BYSI 万春医药

Operator

Good morning and welcome to BeyondSpring's Fourth Quarter and Full Year 2019 Financial Results Conference Call. My name is Ariel, and I will be the operator for today's call. Please be advised that this call is being recorded. At this time, I would like to turn the call over to the host, Caitlin Kasunich, Senior Vice President at KCSA Strategic Communications. Please go ahead.

Caitlin Kasunich

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, marketing potentials, 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 factors sections of the company's 20-F and other filings with the SEC, which are available on the Investors section of BeyondSpring's website. Joining us on today's call is Dr. Lan Huang, BeyondSpring, Co-Founder, Chairman and Chief Executive Officer, Dr. Ramon Mohanlal, Executive Vice President of Research and Development and Chief Medical Officer; Richard Daly, Chief Operating Officer; and Edward Liu, Chief Financial Officer. It is now my pleasure to turn the call over to Dr. Lan Huang. Lan?

Lan Huang

Thank you. Thank you for joining today's call. BeyondSpring is a global biopharmaceutical company focused on the development of transformative, immunology, cancer therapies for patients with high unmet medical need. As you will hear throughout today's discussion, 2019 was a pivotal year for BeyondSpring. Paving a clear pathway to registration in two significant underserved patient population. In 2019, we have made significant advancements in two lead indications for Plinabulin, CIN and non-small cell lung cancer. Plinabulin is a potent antigen presenting cell APC inducer and we consider it a pipeline in a drug. With around 1,000 patients enrolled globally for Plinabulin, we have a clear vision of indications that Plinabulin can be applied in. It starts with the foundational indication in CIN, followed by non-small cell lung cancer and the future potential is in the triple combination with PD-1, PDL-1 antibodies and radiation or chemotherapy. Besides Plinabulin, we are developing three preclinical immune agents and R&D platform in the targeted protein degradation build. In the COVID-19 pandemic environment to reduce cancer patients' infection and hospitalization rates after chemotherapy is of heightened importance to physicians, patients and health care systems. With Plinabulin's benefit in the CIN indication, we believe that it has the potential to raise cancer patients' neutrophil count after chemotherapy use and prevent infections and hospitalization. This will enable Plinabulin to emerge as a transformative new therapy for the millions of cancer patients in dire need of a superior CIN treatment option and an improved quality of life. Let me share with you our three areas of accomplishments, namely in clinical studies, in scientific mechanism discoveries, and in regulatory filings. First, we have multiple clinical studies to prove Plinabulin's clinical benefit. Our first Phase 3 indication is the CIN indication. To date, five clinical studies have demonstrated Plinabulin's benefit in CIN prevention. This data has been presented at several premier center conferences all over the world. With the CIN indication, the current standard of care is G-CSF monotherapy with Neulasta or Onpro being the market leader. After using Neulasta about 90% of patients with high-risk chemotherapy develop grade three or four neutropenia, which requires the chemotherapy dose to be reduced, the next cycle to be delayed, and all the regime to be downgraded or is committed altogether or we say the 4Ds. All of this results in significantly reducing survival rates for patients. Plinabulin when combined with G-CSF have evidently reduced occurrence of Grade 3 or 4 of neutropenia in patients which leads to stable doses sustained cycles and sustained courses of chemotherapy resulting in better survival outcomes. Yesterday, we announced that following discussions with U.S. FDA we have formally changed the primary endpoint for the Study 106 Phase III superiority clinical trial. The new primary endpoint measures the rate of prevention of Grade 4 neutropenia in the first cycle of chemotherapy. We believe that this new primary endpoint which is more clinically relevant and more robust will set a new standard to evaluate superiority for CIN. The primary endpoint for the CIN indication has evolved over the last 30 years. We began with the severe neutropenia rate when Neupogen was compared to no therapy followed by DSN duration of severe neutropenia as a good standard for the Neulasta and biosimilar G-CSF non-inferiority trial. To assess a new superior therapy, it was evident that a new endpoint was needed to better evaluate glycosuria and superiority. As such, this is a timely advancement in clinical trial signs for our program. We believe that the complementary mechanism of action for Plinabulin and G-CSF including Neulasta to standard care and the results of our clinical trials to date suggest a high likelihood of success. If successful, the Plinabulin G-CSF combination with its superior and erratic outset protection from inspection will mark the first significant advancement in preventing neutropenia in 30 years. Our second Phase 3 indication is in second and third-line non-small cell lung cancer with patients who are EGFR wild-type, which accounts for 85% of Western patients. There are very few approved therapies available. Current treatment options have a modest median overall survival rate of eight to 10 months with severe adverse events, such as neutropenia and the decreased quality of life. Plinabulin in combination with docetaxel with its unique mechanism of action can potentially improve patient survival and at the same time reduce neutropenia caused by docetaxel the standard care. Looking forward, we continue to view Plinabulin as a pipeline in the drug. We believe that Plinabulin's transforming potential is in combination with PD-1, PDL-1 antibodies and radiation or chemotherapy to treat multiple cancer types. This triple combo approach optimizes the utility of immunotherapy as radiation or chemotherapy generates tumor antigens. Plinabulin sees the maturation effect optimizes the presentation of this tumor antigen to cytotoxic T-cells and checkpoint inhibitors enable the activated T-cells to kill cancer cells. In other words, Plinabulin steps on the gas and PD-1 releases the brake. We are confident that a triple combination approach could prove to be a powerful cocktail resembling the HIV cocktail therapy which transformed HIV from a cellular disease to a chronic disease with patients able to achieve normal life expectancy. Second, our clinical data is supported by strong scientific rationale. In 2019, Plinabulin's highly differentiated mechanism was published in four peer-reviewed journals including two sales of journals, further validating its potential as a potent T-cell activator through GEF-H1 activation and a DC maturation. It was also shown that the GEF-H1 high signature tumor has long growth survival than those with low signature. In addition, Plinabulin exhibits early protection for neutrophil in bone marrow and its CIN effect have been shown in multiple chemotherapies in animal model. This gives us the scientific foundation for its CIN indication. This publication is as a result of our efforts for over five years by collaborating with leading scientists all over the world including from Mass General [indiscernible] and last University of Basel. Third, the results of our efforts in 2019 have positioned BeyondSpring well for the next 12 months enabling us to leverage the regulatory milestones in multiple NDA filings in China and the U.S., two of the largest pharmaceutical markets in the world. This is first validated by us initiating the rolling NDA submission for the CIN indication in China in the first quarter of this year. We expect to submit for the CIN indication in the U.S. in the second half of 2020. We are also in frequent dialogue with regulatory agencies and plan to submit NDAs in the U.S. and China in the next 6 to 12 months. Overall more than 600 patients have been treated with Plinabulin globally with good tolerability. This means, the safety database requirement for the U.S. FDA and China's NMPA. Additionally Plinabulin has 74 granted patents in 36 jurisdictions including 16 issued U.S. patents with protection through 2036. Therefore, we believe that Plinabulin has a long runway to realize its commercial potential. I will now turn the call over to Dr. Ramon Mohanlal who will discuss our recent chemical development in more detail. Ramon?

Ramon Mohanlal

Thank you Lan. First I would like to provide an update to our registrational trials for Plinabulin. I will start with Studies 105 and 106 which evaluate Plinabulin's efficacy in preventing CIN. We reached alignment with both the U.S. FDA and China's National Medical Products Administration, NMPA on the fact that these studies would support a broad CIN label for all cancers, all chemotherapies combined with G-CSF. Recent data from Studies 105 Phase II portion demonstrated that Plinabulin given as a single dose cycle on the same day of chemotherapy is not only as effective as Neulasta, but also causes much less bone pain and improved quality of life and offers a superior immune profile compared with Neulasta. It also has a benefit regarding thrombocytopenia. As such Plinabulin's non-G-CSF based unique mechanism of action potentially makes it complementary to Neulasta in preventing CIN. Additionally, previous top line data from Study 106 Phase II portion of this trial suggests a significant improvement in efficacy when treating CIN. The significant decrease in the percentage of patients, who are experiencing Grade three or four CIN a more than 90% reduction in patients experiencing bone pain and a reduced potential immune suppressive phenotype when adding Plinabulin to the standard of care. As Lan mentioned on Wednesday, we announced that we discussed with the U.S. FDA our proposed primary endpoint change for the Study 106 Phase III superiority clinical trial. The new primary endpoint is measured by the percentage of patients who did not experience Grade four neutropenia. We believe this new primary endpoint is more clinically relevant and sets a new standard to evaluate superiority in CIN. With the Plinabulin and Neulasta combination 52.5% of patients we have protected from Grade four neutropenia versus 40.9% in G-CSF, a 53% increase in protection compared to Neulasta alone. The improvement in Grade four neutropenia seen with the Plinabulin Neulasta combination is even more important in today's health care environment due to the potential impact of COVID-19 on immune-suppressed patients. Patients on monotherapy G-CSF typically experience Grade three and four CIN by day seven risking infection and simultaneously compromising the chemo regimen. The Phase III portion of Study 106 will compare Plinabulin at a 40-milligram fixed dose combined with 6 milligram of Neulasta versus 6 milligram of Neulasta alone in a double blind study. We enrolled the first patient in October 2019. A pre-specified interim data readout is expected in quarter 2020 and the final data readout is expected in second half 2020. We do not anticipate any impact on this time line due to COVID-19. The data generated to date suggests that Plinabulin offers a novel approach to presenting CIN and bone pain in patients receiving chemotherapy. Minimizing neutropenia and bone pain would allow more patients to receive the full dose of chemotherapy and complete the treatment implying that the addition of Plinabulin to G-CSF has the potential to significantly improve the current CIN standard of care, which would result in better anti-cancer outcomes and patient quality of life. We have high confidence in Plinabulin's benefit in the CIN indication as this effect has been demonstrated in five independent clinical study so far. Number one, in Study 101, Plinabulin reduced the incidence of Grade 4 neutropenia from 3.8% in a docetaxel alone arm to less than 5% in the Plinabulin plus docetaxel arm, P less than 0.0003 on day eight of the cycle of chemotherapy. Title one day eight is the lowest point in neutrophil count after docetaxel dose. In the 138 patients Study 103, Plinabulin reduced the incidence of Grade 4 neutropenia from 27.4% in the docetaxel alone arm to 3.1% in the Plinabulin plus docetaxel arm, P less than 0.0001 on day eight of the first cycle of chemotherapy. Number three. In the Phase II portion of Study 105, both Plinabulin and Neulasta had a 14% incidence of Grade 4 neutropenia with Plinabulin demonstrated superior safety profile of less bone pain, less thrombocytopenia and less immune suppressant. Number four. In the interim analysis of the Phase III portion of Study 105, Plinabulin achieved non-inferior duration of severe neutropenia, DSN and more rapid onset of action compared with Neulasta. Number 5. In the Phase II portion of Study 106, the Plinabulin Neulasta combination increased the rate of prevention of Grade 4 neutropenia to 62.5% from 40.9% in Neulasta monotherapy, demonstrated superior safety profile of less bone pain and enabled patients to stay on the optimal dose of chemotherapy. Second, BeyondSpring Study 103 for non-small cell lung cancer, it's a 554-patient Phase III registrational study, evaluating the anticancer effects of Plinabulin in combination with docetaxel compared to docetaxel alone in second and third-line non-small cell lung cancer with a primary endpoint of median overall survival. To date, we have enrolled over 500 patients in the U.S., Australia and China, and the study has two pre-specified interim analysis; the first with one-third of patient death achieved and the second with two-third of patient death achieved. In early 2019, we reached the first interim analysis and the data and safety monitoring board or DSMB recommended that the trial should continue without changes to the protocol pre-specified number of patients. The final results of the trial at a death event of 439 patients are expected to be available in the second half of 2020. Additionally, Plinabulin's positive clinical results and mechanism data have been presented in world's leading conferences such as ASCO, ASH, IASLC, ESMO SITC, ESCO SITC and AACR. With that, I will now turn the call over to Rich, who will discuss our commercial and partnership strategy. Rich?

Richard Daly

Thanks, Ramon. It's clear that there's a need to address the treatment gap surrounding CIN. Today I'd like to emphasize a number of points that support our case as well as the impact that COVID-19 is having on cancer care and the potential role that Plinabulin can play. First, I want to applaud Ramon and his team for their leadership and vision in the design and conduct of the Plinabulin CIN clinical program. BeyondSpring's approach to addressing CIN has been to move beyond supportive care and to pivot to improving cancer care. The data generated to date demonstrates that Plinabulin has the potential to deliver on this promise. As discussed previously, CIN remains the number one reason for modifications in chemotherapy care. When white blood cells drop to dangerous levels oncologists are forced to alter care. As mentioned before, we call this the 4Ds patients are forced to decrease their dose or even delay downgrade or discontinue therapy. The results can be devastating for patients. Relatively minor changes in care can result in significant changes in outcomes. For instance, a 15% reduction in Relative Dose Intensity or RDI could reduce overall survival by 50%. Additionally, just 15 days of delay in delivering chemotherapy over six cycles in breast cancer patients can result in a statistically significant reduction in overall survival. We believe that Plinabulin has the potential to go beyond supportive care. And we believe that Plinabulin when used in combination with G-CSF can improve compliance and persistency with chemotherapy, and potentially improve cancer care outcomes. Next, I'd like to address the environmental changes that we've experienced in the recent weeks due to COVID-19 that have expanded the CIN market. According to IQVIA, patient visits to oncologists are down 20% nationwide since the pandemic hit, due to social distancing guidelines. This is not unexpected since cancer patients are among our most susceptible citizens. Many of the patients are experiencing pandemic-related 4D adjustments to their therapy. That is they're being forced to decide between downgrading to less effective treatment, delaying treatment or discontinuing treatment to avoid exposure and infection. The result is likely a poorer cancer outcome. The pandemic has exacerbated an already unmet clinical need. In recognition of this the National Comprehensive Cancer Network or NCCN acted quickly. Treatment guidelines promulgated by the NCCN for the prophylaxis of CIN have been dramatically expanded to begin to address this situation. The NCCN guidelines historically recommended prophylactic treatment for patients at high risk of developing CIN. According to our research, high-risk segment represents about 32% of patients receiving chemotherapy. As a result of these guidelines, the CIN market generated over $9 billion in sales annually. Globally, we estimate that approximately four million cycles of G-CSF are given annually. Due to COVID-19 pandemic, NCCN recently updated its guidelines recommending that intermediate risk patients be considered for prophylactic CIN therapy as well. Intermediate risk patients make up approximately 37% of all patients undergoing chemotherapy. BeyondSpring team is excited that Plinabulin has the potential to participate in improving the care for these patients as well. As we have stated previously, monotherapy G-CSFs are not sufficient to ensure that cancer patients will get the chemotherapy regimens that are necessary to optimize their therapeutic outcomes. The data are clear. CIN remains a significant obstacle to optimizing chemotherapy, cancer care and potential outcomes. Our data indicates that Plinabulin has the potential to improve on the standard of care and positively affect the lives of cancer patients, particularly those who require prophylaxis of CIN by transforming the 4Ds into the 4S' and the 4S' are stable doses sustained cycles, strongest regimens, and staying the course of chemotherapy. Finally, I'd like to provide a high-level overview of our market research on Plinabulin. We reviewed our clinical results for Plinabulin G-CSF combination with 110 USA practicing oncologist. Not only did the oncologists recognize the unmet need in therapy, but they also had a very favorable response to combining Plinabulin with G-CSF to the benefit of their patients. The top three benefits for the use of Plinabulin plus G-CSFs for the oncologists we talked to were. Number one, increasing the median absolute neutrophil count or ANC this was very important; number two, was reducing the bone pain associated with monotherapy G-CSF; and number three, was the ability to control the relative dose intensity of chemotherapy. Also, more than 70% of oncologists stated that they strongly favor the combination of Plinabulin plus G-CSF over monotherapy G-CSF. And 65% said that they were likely to use a combination for the benefit of their patients. Our data generated to date demonstrates that Plinabulin plus G-CSF combination represents a significantly better option to the current standard of care. The complementary mechanism of action of both Plinabulin and G-CSF allow for a speedy onset, longer-lasting protection, superior absolute neutrophil count and reduced bone pain for patients. The key takeaway is that, we have the potential to set a new standard of care for CIN with this powerful combination approach. Just to recap the combination approach provides a significant number of benefits for clinicians patients and payers including significant reduced neutropenia with the goal of driving to stable sustained cycles to enable our oncologists to optimize chemotherapy for each patient. An improved bone pain profile to ensure an improved therapeutic experience and the potential for greater persistency. Clinical data that suggests anti-cancer activity, and finally, high receptivity among oncology community to advance the standard of care to Plinabulin plus G-CSF. Given the global nature of our trial and our strong ongoing discussions with key opinion leaders in the industry, all of this continues to build the case for Plinabulin as a potential game-changing therapy in cancer care. By developing Plinabulin to work with an enhanced G-CSF therapy, goal is to allow HCPs to provide stable chemotherapy doses, sustained chemotherapy cycles and the most effective chemotherapy regimen as possible. As we prepare for the upcoming data inflection points, we are well positioned to maximize the value of Plinabulin both in the U.S. and abroad through our go-to-market strategies. As we will file for Plinabulin in China and the U.S. for our U.S. and global commercialization plans, we are aligned with our development and regulatory time line. We are taking these steps to ensure that we can successfully launch and commercialize Plinabulin. With that, I'll turn the call over to Edward who will provide a financial update. Edward?

Edward Liu

Thanks Rich. I'll now briefly discuss our fourth quarter 2019 financial results. For greater details related to these results and our full year 2019 financial results, I refer you to our press release issued this morning and to our 6-K filing both of which can be accessed under the Investors section of our website. With that said, I will now highlight some of the key numbers. R&D expenses in the fourth quarter of 2019 were $12.6 million, compared to $13.3 million in the same period of last year. The decrease of $0.7 million was largely attributable to a $0.5 million decrease in clinical trial expenses and a $0.2 million decrease in non-cash share-based compensation. G&A expenses were $2.7 million in the fourth quarter of 2019, compared to $2.3 million for the same quarter of 2018. The $0.4 million increase was mainly due to an increase in employee salaries and welfare. Net loss attributable to BeyondSpring in the fourth quarter of 2019 was $14.1 million, compared to $14.7 million for the same period of last year. Our cash balance at the end of Q4 was $35.9 million. We are confident that our current cash resources are sufficient to support our clinical trials and NDA submissions in China and the U.S. for Plinabulin for both CIN and non-small cell lung cancer indications, as well as to advance our immuno-oncology pipeline and protein degradation research platform. With that, I will now turn the call back over to Lan to conclude. Lan?

Lan Huang

Thanks Edward. As I'm sure you will agree, we are extremely proud of our clinical development efforts and the flow of data that further validates Plinabulin's favorable drug profile to improve cancer care. Plinabulin is the only novel agent in development that combines both anticancer and CIN prevention potential due to its very unique mode of action. Looking ahead, we expect many important data and regulatory milestones in 2020, which will transform us from a clinical-stage company to a commercial-stage company. Together with our shareholders, investors and partners we are working hard to continue to create value and deliver innovative medicines to patients with severely unmatched medical need all over the world especially during COVID-19. I look forward to keeping you updated on our progress towards that goal in the coming months. Now, we are open to questions. Thank you.

Operator

Thank you. We will now begin the question-and-answer session. [Operator Instructions] Our first question comes from Maury Raycroft of Jefferies. Please go ahead.

Maury Raycroft

Hi. Good morning everyone and thank you for taking my question. Congrats on the endpoint change, it seems to make sense and could be an important update for the program. I'm wondering if you can talk more about the background of how the endpoint change came about. I guess for example was it based on feedback from advisers, FDA advice or from the broader market research that you did?

Lan Huang

Yes. Probably, Maury I can start answering your questions. So as you see that G-CSF is only standard of care currently for the last 30 years. Even with G-CSF, it's primary endpoint has been evolving in the last 30 years starts with severe neutropenia rate, right? And Neupogen compared to no therapy and later in 2000 when Neulasta has to be approved, an NDA actually spend a lot of energy also to get the new primary endpoint which is the duration of severe neutropenia, as the primary endpoint because it's a very good biomarker. And also you can have fewer patients to do the clinical trials and they also have to spend time to correlate DSN with rate. So currently as you see the DSN is a very good primary endpoint for the non-inferiority trials but it does have ceiling effect. With the TAC plus G-CSF it's – currently the DSN is around 1.2 days. So there is a pretty high ceiling and it's very hard to – it is good we can make it better than 1.2 day but the gap is pretty small. So with our discussion with our key opinion leaders and also probably also from our market research from the physicians we had a discussion with FDA. Because as you know G-CSF still did not meet the anemical needs of Grade four neutropenia. And Grade four neutropenia through literature research it is directly correlated to infection, FN, hospitalization and you can also test. And for G-CSF the current – is still at 83% to 93%. So that gives us a big range of reduction for our combination achievable. So if we can achieve that then you have a very good ANC number like what the physicians are saying which is going to maintain the defense for the immune system. And then also can enable the chemo dose for the optimum survivor benefit. So that was for the history and also our thinking. And then also we have aligned with the FDA currently. So probably I can also ask Ramon to add a few words to this.

Ramon Mohanlal

Yes. Thank you, Lan. First of all I would like to state that we are very confident that we will also see a benefit with DSN with the combination over monotherapy alone. But secondly probably more important is that the concept of DSN not only has been poorly understood by the scientific and medical community but also by the commercial community. DSN is a concept. It's very difficult to understand. The concept of having no Grade four neutropenia at all avoidance, total avoidance of Grade four neutropenia and that you have more patients with total avoidance of Grade four neutropenia with the combination of Plinabulin and Pactamycin that is so much clearer for clinicians, scientific community but also from a commercial perspective. It is not only clearer but also more impactful. So those are very arguments that we are able to convey successfully to the FDA and hence their willingness to discuss with us this change in primary endpoints. Thank you.

Maury Raycroft

Got it. That was very helpful. And then the second question I had was – I just wanted to clarify in the press release yesterday, it said a robust plan will be submitted to the FDA to prospectively validate this new primary endpoint I guess is that plan finalized? When will it be submitted? And will it be validated before you eventually file for approval just to clarify on that?

Lan Huang

Yes. So if I can just quickly answer this. This plan has been submitted actually. So, yes. So it's to validate that Phase I neutropenia or no Phase I neutropenia how it's related to the clinical consequences of such as infection or FN or hospitalization and that those kinds of consequences. And we will be able to locate it from our prospective from our 106 Study. And also we will do the integrated efficacy summary to also look at this.

Maury Raycroft

Got it. So in the 106 results that will basically validate the plan then?

Lan Huang

Yes.

Maury Raycroft

Okay. Okay. And then the last question I had was just – we're looking forward to the 106 update. And in your 3Q 2019 press release you stated the study 106 readout would be a final readout in the first half of 2020. But in the press release today it says the 106 update this quarter will be an interim. And so I was just wondering, if you could explain the change and talk about what specifics we could see in the interim update this quarter?

Lan Huang

Yes. So probably, I can answer this quickly. Yes, thanks so much for the great questions. So currently, I think, our time line is for the -- because of all of those very important time point to get to this interim analysis. As you also see there is the primary endpoint change. So currently the time line is 106 Phase 6 interim of like 120 patients will be done this quarter, which is quarter two. And then the final will be done in the second half of this year.

Maury Raycroft

Okay. And then the update this quarter what should we expect -- what kind of specific measures should we expect in that update to be recorded?

Lan Huang

So well at least you will see the -- the new primary endpoint the avoidance and prevention of Phase 1 neutropenia in the primary endpoint with certain p-value right? So we probably will save all the detailed data for a scientific conference.

Maury Raycroft

Got it. Okay. Thank you very much for answering my question. Congrats, again.

Lan Huang

Yeah. Thank you so much, Maurice. Thank you for your support.

Operator

Our next question comes from Andy Hsieh of William Blair. Please go ahead.

Andy Hsieh

Excellent. Thanks for taking my question. Hope everybody at BeyondSpring is well and staying healthy. And congratulations on a great year in 2019. So I have a couple probably more related to the non-small cell lung cancer. So I think, Ramon kind of talked about the first interim look and then the final analysis timing. Just wondering where you are in the second interim analysis? I think last quarter you mentioned that the number of events actually trigger the second analysis. So any sort of information that you can provide would be much appreciated.

Lan Huang

Yes. So probably I can start and Ramon can add to this. So we have reached our second interim analysis for the non-small cell lung cancer at the past event. So we will have a DSMB meeting soon. And with that then the DSMB of -- as a company, we really cannot it's blinded to us on the efficacy data. So with the meeting they will advise us to go forward or not based on the efficacy and also the safety data. So that's all we can say. So Ramon, you have anything to add?

Ramon Mohanlal

Yes. Thank you, Lan. I have nothing to add. Thank you.

Andy Hsieh

Okay. So I also have a related question and I don't know if this has been discussed before, but in the enrollment for Dublin-3 EGFR mutant patients are excluded and that's a little bit different from other second-line studies that we have seen given the fact that they could have already received drugs that specifically address these driver mutations. So just curious about the decision to exclude these patients?

Lan Huang

Yes. So probably, I can start on this. So as you know that currently TKI -- the Tarceva the Tagrisso they are very good for the EGFR mutant population right? So they are -- in our mind they're really not -- the more severely unmet medical need. With the EGFR wild-type patients if you look at the TAILOR study Tarceva actually was worse in the overall survivor versus docetaxel in the EGFR wild-type patients. And meanwhile, EGFR wild patients -- wild-type patients is considering around 85% of the Western population. So in our judgment we do think the lung cancer with EGFR wild-type are the more severely unmet medical need population. Those are the patients we need to develop the agent to help. So that's one of the rationale why we only focus on EGFR wild-type. And secondly, also this is a global trial. There is a difference in the percentage of EGFR mutant or wild-type in the different solicity. So for the western patients EGFR wild-type is around 85%. But in the Asian population it's around 70%. And the patient with biomutant actually live much longer than the EGFR wild-type patients. So it's largely a global trial if we do not get -- if we do not include -- if we do include the EGFR mutant patients then -- so the data will be very hard to analyze. And also EGFR mutant they are living much longer. So the study is going to be very long to conduct. So that's our reasoning why we are only targeting the EGFR wild-type patients. I don't know if I answered your question.

Andy Hsieh

Okay. Yes. No that's actually a perfect answer. Thanks for that. So last question I have, has to do with the endpoint change. So, Lan, I think you kind of talked about the goal of kind of positioning Plinabulin as all cancers, it's broad label. And so, help us understand the endpoint change for 106. Is that going to impact 105 as well, as you're waiting for the final analysis? I'm just curious, because ultimately you have to put all the data package together as one. So just curious, if you're planning on continuing the duration for -- duration endpoint for 105 and then a new endpoint for 106, or are you going to combine them together into one?

Lan Huang

So that's a great question. So as you see that the 105 primary endpoint is not going to change, because 105 is a non-inferiority trial, right? So DSN is a good endpoint for non-inferiority trial. So it's not going to change. Only is going to be changed in the 106, because that is the superiority trial with a new regime, which has potential to improve care as in we need more a clinical relevant and more robust endpoint to measure the superiority. So it's only going to be changed in the 106.

Andy Hsieh

I see. Okay. Yes, that makes sense.

Lan Huang

All together. Yes. 225. Yes.

Andy Hsieh

Okay, great. Thanks for taking all my questions and congratulations again.

Lan Huang

Thank you for you great questions. Thanks, Andy.

Operator

Our next question comes from Christopher Marai of Nomura. Please go ahead.

Christopher Marai

Hey. Good morning and thank you for taking my questions and congratulation on your updates, its great progress. So number one, just to clarify the change in the primary endpoint on Study 106, was that based on an FDA request, or did you initiate this request?

Lan Huang

Okay. Yes, we did initiate this discussion with FDA. Because this is also --

Christopher Marai

You did.

Lan Huang

Yes, it does. But we did discuss with them extensively.

Christopher Marai

Great. In terms of also, obviously, Study 105, there's been an interim analysis of additional data. Have you been able to look at that with respect to the new endpoint? I know it's a different study, it's not in combination, but in terms of prevention of Grade 4 neutropenia, have you any data from that 105 Phase 3 study that might be relevant here?

Lan Huang

Yes. So we do look at -- well, so the 105 Phase 3, if we look at the Grade 4 neutropenia rate in the first week, which is the -- we want to show the early onset of action we do see a benefit there as well. We have less Grade 4 neutropenia percentage in the first week in the 105 study, versus the Neulasta by itself. So you see a rapid offset as well. So that's like a better result. But for the primary endpoint, we're not changing, it's still DSN.

Christopher Marai

Got it. Okay. And then, do you anticipate to also, in your U.S. NDA filing, include data from -- the interim data from 106, as well as obviously the 105, you'd I think previously planned to submit for approval?

Lan Huang

Yes. So that's a great question. So it's always has for the U.S. FDA approval for broad label, we always have planned to submit 105 and 106 data together, because it takes two studies to validate. So they'll both be combined to submit.

Christopher Marai

Okay. And then just with respect to that then, on the 106 interim will you report the DSN endpoint as well as your new primary?

Lan Huang

Well, I don't know if we can at this moment, because usually the interim, I think, well, I cannot -- I have liberty to say, because this is going to be in discussion with the independent -- the decision. But we are confident that the Grade 4 neutropenia avoidance actually is more robust. And what, if it needs, yes, it should meet as well.

Christopher Marai

Got it. Okay. And then, any progress with EU regulators on the path? And how does this endpoint perhaps work with that process?

Lan Huang

Yes. So EU, I think, our strategy is to first file for U.S. and China. For that EU -- is we are planning to have meetings with EMA. And then talking to them about our studies. But of course now with COVID-19, it's a little bit hard to meet with anyone. So -- but it's in the planning to discuss with the EMA.

Christopher Marai

Okay. Excellent. And then I guess you recently presented some new data that highlights Plinabulin's ability to prevent tissue iron overload. So is there any plan to initiate a clinical study around that observation? It's obviously helpful in several diseases and probably also relatively low-hanging fruit like CIN. Maybe walk us through how you might look to explore that data set more clinically?

Lan Huang

Yes. So probably I can let Ramon to comment on this. Ramon has the most experience in this indication. Yes, Ramon?

Ramon Mohanlal

Yes, thank you. Yes, we certainly have plans as you indicate this is low-hanging fruit for us. This is an additional benefit that Plinabulin offers in the chemotherapy setting. So with chemotherapy as we know a common side effect is neutropenia. And that's where the Plinabulin indication in CIN comes in. But equally important as you know, a common side effect with chemotherapy is myelosuppression that often leads to anemia, so not only neutropenia but also anemia. The anemia then typically in chemotherapy patients is addressed by blood transfusion. And most cancer patients they have numerous and chronic blood transfusions over time. With blood transfusions patients get iron overload because then the block in the patient degrades and the iron becomes freely available. Iron that sits in tissue then creates iron overload and tissue damage. So Plinabulin has a very broad benefit in patients receiving chemotherapy. We -- the emphasis currently is on neutropenia prevention. But then, we have all these additional benefits, so with chemotherapy and anemia and the iron overload Plinabulin then also will have that major benefit. This is very relevant. This is a very relevant finding with Plinabulin because we see increasingly that the trend is that cancer patients live longer. Now cancer patients also -- in cancer patients, we also combine chemotherapy with immunotherapy. Therefore paces increasingly live longer. The trend now become for cancer patients to live longer. If then the patient had suffered had been exposed to iron overload due to blood transfusions that will impact the quality of life over time. So with cancer patients increasingly living longer, our attention will switch to how then can they live longer at a high quality of life with the lowest morbidity over time. Iron overload reduces morbidity over time and we see here a benefit that Plinabulin also will address that. And therefore it's a very big advantage looking forward.

Christopher Marai

Excellent. Thank you for the comprehensive reply. Appreciate that and congratulations on all the progress.

Lan Huang

Thank you very much Chris. Thank you for your support and your brilliant question.

Operator

This concludes the question-and-answer session. I would like to turn the conference back over to Dr. Huang for any closing remarks.

Lan Huang

Thank you so much for all your brilliant and insightful questions. And also thank you for all the listeners to our call and I hope everyone has a nice day and a nice week forward. Thank you.

Operator

This concludes today's conference call. You may disconnect your lines. Thank you for participating and have a pleasant day.