So I'm actually on, currently on slide number five. So thank you for being here. So I will present an overview of the results that I presented at the 38th annual SITC meeting on the preclinical and clinical proof of concept for the immunomodulatory role activity of Plinabulin, inducing dendritic cell maturation and resensitization in immunotherapy refractory tumors when combined with radiation and PD-1, PD-L1 inhibitors. So let's go on to the next slide, number six. So Plinabulin is a molecule that binds to a unique site on tubulin that is distinct from other tubulin binding agents such as taxanes, vinca alkaloids, and colchicine. We have strong preclinical proof of concept that Plinabulin, when used in combination with radiation and an anti-PD-1 agent, activates dendritic cells, stimulates T cell proliferation, and achieves abscopal effects, which is defined as a systemic immune response induced by local radiation treatments when coupled to an IO agent. The clinical efficacy or evidence of efficacy was seen in 10 immunotherapy refractory patients, when we saw an 80% disease control rate and durable responses in heavily pre-treated patients. These results demonstrated clinical efficacy in a growing, high unmet need IO refractory population. When we evaluated the patients who responded compared to the patients who didn't respond, we saw clinical evidence of immune activation in the responding patients. These patients exhibited early immune activation with DC maturation and pro-inflammatory monocytes in the peripheral blood. These IO effects were observed across six different cancer types, indicating broad applicability. So let's go on to the next slide, which is slide number seven. To go into briefly the mechanism or action of Plinabulin, the co-crystal structure has been solved, which show that Plinabulin is indeed a unique tubulin binder, with a unique Plinabulin binding site distinct from the other tubulin binders. Upon binding, Plinabulin causes depolymerization of the microtubules, which in turn liberate the Rho guanine, guanine nucleotide exchange factor, H1, which is GEF-H1, that had been sequestered on microtubules, which in turn activates downstream signaling cascades of Rho/ROCK and JNK, which can lead to direct cytotoxicity of cancer cells. But in dendritic cells, the signaling cascade leads to DC maturation and subsequent T cell activation to mediate immunogenic cell death. Next slide, or slide number 8. To understand how Plinabulin can synergize with radiation and anti-PD-L1 agents to generate an optimal anti-tumor immune response, we can make a look at the cancer immunity cycle diagram and see that when there is optimal tumor antigen release induced by radiation or chemotherapy, and coupled with Plinabulin's effect on causing DC maturation, this will further increase antigen presentation and also induce polarization and proliferation of anti-tumor M1-like pro-inflammatory macrophages. This leads to increased priming of DCs at the antigen-presenting cells to migrate to tumor-draining lymph nodes and leads to greater anti-tumor specific T cell activation and an optimal systemic T cell response. Next slide, or slide number nine. As a proof of principle, we have generated preclinical evidence that Plinabulin with radiation and an anti-PD-1 can lead to DC activation, T cell proliferation, and the abscopal effect. In the diagram on the left, we demonstrated in some in vitro experiments that the sequencing of radiation with Plinabulin is quite important, and that antigen release by radiation needs to be done first, within three-six hours before Plinabulin administration, in order to generate the greatest DC activation and maturation. However, if we use Plinabulin first, followed by radiation, DC maturation does not occur as optimally. We see that the primed DCs can stimulate T cell proliferation in a mixed lymphocyte reaction with optimally activated DCs. In the panel on the right, these were in vivo experiments showing that comparing to single agent or double agent combination, that it is only the triple combination strategy of radiation, followed by Plinabulin and anti-PD-1 treatment, will lead to not only best local tumor regression, but also the best abscopal anti-tumor responses. Next slide, or slide number 10. Motivated by these preclinical work, we designed a phase I study at MD Anderson to use this triple combination strategy in any cancer patients who have progressed on prior lines of standard of care anti-PD-1/PD-L1 agents. These patients must have had more than one site of progressive disease, since we only treat 1 or more sites with radiation, but may need to have an area for measuring response and/or for biopsy: a tumor that lies outside the index lesion treated with radiation. So this is an open label, single center, Phase Ib study. The dose-limiting toxicity assessments were done within 30 days of receiving the triple combination therapy. For translational studies, blood was obtained prior to cycle 1 day one, on cycle 1 day four during radiation, and cycle 3 day 1, and tumor biopsies were obtained prior to cycle 1 day 1, and before cycle 3 day 1, if the tumor was still present at the time of treatment at cycle 3 day 1. The primary objectives were safety, tolerability, and overall response rate. For a secondary objective, we looked at the disease control rate, or DCR, as well as PFS and OS. For exploratory objectives, we examined biomarkers of immunologic response by examining immune phenotypes and dendritic cell activation in the blood and tumor samples. Our next slide, or slide number 11. We found that the Plinabulin triple combination strategy produced clinically meaningful responses in the non-radiated tumors across multiple IO-refractory cancers. Overall, we saw an 80% disease control rate in the 10 IO-refractory patients, and durable responses seen in the two Hodgkin's lymphoma patients who regressed or progressed after 12 or 16 prior lines of therapy, including standard IO agents. The pictures on the right captures one of these patient responses. We radiated one site in the right neck and evaluated response in the progressive disease in the mediastinum and upper abdominal lymph nodes. At cycle three, day one, we saw a significant and clinically meaningful abscopal response. This patient continues on therapy till this day. Next slide, or slide number 12. To evaluate the mechanism of action of Plinabulin, we saw that in responding patients, there were signs of early immune activation on cycle 1 day 4, during the course of radiation, as shown by DC maturation markers and the emergence of pro-inflammatory monocytes in the peripheral blood of responding patients. This indicates that before responders, patients are primed to respond to Plinabulin in the dendritic cells, as evidenced by the increased DC maturation seen across six different cancers in the responding patients. Next slide, or slide number 13. So in summary, Plinabulin in combination with radiation and immune checkpoint inhibitors, demonstrated induction of DC maturation and resensitization to anti-PD-1, PD-L1 agents in IO-refractory tumors. Plinabulin was shown to induce DC maturation on cycle 1 day 4, in blood samples of responding patients across six different cancer types. So the overall results were quite impressive, showing high disease control rate of 80% in immune checkpoint inhibitor refractory and heavily pre-treated patients. So while these results are preliminary, these encouraging results warrant further clinical study of Plinabulin IO combination in IO-refractory settings such as Hodgkin's lymphoma and non-Hodgkin cancers. So this concludes my overall presentation. I'm happy to take any questions. Thank you, Dr. Huang. Thank you everyone for your support as we progress to bringing Plinabulin to patients with unmet medical needs. I would like to now open the call for Q&A. Operator? Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate that your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment please while we pull for questions. Thank you. Our first question comes from the line of Joel Beatty with Baird. Please proceed with your question. Hi, this is Ben on for Joel. Thanks so much for taking the questions. I guess to start, Dr. Lin, this question is for you. What is the best way to look at the data that gives you confidence of a real effect, for Plinabulin? Yeah, certainly for the, you know, for looking at the actual response rate that we see in these patients who are actually already mostly refractory, and of course, our criteria is that these patients must have, must have been, IO refractory. So we, of course, this is a huge population of patients, since most patients, you know, more than 30 indications, our patients are on, some kind of IO agents. So we really want to see whether this combination will induce a response. So we were quite impressed. Of course, there we do see responses actually quite, quite dramatically. So as you can see that, you know, out of the, the 10 evaluable patients, the 8 patients actually have response, with disease control probability. But then, of course, the patients who had partial response, were over 30% actually patients had partial responses, which is much higher than what we expected. And, what's most interesting and important is that if you, if you compile patients who have partial response and stable disease or the patients who have DCR, and you look at the blood, and also within, even, even in tumors of these responding patients, you really see there's actually a on-target effect, actually, of Plinabulin. You know as a, as a scientist, you know, and of course, you know, when you talk to a company, they're saying this is a DC maturator. You know you always kind of take it with a grain of salt, right? But then really, as the investigator, to see the actual translational studies and biomarkers to show, wow it's really the responding patients actually have biomarker related effects on the on-target cell, which is the dendritic cell in the blood and tumors. It is quite astounding and is really only seen in patients who are responding. So I think it's, it does seem to hit this target, and that means that the patients who respond do have the DC maturation results. Got it. That, that's very helpful. And then I guess our next question would be, what outcomes would you expect if patients had just gotten radiation and immune checkpoint inhibitors without Plinabulin? Yeah that's a, that's a very good, very good question. So I think you really have to be to look at the actual prospective trials. You know, of course, as radiation oncologists, this is one of the hottest topics, right, in this area. Can we just add radiation to patients who are refractory to therapies? So I can just point you to two studies. One was kind of prior to the IO kind of IO period, when, you know, most of the patients failed chemotherapy and multiple lines of chemotherapy. So there was a study that was published by Steve Chmura's group at the University of Chicago. The first author is Jason Luke at Chicago. So it's published in JCO in 2018. So mostly these are multi-cancer, multiply cancer, chemotherapy, mostly chemotherapy in TKI refractory patients, where the really primary, it's a phase I, however it's in, in about, how many patients? It's actually within 68 patients, 79 patients, actually. And what they found, very interestingly, is that, you know, they only found. So this is basically a study, it's a single arm, but then they treated one of, one or more sites with radiation. However, they leave some other sites for assessment of distant to see if there's response. And then all the patients were given plina, sorry, pembrolizumab as well, along with SBRT. It was not randomized, just single arm. So they looked at the overall response rate in this group. Again, these patients did not receive, but were not IO refractory. So the response rate that they found was 11, 13.2%, the overall response rate, and the DCR was 44%. So the most important, actually, in the kind of more current era of patient IO refractory, very similar to the groups that was treated Plinabulin in this particular study, in our study. So this is actually a second study that was published in Lancet Oncology last year by Jonathan Schoenfeld's group at Harvard. So it was a kind of multicenter across the United States with NCI support. It was a randomized phase II study, and these are all patients with immuno refractory tumors. And, but however, these are all non-small cell lung cancer. They are multi-cancer, but specifically targeting non-small cell lung cancer. They randomized the patients to dual immune checkpoint blockade of durvalumab and tremelimumab, which is a CTLA-4 agent, alone versus SBRT plus durva and tremi. So, unfortunately, this was a negative trial, but if you actually look at the overall response rate in both groups, either durva/tremi in the IO refractory patients or this SBRT plus durva/tremi, the overall response rate for the two groups was, for the radiation combination was only 11.5%, and the dual immune checkpoint blockade therapy alone was 11.5%. So it's actually t hat's why this is a negative study. There's actually no difference in overall response rate between the two groups, but support suggesting that SBRT plus, in unfortunately, this dual, even dual immune checkpoint blockade did not show a response rate above, you know, above the percentage that we saw even with the other study that in patients who are not IO refractory. So that's why it was actually pretty astounding to see a DCR rate in our Plinabulin-treated groups of 80%, but then in the patients who have overall response rate of 30%. Albeit, it's a very small study. But kind of provide some promising preliminary data to potentially thinking about going forward in the future. Got it. And then I guess maybe, on that point, then, this company or this, this question is for the, for the company. Which setting do you see as the most attractive to pursue for, potential approval? Yeah, so we did six different cancer types here, right? So as you see, like, the, they're all heavily pretreated patients and with good response in, selected cancer types. Actually, what we are looking at is one is non-small cell lung cancer, another is Hodgkin's lymphoma. Those are very promising. Got it. Thank you so much. All set from us. Thank you, Ben. Thank you. Our next question comes from the line of Graham Tanaka with Tanaka Capital Management. Please proceed with your question. Yeah. Can you hear me? Hello? Yes. Okay, great. Congratulations on your work. How broad was this, and consistent with response rates between the different cancer types, and what did you learn from that? So, yeah. So of course, you know, this is a small study we did to kind of enroll all patients who are refractory, so we were not discriminant on one versus the other. But so if you actually look at the response rate, which is pretty high, it we seems to be, you know, I think we see great response in non-small cell lung cancer. We saw incredible responses in Hodgkin's lymphoma, and these patients were 16 line of prior therapy, which is pretty astounding, actually. So these two patients actually were Hodgkin's with 13 and 16 lines of therapy prior, and both responded to this combination. In non-small cell lung cancer, we saw responses in head and neck cancer. So it looks It's, so it seems like it's a broad applicability. There was not any one particular group. We, of course, we saw non-responders in renal cell, but then also saw responses in renal cell as well. So it's kind of, you know, we do need to, and that's the reason why we need to expand it to greater number of patients. Because perhaps that there will be one particular group that may respond better with this combination, but we already saw promising results, particularly in Hodgkin's and non-small cell lung cancer so far. Okay, well, those are two very large disease indications, and I'm wondering what strategy the company will take in terms of pursuing additional studies since the data seems so promising. Can you handle several different pathways, paths to study these different, say, the top two indications? Yeah, probably I can answer this question. Thank you, Graham, for this great question. As you see that we do have another IIT study, it's with Merck. This is looking at the second line, third line, non-small cell lung cancer, who also failed IO therapies. The regimen there is docetaxel, plus Keytruda, plus Plinabulin. In that study, docetaxel is serving similar roles like the radiation to generate new antigen. That study is enrolling patients nicely. Potentially, that could be one of the regimen we can go forward, taking advantage Plinabulin's DC maturation benefit in this triple IO combination strategy. So in addition, for the Hodgkin's lymphoma, of course, we're still having the IIT study open currently at MD Anderson, and very potentially, we can also move into the phase II to expand and enrolling more of those type of patients to get us more confirmative data for that really hard to treat patient population. Yeah. Okay, there's obviously, obviously a lot of work that would need to be done. And what kind of size patient studies would be required, do you think? Say, you pursued the non-small cell lung cancer and the Hodgkin's lymphoma cancer types for additional studies, how large would those studies have to be, which would give an indication as to the cost and timing? Thank you. I think the actual number of patient calculation has to be done after we have more data in hand, but it would be probably a few hundred pairs of patients, which would be relevant for a registrational study. Okay. But the actual number is not available at this moment. Thank you. Right. Yeah, understandable. Dr. Lin, I'm just wondering, what did you not see in the studies that maybe you were looking for? Were there any major areas or types of information or data you were looking for, you didn't see and would like to see in additional work? Thank you. Yeah. You know, again, you know, of course, we were pretty open-minded about, you know, what type of cancers we enrolled, but then, you know, in some indications, we only had one, you know, one patient. Let's say melanoma, we had one patient, Merkel cell, we had one patient. So it's impossible to really conclude the responses in these group of patients. We also included, actually, one patient with MSI colorectal cancer, which, you know, of course, these patients respond to IO agents, and these patients, this patient became refractory. We saw stable disease or progressive disease, actually, so eventually, it was initial stable disease, but then, it eventually progressed. So I'm not sure whether, you know, this is in non-MSI, this does not respond to a non-MSI, sorry, does not respond in MSI gastric cancers, whether it's gastric or colorectal cancers with only one, one patient. So I think, I think there's still room potentially to still explore these group of patients until we get more convincing evidence with more patients that it does not respond in certain subgroups of patients. But then, however, again, we do see broad applicability across different cancer types. And actually, one, one patient, one group of patients I failed to mention was the patients with head and neck squamous cell. We actually had two, three patients that were, yeah, had head and neck squamous cell, and we did actually see two responses in those patients as well. Okay, and so how many non-responders did you have in the total patient, the number of patients you looked at? And what were the reasons you think you may have had some non-responses? Thank you. Yeah. So out of the 10, you know, of course, out of the 10 evaluable patients, you know, after exclusion, two patients had progressive disease. And, and so it was interesting, there was not particular patterns. Again, they were like Merkel cell, right? So I'm not sure whether it's because Merkel cell-specific or not in the, the patient with MSI. So, you know, it, it, you know, when we look at the biomarkers is, you know, these patients seems to not have the maybe the immune biology or maybe perhaps it's, it's physiology or the immune system is somehow incapable of launching a response, you know, with, with this triple combination. Because we did not see, at all any, any DC maturation in these, in these patients, both within the tumor as well as in the peripheral blood. I'm not 100% sure why maybe these patients have immune collapse. That means, because of this prior line of therapy, these patients are heavily, heavily pretreated. So I'm not sure whether the immune fitness has a role in why these patients do not respond. And compared to patients that did respond, that maybe they're just somehow their immunology or immune bio or immune fitness is greater, and therefore could able to launch a DC, you know, activation. And maybe there's genetics involved in this, which we just don't know, with a small number of patients to know if there's any correlation to underlying whether tumor genetics or somatic genetics, you know, patients' own underlying genetics is dictating this. However, it is a minority of patients that, you know, surprisingly minority of patients that actually perhaps progressive disease. So seems to be that the, you know, majority of the patients do have enough immune system and physiology to respond to this combination. So, the breadth was pretty wide, and, which is surprising, except that you described the method of action and, and what's happening. So I'm wondering in terms of timing, what is the, w hat do the results, what do the data tell you in terms of how early treatment could, Plinabulin could be used, and what kind of results could you get? I know this is a little bit a guessing on this, on your part, if you're able to answer this, but if treated earlier, what kind of response rates could you see? And, and durability could you see in terms of treatment? Thank you. Yeah. So but probably we would surmise that, you know, certainly, of course, this, in this particular population we targeted, this is a huge group of patients, the unmet need population. You know, in the first-line setting, of course, treatment-naïve group of patients, you know, certainly there's a lot of competition in that space, right? Everybody's in that space, trying to add their drug to first-line therapy, which is currently, of course, chemo IO for a lot of indications and grafting some agents, you know, of their own, of their interest to, to this backbone. And, you know, do we, will we expect a greater response in the treatment-naïve first-line setting? Possibly. You know, but that's, you know, we already see pretty high. You know, I guess we're, it's more the overall response rate. Can we go from what we typically see for, you know, just radiation and IO to like, you know, 10, 15% to, to now what we see only 30%, maybe even greater than 50%, perhaps, you know, in treatment-naïve population. You know, that would be incredible, right? We can see greater than 50% overall response rate, in a treatment-naïve group. So yeah, I think that's, that's a guess. Perhaps that patients who, who are treatment-naïve tend to respond better to, to, to therapies upfront. But again, that's a, that's a huge, you know, competitive space. Therefore, I think in these, you know, unmet need group of patients, I think this is a, an important finding that we have, you know, seeing the type of responses as compared to the data, type of data that's out there. Well, so do you personally hope to be involved in additional studies, and what area of focus would you specifically, personally like to look into? Thank you. Yeah. So at MD Anderson, of course, this, this current IIT is still, is still open. That means, you know, it was designed for the initial, safety and efficacy analysis and then, potentially expanding it to, not only expanding the individual specific cohorts of interest, since it's such a, such a large basket. But then when we see, you know, further responses, the confirmatory responses in specific subset of the patients to further expand to subsequent phase II, randomized trial. And, you know, right now, because I'm a lung cancer specialist in terms of radiation oncologist in thoracic, space, I'm obviously very interested in non-small cell lung cancer. So this is something that we did see response, of course, in non-small cell lung cancer. And of course, Hodgkin's lymphoma, I'm not an expert in, but my colleagues who I've worked very closely with, and actually she was my, well s he was my mentee, actually, when she was a resident. Now she's a faculty at MD Anderson. She's been looking at this data. She's very interested in Hodgkin's lymphoma, and that's her research as well. So she may actually be running the specific one for Hodgkin's lymphoma. But I have collaborators in the head, neck space, et cetera. So it really depends on which particular subset of the disease that we'll expand on. We'll bring in the people who are stakeholders in those specific areas. Bye. Yeah. Thank you so much, Graham, for your great questions. We'll turn it to operator now, and thank you, Dr. Lin. Thank you. There are no further questions, and I would now like to turn the call over to Dr. Huang for closing remarks. Thank you again for everyone to join the call today. Have a nice day and a beautiful week. Bye-bye. Thank you. This concludes today's teleconference. You may now disconnect your lines at this time. Thank you for your participation.